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INTRODUCTION: The C-Brace microprocessor stance and swing control orthosis was designed to overcome safety and functional limitations of traditional knee-ankle-foot orthoses (KAFOs) for individuals with lower limb paresis. However, a systematic comparison to established KAFO types has not been performed in a bigger sample. METHODS: International multicenter, randomized, controlled, cross-over clinical trial. Legacy KAFO users at risk of falling were randomized to KAFO/C-Brace or C-Brace/KAFO use for three months with each orthosis. Primary outcome was balance assessed with the Berg Balance Scale (BBS). Secondary outcomes were falls, mobility, function, and quality of life. RESULTS: Intention-to-treat analysis with 102 participants. With the C-Brace, the BBS improved by 3.3 ± 6.3 points (p < 0.0001). Significantly fewer participants presented BBS scores <40 indicative of increased fall risk (16 vs. 36, p = 0.018). Mean falls reduced from 4.0 ± 16.8 to 1.1 ± 3.3 (p = 0.002). Outcomes for function, mobility, and quality of life showed significant improvements with the C-Brace. DISCUSSION: The improvements in fall risk and mobility can be attributed to the stumble recovery and controlled knee flexion during weight bearing of the C-Brace and have a positive impact on the quality of life of users. CONCLUSION: The C-Brace represents an option for KAFO users with increased fall risk and reduced mobility.
When prescribing traditional knee-ankle-foot orthoses (KAFOs), their known limitations, such as limited function and mobility, and the requirement to walk with compensatory mechanisms, especially on non-level terrains, should be considered.For patients with compromised balance and increased risk of falling when using a traditional KAFO, a microprocessor stance and swing control orthosis (MP-SSCO) may be considered as an orthotic option to reduce their fall risk.For patients with mobility restrictions using a traditional KAFO, a MP-SSCO may be considered to improve function, mobility, reintegration into normal living, and quality of life.
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Reference intervals for laboratory test results have to be appropriate for the population in which they are used to be clinically useful. While sex and age are established partitioning criteria, patients' origin also influences laboratory test results, but is not commonly considered when creating or applying reference intervals. In the German population, stratification for ethnicity is rarely performed, and no ethnicity-specific hematology reference intervals have been reported yet. In this retrospective study, we investigated whether specific reference intervals are warranted for the numerically largest group of non-German descent, individuals originating from Turkey. To this end, we analyzed 1,314,754 test results from 167,294 patients from six German centers. Using a name-based algorithm, 1.9% of patients were identified as originating from Turkey, in line with census data and the algorithm's sensitivity. Reference intervals and their confidence intervals were calculated using an indirect data mining approach, and Turkish and non-Turkish reference limits overlapped completely or partially in nearly all analytes, regardless of age and sex, and only 5/144 (3.5%) subgroups' reference limits showed no overlap. We therefore conclude that the current practice of using common reference intervals is appropriate and allows correct clinical decision-making in patients originating from Turkey.
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Análisis Químico de la Sangre , Emigrantes e Inmigrantes , Etnicidad , Femenino , Alemania/etnología , Humanos , Masculino , Valores de Referencia , Estudios Retrospectivos , Turquía/etnologíaRESUMEN
OBJECTIVES: Assessment of children's laboratory test results requires consideration of the extensive changes that occur during physiological development and result in pronounced sex- and age-specific dynamics in many biochemical analytes. Pediatric reference intervals have to account for these dynamics, but ethical and practical challenges limit the availability of appropriate pediatric reference intervals that cover children from birth to adulthood. We have therefore initiated the multi-center data-driven PEDREF project (Next-Generation Pediatric Reference Intervals) to create pediatric reference intervals using data from laboratory information systems. METHODS: We analyzed laboratory test results from 638,683 patients (217,883-982,548 samples per analyte, a median of 603,745 test results per analyte, and 10,298,067 test results in total) performed during patient care in 13 German centers. Test results from children with repeat measurements were discarded, and we estimated the distribution of physiological test results using a validated statistical approach (kosmic). RESULTS: We report continuous pediatric reference intervals and percentile charts for alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, γ-glutamyl-transferase, total protein, albumin, creatinine, urea, sodium, potassium, calcium, chloride, anorganic phosphate, and magnesium. Reference intervals are provided as tables and fractional polynomial functions (i.e., mathematical equations) that can be integrated into laboratory information systems. Additionally, Z-scores and percentiles enable the normalization of test results by age and sex to facilitate their interpretation across age groups. CONCLUSIONS: The provided reference intervals and percentile charts enable precise assessment of laboratory test results in children from birth to adulthood. Our findings highlight the pronounced dynamics in many biochemical analytes in neonates, which require particular consideration in reference intervals to support clinical decision making most effectively.
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Fosfatasa Alcalina , gamma-Glutamiltransferasa , Adulto , Alanina Transaminasa , Aspartato Aminotransferasas , Niño , Humanos , Recién Nacido , Valores de ReferenciaRESUMEN
An 8-year-old spayed female 32 kg Labrador retriever was presented for further investigation into the underlying cause of dyspnea, stertor, and sleep apnea present for three months and worsening over 30 days. There were significant reduction in airflow through the nares and loud inspiratory stridor. Thoracic and cervical radiographs made were normal. A skull CT and retrograde rhinoscopy showed a mass occluding the majority of the nasopharynx above the caudal third of the hard palate. The main differential diagnoses included a neoplastic mass vs. inflammatory mass vs. cyst vs. mucous obstruction. There was no destruction of nasal turbinates, making a benign etiology more likely. Biopsy of the mass showed an inflammatory process. En bloc excision of the mass was performed via ventral rhinotomy without complication. Histopathology of the excised mass revealed it to be a mucosal vascular hamartoma. The dog recovered uneventfully and had no further respiratory issues, short or long term. Although vascular hamartomas are a rare finding in veterinary medicine, they can be found in a wide variety of species and anatomic locations. They should be considered when naming differentials for benign mass lesions throughout the body, including the nasopharynx. Although they are benign masses in nature, they can be clinically significant and should be addressed. Prognosis after removal in this location is excellent.
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The blood count is one of the most common tests used for health assessment. In elderly individuals, selection of a 'healthy' reference population for laboratory assessment is difficult due to the high prevalence of chronic morbidities, leading to uncertainty regarding appropriate reference intervals. In particular, age-specific lower haemoglobin reference limits to define anaemia are controversial. Here, we applied a data mining approach to a large dataset of 3 029 904 clinical routine samples to establish blood count reference intervals. We excluded samples from units/specialists with a high proportion of abnormal blood counts, samples from patients with an unknown or decreased estimated glomerular filtration rate, and samples with abnormal test results in selected other analytes. After sample exclusion, 566 775-572 060 samples from different individuals aged 20-100 years were available for analysis. We then used an established statistical algorithm to determine the distribution of physiological test results and calculated age- and sex-specific reference intervals. Our results show substantial trends with age in haematology analytes' reference intervals. Most notably, haemoglobin and red cell counts decline in men with advanced age, accompanied by increases in red cell volume in both sexes. These findings were confirmed in an independent dataset, and suggest an at least partly physiologic cause.
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Background: Cortical superficial siderosis (cSS) represents a key neuroimaging marker of cerebral amyloid angiopathy (CAA) that is associated with intracranial hemorrhages and cognitive impairment. Nevertheless, the association between cSS and core cerebrospinal fluid (CSF) biomarkers for dementia remain unclear. Methods: One hundred and one patients with probable (79%, 80/101) or possible (21%, 21/101) CAA according to the modified Boston criteria and mild cognitive impairment according to Petersen criteria were prospectively included between 2011 and 2016. CSF analyses of ß-amyloid 42, ß-amyloid 40, total tau and phosphorylated tau were performed using sandwich-type enzyme-linked immunosorbent-assay. All patients received MRI and Mini-Mental-State Examination (MMSE). Logistic regression analysis was used to adjust for possible confounders. Results: cSS was present in 61% (62/101). Of those, 53% (33/62) had disseminated cSS and 47% (29/62) focal cSS. ß-amyloid 42 was lower in patients with cSS than in patients without cSS (OR 0.2; 95% CI 0.08-0.6; p = 0.0052) and lower in patients with disseminated cSS than in those with focal cSS (OR 0.02; 95% CI 0.003-0.2; p = 0.00057). Presence of cSS had no association with regard to ß-amyloid 40, total tau and phosphorylated tau. Conclusions: Our results demonstrate that the presence and extent of cSS are associated with reduced CSF ß-amyloid 42 levels. Further studies are needed to investigate the underlying mechanisms of this association.
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Background Interpreting hematology analytes in children is challenging due to the extensive changes in hematopoiesis that accompany physiological development and lead to pronounced sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, and limitations in current approaches to laboratory test result displays restrict their use when guiding clinical decisions. Methods We employed an improved data-driven approach to create percentile charts from laboratory data collected during patient care in 10 German centers (9,576,910 samples from 358,292 patients, 412,905-1,278,987 samples per analyte). We demonstrate visualization of hematology test results using percentile charts and z-scores (www.pedref.org/hematology) and assess the potential of percentiles and z-scores to support diagnosis of different hematological diseases. Results We created percentile charts for hemoglobin, hematocrit, red cell indices, red cell count, red cell distribution width, white cell count and platelet count in girls and boys from birth to 18 years of age. Comparison of pediatricians evaluating complex clinical scenarios using percentile charts versus conventional/tabular representations shows that percentile charts can enhance physician assessment in selected example cases. Age-specific percentiles and z-scores, compared with absolute test results, improve the identification of children with blood count abnormalities and the discrimination between different hematological diseases. Conclusions The provided reference intervals enable precise assessment of pediatric hematology test results. Representation of test results using percentiles and z-scores facilitates their interpretation and demonstrates the potential of digital approaches to improve clinical decision-making.
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Hematócrito/métodos , Hematología/métodos , Hematología/normas , Adolescente , Adulto , Niño , Preescolar , Recuento de Eritrocitos , Índices de Eritrocitos , Femenino , Hematócrito/normas , Hemoglobinas/análisis , Humanos , Lactante , Recién Nacido , Recuento de Leucocitos , Masculino , Recuento de Plaquetas , Valores de Referencia , Adulto JovenRESUMEN
Initial and maximum intraluminal leak pressures of four enterotomy closures were compared. Closure patterns included a modified Gambee, simple interrupted, simple continuous, and skin staple closure. Forty-eight 3-cm enterotomy constructs were created from jejunal segments harvested from 12 dogs. Twelve each were randomly assigned to the four closure methods. Time of closure, as well as initial and maximum leak pressures, were measured and compared. The modified Gambee closure was the slowest closure to perform, with skin staple closure being the fastest. All suture patterns tested had higher mean initial leak pressures than reported physiologic intestinal pressures during peristalsis, although the skin staple closures resulted in leakage below normal physiologic pressure in several samples. The modified Gambee closure was able to sustain a significantly higher initial leak pressure than skin staple closures. The modified Gambee suture pattern had the greatest maximum leak pressure of all enterotomy closure patterns tested. Use of the modified Gambee suture pattern should be considered in enterotomy closure, although in vivo studies are required to determine if these differences are clinically significant.
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Anastomosis Quirúrgica/veterinaria , Enfermedades de los Perros , Técnicas de Sutura , Animales , Perros , Presión , Técnicas de Sutura/veterinaria , SuturasRESUMEN
OBJECTIVE: To compare leak pressures following simple continuous closure of cystotomy with barbed suture to an analogous monofilament suture, in an ex vivo canine model. STUDY DESIGN: Ex vivo, simple randomized study. ANIMALS OR SAMPLE POPULATION: Urinary bladders harvested from canine cadavers (n = 21). METHODS: Urinary bladders were harvested from cadavers immediately following euthanasia. A 3-cm cystotomy was made on ventral midline of the urinary bladder. Urinary bladders were randomly assigned a suture for closure. A digital pressure transducer was inserted through 1 ureter, and the other ligated, while colored isotonic saline was infused into the urinary bladder via a Foley catheter inserted in the urethra. The initial leak pressure was defined as the pressure at which the colored saline solution first leaked from the cystotomy, and the maximum leak pressure was recorded when the pressure reached a plateau or catastrophic failure occurred. A Welch's 2-sample t test was used to compare leak pressure between the barbed and non-barbed closures, with significance set at P < .05. RESULTS: There was no significant difference in the initial or maximum leak pressure between the barbed and non-barbed closures. CONCLUSIONS: This study showed no difference in initial or maximum leak pressure between cystotomy closures with barbed or non-barbed suture under ex vivo conditions. This indicates barbed suture may be appropriate for cystotomy closure but in vivo studies are needed to support this finding.
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Cistotomía/veterinaria , Suturas/veterinaria , Vejiga Urinaria/cirugía , Animales , Fenómenos Biomecánicos , Cadáver , Perros , Ensayo de Materiales , Procedimientos Quirúrgicos Mínimamente Invasivos/veterinaria , Modelos Animales , Presión , Técnicas de Sutura/veterinaria , Vejiga Urinaria/fisiopatologíaRESUMEN
BACKGROUND: Interpretation of alkaline phosphatase activity in children is challenging due to extensive changes with growth and puberty leading to distinct sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics and seem reasonable for an analyte as closely linked to growth as alkaline phosphatase. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, resulting in limitations when clinical decisions are based on alkaline phosphatase activity. METHODS: We applied an indirect method to generate percentile charts for alkaline phosphatase activity using clinical laboratory data collected during the clinical care of patients. A total of 361,405 samples from 124,440 patients from six German tertiary care centers and one German laboratory service provider measured between January 2004 and June 2015 were analyzed. Measurement of alkaline phosphatase activity was performed on Roche Cobas analyzers using the IFCC's photometric method. RESULTS: We created percentile charts for alkaline phosphatase activity in girls and boys from birth to 18 years which can be used as reference intervals. Additionally, data tables of age- and sex-specific percentile values allow the incorporation of these results into laboratory information systems. CONCLUSIONS: The percentile charts provided enable the appropriate differential diagnosis of changes in alkaline phosphatase activity due to disease and changes due to physiological development. After local validation, integration of the provided percentile charts into result reporting facilitates precise assessment of alkaline phosphatase dynamics in pediatrics.
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Fosfatasa Alcalina/análisis , Pediatría , Adolescente , Fosfatasa Alcalina/metabolismo , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Valores de ReferenciaRESUMEN
OBJECTIVE: To compare 2-0 polyglyconate barbed suture (V-LOC™ 180 Absorbable Wound Closure Device, Covidien, Mansfield, MA) to standard 2-0 monofilament absorbable polyglyconate suture (Maxon™, Covidien) for maximum load to failure and failure mode when used to appose standardized defects in canine diaphragm muscle. STUDY DESIGN: Randomized, cadaveric ex vivo mechanical testing. SAMPLE POPULATION: Canine cadaveric hemi-diaphragmatic specimens (n = 32 pairs). METHODS: Thirty-two cadaveric diaphragm specimens were collected and divided to obtain 64 muscle specimens (9 cm × 4 cm). Paired specimens were bisected in the midpoint of their 9 cm length in the direction of the muscle fibers and apposed using either 2-0 polyglyconate or 2-0 barbed polyglyconate (V-LOC™ 180 Absorbable Wound Closure Device) in a simple continuous pattern. Increasing tension was applied perpendicular to the suture line until specimen failure. Failure mode and maximum load to failure were recorded for each specimen. RESULTS: Mean ± SD failure load of simulated herniorrhaphies performed with barbed polyglyconate suture (54.5 ± 10.27 N) was not significantly different than repair with polyglyconate (56.9 ± 10.87 N). Failure mode for both construct types was suture tear out rather than suture failure. CONCLUSIONS: Clinical application of 2-0 barbed polyglyconate suture can be considered as an alternative to the use of 2-0 polyglyconate for diaphragmatic herniorrhaphy.
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Perros/cirugía , Herniorrafia/veterinaria , Suturas , Animales , Fenómenos Biomecánicos , Cadáver , Herniorrafia/métodos , Modelos Animales , PolímerosRESUMEN
OBJECTIVE: To describe and compare onset and intensity of thoracic duct (TD) coloration after injection of methylene blue into the diaphragmatic crus and mesenteric lymph node. STUDY DESIGN: Experimental study. ANIMALS: Adult dogs (n = 18). METHODS: Methylene blue (≤0.5 mg/kg 1% solution) was injected into the left (n = 9) or right (n = 9) diaphragmatic crus via right 10th intercostal thoracotomy. TD coloration was graded over 10 minutes. A right paracostal laparotomy was then performed in all dogs, and an equal volume of methylene blue injected into a mesenteric lymph node (n = 18). TD color grading was repeated. Statistical analysis was performed on subject weight, volume of contrast agent injected between left and right crus, and number of successful outcomes between diaphragmatic crus injection and mesenteric lymph node injection. RESULTS: TD coloration occurred in 6 dogs with left crus injection and 4 dogs with right crus injection with obvious staining present in 2 and 3 dogs, respectively. Successful outcome was noted in all dogs with mesenteric lymph node injection. The number of successful outcomes was significantly greater after mesenteric lymph node injection compared with diaphragmatic crus injection (P < .001). CONCLUSIONS: Methylene blue injected into the diaphragmatic crura and mesenteric lymph node was successful in coloring the TD; however, mean thoracic duct color grade and number of successful outcomes were significantly higher after mesenteric injection.
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Quilotórax/veterinaria , Medios de Contraste , Enfermedades de los Perros/cirugía , Azul de Metileno , Conducto Torácico/diagnóstico por imagen , Animales , Quilotórax/cirugía , Diafragma , Enfermedades de los Perros/diagnóstico por imagen , Perros , Femenino , Inyecciones/veterinaria , Ganglios Linfáticos/diagnóstico por imagen , Masculino , Radiografía Torácica/veterinariaRESUMEN
Rhino- and/or otoliquorrhea can be diagnosed by detecting beta-trace protein (ß-TP) in nasal or ear secretions, as ß-TP is found in high concentrations in cerebrospinal fluid (CSF) but not in serum. CSF fistulae following trauma or surgery can also occur at other anatomical sites, resulting in CSF leakage into the thoracic and abdominal cavities. By analogy, determination of ß-TP has also been used to diagnose CSF admixture in pleural effusions and ascites. However, no systematic study has yet evaluated the concentrations of ß-TP in such fluids in the absence of CSF. To determine the validity of ß-TP determination as a marker for the presence of CSF, we investigated ß-TP concentrations in pleural effusions and ascites without CSF admixture. Patients from whom samples of ascites or pleural effusion and a paired plasma sample were available were investigated. One hundred sixty-four patients were prospectively recruited. ß-TP concentrations were determined by nephelometry. Mass spectrometric proteome analysis confirmed the presence of ß-TP in the samples. Median ß-TP concentrations detected in ascites and pleural effusions (range, 0.014-26.5 mg/L, median 2.29 mg/L) exceeded the corresponding plasma concentrations 2.6-fold. According to cutoffs published to diagnose rhino- and otoliquorrhea, between 6.1% and 95.7% of the specimens would have been erroneously rated CSF-positive. Protein analysis confirmed the presence of ß-TP in pleural effusion and ascites. Ascites and pleural effusion contain high concentrations of ß-TP that exceed the levels in corresponding plasma. Therefore, ß-TP is not a specific marker for the presence of CSF in these fluids.
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Ascitis/metabolismo , Oxidorreductasas Intramoleculares/líquido cefalorraquídeo , Lipocalinas/líquido cefalorraquídeo , Derrame Pleural/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Lesiones Encefálicas/líquido cefalorraquídeo , Lesiones Encefálicas/diagnóstico , Otorrea de Líquido Cefalorraquídeo/líquido cefalorraquídeo , Rinorrea de Líquido Cefalorraquídeo/líquido cefalorraquídeo , Dermatoglifia del ADN , Electroforesis en Gel de Poliacrilamida , Reacciones Falso Positivas , Femenino , Humanos , Oxidorreductasas Intramoleculares/metabolismo , Lipocalinas/metabolismo , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Derrame Pleural/metabolismo , Proteoma , Adulto JovenRESUMEN
OBJECTIVE: Multidrug resistance-related protein 2 (Mrp2) is expressed in apical membranes of renal proximal tubular cells and contributes to the renal secretion of cyclosporine A (CsA). Mrp2â»/â» deficiency may lead to local renal CsA accumulation. We investigated whether kidney-specific Mrp2 deficiency enhances acute CsA nephrotoxicity in rats. METHODS: Kidney-specific Mrp2 deletion was achieved by bilateral nephrectomy and transplantation of a congenic Mrp2-deficient kidney into wild-type recipients. Controls received a wild-type kidney. Animals were treated with CsA (10 or 30 mg/kg/day) for 7 days. Renal hemodynamics and renal cortical mRNA expression profile, oxidative stress, and the abundance of multidrug resistance protein 1 (Mdr1) and Mrp2 were assessed. RESULTS: CsA accumulation and CsA-induced reduction in glomerular filtration rate were similar in wild-type and Mrp2â»/â» kidneys. Renal vascular resistance and agonist-induced renal vascular responses were similar in both groups. A PCR array on 84 genes involved in the biotransformation and antioxidant defense revealed increased CsA-induced mRNA expression of genes involved in oxidative and metabolic stress, inflammation, and apoptosis. This gene expression pattern was similar in wild-type and Mrp2â»/â» kidneys. CsA increased the renal cortical oxidized glutathione, did not affect xanthine oxidase-dependent superoxide formation, and decreased renal cortical NADPH oxidase-dependent superoxide formation. Furthermore, CsA increased Mdr1 protein abundance to a greater extent in Mrp2â»/â» than in wild-type kidneys. CONCLUSION: Mrp2 is not critical for renal CsA disposition and its deficiency does not enhance acute CsA nephrotoxicity. The high Mdr1 abundance may at least in part prevent exaggerated CsA accumulation in Mrp2â»/â» kidneys.
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Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Ciclosporina/efectos adversos , Eliminación de Gen , Enfermedades Renales/inducido químicamente , Enfermedades Renales/genética , Riñón/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Ciclosporina/sangre , Regulación de la Expresión Génica/efectos de los fármacos , Tasa de Filtración Glomerular/efectos de los fármacos , Disulfuro de Glutatión/metabolismo , Hemodinámica/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiopatología , Corteza Renal/metabolismo , Corteza Renal/patología , Corteza Renal/fisiopatología , Enfermedades Renales/patología , Enfermedades Renales/fisiopatología , Masculino , Especificidad de Órganos/efectos de los fármacos , Especificidad de Órganos/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Superóxidos/metabolismoRESUMEN
OBJECTIVE: Because population-based data are lacking, we assessed the cross-sectional association between serum testosterone levels and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in men from the population-based Study of Health in Pomerania. METHODS AND RESULTS: Personal characteristics, including major cardiovascular confounders, were collected in 722 men, aged 25 to 85 years. Serum total testosterone and sexual hormone-binding globulin (SHBG) levels were determined by chemiluminescence immunoassays. Free testosterone levels were calculated according to the law of mass action. FMD and NMD measurements were performed using standardized ultrasound techniques. FMD and NMD values below the 20th percentile were considered decreased. Multivariable logistic regression analyses revealed an association for each decrement of total testosterone standard deviation (6.0 nmol/L) with decreased FMD after adjustment for potential confounders (odds ratio 1.30, 95% confidence interval 1.04-1.63; P=0.023). Multiple adjusted findings for free testosterone were similar (odds ratio 1.37, 95% confidence interval 1.06-1.76; P=0.016). There was no such association of SHBG levels with decreased FMD. Neither testosterone nor SHBG levels were significantly associated with decreased NMD. CONCLUSIONS: Lower serum total and free testosterone levels are associated with impaired endothelial function in this population-based sample of men.
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Arteria Braquial/fisiología , Endotelio Vascular/fisiología , Flujo Sanguíneo Regional/fisiología , Testosterona/sangre , Adulto , Anciano , Anciano de 80 o más Años , Arteria Braquial/efectos de los fármacos , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Estudios Transversales , Endotelio Vascular/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Nitroglicerina/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Factores de Riesgo , Globulina de Unión a Hormona Sexual/metabolismo , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Vasodilatadores/farmacologíaRESUMEN
We present a genome-wide association study of metabolic traits in human urine, designed to investigate the detoxification capacity of the human body. Using NMR spectroscopy, we tested for associations between 59 metabolites in urine from 862 male participants in the population-based SHIP study. We replicated the results using 1,039 additional samples of the same study, including a 5-year follow-up, and 992 samples from the independent KORA study. We report five loci with joint P values of association from 3.2 × 10(-19) to 2.1 × 10(-182). Variants at three of these loci have previously been linked with important clinical outcomes: SLC7A9 is a risk locus for chronic kidney disease, NAT2 for coronary artery disease and genotype-dependent response to drug toxicity, and SLC6A20 for iminoglycinuria. Moreover, we identify rs37369 in AGXT2 as the genetic basis of hyper-ß-aminoisobutyric aciduria.
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Estudio de Asociación del Genoma Completo , Riñón/metabolismo , Sistemas de Transporte de Aminoácidos Básicos/genética , Ácidos Aminoisobutíricos/orina , Arilamina N-Acetiltransferasa/genética , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Proteínas de Transporte de Membrana/genética , Polimorfismo de Nucleótido Simple , Vigilancia de la Población , Reproducibilidad de los ResultadosRESUMEN
Testosterone exerts a widespread pattern of effects on metabolism and body composition, and interest is gaining in its correlation with physical fitness. The main focus of our study was to investigate the association of total serum testosterone and sex hormone-binding globulin (SHBG) levels on exercise capacity and maximal power output in men using a cross-sectional, population-based adult cohort. From the Study of Health in Pomerania (SHIP), 624 men age 25 to 85 years who underwent a standardized progressive incremental exercise protocol on a cycle ergometer were included in the analyses. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (V'O(2) at L) and peak exercise (V'O(2 peak)) as well as maximal power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity, and smoking were performed. Further, linear regression analyses with cubic splines and sensitivity analyses were undertaken. At peak exercise performance, testosterone and SHBG levels showed no associations with V'O(2 peak), V'O(2) at L as well as maximal power output, even after controlling for confounding factors including age, body mass index, physical activity, and smoking. An adverse association between the free testosterone index and V'O(2) at L was found. Linear regression analyses with cubic splines did not change the main results. In conclusion, this is the first study focusing on the association of total serum testosterone and SHBG on exercise capacity and physical performance in healthy volunteers based on a large-scale population-based study. After adjustment for relevant influencing factors, neither total serum testosterone nor SHBG levels had any interference with peak exercise capacity, aerobic exercise capacity, or maximal power output in men.
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Ejercicio Físico , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Prueba de Esfuerzo , Humanos , Masculino , Persona de Mediana Edad , Consumo de OxígenoRESUMEN
BACKGROUND: Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are central mediators of endocrine effects of growth hormone and there is increasing evidence for an association with muscle strength and exercise capacity. The aim of the present study was to clarify the possible association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in a general adult population. MATERIALS AND METHODS: From the Study of Health in Pomerania (SHIP) 1332 subjects aged 25 to 85 years participated in a standardised symptom limited cardiopulmonary exercise test on a bicycle. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2), oxygen pulse and maximum power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity and smoking were performed. RESULTS: At peak exercise performance, in women IGF-I showed significant associations to peakVO2 and maximum power output, IGF-I/IGFBP-3 ratio was associated with maximum power output. In men, this association was not consistently reproducible. Neither IGF-I nor IGFBP-3 did reveal any association to VO2@AT in both genders. CONCLUSION: Serum IGF-I concentrations are associated with peak exercise capacity in healthy women, but not in men over a wide range in ages, body sizes and activity scores.
Asunto(s)
Tolerancia al Ejercicio/fisiología , Salud , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Adulto , Anciano , Anciano de 80 o más Años , Rendimiento Atlético/fisiología , Ejercicio Físico/fisiología , Prueba de Esfuerzo , Femenino , Alemania , Voluntarios Sanos , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana Edad , Concentración Osmolar , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND: Studies from iodine-sufficient areas have shown that a high proportion of patients taking medication for thyroid diseases have thyroid stimulating hormone (TSH) levels outside the reference range. Next to patient compliance, inadequate dosing adjustment resulting in under- and over-treatment of thyroid disease is a major cause of poor therapy outcomes. Using thyroid function tests, we aim to measure the proportions of subjects, who are under- or over-treated with thyroid medication in a previously iodine-deficient area. FINDINGS: Data from 266 subjects participating in the population-based Study of Health in Pomerania (SHIP) were analysed. All subjects were taking thyroid medication. Serum TSH levels were measured using immunochemiluminescent procedures. TSH levels of < 0.27 or > 2.15 mIU/L in subjects younger than 50 years and < 0.19 or > 2.09 mIU/L in subjects 50 years and older, were defined as decreased or elevated, according to the established reference range for the specific study area. Our analysis revealed that 56 of 190 (29.5%) subjects treated with thyroxine had TSH levels outside the reference range (10.0% elevated, 19.5% decreased). Of the 31 subjects taking antithyroid drugs, 12 (38.7%) had TSH levels outside the reference range (9.7% elevated, 29.0% decreased). These proportions were lower in the 45 subjects receiving iodine supplementation (2.2% elevated, 8.9% decreased). Among the 3,974 SHIP participants not taking thyroid medication, TSH levels outside the reference range (2.8% elevated, 5.9% decreased) were less frequent. CONCLUSION: In concordance with previous studies in iodine-sufficient areas, our results indicate that a considerable number of patients taking thyroid medication are either under- or over-treated. Improved monitoring of these patients' TSH levels, compared to the local reference range, is recommended.