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1.
J Vet Cardiol ; 41: 99-120, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35316716

RESUMEN

OBJECTIVES: To describe the medical treatment prescribed or modified by veterinary cardiologists at the enrollment visit in dogs included in the longitudinal outcome of canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-mitral registry) and to evaluate the influence of the EPIC trial and other selected variables on cardiologist prescription habits. ANIMALS: The medical records of 6,102 dogs enrolled in the LOOK_mitral registry between 2015 and 2018 were retrospectively reviewed and 6,016 dogs were included. RESULTS: A medical treatment was prescribed by a cardiologist to 2,599 dogs (15% Stage-B1, 90% Stage-B2 and to all dogs in Stage-C). Angiotensin converting enzyme inhibitors (Ace-i) were the treatment most commonly prescribed for dogs in Stage-B1 (n = 352, 9%). The combination of pimobendan and an Ace-i was the most common treatment in Stage-B2 dogs (n = 367, 41%). Furosemide, an Ace-i, and pimobendan was the most common cardiac medical treatment prescribed for ACVIM Stage-C dogs (n = 704, 57%). Within each stage, dogs with larger left atrial and left ventricular dimensions were more likely to receive Ace-i, pimobendan or spironolactone. There was a four-fold increase in pimobendan prescription in Stage-B2 dogs after the publication of the EPIC trial. Moreover, a 15% reduction in Ace-i prescription and a 30% reduction in spironolactone prescription occurred after EPIC. In 974 dogs, a medical treatment was prescribed by the referring veterinarian. This was not changed (12%), modified (74%), or discontinued (14%) by the cardiologist. CONCLUSIONS: The EPIC trial and the echocardiographic assessment of left atrial and ventricular dimensions influence cardiologists' prescription habits.


Asunto(s)
Enfermedades de los Perros , Insuficiencia Cardíaca , Enfermedades de las Válvulas Cardíacas , Animales , Cardiotónicos/farmacología , Enfermedades de los Perros/tratamiento farmacológico , Perros , Insuficiencia Cardíaca/veterinaria , Enfermedades de las Válvulas Cardíacas/veterinaria , Válvula Mitral , Sistema de Registros , Estudios Retrospectivos , Espironolactona
2.
J Vet Cardiol ; 40: 170-183, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34785174

RESUMEN

OBJECTIVES: This study aimed to characterize the clinical and histopathological features of arrhythmogenic right ventricular cardiomyopathy (ARVC) in English Bulldogs, American Bulldogs, and Bulldog-type mixed breed dogs and assess affected Bulldogs for a striatin gene mutation previously reported in Boxers with ARVC. ANIMALS: Seventy-one Bulldogs fit the inclusion criteria. Genetic analysis was performed on five dogs. Cardiac post-mortem evaluations were performed on two dogs. METHODS: Medical records from a single veterinary cardiology group (CVCA) were retrospectively evaluated. Tissue and blood samples were submitted for histopathological analysis and genetic testing in select patients. RESULTS: Presenting complaints included syncope (38%), arrhythmia (81.7%), or murmur (34.2%) documented on examination. On presentation, congestive heart failure (CHF) was diagnosed in 22 (31%) dogs, and 58 (81.7%) had ventricular arrhythmias. On bivariable analyses, the two-dimensional (2D) left atrial-to-aortic root ratio (LA:Ao) was the only prognostic variable significantly associated with survival time. Dogs with 2D LA:Ao below the mean (1.41) had longer median survival to all-cause mortality (12 months; 95% confidence interval [CI] six-15 months) than those with 2D LA:Ao above the mean (four months; 95% CI two-six months; p=0.0384). Most dogs (54%) died from cardiac disease, with 42.1% experiencing sudden death. The median time from diagnosis to cardiac death was four months. CONCLUSIONS: Arrhythmogenic right ventricular cardiomyopathy affects Bulldogs with both arrhythmogenic and dilated-type phenotypes. Despite variable arrhythmia severity and predominantly right-sided involvement in many dogs, an increase in left atrial size was the only significant predictor of mortality in this sample of dogs.


Asunto(s)
Displasia Ventricular Derecha Arritmogénica , Enfermedades de los Perros , Animales , Arritmias Cardíacas/veterinaria , Displasia Ventricular Derecha Arritmogénica/genética , Displasia Ventricular Derecha Arritmogénica/veterinaria , Enfermedades de los Perros/diagnóstico , Perros , Atrios Cardíacos , Estudios Retrospectivos
3.
J Vet Cardiol ; 36: 32-47, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34062479

RESUMEN

INTRODUCTION: The Longitudinal Outcome Of Canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-Mitral registry) was established to describe the natural history and predictors of outcome in dogs affected by MMVD. This study was intended to describe the baseline characteristics of dogs in the LOOK-mitral registry. ANIMALS: Dogs with echocardiographic evidence of MMVD were prospectively enrolled by thirteen referral centers. RESULTS: A total of 6102 dogs with MMVD were included. The median age was 10 years (1-19 years), and mixed breed was the most common breed (n = 1,360, 22%). Concomitant diseases were reported in 2459 dogs with chronic respiratory diseases occurring most frequently (14%), followed by the presence of azotemia (6%) and orthopedic diseases (5%). Regarding disease severity, 65% of dogs were in ACVIM Stage-B1, 15% in Stage-B2, and 20% in Stage-C. Dogs in Stage-B1 were younger (p<0.001) than dogs in other stages. Murmur intensity, heart rate during physical examination, and radiographic vertebral heart score were positively associated with the stage. Dogs in Stage-C were more likely to have tachypnea (p<0.001), dyspnea (p<0.001), cough (p<0.001), syncopal episodes (p<0.001), and tachyarrhythmias (p<0.001) compared to dogs in Stage-B1 and B2. Echocardiographic indices of left atrial and ventricular size were positively correlated with the ACVIM stage. Interestingly, 4% of dogs that weighed <20 kg had an increased normalized end-systolic left ventricle internal diameter (>1.26). CONCLUSIONS: This study contributes to a better understanding of the clinical characteristics of dogs affected by MMVD and provides new findings that may be of clinical relevance.


Asunto(s)
Enfermedades de los Perros , Enfermedades de las Válvulas Cardíacas , Animales , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/epidemiología , Perros , Ecocardiografía/veterinaria , Enfermedades de las Válvulas Cardíacas/veterinaria , Válvula Mitral/diagnóstico por imagen , Sistema de Registros
4.
J Vet Cardiol ; 34: 112-119, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33706221

RESUMEN

INTRODUCTION: Myxomatous mitral valve disease (MMVD) is the most common cause of left-sided congestive heart failure in dogs. We sought to identify predictors of first reoccurrence of congestive signs (CS) within 180 days in dogs with MMVD and clinically stable heart failure. ANIMALS: A total of 445 dogs affected by stable American College of Veterinary Internal Medicine (ACVIM)-Stage-C MMVD were included, 106 in the reoccurrence group (RG) and 339 in no reoccurrence group (NRG). Patients were considered "stable" if medical treatment had been unchanged for at least 4 weeks since the first identification of CS. METHODS: Medical records of dogs with stable ACVIM-Stage-C MMVD included in a registry of dogs affected by MMVD were reviewed. Follow-up was required for inclusion in this investigation. Logistic regression was used to identify clinical and echocardiographic variables that independently predict first reoccurrence of CS. RESULTS: Baseline left atrial-aortic ratio (p=0.022, OR: 1.89, 90% CI: 1.20-2.98), left ventricular internal diameter at end-diastole (LVIDd_N) (p=0.014, OR: 2.84, 90% CI: 1.41-5.77), peak velocity of early diastolic transmitral flow (p=0.049, OR: 1.81, 90% CI: 1.10-3.00) and furosemide daily dosage (p=0.039, OR: 1.19, 90% CI: 1.04-1.37) were associated with reoccurrence of CS in univariable analyses. The LVIDd_N (p=0.014) remained significant in the multivariable analysis, but the area under the receiver operator characteristic curve was 0.57. CONCLUSION: This study failed to identify accurate predictors of reoccurrence of CS. However, dogs with larger value of LVIDd_N are more likely to have reoccurrence of CS within 180 days.


Asunto(s)
Enfermedades de los Perros , Insuficiencia Cardíaca , Enfermedades de las Válvulas Cardíacas , Animales , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/tratamiento farmacológico , Perros , Ecocardiografía/veterinaria , Insuficiencia Cardíaca/veterinaria , Enfermedades de las Válvulas Cardíacas/veterinaria , Válvula Mitral/diagnóstico por imagen
5.
Horm Res Paediatr ; 91(6): 357-372, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31319416

RESUMEN

This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses topics related to changes in GnRHa usage in children and adolescents over the last decade. Topics related to the use of GnRHa in precocious puberty include diagnostic criteria, globally available formulations, considerations of benefit of treatment, monitoring of therapy, adverse events, and long-term outcome data. Additional sections review use in transgender individuals and other pediatric endocrine related conditions. Although there have been many significant changes in GnRHa usage, there is a definite paucity of evidence-based publications to support them. Therefore, this paper is explicitly not intended to evaluate what is recommended in terms of the best use of GnRHa, based on evidence and expert opinion, but rather to describe how these drugs are used, irrespective of any qualitative evaluation. Thus, this paper should be considered a narrative review on GnRHa utilization in precocious puberty and other clinical situations. These changes are reviewed not only to point out deficiencies in the literature but also to stimulate future studies and publications in this area.


Asunto(s)
Hormona Liberadora de Gonadotropina/uso terapéutico , Pubertad Precoz , Adolescente , Niño , Femenino , Humanos , Masculino , Pubertad Precoz/diagnóstico , Pubertad Precoz/tratamiento farmacológico , Pubertad Precoz/patología , Pubertad Precoz/fisiopatología
6.
Bioinformatics ; 35(5): 815-822, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30102349

RESUMEN

MOTIVATION: Modern biological experiments often produce candidate lists of genes presumably related to the studied phenotype. One can ask if the gene list as a whole makes sense in the context of existing knowledge: Are the genes in the list reasonably related to each other or do they look like a random assembly? There are also situations when one wants to know if two or more gene sets are closely related. Gene enrichment tests based on counting the number of genes two sets have in common are adequate if we presume that two genes are related only when they are in fact identical. If by related we mean well connected in the interaction network space, we need a new measure of relatedness for gene sets. RESULTS: We derive entropy, interaction information and mutual information for gene sets on interaction networks, starting from a simple phenomenological model of a living cell. Formally, the model describes a set of interacting linear harmonic oscillators in thermal equilibrium. Because the energy function is a quadratic form of the degrees of freedom, entropy and all other derived information quantities can be calculated exactly. We apply these concepts to estimate the probability that genes from several independent genome-wide association studies are not mutually informative; to estimate the probability that two disjoint canonical metabolic pathways are not mutually informative; and to infer relationships among human diseases based on their gene signatures. We show that the present approach is able to predict observationally validated relationships not detectable by gene enrichment methods. The converse is also true; the two methods are therefore complementary. AVAILABILITY AND IMPLEMENTATION: The functions defined in this paper are available in an R package, gsia, available for download at https://github.com/ucsd-ccbb/gsia.


Asunto(s)
Biología Computacional , Redes Reguladoras de Genes , Estudio de Asociación del Genoma Completo , Algoritmos , Entropía , Humanos
7.
Contraception ; 2018 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-29678366

RESUMEN

PURPOSE: To explore the acceptability of advance provision of emergency contraceptive pills (ECPs) to young men seeking health care. METHODS: For this exploratory study in a clinic setting, we approached young men aged 16-35 to participate in a survey eliciting socio-demographics, sexual and contraceptive history, and knowledge about ECPs. We offered young men advance provision of ECPs and compared characteristics of 126 young men who did and did not accept the ECPs. RESULTS: Most (76%) of the participants accepted advance provision and left with an ECP pack, with even higher proportions among males whose sexual histories were suggestive of increased risk of involvement in an unintended pregnancy. CONCLUSIONS: This study holds promise to inform scale up of advance provision of ECPs among young men.

8.
J Vet Intern Med ; 32(1): 72-85, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29214723

RESUMEN

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.


Asunto(s)
Cardiotónicos/uso terapéutico , Prolapso de la Válvula Mitral/tratamiento farmacológico , Piridazinas/uso terapéutico , Animales , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Perros , Ecocardiografía/veterinaria , Cardiopatías/mortalidad , Cardiopatías/veterinaria , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/veterinaria , Prolapso de la Válvula Mitral/diagnóstico por imagen , Prolapso de la Válvula Mitral/patología , Estudios Prospectivos , Calidad de Vida
10.
J Vet Intern Med ; 30(6): 1765-1779, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27678080

RESUMEN

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.


Asunto(s)
Cardiomegalia/veterinaria , Cardiotónicos/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Insuficiencia de la Válvula Mitral/veterinaria , Piridazinas/uso terapéutico , Animales , Cardiomegalia/tratamiento farmacológico , Cardiotónicos/efectos adversos , Perros , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/veterinaria , Masculino , Insuficiencia de la Válvula Mitral/tratamiento farmacológico , Insuficiencia de la Válvula Mitral/mortalidad , Piridazinas/efectos adversos
11.
Z Rheumatol ; 75(9): 910-916, 2016 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-26951194

RESUMEN

INTRODUCTION: In the MEPEX trial the poor prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with severe renal manifestation (AAVr) could be significantly improved in the first year by plasmapheresis. How and to what extent is this knowledge of AAVr therapy implemented into routine practice and what effectiveness and adverse events resulted? METHODS: This was a retrospective cohort study in which all patients who received remission induction therapy for AAVr under routine clinical conditions (RCC) in this hospital from 2009 to 2014 after publication of the MEPEX trial (n = 22) were compared with those in the plasmapheresis arm of the MEPEX trial (n = 70). Endpoints were dialysis-dependent chronic kidney disease and mortality after 3 and 12 months and severe life-threatening adverse events during the first 12 months. RESULTS: All patients with AAVr were treated by plasmapheresis under RCC. The two groups showed no differences with respect to the rate of dialysis dependency (after 3 months RCC 14 % versus MEPEX 16 %, P = 1.00 and after 12 months RCC 23 % versus MEPEX 14 %, P = 0.55) or mortality (after 3 months RCC 18 % versus MEPEX 16 %, P = 0.75 and after 12 months RCC 18 % versus MEPEX 27 %, P = 0.57). The rate of severe life-threatening adverse events was similar under RCC and under controlled study conditions (64 % versus 69 %, P = 0.87). CONCLUSION: Under RCC there is a high quality of medical treatment for AAVr. All patients received plasmapheresis for remission induction with comparable effectiveness and safety compared to controlled study conditions.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Plasmaféresis/mortalidad , Diálisis Renal/mortalidad , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/terapia , Adolescente , Adulto , Anciano , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Plasmaféresis/estadística & datos numéricos , Prevalencia , Diálisis Renal/estadística & datos numéricos , Factores de Riesgo , Tasa de Supervivencia , Adulto Joven
12.
Phys Rev Lett ; 116(6): 065001, 2016 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-26918996

RESUMEN

Enhanced implosion stability has been experimentally demonstrated for magnetically accelerated liners that are coated with 70 µm of dielectric. The dielectric tamps liner-mass redistribution from electrothermal instabilities and also buffers coupling of the drive magnetic field to the magneto-Rayleigh-Taylor instability. A dielectric-coated and axially premagnetized beryllium liner was radiographed at a convergence ratio [CR=Rin,0/Rin(z,t)] of 20, which is the highest CR ever directly observed for a strengthless magnetically driven liner. The inner-wall radius Rin(z,t) displayed unprecedented uniformity, varying from 95 to 130 µm over the 4.0 mm axial height captured by the radiograph.

13.
Neurosci Lett ; 570: 42-6, 2014 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-24746929

RESUMEN

Dementia is a major public health problem worldwide. Alzheimer's disease (AD) is a major form of dementia and the APOE 4 allele is an established genetic risk factor for AD. Similarly, stressful life events are also associated with dementia. The objective of this study was to examine the association of APOE 4 and stressful life events with dementia in a Pakistani sample, which to our knowledge has not been reported previously. We also tested for an interaction between stressful life events and APOE 4 on dementia risk. A total of 176 subjects (61 cases and 115 controls) were recruited. All cases and healthy controls were interviewed to assess cognition, co-morbidities, history of stressful life events and demographics. Blood genotyping for the APOE polymorphism (E2/E3/E4) was performed. APOE 4 and stressful life events were each independently and significantly associated with the risk of dementia (APOE 4: P=0.00697; stressful life events: P=5.29E-09). However, we did not find a significant interaction between APOE 4 carrier status and stressful life events on risk of dementia (P=0.677). Although the sample size of this study was small, the established association of APOE 4 with dementia was confirmed the first time in a Pakistani sample. Furthermore, stressful life events were also found to be significantly associated with dementia in this population.


Asunto(s)
Apolipoproteínas E/genética , Demencia/genética , Acontecimientos que Cambian la Vida , Estrés Psicológico/complicaciones , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Demencia/etiología , Demencia/psicología , Susceptibilidad a Enfermedades , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Pakistán , Polimorfismo Genético , Estrés Psicológico/psicología
14.
Nat Commun ; 4: 1576, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23481384

RESUMEN

Photon-enhanced thermionic emission is a method of solar-energy conversion that promises to combine photon and thermal processes into a single mechanism, overcoming fundamental limits on the efficiency of photovoltaic cells. Photon-enhanced thermionic emission relies on vacuum emission of photoexcited electrons that are in thermal equilibrium with a semiconductor lattice, avoiding challenging non-equilibrium requirements and exotic material properties. However, although previous work demonstrated the photon-enhanced thermionic emission effect, efficiency has until now remained very low. Here we describe electron-emission measurements on a GaAs/AlGaAs heterostructure that introduces an internal interface, decoupling the basic physics of photon-enhanced thermionic emission from the vacuum emission process. Quantum efficiencies are dramatically higher than in previous experiments because of low interface recombination and are projected to increase another order of magnitude with more stable, low work-function coatings. The results highlight the effectiveness of the photon-enhanced thermionic emission process and demonstrate that efficient photon-enhanced thermionic emission is achievable, a key step towards realistic photon-enhanced thermionic emission based energy conversion.

15.
Diabetologia ; 56(2): 391-400, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23086558

RESUMEN

AIMS/HYPOTHESIS: Type 1 diabetes results from a chronic autoimmune process continuing for years after presentation. We tested whether treatment with teplizumab (a Fc receptor non-binding anti-CD3 monoclonal antibody), after the new-onset period, affects the decline in C-peptide production in individuals with type 1 diabetes. METHODS: In a randomised placebo-controlled trial we treated 58 participants with type 1 diabetes for 4-12 months with teplizumab or placebo at four academic centres in the USA. A central randomisation centre used computer generated tables to allocate treatments. Investigators, patients, and caregivers were blinded to group assignment. The primary outcome was a comparison of C-peptide responses to a mixed meal after 1 year. We explored modification of treatment effects in subgroups of patients. RESULTS: Thirty-four and 29 subjects were randomized to the drug and placebo treated groups, respectively. Thirty-one and 27, respectively, were analysed. Although the primary outcome analysis showed a 21.7% higher C-peptide response in the teplizumab-treated group (0.45 vs 0.371; difference, 0.059 [95% CI 0.006, 0.115] nmol/l) (p = 0.03), when corrected for baseline imbalances in HbA(1c) levels, the C-peptide levels in the teplizumab-treated group were 17.7% higher (0.44 vs 0.378; difference, 0.049 [95% CI 0, 0.108] nmol/l, p = 0.09). A greater proportion of placebo-treated participants lost detectable C-peptide responses at 12 months (p = 0.03). The teplizumab group required less exogenous insulin (p < 0.001) but treatment differences in HbA(1c) levels were not observed. Teplizumab was well tolerated. A subgroup analysis showed that treatment benefits were larger in younger individuals and those with HbA(1c) <6.5% at entry. Clinical responders to teplizumab had an increase in circulating CD8 central memory cells 2 months after enrolment compared with non-responders. CONCLUSIONS/INTERPRETATIONS: This study suggests that deterioration in insulin secretion may be affected by immune therapy with teplizumab after the new-onset period but the magnitude of the effect is less than during the new-onset period. Our studies identify characteristics of patients most likely to respond to this immune therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00378508 FUNDING: This work was supported by grants 2007-502, 2007-1059 and 2006-351 from the JDRF and grants R01 DK057846, P30 DK20495, UL1 RR024139, UL1RR025780, UL1 RR024131 and UL1 RR024134 from the NIH.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Péptido C/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Adolescente , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Insulina/metabolismo , Masculino
16.
Prilozi ; 33(1): 27-48, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22952093

RESUMEN

Acute kidney injury (AKI) comprises several syndromes that are associated with a sudden decrease in renal function. AKI is a common condition especially among critically ill patients. It is typically multifactorial and of great prognostic significance. The incidence of AKI has increased while the associated mortality rate has remained unchanged over the last years. Recent definitions of AKI, namely the Risk, Injury, Failure, Loss of renal function and End-stage kidney disease (RIFLE) classifycation or the Acute Kidney Injury Network (AKIN) criteria, incorporate serum creatinine and urine output as the principal markers to define and detect AKI. However, elevated serum creatinine or oliguria were demonstrated to detect AKI at late stages of renal injury when preventive strategies may be less effective. Therefore, there has recently been a great scientific interest in obtainng valuable markers for early AKI detection. In the last 5 years numerous new markers such as neutrophil-gelatinase associated lipo-calin, interleukin-18, cystatin C and kidney injury molecule 1 in the urine and/or serum have been studied and proposed as early detection markers of AKI. Persistently, these markers performed well in initial pilot trials. However, these promising results could often not be confirmed in later, larger multicentre trials and limitation of these biomarkers in the early diagnosis of renal injury were discovered. Furthermore, as AKI is multi-factorial and heterogeneous in origin, it seems likely that not one single marker but a panel of biomarkers will be required to detect all subtypes of AKI early during their evolution. This has initiated proteomic studies to develop panels of biomarkers which may facilitate early detection of AKI. The present review will focus on the most important clinical studies evaluating the ability of single AKI biomarkers and on those in clinical proteomics that attempted to establish panels of biomarkers in urine for early and accurate AKI diagnosis and prognosis.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Biomarcadores , Proteómica , Humanos , Pronóstico
17.
Transl Psychiatry ; 2: e77, 2012 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-22832814

RESUMEN

The human serotonin transporter (SERT) gene possesses a 43-base pair (bp) insertion-deletion promoter polymorphism, the h5-HTTLPR. Genotype at this locus correlates with variation in anxiety-related personality traits and risk for major depressive disorder in many studies. Yet, the complex effects of the h5-HTTLPR, in combination with closely associated single-nucleotide polymorphisms (SNPs), continue to be debated. Moreover, although SERT is of high clinical significance, transporter function in vivo remains difficult to assess. Rhesus express a promoter polymorphism related to the h5-HTTLPR. The rh5-HTTLPR has been linked to differences in stress-related behavior and cognitive flexibility, although allelic variations in serotonin uptake have not been investigated. We studied the serotonin system as it relates to the 5-HTTLPR in rhesus peripheral blood cells. Sequencing of the rh5-HTTLPR revealed a 23-bp insertion, which is somewhat longer than originally reported. Consistent with previous reports, no SNPs in the rh5-HTTLPR and surrounding genomic regions were detected in the individuals studied. Reductions in serotonin uptake rates, cell surface SERT binding, and 5-hydroxyindoleacetic acid/serotonin ratios, but not SERT mRNA levels, were associated with the rh5-HTTLPR short allele. Thus, serotonin uptake rates are differentiable with respect to the 5-HTTLPR in an easily accessible native peripheral tissue. In light of these findings, we foresee that primary blood cells, in combination with high sensitivity functional measurements enabled by chronoamperometry, will be important for investigating alterations in serotonin uptake associated with genetic variability and antidepressant responsiveness in humans.


Asunto(s)
Células Sanguíneas/metabolismo , Genotipo , Mutación INDEL/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Alelos , Animales , Femenino , Regulación de la Expresión Génica/genética , Interacción Gen-Ambiente , Humanos , Macaca mulatta , Masculino , Polimorfismo Genético/genética , ARN Mensajero/genética , Especificidad de la Especie
18.
Internist (Berl) ; 53(3): 282-90, 2012 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-22349237

RESUMEN

Ultrasound is the most important non-invasive diagnostic tool for detecting morphological pathological alterations of the kidneys. With a low patient burden it permits rapid, potentially serial and highly reproducible bed-side diagnoses of postrenal acute kidney injury and chronic kidney disease. Within chronic kidney disease, polycystic kidney disease can reliably be detected and evidence can be obtained for ischemic nephropathy, diabetic nephropathy and chronic pyelonephritis by renal size and intrarenal morphological alterations. An additional domain of ultrasound is the differentiation of the dignity of solid and cystic renal lesions. Newly introduced contrast-enhanced ultrasound is of additional help as benign and malignant lesions display different perfusion patterns. Renal artery stenosis can reliably be identified and its hemodynamic effect can be assessed with a combination of direct and indirect criteria by Doppler and duplex ultrasound.


Asunto(s)
Enfermedades Renales/diagnóstico por imagen , Riñón/diagnóstico por imagen , Imagen de Perfusión/métodos , Ultrasonografía/métodos , Humanos
19.
Infection ; 40(4): 405-13, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22237474

RESUMEN

PURPOSE: In the USA, the burden of hepatitis B disproportionately affects high-risk adults who alone account for more than 75% of newly reported hepatitis B virus infections each year. Despite the localization of new infections in identifiable high-risk groups, vaccination rates in this subgroup, with the exception of health care workers, remain consistently low. The purpose of this study was to characterize those at risk for hepatitis B transmission and quantify the association between missed opportunities and hepatitis B vaccination. METHODS: Data from the 2007 Behavioral Risk Factor Surveillance Survey (BRFSS) of adults aged 18 years and older who were at high risk for hepatitis B infection (n = 15,432) were analyzed. Multivariate regression analysis was conducted to determine factors independently associated with vaccination. RESULTS: In a nationally representative sample, 51.4% of high-risk adults remained unvaccinated against hepatitis B and more than 50% had a missed opportunity for vaccination. High-risk adults who were vaccinated against pneumonia and influenza had a higher odds ratio of being vaccinated against hepatitis B than those not vaccinated against pneumonia and influenza (OR 2.27 and 1.67, respectively). Also, high-risk adults tested for human immunodeficiency virus (HIV) at a counseling and testing site or a drug treatment facility had a higher OR of being vaccinated than those who had not been tested for HIV (OR 1.78 and 1.73, respectively). The opposite relationship was true among individuals tested for HIV at a correctional facility (OR 0.60). CONCLUSIONS: The findings of this study underscore the inadequacy of vaccination coverage in high-risk adults and highlight advantageous opportunities to bridge gaps in vaccination coverage.


Asunto(s)
Vacunas contra Hepatitis B/inmunología , Hepatitis B/prevención & control , Vacunación , Adolescente , Adulto , Anciano , Femenino , Hepatitis B/epidemiología , Humanos , Seguro de Salud , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , Estados Unidos/epidemiología , Vacunación/economía , Vacunación/estadística & datos numéricos
20.
Clin Oncol (R Coll Radiol) ; 24(1): 43-51, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21875782

RESUMEN

The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. This review focuses on locally advanced prostate cancer and the evidence for treatment outcomes, both toxicity and efficacy, across the three major treatment modalities of external beam radiotherapy, brachytherapy and surgery. Only data that could pass contemporary quality metrics were used to form this report. This body of literature suffers from an absence of trials prospectively comparing therapies for efficacy and a lack of long-term prospective comparisons of toxicity. Upon review of these data, the authors concluded that there are several acceptable methods for the treatment of locally advanced prostate cancer that is highly dependent of the patient's clinical (both prostate cancer-specific and comorbidity-specific) parameters at diagnosis.


Asunto(s)
Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Antineoplásicos/uso terapéutico , Humanos , Masculino , Prostatectomía , Neoplasias de la Próstata/tratamiento farmacológico , Radioterapia/métodos
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