RESUMO
BACKGROUND: The aim of this systematic review and meta-analysis was to analyze the scientific evidence about the association between osteoporosis in postmenopausal women and the prevalence of apical periodontitis, assessed radiographically. MATERIAL AND METHODS: PRISMA Guidelines have been followed. The research question was: In adult women, does the presence or absence of osteoporosis affect the prevalence of AP, radiographically diagnosed? A systematic search was performed in PubMed/MEDLINE, Web of Science, Scopus and EMBASE. The meta-analyses were calculated with the Open Meta Analyst software. Risk of bias was assessed using the Newcastle Ottawa Scale. The certainty of evidence was assessed by GRADE. RESULTS: Four studies were selected. Meta-analysis showed an overall OR = 2.2 (95% CI = 0.94 - 4.97; p = 0.07), indicating that osteoporotic women had approximately twice the probability of having periapical lesions, compared to control women, although the difference was only marginally significant. The overall risk of bias of the included studies was moderate, and the certainty of evidence was low. CONCLUSIONS: Apical periodontitis, assessed as periapical lesion, is more frequently diagnosed in osteoporotic women, who are twice as likely to have periapical radiolucent lesions.
Assuntos
Osteoporose Pós-Menopausa , Periodontite Periapical , Humanos , Feminino , Periodontite Periapical/epidemiologia , Periodontite Periapical/complicações , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/epidemiologia , Prevalência , Pós-MenopausaRESUMO
Chicken meat is the most popularly consumed meat worldwide, with free-range and ethically produced meat a growing market among consumers. However, poultry is frequently contaminated with spoilage microbes and zoonotic pathogens which impact the shelf-life and safety of the raw product, constituting a health risk to consumers. The free-range broiler microbiota is subject to various influences during rearing such as direct exposure to the external environment and wildlife which are not experienced during conventional rearing practices. Using culture-based microbiology approaches, this study aimed to determine whether there is a detectable difference in the microbiota from conventional and free-range broilers from selected Irish processing plants. This was done through analysis of the microbiological status of bone-in chicken thighs over the duration of the meat shelf-life. It was found that the shelf-life of these products was 10 days from arrival in the laboratory, with no statistically significant difference (P > 0.05) evident between free-range and conventionally raised chicken meat. A significant difference, however, was established in the presence of pathogenesis-associated genera in different meat processors. These results reinforce past findings which indicate that the processing environment and storage during shelf-life are key determinants of the microflora of chicken products reaching the consumer.
Assuntos
Galinhas , Microbiota , Animais , Galinhas/microbiologia , Microbiologia de Alimentos , Embalagem de Alimentos/métodos , Carne/microbiologiaRESUMO
Dental caries is characterized by a dysbiotic shift at the biofilm-tooth surface interface, yet comprehensive biochemical characterizations of the biofilm are scant. We used metabolomics to identify biochemical features of the supragingival biofilm associated with early childhood caries (ECC) prevalence and severity. The study's analytical sample comprised 289 children ages 3 to 5 (51% with ECC) who attended public preschools in North Carolina and were enrolled in a community-based cross-sectional study of early childhood oral health. Clinical examinations were conducted by calibrated examiners in community locations using International Caries Detection and Classification System (ICDAS) criteria. Supragingival plaque collected from the facial/buccal surfaces of all primary teeth in the upper-left quadrant was analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. Associations between individual metabolites and 18 clinical traits (based on different ECC definitions and sets of tooth surfaces) were quantified using Brownian distance correlations (dCor) and linear regression modeling of log2-transformed values, applying a false discovery rate multiple testing correction. A tree-based pipeline optimization tool (TPOT)-machine learning process was used to identify the best-fitting ECC classification metabolite model. There were 503 named metabolites identified, including microbial, host, and exogenous biochemicals. Most significant ECC-metabolite associations were positive (i.e., upregulations/enrichments). The localized ECC case definition (ICDAS ≥1 caries experience within the surfaces from which plaque was collected) had the strongest correlation with the metabolome (dCor P = 8 × 10-3). Sixteen metabolites were significantly associated with ECC after multiple testing correction, including fucose (P = 3.0 × 10-6) and N-acetylneuraminate (p = 6.8 × 10-6) with higher ECC prevalence, as well as catechin (P = 4.7 × 10-6) and epicatechin (P = 2.9 × 10-6) with lower. Catechin, epicatechin, imidazole propionate, fucose, 9,10-DiHOME, and N-acetylneuraminate were among the top 15 metabolites in terms of ECC classification importance in the automated TPOT model. These supragingival biofilm metabolite findings provide novel insights in ECC biology and can serve as the basis for the development of measures of disease activity or risk assessment.
Assuntos
Cárie Dentária , Criança , Pré-Escolar , Estudos Transversais , Cárie Dentária/diagnóstico , Cárie Dentária/epidemiologia , Suscetibilidade à Cárie Dentária , Humanos , Metabolômica , North Carolina/epidemiologia , PrevalênciaRESUMO
Understanding the triad of host response, microbiome and disease status is potentially informative for disease prediction, prevention, early intervention and treatment. Using longitudinal assessment of saliva and disease status, we demonstrated that partial least squares modelling of microbial, immunological and clinical measures, grouped children according to future dental disease status. Saliva was collected and dental health assessed in 33 children aged 4 years, and again 1-year later. The composition of the salivary microbiome was assessed and host defence peptides in saliva were quantified. Principal component analysis of the salivary microbiome indicated that children clustered by age and not disease status. Similarly, changes in salivary host defence peptides occurred with age and not in response to, or preceding dental caries. Partial least squares modelling of microbial, immunological and clinical baseline measures clustered children according to future dental disease status. These data demonstrate that isolated evaluation of the salivary microbiome or host response failed to predict dental disease. In contrast, combined assessment of both host response together with the microbiome revealed clusters of health and disease. This type of approach is potentially relevant to myriad diseases that are modified by host-microbiome interactions.
Assuntos
Microbiota , Saliva/microbiologia , Proteínas e Peptídeos Salivares/análise , Doenças Estomatognáticas/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Saúde Bucal , RNA Ribossômico 16S/genética , Saliva/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Doenças Estomatognáticas/metabolismo , Doenças Estomatognáticas/microbiologiaRESUMO
The microbiological characteristics of both caries and periodontal disease show significant change from those in health. In both instances, there is evidence of co-association of different organisms into consortia. AIM: We review and summarize a number of issues pertinent to the community organization and functional activity of the bacterial populations resident on supra- and subgingival tooth surface and the influence of these populations on disease. METHODS: A literature review was undertaken with a particular emphasis on recent publications involving high-throughput, deep sequencing approaches to the analysis of microbial populations and their functional activity. RESULTS: There is increasing evidence to suggest that both caries and periodontal disease represent dysbiotic states of the oral microbiome. The mode of acquisition of the oral microbial communities may be less passive than previously recognized but once established remains relatively stable within an individual although there are very significant site variations. A repertoire of stable dysbiotic states may occur in both caries and periodontitis involving different microbial community structures with potentially similar functional properties. CONCLUSIONS: The processes which underlie the development and stability of microbial populations in the healthy mouth are fundamental to understanding how these populations are transformed into a dysbiotic state in disease.
Assuntos
Cárie Dentária/microbiologia , Boca/microbiologia , Doenças Periodontais/microbiologia , Disbiose , Humanos , Microbiota , SimbioseRESUMO
Current understanding of dental caries considers this disease a demineralization of the tooth tissues due to the acid produced by sugar-fermenting microorganisms. Thus, caries is considered a diet- and pH-dependent process. We present here the first metagenomic analysis of the bacterial communities present at different stages of caries development, with the aim of determining whether the bacterial composition and biochemical profile are specific to the tissue affected. The data show that microbial composition at the initial, enamel-affecting stage of caries is significantly different from that found at subsequent stages, as well as from dental plaque of sound tooth surfaces. Although the relative proportion of Streptococcus mutans increased from 0.12% in dental plaque to 0.72% in enamel caries, Streptococcus mitis and Streptococcus sanguinis were the dominant streptococci in these lesions. The functional profile of caries-associated bacterial communities indicates that genes involved in acid stress tolerance and dietary sugar fermentation are overrepresented only at the initial stage (enamel caries), whereas other genes coding for osmotic stress tolerance as well as collagenases and other proteases enabling dentin degradation are significantly overrepresented in dentin cavities. The results support a scenario in which pH and diet are determinants of the disease during the degradation of enamel, but in dentin caries lesions not only acidogenic but also proteolytic bacteria are involved. We propose that caries disease is a process of varying etiology, in which acid-producing bacteria are the vehicle to penetrate enamel and allow dentin degrading microorganisms to expand the cavity.
Assuntos
Bactérias/classificação , Cárie Dentária/microbiologia , Metagenoma/genética , Ácidos , Bactérias/genética , Proteínas de Bactérias/análise , Candida/classificação , Colagenases/análise , DNA Bacteriano/análise , Cárie Dentária/classificação , Esmalte Dentário/microbiologia , Placa Dentária/microbiologia , Dentina/microbiologia , Sacarose Alimentar/metabolismo , Progressão da Doença , Fermentação/genética , Humanos , Concentração de Íons de Hidrogênio , Lactobacillus/classificação , Osmose , Peptídeo Hidrolases/análise , Prevotella/classificação , Análise de Sequência de DNA , Streptococcus mitis/enzimologia , Streptococcus mitis/isolamento & purificação , Streptococcus mutans/enzimologia , Streptococcus mutans/isolamento & purificação , Streptococcus sanguis/enzimologia , Streptococcus sanguis/isolamento & purificaçãoRESUMO
We aimed to determine the bacterial diversity of different oral micro-niches and to assess whether saliva and plaque samples are representative of oral microbial composition. We took minute samples from each surface of the individual teeth and gingival crevices of two healthy volunteers (112 samples per donor), as well as samples from the tongue dorsum and non-stimulated and stimulated saliva. DNA was extracted from 67 selected samples of each donor, and the 16S rRNA gene was amplified by PCR and pyrosequenced to obtain, on average, over 2,700 reads per sample, which were taxonomically assigned to obtain a geographic map of bacterial diversity at each tooth and sulcus location. Analysis of the data shows considerable differences in bacterial composition between teeth at different intra-oral locations and between surfaces of the same tooth. The most pronounced differences were observed in incisors and canines, where genera like Streptococcus were found at 40% to 70% on the vestibular surfaces but were almost absent on the lingual sides. Saliva samples, especially non-stimulated saliva, were not representative of supra-and subgingival plaque in the two individuals tested. We suggest that more precise sampling is required for the proper determination of oral microbial composition and to relate that diversity to epidemiological, clinical, and etiological parameters.
Assuntos
Bactérias/classificação , Boca/microbiologia , Actinobacillus/classificação , Actinomycetaceae/classificação , Adulto , Dente Pré-Molar/microbiologia , Capnocytophaga/classificação , Dente Canino/microbiologia , DNA Bacteriano/análise , Placa Dentária/microbiologia , Fusobacterium/classificação , Gengiva/microbiologia , Haemophilus/classificação , Humanos , Incisivo/microbiologia , Masculino , Dente Molar/microbiologia , Mucosa Bucal/microbiologia , Palato/microbiologia , Reação em Cadeia da Polimerase , Prevotella/classificação , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Saliva/microbiologia , Streptococcus/classificação , Língua/microbiologia , Veillonella/classificação , Adulto JovemRESUMO
We present the results of an exploratory study of the bacterial communities from the human oral cavity showing the advantages of pyrosequencing complex samples. Over 1.6 million reads from the metagenomes of eight dental plaque samples were taxonomically assigned through a binning procedure. We performed clustering analysis to discern if there were associations between non-caries and caries conditions in the community composition. Our results show a given bacterial consortium associated with cariogenic and non-cariogenic conditions, in agreement with the existence of a healthy oral microbiome and giving support to the idea of dental caries being a polymicrobial disease. The data are coherent with those previously reported in the literature by 16S rRNA amplification, thus giving the chance to link gene functions with taxonomy in further studies involving larger sample numbers.
Assuntos
Metagenoma , Metagenômica/métodos , Boca/microbiologia , Boca/fisiologia , Bactérias/classificação , Bactérias/genética , Biodiversidade , DNA Bacteriano/química , DNA Bacteriano/genética , Humanos , Análise de Sequência de DNA/métodosRESUMO
Eusociality is widely considered a major evolutionary transition. The socially polymorphic sweat bee Halictus rubicundus, solitary in cooler regions of its Holarctic range and eusocial in warmer parts, is an excellent model organism to address this transition, and specifically the question of whether sociality is associated with a strong barrier to gene flow between phenotypically divergent populations. Mitochondrial DNA (COI) from specimens collected across the British Isles, where both solitary and social phenotypes are represented, displayed limited variation, but placed all specimens in the same European lineage; haplotype network analysis failed to differentiate solitary and social lineages. Microsatellite genetic variability was high and enabled us to quantify genetic differentiation among populations and social phenotypes across Great Britain and Ireland. Results from conceptually different analyses consistently showed greater genetic differentiation between geographically distant populations, independently of their social phenotype, suggesting that the two social forms are not reproductively isolated. A landscape genetic approach revealed significant isolation by distance (Mantel test r = 0.622, P < 0.001). The Irish Sea acts as physical barrier to gene flow (partial Mantel test r = 0.453, P < 0.01), indicating that geography, rather than expression of solitary or social behaviour (partial Mantel test r = -0.238, P = 0.053), had a significant effect on the genetic structure of H. rubicundus across the British Isles. Although we cannot reject the hypothesis of a genetic underpinning to differences in solitary and eusocial phenotypes, our data clearly demonstrate a lack of reproductive isolation between the two social forms.
Assuntos
Abelhas/genética , Fluxo Gênico , Genética Populacional , Comportamento Social , Animais , Teorema de Bayes , Análise por Conglomerados , DNA Mitocondrial/genética , Feminino , Variação Genética , Haplótipos , Irlanda , Repetições de Microssatélites , Fenótipo , Alinhamento de Sequência , Análise de Sequência de DNA , Reino UnidoRESUMO
BACKGROUND: Low high-density lipoprotein cholesterol (HDL-C) is associated with increased risk for developing coronary artery disease. Cardiovascular disease is characterized by increased intima-media thickness (IMT) and arterial stiffness, but the effect of low HDL on these measurements has not been reported. MATERIALS AND METHODS: We studied 18 apparently healthy subjects from families with low HDL-C and 18 control subjects, which were pair-matched to maximize statistical power. Intima-media thickness was assessed using ultrasound examination of the carotid arteries. Arterial stiffness was measured using applanation tonometry on the radial artery and pulse-wave analysis to obtain central aortic pulse-pressure waveform, from which the augmentation index, a measure of global large artery stiffness, was calculated. RESULTS: Low HDL subjects (age 41 +/- 3 years, BMI 26.6 +/- 1.0 kg m(-2) had significantly lower HDL-C than the control subjects (age 41 +/- 3 years, BMI 26.5 +/- 1.0 kg m-2; 1.00 +/- 0.05 vs. 1.49 +/- 0.09 mmol L-1, low HDL vs. control subjects, P < 0.0001). Subjects with low HDL-C had significantly thicker mean IMTs than the control subjects (0.77 +/- 0.03 vs. 0.70 +/- 0.02 mm, low HDL vs. control subjects, P < 0.01). The maximal (0.99 +/- 0.04 vs. 0.89 +/- 0.03 mm, P < 0.01), far wall (0.76 +/- 0.04 vs. 0.69 +/- 0.02 mm, P < 0.05) and carotid bulb (1.11 +/- 0.06 vs. 0.97 +/- 0.04 mm) IMTs were also significantly increased, whereas the mean common carotid and the internal artery IMT were not. The age-related increase in mean IMT was more pronounced in the low HDL subjects than the control subjects (P < 0.01 for difference between elevations of age vs. IMT slopes). There were no differences in central pressure augmentation, the augmentation index, peripheral or central blood pressures between the groups. CONCLUSIONS: A low HDL-C concentration is associated with thickening of carotid IMT independent of other risk factors in healthy affected members of low HDL families.
Assuntos
Doenças das Artérias Carótidas/patologia , HDL-Colesterol/sangue , Doença da Artéria Coronariana/etiologia , Túnica Média/diagnóstico por imagem , Adulto , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/etiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Túnica Íntima/diagnóstico por imagem , UltrassonografiaRESUMO
Essential hypertension is a common disease the genetic determinants of which have been difficult to unravel because of its clinical heterogeneity and complex, multifactorial, polygenic etiology. Based on our observations that alpha(1)-Na,K-ATPase (ATP1A1) and renal-specific, bumetanide-sensitive Na,K,2Cl-cotransporter (NKCC2) genes interactively increase susceptibility to hypertension in the Dahl salt-sensitive hypertensive (Dahl S) rat model, we investigated whether parallel molecular genetic mechanisms might exist in human essential hypertension in a relatively genetic homogeneous cohort in northern Sardinia. Putative ATP1A1-NKCC2 gene interaction was tested by comparing hypertensive patients (blood pressure [BP] >165/95 mm Hg) with normotensive controls age >60 years with BP <140/85 mm Hg. Genotype analysis with microsatellite markers revealed conformation to Hardy-Weinberg proportions for 6 alleles of both ATP1A1 (D1S453) and NKCC2 (NKCGT7) markers, respectively. Two-by-six chi(2) analysis of alleles identified overrepresentation of ATP1A1 No. 4 and NKCC2 No. 4 alleles, respectively, in hypertensives compared with controls. With a qualitative trait framework, single-gene analysis detected association of both the ATP1A1 No. 4 allele (P=0.004, chi(2)=8.094, df=1) and the NKCC2 No. 4 allele (P=0.0002, chi(2)=14.279, df=1) with moderate to severe hypertension. Digenic analysis revealed that ATP1A1 No. 4-NKCC2 No. 4 allele interaction increases susceptibility to hypertension (P<0.0001, chi(2)=22.3, df=1) beyond levels obtained in single-gene analysis. Analysis was also performed in a quantitative trait framework with BP as the continuous trait parameter. Digenic analysis of ATP1A1 No. 4-NKCC2 No. 4 allele interaction revealed significant association with systolic (1-way ANOVA, P=0.000076) and diastolic (P=0.00099) BP. Interaction was corroborated by 2x2 factorial ANOVA for interaction (systolic BP interaction term, P<0.05, diastolic BP interaction term, P=0.035). The data are compelling that ATP1A1 and NKCC2 genes are candidate interacting hypertension-susceptibility loci in human essential hypertension and affirm gene interaction as an important genetic mechanism underlying hypertension susceptibility. Although corroboration in other cohorts and identification of functionally significant mutations are imperative next steps, the data provide a genotype-stratification scheme, with 4-fold predictive value (odds ratio, 4.28; 95% confidence interval, 2.29 to 8.0), which could help decipher the complex genetics of essential hypertension.
Assuntos
Proteínas de Transporte/genética , Hipertensão/genética , ATPase Trocadora de Sódio-Potássio/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Característica Quantitativa Herdável , Simportadores de Cloreto de Sódio-PotássioRESUMO
OBJECTIVE: 11beta-Hydroxylase and aldosterone synthase are two highly homologous genes involved in different forms of human hypertension and in different animal models of hypertension. It has been shown that the conservative substitution D147E in the human CYP11B2 gene results in an increased production of corticosterone and aldosterone in vitro. A gene conversion between the CYP11B1 and CYP11B2 genes could be responsible for such a substitution. METHODS: In this study we investigated the presence of the mutation D147E of CYP11B2 in a group of 128 patients with primary aldosteronism, 68 patients with essential hypertension and increased corticosterone production and in 48 normal volunteers. RESULTS AND CONCLUSIONS: We did not identify any patient carrying this mutation, indicating that if it exists it is very rare and so has no relevance in determining the increased steroid excretion seen in some subtypes of human hypertension.
Assuntos
Aldosterona/biossíntese , Corticosterona/biossíntese , Citocromo P-450 CYP11B2/genética , Hipertensão/sangue , Hipertensão/genética , Mutação/genética , Idoso , Aldosterona/sangue , Corticosterona/sangue , Éxons/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Renina/sangue , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
In a large cohort (no. = 361) of NIDDM probands and their concordant/discordant siblings from no. = 132 families we studied: 1. the levels of plasma prorenin in non affected siblings of NIDDM probands as opposed to normal subjects without family history of diabetes, and 2. whether plasma prorenin raises in parallel to urinary protein loss in NIDDM patients. Prorenin (solid-phase trypsin) and micro-macroalbuminuria (radioimmunoassay) were evaluated. Plasma prorenin was higher in NIDDM probands and siblings than in non NIDDM siblings (37+/-31 vs. 25+/-15 ng/ml/h, p<0.0005) who, in turn, showed higher plasma prorenin than non diabetic controls without family history of diabetes (25+/-15 vs. 17+/-8 ng/ml/h, p<0.005). Plasma prorenin was higher in NIDDM siblings of micro-macroalbuminuric probands than in NIDDM siblings of non micro-macroalbuminuric probands (40+/-26 vs. 29+/-20 ng/ml/h, mean +/- SD, p = 0.0058) whereas no difference was found among non diabetic siblings (24+/-14 vs. 22+/-11 ng/ml/h, NS). Our data confirm that plasma prorenin is elevated in NIDDM patients, and show: 1. that the raise of plasma prorenin in non-NIDDM siblings of a diabetic patient does not depend entirely from the presence of diabetes, and 2. that plasma prorenin in NIDDM probands and their concordant siblings goes along with micro-macroalbuminuria.
Assuntos
Diabetes Mellitus Tipo 2/genética , Precursores Enzimáticos/sangue , Renina/sangue , Pressão Sanguínea , Estudos de Coortes , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria/urina , Triglicerídeos/sangueRESUMO
Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29+/-0.52 mmol/L, systolic and diastolic blood pressure 149+/-6 and 97+/-2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both -1.09 mmol/L, P=0.001), systolic and diastolic blood pressure (-8 and -5 mm Hg, both P=0.001), and pulse pressure (-3 mm Hg, P=0.011) and blunted the blood pressure increase caused by the cold pressor test (-4 mm Hg, P=0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (P=0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/complicações , Hipertensão/tratamento farmacológico , Pravastatina/uso terapêutico , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Colesterol/sangue , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Temperatura Baixa , Estudos Cross-Over , Método Duplo-Cego , Endotelinas/sangue , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertensão/complicações , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Pravastatina/efeitos adversos , Pravastatina/farmacologia , Resultado do TratamentoRESUMO
The basic requirement for declaring an association study positive is that the "hypertension-favoring" allele is more frequent in hypertensive cases than in normotensive controls. However, both positive and negative associations with hypertension have been found for the same polymorphism when studied in different populations. In the present study, we addressed the question of the possible cause(s) of this discrepancy among populations by using the alpha-adducin polymorphism as a paradigm. Four hundred ninety hypertensives and 176 normotensives enrolled in Sassari, Italy, and 468 hypertensives and 181 normotensives enrolled in Milano, Italy, were genotyped for the alpha-adducin Gly460Trp polymorphism. The blood pressure response to 2 months of hydrochlorothiazide therapy could be evaluated in 143 (85 in Sassari and 58 in Milano) hypertensives with and without the 460Trp alpha-adducin allele. The alpha-adducin 460Trp allele was not significantly more frequent in hypertensives in the Sassari population but was more frequent in hypertensives than in normotensives in Milano (P=0.019). Basal plasma renin activity was lower and blood pressure fall after diuretic therapy more pronounced (P<0.01) in hypertensives carrying at least one 460Trp allele than in Gly460Gly homozygotes, irrespective of their membership in the Sassari or Milano cohort. The effect of alpha-adducin genotype in predicting basal plasma renin activity and blood pressure decrease with diuretic treatment is similar in Sassari and Milano, despite the lack of association of the alpha-adducin genotype with hypertension in Sassari.
Assuntos
Pressão Sanguínea/genética , Proteínas de Ligação a Calmodulina/genética , Hipertensão/genética , Sódio/metabolismo , Idoso , Alelos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Genética Populacional , Genótipo , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Renina/sangue , Sódio/sangueRESUMO
BACKGROUND: The surgical treatment of type A aortic dissection is usually palliative and most surviving patients remain at considerable risk to develop late postoperative complications; consequently, there is the need for careful long-term follow-up. The present study reports on our experience in the postoperative follow-up of a consecutive series of patients with type A aortic dissection. METHODS: Between January 1986 and December 1996, 89 patients underwent emergency surgery for type A acute aortic dissection; the overall hospital mortality rate was 22% (20/89). This study includes the 69 hospital survivors (49 men and 20 women). Forty-six patients had ascending aortic graft replacement, 13 patients underwent replacement of aortic valve and ascending aorta by a composite graft. The surgical repair was extended to the aortic arch in 5 patients. All patients were serially evaluated by clinical examination and imaging techniques (transthoracic echocardiography in all patients, magnetic resonance imaging in 40, transesophageal echocardiography in 33 and computed tomography in 25). Follow-up was complete in 97% of patients (two patients were lost to follow-up and excluded from the study) and extended to a maximum of 152 months (mean 74 +/- 39 months). The postoperative quality of life was assessed by a questionnaire in 51 current survivors. Risk factors for cardiovascular death, reoperation and poor quality of life were investigated with univariate and multivariate analysis. RESULTS: During the follow-up period 15 patients (22%) died; in 13 cases death was due to cardiovascular causes and in 6 of them it was related to aortic disease. The Kaplan-Meier survival was 92 +/- 3%, 87 +/- 5%, 78 +/- 6% and 70 +/- 8% at 2, 4, 6 and 8 years, respectively. A persistent aortic dissection was demonstrated in 50 patients (75%) and 42 of them showed the presence of flow in the false lumen. A dilatation of one or more aortic segments was found in 59 patients (88%), with a diameter > or = 50 mm in 17 and > or = 60 mm in 8. In 30 patients who underwent transesophageal echocardiography the relation between aortic dimensions and flow pattern in the false lumen was examined; the presence of aneurysmal dilatation with a diameter > or = 50 mm was significantly correlated with a "high flow" pattern. Ten patients (15%) underwent reoperation from 13 to 83 months postoperatively. Reoperation was indicated for: sinus of Valsalva aneurysm and severe aortic regurgitation (2 patients), severe aortic regurgitation (2 patients), aneurysm of the arch (1 patient), thoracoabdominal aneurysm (1 patient), periprosthetic pseudoaneurysm (4 patients). The hospital mortality rate was 20% (2 patients). Sixty-two% of current survivors are asymptomatic; 30 patients returned to their predissection status. Quality of live is judged "good" by 23 patients, "fairly good" by 21 patients and "poor" by 7 patients. No significant independent risk factor for cardiovascular death, reoperation and poor quality of life was identified. CONCLUSIONS: The long-term prognosis after surgical treatment of type A aortic dissection is not satisfactory because of a significant risk of late complications. However, the results of our study can be judged fairly good, particularly if we consider the natural history of the disease.
Assuntos
Aneurisma Aórtico/cirurgia , Dissecção Aórtica/cirurgia , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/mortalidade , Dilatação Patológica/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Recidiva , Reoperação , Fatores de Risco , UltrassonografiaAssuntos
Hiperaldosteronismo/etiologia , Hipertensão/etiologia , Mineralocorticoides , Adolescente , Neoplasias das Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Adulto , Aldosterona/metabolismo , Animais , Criança , Pré-Escolar , Glucocorticoides/uso terapêutico , Glycyrrhiza/efeitos adversos , Humanos , Hiperaldosteronismo/tratamento farmacológico , Hiperplasia , Hipertensão/genética , Hipertensão/fisiopatologia , Lactente , Mineralocorticoides/fisiologia , Plantas Medicinais , Ratos , Ratos Endogâmicos SHR , SíndromeRESUMO
BACKGROUND: Several approaches have been used for noninvasive estimation of right atrial pressure (RAP), but, no currently available method has gained any definite validation. The purpose of this study was to evaluate the accuracy of two-dimensional and Doppler echocardiography in estimating mean RAP in patients with cardiac disease. METHODS: We examined the relation of mean RAP to right atrial size and function, size and respiratory changes of inferior vena cava and Doppler parameters of tricuspid and hepatic vein flow in 114 consecutive patients (77 men, 37 women; mean age 57 +/- 12 years) with various cardiac diseases undergoing cardiac catheterization. Echocardiographic studies were performed within 24 hours before catheterization (mean interval 6 +/- 3 hours). Patients were assigned to 3 groups according to the values of mean RAP (group 1, < or = 8 mmHg; group 2, between 9 and 12 mmHg; group 3, > 12 mmHg). RESULTS: Mean RAP ranged from 3 to 20 mmHg (mean 9.1 +/- 4.3 mmHg). It correlated most strongly with the collapsibility index of inferior vena cava (IVCCI) (r = -0.76), minimal inspiratory diameter of inferior vena cava (r = 0.72) and deceleration time of early tricuspid flow (DT) (r = -0.61). Discriminant analysis demonstrated that IVCCI and DT were major determinants of mean RAP with 81.6% of cases correctly assigned to study groups: 96% of patients of group 1 and 87% of patients of group 3 were identified, whereas the accuracy in identifying the patients of group 2 was lower (46%). An IVCCI > 45% was the best cutoff point in predicting a mean RAP < or = 8 mmHg; an IVCCI < 35% and a DT < 150 msec were the best cutoff points in predicting a mean RAP > or = 15 mmHg. The best multivariate equation predicting mean RAP was: mean RAP = 23.3 - 0.2 IVCCI -0.026 DT (r = 0.80, R2 = 0.64). This equation was 81% sensitive and 84% specific in detecting a mean RAP < or = 8 mmHg and 74% sensitive and 97% specific in detecting a mean RAP > 12 mmHg. CONCLUSIONS: Mean RAP can be estimated noninvasively by two-dimensional and Doppler echocardiography. The combined analysis of IVCCI and DT provides an accurate prediction on mean RAP < or = 8 mmHg and > 12 mmHg, whereas the prediction of intermediate values is less accurate.
Assuntos
Função do Átrio Direito/fisiologia , Pressão Sanguínea/fisiologia , Cardiopatias/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco , Ecocardiografia , Ecocardiografia Doppler , Feminino , Cardiopatias/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: We stress the importance of dynamic radiologic studies of swallowing in the patients submitted to reconstructive laryngectomy. MATERIAL AND METHODS: January, 1989, to December, 1996, we examined 36 patients submitted to reconstructive laryngectomy, namely cricohyoidoepiglottopexy in 34 cases, cricohyoidopexy in 1 case and Guerrier's cricohyoidoepiglottopexy in 1 case. Dynamic radiologic studies were performed with fluoroscopic videorecording (Sony U-Matic RM 580) from an X-ray unit. The study was performed with the patients standing or sitting, initially acquiring AP and LL fluoroscopic images of the oropharyngeal region at rest and during swallowing. The patients then swallowed 2 boluses of 5 ml liquid (60%) and semiliquid (250%) barium. When aspiration was suspected, we began with a 2-ml bolus. RESULTS: The patients were grouped by symptoms: group A patients had no symptoms, group B patients had dysphagia and group C patients presented aspiration. The functional changes were: reduced pharyngeal contraction, reduced epiglottis deflection, reduced hyoid bone elevation, aspiration, altered upper esophageal sphincter function. The organic alterations were: parapharyngeal diverticulum, pharyngeal stenosis, posterior pharyngeal wall introflexion. Three group A patients had severe posterior pharyngeal wall introflexion, 4 had marked retention and 2 of them presented postswallowing aspiration. Two group B patients had major retention, 1 cricopharyngeal incoordination, 3 posterior pharyngeal wall introflexion, 2 a pseudodiverticulum and 2 a luminal stenosis. Seven group C patients had intraswallowing and 3 postswallowing aspiration. CONCLUSION: The videofluorographic identification of organic and functional complications, sometimes unknown in asymptomatic patients, is useful for therapy and suggests the speech specialist the best compensatory mechanism to improve the patients' swallowing and consequently their quality of life. Moreover, videofluorography of swallowing is a very useful tool in the follow-up, to monitor treatment outcome after rehabilitation.
Assuntos
Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/fisiopatologia , Deglutição , Laringectomia/efeitos adversos , Laringe/diagnóstico por imagem , Laringe/fisiopatologia , Pneumonia Aspirativa/diagnóstico por imagem , Pneumonia Aspirativa/fisiopatologia , Transtornos de Deglutição/etiologia , Humanos , Laringe/cirurgia , Pneumonia Aspirativa/etiologia , Radiografia , Gravação em VídeoRESUMO
Carbenoxolone potentiates the mineralocorticoid activity of endogenous glucocorticoid hormones by inhibiting the enzyme 11 beta-hydroxysteroid dehydrogenase, which converts cortisol and corticosterone to inactive 11-oxo-derivatives. We addressed the question of whether glucocorticoid activity is also affected by carbenoxolone. Using a rat model involving low dose corticosterone treatment, we found that carbenoxolone neither potentiated nor inhibited the modest increases in blood pressure or reductions in weight gain caused by steroid treatment. Other indices of glucocorticoid activity including white blood cell number, thymus weight, and down regulation of the glucocorticoid receptor were unaffected. In vitro studies with liver and kidney cytosol preparations indicated that carbenoxolone did compete for 3H-dexamethasone binding sites. Carbenoxolone was 5-10 times more effective than glycyrrhetinic acid, 20-30 thousand times less effective than dexamethasone, and is therefore, approximately 1000 times less effective than corticosterone. Analysis of dexamethasone-binding curves indicated a single class of receptor. We conclude that carbenoxolone at the dose tested does not have intrinsic glucocorticoid activity in vivo, nor does it modulate the activities of corticosterone. Carbenoxolone binds weakly to the glucocorticoid receptor. It is not clear whether this weak affinity accounts for some or any of the direct in vitro effects of high concentrations of carbenoxolone that others have described.