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1.
Skin Health Dis ; 1(2): e24, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35664970

RESUMEN

A decrease of 7,2 % in productivity was found in patients suffering from palmar hyperhidrosis. A correction of this could more than pay for the treatment with botulinum-toxins, even 3 or 4 times a year.

2.
Org Biomol Chem ; 15(20): 4351-4358, 2017 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-28474719

RESUMEN

18F-Labelling of aromatic moieties was limited to electron deficient aromatic systems for many years but recent developments have provided access to the direct labelling of electron rich aromatic systems. Herein we report the synthesis and 18F-labelling of iodonium ylide precursors in the pursuit of 18F-labelled 5-HT2A receptor agonist PET-ligands. Subsequent evaluation in pigs showed high brain uptake of the PET ligands but a blocking dose of ketanserin did not significantly reduce the signal in relevant brain regions - indicating that the ligands do not interact specifically with the 5-HT2A receptor in vivo.


Asunto(s)
Electrones , Tomografía de Emisión de Positrones , Radiofármacos/farmacología , Receptor de Serotonina 5-HT2A/metabolismo , Agonistas del Receptor de Serotonina 5-HT2/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Radioisótopos de Flúor , Marcaje Isotópico , Ligandos , Estructura Molecular , Radiofármacos/síntesis química , Radiofármacos/química , Agonistas del Receptor de Serotonina 5-HT2/química , Porcinos
3.
J Thromb Haemost ; 14(9): 1803-13, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27378673

RESUMEN

UNLABELLED: Essentials Von Willebrand factor (VWF) stabilizes factor VIII (FVIII) and prevents its premature clearance. Rat anatomical and hepatocellular distribution studies assessed the VWF effect on FVIII clearance. Hepatocytes and liver sinusoidal endothelial cells play a key role in FVIII clearance. Anatomical and hepatocellular distribution of FVIII is independent of high-affinity VWF binding. ABSTRACT: Background Von Willebrand factor (VWF) stabilizes factor VIII in the circulation and prevents its premature clearance. Objective To study the effects of VWF on FVIII clearance in rats with endogenous VWF. Methods Anatomical and hepatocellular distribution studies were performed in rats following intravenous administration of glycoiodinated recombinant FVIII (rFVIII) and a FVIII variant, FVIII-Y1680F, lacking high-affinity VWF binding. Radioactivity was quantified in organs, and in distinct liver cell populations. The role of VWF binding was also studied by immunohistochemical staining of rat livers perfused ex vivo with rFVIII alone or with a FVIII-binding VWF fragment. Results The liver was the predominant organ of rFVIII distribution, and a radioactivity peak was also observed in the intestines, suggesting FVIII secretion to the bile by hepatocytes. In the liver, ~60% of recovered radioactivity was associated with hepatocytes, 32% with liver sinusoidal endothelial cells (LSECs), and 9% with Kupffer cells (KCs). When calculated per cell, 1.5-fold to 3-fold more radioactivity was associated with LSECs than with hepatocytes. The importance of hepatocytes and LSECs was confirmed by immunohistochemical staining; strong staining was seen in LSECs, and less intense, punctate staining in hepatocytes. Minor staining in KCs was observed. Comparable anatomical and hepatocellular distributions were observed with rFVIII and FVIII-Y1680F, and the presence of the VWF fragment, D'D3A1, did not change the FVIII staining pattern in intact livers. Conclusions The present data support FVIII clearance via the liver, with hepatocytes and LSECs playing a key role. High-affinity VWF binding did not alter the anatomical or hepatocellular distribution of FVIII.


Asunto(s)
Células Endoteliales/metabolismo , Factor VIII/metabolismo , Hepatocitos/citología , Hígado/metabolismo , Factor de von Willebrand/metabolismo , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Combinación de Medicamentos , Ensayo de Inmunoadsorción Enzimática , Factor VIII/uso terapéutico , Glioblastoma/metabolismo , Hepatocitos/metabolismo , Humanos , Inmunohistoquímica , Yodo/química , Lactoperoxidasa/metabolismo , Masculino , Unión Proteica , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Enfermedades de von Willebrand/sangre , Enfermedades de von Willebrand/tratamiento farmacológico , Factor de von Willebrand/uso terapéutico
4.
J Comp Pathol ; 153(4): 357-62, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26381675

RESUMEN

A 7-year-old female harbour porpoise (Phocoena phocoena), born and held in captivity, suffered from reduced consciousness, imprecise and circling swimming movements and long phases of immobility over a period of 3 weeks. The animal died during treatment in a Danish open sea facility. Pathological examination revealed multifocal pyogranulomatous to necrotizing meningoencephalomyelitis, ganglioneuritis, plexus chorioiditis, myocarditis, hepatitis and adrenalitis with few intralesional protozoal tachyzoites and bradyzoites within cysts. Immunohistochemistry was positive for Toxoplasma gondii antigen within the lesions. Using polymerase chain reaction (PCR), the presence of T. gondii-specific genome fragments was confirmed. A multilocus PCR-restriction fragment length polymorphism analysis using nine unlinked marker regions (nSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) resulted in the identification of T. gondii type II (variant Apico Type I), which is the T. gondii genotype dominating in Germany. This is the first description of disseminated fatal toxoplasmosis in a captive harbour porpoise that lived in an open sea basin. Surface water contaminated with toxoplasma oocysts is regarded as the most likely source of infection.


Asunto(s)
Phocoena , Toxoplasma , Toxoplasmosis Animal/patología , Animales , Phocoena/parasitología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción
5.
Clin Biochem ; 48(16-17): 1083-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26164539

RESUMEN

OBJECTIVES: Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the quantification of MMP-7 generated elastin fragments (ELM7) was therefore developed to investigate MMP-7 derived elastin degradation in pulmonary disorders such as idiopathic pulmonary fibrosis (IPF) and lung cancer. DESIGN AND METHODS: Monoclonal antibodies (mABs) were raised against eight carefully selected MMP-7 cleavage sites on elastin. After characterisation and validation of the mABs, one mAB targeting the ELM7 fragment was chosen. ELM7 fragment levels were assessed in serum samples from patients diagnosed with IPF (n=123, baseline samples, CTgov reg. NCT00786201), and lung cancer (n=40) and compared with age- and sex-matched controls. RESULTS: The ELM7 assay was specific towards in vitro MMP-7 degraded elastin and the ELM7 neoepitope but not towards other MMP-7 derived elastin fragments. Serum ELM7 levels were significantly increased in IPF (113%, p<0.0001) and lung cancer (96%, p<0.0001) compared to matched controls. CONCLUSIONS: MMP-7-generated elastin fragments can be quantified in serum and may reflect pathological lung tissue turnover in several important lung diseases.


Asunto(s)
Elastina/metabolismo , Enfermedades Pulmonares/sangre , Enfermedades Pulmonares/metabolismo , Metaloproteinasa 7 de la Matriz/sangre , Anciano , Animales , Estudios de Casos y Controles , Femenino , Humanos , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/metabolismo , Pulmón/metabolismo , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Proteolisis
6.
Clin Biomech (Bristol, Avon) ; 28(3): 318-24, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23375787

RESUMEN

BACKGROUND: The purpose of the study was to investigate if differences of the head and trunk stability and stabilization strategies exist between subjects classified with Generalized Joint Hypermobility and healthy controls during gait. It was hypothesized that joint hypermobility could lead to decreased head and trunk stability and a head stabilization strategy similar to what have been observed in individuals with decreased locomotor performance. METHODS: A comparative study design was used wherein 19 hypermobile children were compared to 19 control children, and 18 hypermobile adults were compared to 18 control adults. The subjects were tested during normal walking and walking on a line. Kinematics of head, shoulder, spine and pelvis rotations were measured by five digital video cameras in order to assess the segmental stability (angular dispersion) and stabilization strategies (anchoring index) in two rotational components: roll and yaw. FINDINGS: Hypermobile children and adults showed decreased lateral trunk stability in both walking conditions. In hypermobile children, it was accompanied with decreased head stability as the head was stabilized by the inferior segment when walking on a line. Several additional differences were observed in stability and stabilization strategies for both children and adults. INTERPRETATION: Stability of the trunk was decreased in hypermobile children and adults. This may be a consequence of decreased stability of the head. Hypermobile children showed a different mode of head stabilization during more demanding locomotor conditions indicating delayed locomotor development. The findings reflect that Generalized Joint Hypermobility probably include motor control deficits.


Asunto(s)
Marcha , Inestabilidad de la Articulación/fisiopatología , Equilibrio Postural , Adulto , Factores de Edad , Fenómenos Biomecánicos , Niño , Femenino , Humanos , Inestabilidad de la Articulación/complicaciones , Articulaciones/fisiopatología , Masculino , Persona de Mediana Edad , Caminata , Adulto Joven
7.
Diabetologia ; 55(9): 2361-70, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22736395

RESUMEN

AIMS/HYPOTHESIS: In a population-based setting, we investigated whether diabetes-related morbidity and all-cause mortality within 2 years of HbA(1c) measurement were associated with that HbA(1c) level in individuals with type 2 diabetes. The main objective was to compare outcomes in those with HbA(1c) ≥ and <7% (53 mmol/mol). METHODS: Individuals with type 2 diabetes from Aarhus County, Denmark, were identified from public data files in a 3 year period (2001-2003). Stratifying the 17,760 individuals by HbA(1c), we estimated HRs for diabetes-related morbidities and all-cause mortality using Cox regression. Results were also stratified by treatment modality. RESULTS: In total, 1,805 individuals experienced at least one diabetes-related morbidity and 1,859 individuals died. In general, the HRs in adjusted analyses of diabetes-related morbidity and mortality were increased for HbA(1c) ≥ 7% (53 mmol/mol): morbidity, HR 1.48 (95% CI 1.34, 1.63); and mortality, HR 1.26 (95% CI 1.15, 1.39). On grouping individuals according to HbA(1c) <5% (31 mmol/mol), 5.0-5.9% (31-41 mmol/mol), 6.0-6.9% (42-52 mmol/mol), 7.0-7.9% (53-63 mmol/mol), 8.0-8.9% (64-74 mmol/mol) and ≥ 9% (75 mmol/mol), the HRs for mortality formed a U shape, with HbA(1c) 6.0-6.9% (42-52 mmol/mol) at the lowest point. For diabetes-related morbidity, a dose-response pattern appeared (lowest for HbA(1c) < 5% [31 mmol/mol]). Patterns of HR differed with treatment modality. CONCLUSIONS/INTERPRETATION: An HbA(1c) level ≥ 7% (53 mmol/mol) was associated with increased morbidity and mortality. Both high and very low levels of HbA(1c) were associated with increased mortality. A dose-response pattern appeared for morbidity. The impact of HbA(1c) level on morbidity and mortality depended on treatment modality.


Asunto(s)
Glucemia/metabolismo , Enfermedades Cardiovasculares/sangre , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/sangre , Hemoglobina Glucada/metabolismo , Hiperglucemia/sangre , Anciano , Algoritmos , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Dinamarca/epidemiología , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/mortalidad , Angiopatías Diabéticas/fisiopatología , Femenino , Humanos , Hiperglucemia/mortalidad , Hiperglucemia/fisiopatología , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios
8.
Acta Physiol (Oxf) ; 205(2): 314-20, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22192354

RESUMEN

AIM: To study whether the phenotypical characteristics (exercise intolerance; reduced spontaneous activity) of the AMPKα2 kinase-dead (KD) mice can be explained by a reduced mitochondrial respiratory flux rates (JO(2) ) in skeletal muscle. Secondly, the effect of the maturation process on JO(2) was studied. METHODS: In tibialis anterior (almost exclusively type 2 fibres) muscle from young (12-17 weeks, n = 7) and mature (25-27 weeks, n = 12) KD and wild-type (WT) (12-17 weeks, n = 9; 25-27 weeks, n = 11) littermates, JO(2) was quantified in permeabilized fibres ex vivo by respirometry, using a substrate-uncoupler-inhibitor-titration (SUIT) protocol: malate, octanoyl carnitine, ADP and glutamate (GMO(3) ), + succinate (GMOS(3) ), + uncoupler (U) and inhibitor (rotenone) of complex I respiration. Citrate synthase (CS) activity was measured as an index of mitochondrial content. RESULTS: Citrate synthase activity was highest in young WT animals and lower in KD animals compared with age-matched WT. JO(2) per mg tissue was lower (P < 0.05) in KD animals (state GMOS(3) ). No uncoupling effect was seen in any of the animals. Normalized oxygen flux (JO(2) /CS) revealed a uniform pattern across the SUIT protocol with no effect of KD. However, JO(2) /CS was higher [GMO(3) , GMOS(3) , U and rotenone (only WT)] in the mature compared with the young mice - irrespective of the genotype (P < 0.05). CONCLUSION: Exercise intolerance and reduced activity level seen in KD mice may be explained by reduced JO(2) in the maximally coupled respiratory state. Furthermore, an enhancement of oxidative phosphorylation capacity per mitochondrion is seen with the maturation process.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Mitocondrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Consumo de Oxígeno/fisiología , Proteínas Quinasas Activadas por AMP/genética , Animales , Citrato (si)-Sintasa/metabolismo , Ratones , Condicionamiento Físico Animal/fisiología
9.
Acta Physiol (Oxf) ; 205(2): 224-35, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21991887

RESUMEN

AIM: The aim of this study was to test the hypothesis that IL-6 regulates exercise-induced gene responses in subcutaneous adipose tissue in mice. METHODS: Four-month-old male IL-6 whole body knockout (KO) mice and C57B wild-type (WT) mice performed 1 h of treadmill exercise, where subcutaneous adipose tissue (AT) was removed either immediately after, 4 h or 10 h after exercise as well as from mice not running acutely. Moreover, AT was sampled at resting conditions after 5 weeks of exercise training. RESULTS: AT leptin mRNA decreased immediately after a single running exercise bout in both genotypes and returned to baseline within 10 h of recovery in IL-6 KO mice, but not WT mice. Leptin mRNA content decreased in WT and increased in IL-6 KO mice with training, but without significant alterations in leptin protein. Acute exercise induced a decrease in the AT TNFα mRNA content in WT, but not in IL-6-KO mice, while training lowered resting levels of TNFα mRNA in both genotypes. In addition, an exercise-induced decline in AT PPARγ mRNA content was absent in IL-6 KO mice and in line training increased PPARγ mRNA only in IL-6 KO mice. CONCLUSION: The present findings indicate a role of IL-6 in regulating exercise- and training-induced leptin and PPARγ expression in adipose tissue. In addition, while IL-6 is required for TNF-α mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue.


Asunto(s)
Adaptación Fisiológica/fisiología , Interleucina-6/metabolismo , Condicionamiento Físico Animal/fisiología , Grasa Subcutánea/fisiología , Animales , Inflamación/genética , Inflamación/metabolismo , Interleucina-6/genética , Leptina/genética , Leptina/metabolismo , Masculino , Ratones , Ratones Noqueados , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
10.
Clin Pharmacol Ther ; 89(6): 830-6, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21525869

RESUMEN

The likelihood of significant exposure to drugs in infants through breast milk is poorly defined, given the difficulties of conducting pharmacokinetics (PK) studies. Using fluoxetine (FX) as an example, we conducted a proof-of-principle study applying population PK (popPK) modeling and simulation to estimate drug exposure in infants through breast milk. We simulated data for 1,000 mother-infant pairs, assuming conservatively that the FX clearance in an infant is 20% of the allometrically adjusted value in adults. The model-generated estimate of the milk-to-plasma ratio for FX (mean: 0.59) was consistent with those reported in other studies. The median infant-to-mother ratio of FX steady-state plasma concentrations predicted by the simulation was 8.5%. Although the disposition of the active metabolite, norfluoxetine, could not be modeled, popPK-informed simulation may be valid for other drugs, particularly those without active metabolites, thereby providing a practical alternative to conventional PK studies for exposure risk assessment in this population.


Asunto(s)
Lactancia Materna , Fluoxetina/farmacocinética , Leche Humana/efectos de los fármacos , Leche Humana/metabolismo , Dinámicas no Lineales , Adulto , Factores de Edad , Lactancia Materna/efectos adversos , Preescolar , Femenino , Fluoxetina/sangre , Predicción , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Adulto Joven
11.
Diabet Med ; 28(3): 325-32, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21309841

RESUMEN

AIMS: To evaluate the effect of an electronic feedback system to general practitioners on quality of Type 2 diabetes care. METHODS: A cluster randomized, controlled trial with 15 months follow-up. Eighty-six general practices (158 general practitioners) in a Danish county caring for 2458 people 40-70 years old with Type 2 diabetes were randomized to receive or not to receive electronic feedback on quality of care. People with Type 2 diabetes were identified using a validated algorithm. Primary end-points were processes of care according to guidelines on prescriptions redeemed for Type 2 diabetes treatments, measuring of glycated haemoglobin and cholesterol and visits to ophthalmologists. Secondary end-points were changes in level of glycated haemoglobin and serum cholesterol. Data were analysed using generalized linear models accounting for clustering at practice level. RESULTS: During follow-up, people with Type 2 diabetes in the intervention group more often redeemed recommended prescriptions than people in the control group, respectively, as follows: oral antidiabetic treatment (32.8 vs. 12.0%, P =0.002), insulin treatment (33.8 vs. 12.4%, P < 0.001), lipid-lowering medication (38.3 vs. 18.6%, 0.004) and blood pressure medication (27.6 vs. 16.3%, P = 0.026). There were no differences in mean glycated haemoglobin and serum cholesterol between the two groups. CONCLUSIONS: Electronic feedback to general practitioners on the quality of Type 2 diabetes care resulted in significantly improved quality regarding processes of care according to guidelines. It was not possible to demonstrate any effect on secondary end-point measures within the follow-up period. Electronic feedback on quality of diabetes care can be effective in improving adherence to treatment according to evidence-based guidelines.


Asunto(s)
Atención a la Salud/normas , Diabetes Mellitus Tipo 2/terapia , Medicina General/normas , Médicos de Familia/normas , Calidad de la Atención de Salud/normas , Adulto , Anciano , Algoritmos , Dinamarca , Diabetes Mellitus Tipo 2/psicología , Retroalimentación Psicológica , Femenino , Hemoglobina Glucada , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto
12.
Spinal Cord ; 48(1): 27-33, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19488052

RESUMEN

STUDY DESIGN: Epidemiological follow-up study. OBJECTIVE: To evaluate urinary incontinence and its management in a population of individuals with long-term spinal cord injury (SCI). SETTING: Clinic for Spinal Cord Injuries and Department of Urology, Copenhagen University Hospital, Rigshospitalet, Denmark. METHODS: Retrospective data collection from the patient records and information from a follow-up questionnaire of traumatic SCI individuals at least 10 years after injury. A total of 236 patients participated (84.6% response), 82% males and 18% females, 47% tetraplegic and 53% paraplegic, injured between 1956 and 1990. Age at the time of follow-up was 28-84 years (mean 50.5 years). Years of follow-up were 10-45 years (mean 24.1 years). RESULTS: A total of 43% of the participants reported incontinence from less than once a week to daily. There was a significant linear trend across the groups of incontinence with more paraplegics reporting daily incontinence compared with tetraplegics. A higher proportion of participants using clean intermittent catheterization reported incontinence (56%) compared with participants using other bladder-emptying methods. Only 19% of the participants used medication for the management of incontinence. CONCLUSION: Urinary incontinence is a common problem in individuals with SCI. Only a minority of individuals used medication for the treatment of incontinence. SPONSORSHIP: This study was carried out as a part of the primary author's PhD study, financed by the Medicon Valley Academy and Coloplast A/S.


Asunto(s)
Traumatismos de la Médula Espinal/complicaciones , Incontinencia Urinaria/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Registros Médicos/estadística & datos numéricos , Persona de Mediana Edad , Paraplejía/complicaciones , Cuadriplejía/complicaciones , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Incontinencia Urinaria/terapia
13.
Biofouling ; 26(2): 141-53, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-19882418

RESUMEN

The antifouling (AF) potential of hydrogen peroxide (H(2)O(2)) produced enzymatically in a coating containing starch, glucoamylase, and hexose oxidase was evaluated in a series of laboratory tests and in-sea field trials. Dissolved H(2)O(2) inhibited bacterial biofilm formation by eight of nine marine Proteobacteria, tested in microtiter plates. However, enzymatically produced H(2)O(2) released from a coating did not impede biofilm formation by bacteria in natural seawater tested in a biofilm reactor. A field trial revealed a noticeable effect of the enzyme system: after immersion in the North Sea for 97 days, the reference coating without enzymes had 35-40 barnacles, 10% area coverage by diatoms and 15% area coverage by tunicates. The enzyme containing coating had only 6-12 barnacles, 10% area coverage by diatoms and no tunicates. The enzyme system had a performance similar to a copper-based commercial coating and thus appears to have potential as a non-persistent AF agent.


Asunto(s)
Biopelículas/efectos de los fármacos , Incrustaciones Biológicas/prevención & control , Peróxido de Hidrógeno/farmacología , Proteobacteria/efectos de los fármacos , Oxidorreductasas de Alcohol/química , Biopelículas/crecimiento & desarrollo , Reactores Biológicos , Glucano 1,4-alfa-Glucosidasa/química , Peróxido de Hidrógeno/química , Pruebas de Sensibilidad Microbiana , Proteobacteria/fisiología , Agua de Mar/química , Almidón/química
14.
Can J Cardiol ; 25(3): 149-55, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19279982

RESUMEN

BACKGROUND: Assessment of pulmonary congestion in left-sided heart failure is necessary for guiding anticongestive therapy. Clinical examination and chest x-ray are semiquantitative methods with poor diagnostic accuracy and reproducibility. OBJECTIVES: To establish reference values, describe reproducibility, and investigate the diagnostic and monitoring properties in relation to pulmonary congestion of new pulmonary gas exchange parameters describing ventilation/perfusion mismatch (variable fraction of ventilation [fA2] or the drop in oxygen pressure from the mixed alveolar air of the two ventilated compartments to the nonshunted end-capillary blood [DeltaPO(2)]) and pulmonary shunt. METHODS: Sixty healthy volunteers and 69 patients requiring an acute chest x-ray in a cardiac care unit were included. The gas exchange parameters were estimated by analyzing standard bedside respiratory and circulatory measurements obtained during short-term exposure to different levels of inspired oxygen. Nine patients were classified as having pulmonary congestion using a reference diagnosis and were followed during 30 days of anticongestive therapy. Diagnostic and monitoring properties were compared with chest x-ray, N-terminal probrain natriuretic peptide (NT-proBNP), spirometry values, arterial oxygen tension, alveolar-arterial oxygen difference and venous admixture. RESULTS: The 95% reference intervals for healthy subjects were narrow (ie, fA2 [0.75 to 0.90], DeltaPO(2) [0.0 kPa to 0.5 kPa] and pulmonary shunt [0.0% to 8.2%]). Reproducibility was relatively good with small within subject coefficients of variation (ie, fA2 [0.05], DeltaPO(2) [0.4 kPa] and pulmonary shunt [2.0%]). fA2, DeltaPO(2) and NT-proBNP had significantly better diagnostic properties, with high sensitivities (100%) but low specificities (30% to 40%). During successful anticongestive therapy, fA2, DeltaPO(2), NT-proBNP and spirometry values showed significant improvements. CONCLUSIONS: The gas exchange parameter for ventilation/perfusion mismatch but not pulmonary shunt can have a possible role in rejecting the diagnosis of pulmonary congestion and in monitoring anticongestive therapy.


Asunto(s)
Insuficiencia Cardíaca/fisiopatología , Edema Pulmonar/fisiopatología , Intercambio Gaseoso Pulmonar/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espirometría , Relación Ventilacion-Perfusión/fisiología , Adulto Joven
15.
Aliment Pharmacol Ther ; 29(2): 198-206, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18945254

RESUMEN

BACKGROUND: There is currently no treatment available to manage acute pain attacks in IBS patients regardless of subtype. AIMS: To evaluate efficacy and safety of the GLP-1 analogue ROSE-010 in patients with irritable bowel syndrome (IBS) through a randomized, double-blind, placebo-controlled study. METHODS: Eligible patients (n = 166) meeting Rome II criteria were randomly assigned to receive single subcutaneous injections of ROSE-010 100 microg, 300 microg and placebo in a cross-over design. Safety was assessed from spontaneously reported adverse events and measurement of vital signs. Patient-rated pain relief and intensity were measured on a 100-mm visual analogue scale. The primary efficacy variable was proportion of patients with >50% maximum total pain relief response from 10 to 60 min after treatment. Secondary endpoints included the maximum summed pain intensity difference, time to meaningful pain relief and patient ratings of satisfaction with treatment. RESULTS: Twice as many patients were responders in the primary efficacy endpoint after both ROSE-010 injections compared to placebo (24%P = 0.011, 23%P = 0.005, and 12% after 300 microg, 100 microg and placebo injections, respectively). Similar results were obtained for the proportion of patients with total pain intensity response. Times to meaningful and total pain relief were shorter for both doses of ROSE-010 compared with placebo. Compared with placebo, more patients (P < 0.05) were satisfied with ROSE-010 and considered ROSE-010 better than previous IBS medications used. CONCLUSION: ROSE-010 was well tolerated and provided fast and effective relief of acute pain attacks on demand in IBS patients.


Asunto(s)
Péptido 1 Similar al Glucagón/análogos & derivados , Síndrome del Colon Irritable/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Humanos , Infusiones Subcutáneas , Masculino , Persona de Mediana Edad , Dolor , Dimensión del Dolor , Resultado del Tratamiento
16.
Diabetologia ; 51(12): 2187-96, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18815769

RESUMEN

AIMS/HYPOTHESIS: The aim of the study was to describe trends in the incidence rate, prevalence and mortality rate for diabetes in Denmark. METHODS: Healthcare registers at the National Board of Health were used to compile a register of diabetic patients in the Danish population (5.4 million people). Age- and sex-specific prevalence, incidence rates, mortality rates and standardised mortality ratios relative to the non-diabetic part of the population were calculated. RESULTS: The register contains records for about 360,000 persons with diabetes; 230,000 were alive at 1 January 2007, corresponding to an overall prevalence of 4.2%. The prevalence increased by 6% per year. In 2004 the incidence rates were 1.8 per 100,000 at age 40 years and 10.0 per 100,000 at age 70 years. The incidence rate increased 5% per year before 2004 and then stabilised. The mortality rate in the diabetic population decreased 4% per year, compared with 2% per year in the non-diabetic part of the population. The mortality rate decreased 40% during the first 3 years after inclusion in the register. The standardised mortality ratio decreased with age, from 4.0 at age 50 years to 2.5 at age 70 years and just under 2 at age 85 years, identically for men and women. The standardised mortality ratio decreased 1% per calendar year. The lifetime risk of diabetes was 30%. CONCLUSIONS/INTERPRETATION: The prevalence of diabetes in Denmark rose in 1995-2006, but the mortality rate in diabetic patients decreased faster than that of the non-diabetic population. The mortality rate decreased markedly just after inclusion in the register. Incidence rates have shown a tendency to decrease during the last few years, but this finding should be viewed with caution.


Asunto(s)
Diabetes Mellitus/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Dinamarca/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores de Riesgo , Caracteres Sexuales , Factores de Tiempo
17.
Neurogastroenterol Motil ; 20(6): 649-59, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18298441

RESUMEN

Glucagon-like peptide-1 (GLP-1) is released after food intake to act as an incretin. GLP-1 also inhibits gastric emptying and increases satiety. In rats, GLP-1 inhibits small bowel motility. Our aim was to study the effects of GLP-1 on gastrointestinal motility in healthy subjects and patients with irritable bowel syndrome (IBS). Antro-duodeno-jejunal manometry was carried out during a 4-h control period with saline, followed by a 4-h period with intravenous GLP-1 (healthy: 0.7 and 1.2 pmol kg(-1) min(-1) (n = 16); IBS, 1.2 and 2.5 pmol kg(-1) min(-1) (n = 14). Plasma was analysed for GLP-1 and gut hormones, and gut tissue expression of GLP-1 receptor was studied. In healthy subjects, GLP-1 0.7 pmol kg(-1) min(-1) reduced the migrating motor complexes (MMCs) from a median of 2 (range 2-3) to 0.5 (0-2), and motility index from 4.9 +/- 0.1 to 4.3 +/- 0.3 ln Sigma(mmHg*s min(-1)) in jejunum, while GLP-1 1.2 pmol kg(-1) min(-1) diminished MMCs from 2 (2-3) to 1.5 (1-2.5), and motility index from 5.2 +/- 0.2 to 4.4 +/- 0.2. In IBS patients, GLP-1 1.2 pmol kg(-1) min(-1) reduced the MMCs from 2.5 (2-3.5) to 1 (0-1.5) without affecting motility index. At 2.5 pmol kg(-1) min(-1) GLP-1 decreased MMCs from 2 (1.5-3) to 1 (0.5-1.5), and motility index from 5.2 +/- 0.2 to 4.0 +/- 0.5. Motility responses to GLP-1 were similar in antrum and duodenum. Presence of the GLP-1 receptor in the gut was verified by reverse transcriptase PCR. In conclusion, the gut peptide GLP-1 decreases motility in the antro-duodeno-jejunal region and inhibits the MMC in healthy subjects and IBS patients.


Asunto(s)
Motilidad Gastrointestinal/fisiología , Péptido 1 Similar al Glucagón/fisiología , Péptido 1 Similar al Glucagón/uso terapéutico , Síndrome del Colon Irritable/fisiopatología , Complejo Mioeléctrico Migratorio/fisiología , Adolescente , Adulto , Duodeno/efectos de los fármacos , Duodeno/inervación , Duodeno/fisiología , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Péptido 1 Similar al Glucagón/administración & dosificación , Humanos , Síndrome del Colon Irritable/tratamiento farmacológico , Yeyuno/efectos de los fármacos , Yeyuno/inervación , Yeyuno/fisiología , Masculino , Persona de Mediana Edad , Complejo Mioeléctrico Migratorio/efectos de los fármacos , Antro Pilórico/efectos de los fármacos , Antro Pilórico/inervación , Antro Pilórico/fisiología
18.
Int J Pharm ; 342(1-2): 115-23, 2007 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-17582712

RESUMEN

The effects of roller compaction process parameters, morphological forms of calcium carbonate and particle size of sorbitol on flow, compaction and compression properties were investigated. The morphology of the calcium carbonate and the sorbitol particle size were more influential on the compaction properties than the settings of the roller compactor. The roller compaction process was demonstrated to be robust and stable in regard to flowability and compactibility. The flowability of the granules was improved adequately to facilitate compression in a production scale rotary tablet press. By adding sorbitol to the calcium carbonate, the compressibility - characterized by the Walker coefficient W(ID) - and the compactibility C(P) were improved considerably. A correlation between the consolidation characteristics was demonstrated. Compactibility data from the compaction simulator correlated with the tablet press for two of the calcium carbonates, the cubic form and the ground quality.


Asunto(s)
Carbonato de Calcio/química , Composición de Medicamentos/instrumentación , Algoritmos , Industria Farmacéutica/instrumentación , Excipientes , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Excipientes Farmacéuticos/química , Polvos , Presión , Sorbitol/química , Ácidos Esteáricos , Comprimidos
19.
Br J Clin Pharmacol ; 63(3): 322-7, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16970569

RESUMEN

AIMS: To investigate the transfer of mirtazapine and desmethylmirtazapine into milk and to calculate dose to the infant via milk. METHODS: Plasma and milk samples were obtained from eight breast-feeding women who were taking a median dose of 38 mg mirtazapine per day. Milk/plasma ratio (M/P) and infant doses were estimated by standard methods. The infants were examined clinically and in four infants blood was taken for analysis. RESULTS: Mean (95% confidence interval) relative infant doses for mirtazapine and desmethylmirtazapine (n = 8) were 1.5% (0.8, 2.2) and 0.4% (0.2, 0.6) respectively. The mean M/P (area under curve n = 4, single or paired samples n = 3) was 1.1 (0.7,1.5) for mirtazapine and 0.6 (0.5, 0.7) for desmethylmirtazapine. No adverse effects were seen. Mirtazapine was detected (1.5 microg l(-1)) in only one of four infants tested. CONCLUSION: We suggest that mirtazapine use by lactating women is safe for the breast-fed infant. Nevertheless, each decision to breast feed should always be made on the basis of an individual risk/benefit analysis.


Asunto(s)
Antidepresivos de Segunda Generación/efectos adversos , Antidepresivos Tricíclicos/efectos adversos , Lactancia Materna , Depresión Posparto/tratamiento farmacológico , Mianserina/análogos & derivados , Femenino , Humanos , Lactante , Recién Nacido , Mianserina/efectos adversos , Leche Humana/química , Mirtazapina , Embarazo
20.
Acta Neurochir Suppl ; 93: 159-63, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15986748

RESUMEN

PURPOSE: Present the possibility for treatment of male infertility, spasticity, and neurogenic detrusor overactivity in spinal cord lesioned (SCL) individuals with penile vibratory stimulation (PVS). METHOD: Obtaining reflex-ejaculation by PVS, by using a vibrator developed for this purpose. The stimulation was performed with a vibrating disc of hard plastic placed against the frenulum of the penis (amplitude > or = 2.5 mm). The vibration continued until antegrade ejaculation or for a maximum of 3 minutes followed by a pause of 1 minute before the cycle was repeated, maximally 4 times. RESULTS: >80% SCL men are able to obtain ejaculation with PVS. Pregnancy rates obtained with home PVS and intra-vaginal insemination was 22-62% (4 studies), and with PVS or electroejaculation and intrauterine insemination/in-vitro fertilization/intracytoplasmatic sperm injection 39-64% (9 studies). PVS was demonstrated to decrease spasticity significantly when measured by the modified Ashworth scale. In addition, a decrease of the number of spontaneous EMG events which probably indicate spasms was observed. Increase in bladder capacity at leakpoint following 4 weeks of frequent ejaculation with PVS treatment was likewise demonstrated. CONCLUSION: PVS has proved its importance for SCL male fertility, in the years to come its place in treatment of spasticity and neurogenic detrusor overactivity has to be established.


Asunto(s)
Infertilidad Masculina/rehabilitación , Hipertonía Muscular/etiología , Hipertonía Muscular/rehabilitación , Pene/fisiopatología , Estimulación Física/métodos , Traumatismos de la Médula Espinal/rehabilitación , Vibración/uso terapéutico , Humanos , Infertilidad Masculina/etiología , Masculino , Pene/inervación , Recuperación de la Función , Traumatismos de la Médula Espinal/complicaciones , Resultado del Tratamiento
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