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Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by pathophysiological deposits of extracellular amyloid beta (Aß) peptides and intracellular neurofibrillary tangles of tau. The central role of Aß in AD pathology is well-established, with its increased deposition attributed mainly to its decreased cerebral clearance. Here, it is noteworthy that apolipoprotein E (ApoE), the most significant risk factor for AD, has been shown to play an isoform-specific role in clearing Aß deposits (ApoE2 > ApoE3 > ApoE4), owing mainly to its lipidation status. In addition to the pathophysiological Aß deposits, AD is also characterized by abnormal glucose metabolism, which is a distinct event preceding Aß deposition. The present study established, for the first time, a possible link between these two major AD etiologies, with glucose metabolism directly influencing ApoE lipidation and its secretion by astrocytes expressing human ApoE4. Specifically, glucose dose-dependently activated liver X receptor (LXR), leading to elevated ABCA1 and ABCG1 protein levels and enhanced ApoE lipidation. Moreover, co-treatment with a glycolytic inhibitor significantly inhibited this LXR activation and subsequent ApoE lipidation, further supporting a central role of glucose metabolism in LXR activation leading to enhanced ApoE lipidation, which may help against AD through potential Aß clearance. Therefore, we hypothesized that pharmacological agents that can target cellular energy metabolism, specifically aerobic glycolysis, may hold significant therapeutic potential against AD. In this context, the present study also led to the discovery of novel, small-molecule stimulants of astrocytic glucose metabolism, leading to significantly enhanced lipidation status of ApoE4 in astrocytic cells. Three such newly discovered compounds (lonidamine, phenformin, and berberine), owing to their promising cellular effect on the glycolysis-ApoE nexus, warrant further investigation in suitable in vivo models of AD.
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PURPOSE: To evaluate the surgical effect of the Wright central plication on vertical rectus muscles to correct vertical strabismus. METHODS: In this multicenter, retrospective, observational outcomes study, data were collected from two surgeons in different practice settings (2017-22). All patients who underwent vertical rectus central plication were included; those undergoing any concurrent strabismus surgery for vertical strabismus were excluded. Primary outcome was amount of strabismus correction in prism diopters per vertical rectus central plication. Secondary outcome was to determine factors associated with better or worse surgical outcomes and patient and patient responses. Data were analyzed using descriptive and bivariate statistics. RESULTS: A total of 36 patients were included. Mean age was 60 years. Mean follow-up was 8.4 months. Of the 36 patients, 11 (31%) had idiopathic strabismus, and 7 (19%) had congenital superior oblique palsy. The remainder had a history that included prior ocular surgery, trauma, and Brown syndrome; 16 (44 %) had prior strabismus surgery. Of 31 patients with preoperative diplopia, 23 (74%) had postoperative resolution of diplopia, and 10 of 16 patients with preoperative prisms (63%) no longer required prisms postoperatively. Mean vertical deviation change was 4.7Δ. Subgroup analysis removing patients with congenital superior oblique palsy showed a larger response of 5.5Δ. 78% of patients had a final deviation <5Δ. No complications or induced postoperative diplopia was reported. CONCLUSIONS: In our study cohort, vertical rectus central plication corrected approximately 5Δ (range, 4.5Δ-5.5Δ) of vertical strabismus due to a variety of causes.
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Procedimientos Quirúrgicos Oftalmológicos , Estrabismo , Humanos , Persona de Mediana Edad , Diplopía/etiología , Diplopía/cirugía , Estudios Retrospectivos , Estrabismo/etiología , Estrabismo/cirugía , Músculos Oculomotores/cirugía , Parálisis/cirugía , Resultado del TratamientoAsunto(s)
Vacunas contra la COVID-19 , COVID-19 , Hidradenitis Supurativa , Psoriasis , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inmunología , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Estudios Transversales , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , Masculino , Femenino , SARS-CoV-2/inmunología , Agentes Inmunomoduladores/uso terapéutico , Bases de Datos Factuales , Adulto , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Aim: To evaluate the safety and efficacy of insulin Aspart-Mix biosimilar candidate GP40081 (GP-Asp30) compared with NovoMix® 30 (NN-Asp30). Materials & methods: In a randomized open-label, active-controlled, 26-week non-inferiority clinical trial 264 patients with Type 2 diabetes mellitus were randomized 1:1 to receive once-daily GP-Asp30 or NN-Asp30. The primary safety end point was the immune response rate. Efficacy outcomes were a mean change in HbA1c (primary), frequency of achieving a glycemic g fasting plasma glucose levels, 7-point glucose profiles, and insulin doses. Results: The immune response developed in 10/126 (8%) participants in the GP-Asp30 group and in 10/125 (8%) participants in the NN-Asp30 group (p = 1.000). The mean difference in HbA1c change between groups was 0.12 (95%CI [-0.14, 0.38]). Other secondary efficacy and safety outcomes weren't statistically different between the two groups. Conclusion: GP-Asp30 demonstrated similar safety and efficacy compared with NN-Asp30 and may be considered a biosimilar insulin.
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Biosimilares Farmacéuticos , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Insulina Aspart , Humanos , Biosimilares Farmacéuticos/uso terapéutico , Insulinas Bifásicas , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Insulina Aspart/uso terapéutico , Insulina IsófanaRESUMEN
This paper presents an analysis of data from a comparative study of biosimilarity in terms of pharmacokinetics and pharmacodynamics in healthy volunteers using a hyperinsulinemic euglycemic clamp for reference and test biphasic insulin aspart 30 (BIAsp 30). As a result of the study, one of the secondary pharmacodynamic (PD) endpoints did not satisfy the classical criterion of 80%-125% (the lower limit for PD parameter area under the glucose infusion rate-time curve [ AUC GIR 0 - t ${\rm{AUC}}_{{\rm{GIR}}_{0 - {\rm{t}}}}$ ] turned out to be 79.5%). The main hypothesis explaining this result is that the sample size is insufficient to conduct a PD test with 90% statistical power, since the sample size has been calculated based on the coefficient of variation (CV) of pharmacokinetic (PK) parameters. To test this hypothesis, population PKPD (popPKPD) modeling and subsequent simulations of the required number of PD profiles were used. Two popPKPD models were constructed (a one-compartment double simultaneous absorption model for PK and an effect compartment Emax model for PD) to describe the PKPD data of reference and test insulins. As a result, using real data along with model-based simulation data, a biosimilarity test for PD was performed, and the lower limit for AUC GIR 0 - t ${\rm{AUC}}_{{\rm{GIR}}_{0 - {\rm{t}}}}$ became 82.6%, while the CV decreased from 31.7% to 24.1%. Thus, popPKPD modeling and simulations have been shown to be effective in interpreting and supporting the results of clinical biosimilarity trials.
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Biosimilares Farmacéuticos , Humanos , Hipoglucemiantes/farmacocinética , Método Doble Ciego , Estudios CruzadosRESUMEN
This study includes modeling and simulation of insulin aspart pharmacokinetics (PK). The authors used PK data of biosimilar insulins-insulin aspart and biphasic insulin aspart 30/70-to develop a predictive population PK model for the insulins. The model was built via Monolix software, taking into account the weight-based dosing and the dose and body-weight effects on the parameters. The model-based simulations were performed using the R package mlxR for various administered doses and various ratios of insulin aspart forms for a better understanding of the insulin behavior. The optimal model was a 1-compartment model with a combination of zero- and first-order absorptions, with absorption lag for the soluble form of insulin aspart and first-order absorption for the insulin aspart protamine suspension. The assumption of identical behavior of 2 insulins at the distribution and elimination phases was made. The developed PK model was fitted successfully to the experimental data, and all fitted parameters displayed a moderate coefficient of variation. The PK model allows us to predict PK profiles for various doses and formulations of insulin aspart and can be used to improve the accuracy, safety, and ethics of novel clinical trials of insulin.
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Insulinas , Insulinas Bifásicas/farmacocinética , Insulinas Bifásicas/uso terapéutico , Glucemia , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes , Insulina , Insulina Aspart/farmacocinética , Insulina Aspart/uso terapéutico , Insulina Isófana , Insulinas/farmacocinéticaRESUMEN
Aim: To compare safety (immunogenicity) and efficacy of a biosimilar insulin GP-Lis25 and a reference insulin Ly-Lis25 (Humalog Mix 25) in Type 2 diabetes mellitus (T2D) patients. Materials & methods: This randomized open-label, 26-week clinical trial enrolled 210 T2D patients, randomized 1:1 to twice-daily GP-Lis25 or Ly-Lis25. The primary end point was immune response at 26th week. Noninferiority margin for HbA1c was 0.4%. Results: Immune response frequency was similar in GP-Lis25 and Ly-Lis25 groups both at week 12 (p = 0.651) and 26 (p = 0.164). The difference of HbA1c change at week 26 was (95% CI) 0.01 (-0.27-0.28)%. Fasting plasma glucose, seven-point glucose profile and insulin dose were similar between groups. Safety did not differ between groups. Conclusion: GP-Lis25 and Ly-Lis25 demonstrated similar safety and efficacy. ClincalTrials.gov identifier: NCT04023344.
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Diabetes Mellitus Tipo 2 , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , Humanos , Hipoglucemiantes/uso terapéutico , Insulina Glargina , Insulina Lispro/uso terapéuticoRESUMEN
PURPOSE: Phosphorus (P) lost from agricultural land by erosion, runoff, throughflow and leaching is of major concern for water resource managers worldwide. Previous study on soils from cropping land of southwest Western Australia suggested P loss as dissolved unreactive P (DURP) via leaching, but the implications for processes and rates of P transport in soils are not known. MATERIAL AND METHODS: Two contrasting soil profiles (sand and loam) from cropping land of southwest Western Australia were exposed to artificial rain in packed boxes and field runoff plots to examine P forms and fluxes in runoff, throughflow, leachate and soil solution after three P rates of application (equivalent to 0, 20 and 40kg P/ha). Solutions were analyzed for total P (TP), dissolved reactive P (DRP) and total dissolved P (TDP). Particulate P (PP) and DURP were calculated by subtracting DRP from TP and TDP respectively. RESULT AND DISCUSSION: In the sand profile, about 90% or more of P losses via runoff and leachate were in DURP and PP forms, whereas DRP was a minor contributor. Phosphorus load in soil solution, throughflow, leachate and run-off increased with increasing P rate. The relatively higher affinity of soil for DRP compared to DURP might cause the latter to be more mobile through profile in association with colloidal compounds <0.2µm. Higher PP concentration for loam soil via throughflow is exacerbated by dispersed clay, which could be an additional process influencing P mobility in loam and duplex soils. CONCLUSION: The DRP played a limited role in P transport compared to PP and DURP that both appeared to be associated with soil particles or soil colloids in runoff, throughflow, leachate and soil solution. Further characterization of the latter forms of P is needed so that management practices can be developed to minimize P losses.
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A CRISPR/Cas9 gene editing strategy has been remarkable in excising segments of integrated HIV-1 DNA sequences from the genome of latently infected human cell lines and by introducing InDel mutations, suppressing HIV-1 replication in patient-derived CD4+ T-cells, ex vivo. Here, we employed a short version of the Cas9 endonuclease, saCas9, together with a multiplex of guide RNAs (gRNAs) for targeting the viral DNA sequences within the 5'-LTR and the Gag gene for removing critically important segments of the viral DNA in transgenic mice and rats encompassing the HIV-1 genome. Tail-vein injection of transgenic mice with a recombinant Adeno-associated virus 9 (rAAV9) vector expressing saCas9 and the gRNAs, rAAV:saCas9/gRNA, resulted in the cleavage of integrated HIV-1 DNA and excision of a 978 bp DNA fragment spanning between the LTR and Gag gene in the spleen, liver, heart, lung and kidney as well as in the circulating lymphocytes. Retro-orbital inoculation of rAAV9:saCas9/gRNA in transgenic rats eliminated a targeted segment of viral DNA and substantially decreased the level of viral gene expression in circulating blood lymphocytes. The results from the proof-of-concept studies, for the first time, demonstrate the in vivo eradication of HIV-1 DNA by CRISPR/Cas9 on delivery by an rAAV9 vector in a range of cells and tissues that harbor integrated copies of viral DNA.
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Sistemas CRISPR-Cas , ADN Viral/genética , Edición Génica/métodos , VIH-1/genética , Animales , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Dependovirus/genética , Productos del Gen gag/genética , Marcación de Gen/métodos , Riñón/metabolismo , Hígado/metabolismo , Pulmón/metabolismo , Ratones , Miocardio/metabolismo , RatasRESUMEN
Major depression is one of the leading causes of disabling condition worldwide and its treatment is often challenging and unsatisfactory, since many patients become refractory to pharmacological therapies. Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiological investigation mainly used to study the integrity of the primary motor cortex excitability and of the cortico-spinal tract. The development of paired-pulse and repetitive TMS (rTMS) paradigms has allowed investigators to explore the pathophysiology of depressive disorders and other neuropsychiatric diseases linked to brain excitability dysfunctions. Repetitive transcranial magnetic stimulation has also therapeutic and rehabilitative capabilities since it is able to induce changes in the excitability of inhibitory and excitatory neuronal networks that may persist in time. However, the therapeutic effects of rTMS on major depression have been demonstrated by analyzing only the improvement of neuropsychological performance. The aim of this study was to investigate cortical excitability changes on 12 chronically-medicated depressed patients (test group) after rTMS treatment and to correlate neurophysiological findings to neuropsychological outcomes. In detail, we assessed different parameters of cortical excitability before and after active rTMS in the test group, then compared to those of 10 age-matched depressed patients (control group) who underwent sham rTMS. In line with previous studies, at baseline both groups exhibited a significant interhemispheric difference of motor cortex excitability. This neurophysiological imbalance was then reduced in the patients treated with active rTMS, resulting also in a clinical benefit as demonstrated by the improvement in neuropsychological test scores. On the contrary, after sham rTMS, the interhemispheric difference was still evident in the control group. The reported clinical benefits in the test group might be related to the plastic remodeling of synaptic connection induced by rTMS treatment.
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Trastorno Depresivo Mayor/fisiopatología , Corteza Motora/fisiopatología , Corteza Motora/efectos de la radiación , Estimulación Magnética Transcraneal/métodos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/prevención & control , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoAsunto(s)
Bancos de Muestras Biológicas/legislación & jurisprudencia , Investigación Biomédica/legislación & jurisprudencia , Consentimiento Informado/legislación & jurisprudencia , Propiedad/legislación & jurisprudencia , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Bancos de Muestras Biológicas/ética , Investigación Biomédica/ética , Humanos , Consentimiento Informado/ética , Propiedad/ética , Privacidad/legislación & jurisprudencia , Manejo de Especímenes , Obtención de Tejidos y Órganos/éticaRESUMEN
BACKGROUND: The complete regression of melanocytic tumors, confirmed by histology, has rarely been reported in the literature. It is very difficult to determine the malignant or benign nature of a regressed tumor, and on occasions, the only indication of malignancy is the subsequent development of metastasis. MATERIAL AND METHODS: We performed a descriptive study of melanocytic nevi that had undergone complete, histologically confirmed regression prior to excision in the dermatology department of our hospital over a period of 3 years. We included only lesions in which dermoscopy performed prior to regression showed features that suggested benignity. We assessed various clinical, dermoscopic, histologic, and immunohistochemical features. RESULTS: The mean time to complete regression was 6.4 months. The main dermoscopic patterns observed were reticular and mixed reticular/globular. Unlike what is generally seen in melanomas, the main histologic finding was the presence of fine or lamellar fibrosis. In all cases, there was a predominance of CD8+ T cells. CONCLUSIONS: The clinical, dermoscopic, and histologic features of the melanocytic nevi studied suggest the existence of a highly characteristic form of tumor regression characterized by very rapid regression and the involvement of a cytotoxic mechanism.
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Dermoscopía , Regresión Neoplásica Espontánea , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: Restless legs syndrome (RLS) might represent a condition at risk of cardiovascular (and cerebrovascular) disease; the role of sleep periodic leg movements, sleep deprivation, and presence of common risk factors for heart disease in these patients remains to be determined. The aim of this study was to evaluate the eventual presence of risk factors for cerebrovascular disease in RLS. MATERIALS & METHODS: Eighty-seven consecutive patients affected by idiopathic RLS were included in this study together with 81 controls. Blood count, chemistry, and kidney function tests were obtained. We detected subjects suffering from diabetes mellitus, kidney diseases, heart diseases, disk herniation, neuropathy, blood diseases, liver diseases, artery diseases, dyslipidemia, or hypertension. Polysomnography was recorded in 66 patients, and cerebral neuroimaging was obtained in 59 patients with RLS. RESULTS: None of the differences in blood test parameters was statistically significant; however, hypertension was found to be more frequent in controls and dyslipidemia was more frequent in patients with RLS, but this was explained by its higher frequency in patients also affected by obstructive sleep apnea. A diagnosis of cerebrovascular disease was posed for 14 patients with RLS (16.1%), but no predictive factor for its presence was found at the binomial logistic regression. CONCLUSION: Our findings argue against the presence of an altered lipid metabolism as a risk factor for the development of cerebrovascular disease in patients with RLS, even if they do support the idea that cerebrovascular disease might be frequent in this condition.
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Enfermedades Cardiovasculares/epidemiología , Trastornos Cerebrovasculares/epidemiología , Síndrome de las Piernas Inquietas/epidemiología , Apnea Obstructiva del Sueño/epidemiología , Anciano , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/diagnóstico , Comorbilidad/tendencias , Dislipidemias/sangre , Dislipidemias/diagnóstico , Dislipidemias/epidemiología , Femenino , Humanos , Hipertensión/sangre , Hipertensión/diagnóstico , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Síndrome de las Piernas Inquietas/sangre , Síndrome de las Piernas Inquietas/fisiopatología , Factores de Riesgo , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/diagnósticoRESUMEN
Transcranial magnetic stimulation (TMS) is the most important technique currently available to study cortical excitability. Additionally, TMS can be used for therapeutic and rehabilitation purposes, replacing the more painful transcranial electric stimulation (TES). In this paper we present an innovative and easy-to-use tool that enables neuroscientists to design, carry out and analyze scientific studies based on TMS experiments for both diagnostic and research purposes, assisting them not only in the practicalities of administering the TMS but also in each step of the entire study's workflow. One important aspect of this tool is that it allows neuroscientists to specify research designs at will, enabling them to define any parameter of a TMS study starting from data acquisition and sample group definition to automated statistical data analysis and RDF data storage. It also supports the diagnosing process by using on-line support vector machines able to learn incrementally from the diseases instances that are continuously added into the system. The proposed system is a neuroscientist-centred tool where the protocols being followed in TMS studies are made explicit, leaving to the users flexibility in exploring and sharing the results, and providing assistance in managing the complexity of the final diagnosis. This type of tool can make the results of medical experiments more easily exploitable, thus accelerating scientific progress.
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Corteza Motora/fisiología , Máquina de Vectores de Soporte , Estimulación Magnética Transcraneal/estadística & datos numéricos , Sistemas de Administración de Bases de Datos , Estimulación Encefálica Profunda , Diagnóstico por Computador , Potenciales Evocados Motores/fisiología , Humanos , Procesamiento de Señales Asistido por Computador , Programas Informáticos , Estimulación Magnética Transcraneal/métodosRESUMEN
Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease with characteristic foci of inflammatory demyelination in the brain, spinal cord, and optic nerves. Recent studies have demonstrated not only that axonal damage and neuronal loss are significant pathologic components of MS, but that this neuronal damage is thought to cause the permanent neurologic disability often seen in MS patients. Emerging finding suggests that altered redox homeostasis and increased oxidative stress, primarily implicated in the pathogenesis of MS, are a trigger for activation of a brain stress response. Relevant to maintenance of redox homeostasis, integrated mechanisms controlled by vitagenes operate in brain in preserving neuronal survival during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. In the present study we assess stress response mechanisms in the CSF, plasma and lymphocytes of control patients compared to MS patients. We found that the levels of vitagenes Hsp72, Hsc70, HO-1, as well as oxidative stress markers carbonyls and hydroxynonenals were significantly higher in the blood and CSF of MS patients than in control patients. In addition, an increased expression of Trx and sirtuin 1, together with a decrease in the expression of TrxR were observed. Our data strongly support a pivotal role for redox homeostasis disruption in the pathogenesis of MS and, consistently with the notion that new therapies that prevent neurodegeneration through nonimmunomodulatory mechanisms can have a tremendous potential to work synergistically with current MS therapies, unravel important targets for new cytoprotective strategies.
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Esclerosis Múltiple/metabolismo , Estrés Fisiológico/fisiología , Adulto , Estudios de Casos y Controles , Regulación de la Expresión Génica , Proteínas de Choque Térmico/líquido cefalorraquídeo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Persona de Mediana Edad , Oxidación-Reducción , Adulto JovenAsunto(s)
Suplementos Dietéticos/efectos adversos , Rosácea/inducido químicamente , Complejo Vitamínico B/efectos adversos , Adulto , Femenino , Humanos , Neuralgia/tratamiento farmacológico , Óxido Nítrico/metabolismo , Prostaglandinas/metabolismo , Rosácea/metabolismo , Complejo Vitamínico B/uso terapéuticoRESUMEN
BACKGROUND: Hyperactive/inattentive (HI) behaviors are common in preschoolers, but they result in functional impairment and attention deficit/hyperactivity disorder (ADHD) diagnoses in only some children. We examined whether the quality of mother-child interaction accounts for variance in level of functioning among preschool children with elevated ADHD symptoms. METHOD: Parent and teacher ADHD-RS ratings were used to assess 126 HI preschoolers, and clinician Children's Global Assessment Scale (CGAS) ratings were used to quantify level of functioning. Mother-child interactions during a 5-minute free-play and a 5-minute structured task were coded for child, parent and dyadic behaviors. RESULTS: Partial correlations, controlling for symptom severity and IQ, revealed child and dyad factors that were related to children's functioning. Regression analyses revealed that low dyadic synchrony accounted for additional unique variance in children's functioning, above and beyond the influence of symptom severity and IQ. CONCLUSIONS: Dyadic synchrony between mother and child plays a role in the functioning of preschool children displaying elevated symptoms of hyperactivity/inattention, and may represent a potential area for intervention that is not generally addressed in most parent management training programs.
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Trastorno por Déficit de Atención con Hiperactividad/psicología , Relaciones Madre-Hijo , Preescolar , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Juego e Implementos de Juego/psicología , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Análisis y Desempeño de TareasRESUMEN
BACKGROUND: Vascular damage of frontal-subcortical circuits involved in mood regulation and cognition might be the main contributor to the pathogenesis of late-life depression, and it is linked to poor response to treatment. OBJECTIVE: To investigate the relationship between executive dysfunction and outcome of depressive symptoms among elderly patients with subcortical ischemic vascular disease. METHODS: Ninety-two elderly patients with white matter lesions (WMLs) or lacunar infarcts (LAs) on brain MRI and depressive symptomatology were consecutively recruited. Depression was rated with the Hamilton Depression Rating Scale (HDRS). Evaluation of executive functions by means of the Stroop color-word test was performed at entry of the study, and WMLs were categorized into mild, moderate or severe. Mood was reevaluated by means of HDRS after the 12th week of pharmacological treatment. RESULTS: Psychomotor retardation, difficulties at work, apathy, and lack of insight were the predominant symptoms. Fifty-six patients (62.8%) had a neuroradiological picture of WMLs, while the remaining 33 (37.1%) had LAs. Executive dysfunctions significantly and independently predict poor outcome of depressive symptoms. Patients with the severest WMLs showed not only a greater executive dysfunction, but also a minor response to antidepressant treatment. CONCLUSION: This study supports the vascular depression hypothesis. WMLs are of crucial clinical relevance as they are linked with cognitive symptoms and poor antidepressant outcome.
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Isquemia Encefálica/psicología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/etiología , Actividades Cotidianas , Anciano , Antidepresivos de Segunda Generación/uso terapéutico , Isquemia Encefálica/patología , Isquemia Encefálica/terapia , Citalopram/uso terapéutico , Trastornos del Conocimiento/terapia , Estudios de Cohortes , Trastorno Depresivo/patología , Escolaridad , Femenino , Humanos , Masculino , Test de Stroop , Resultado del TratamientoRESUMEN
Carcinoids of the appendix are rare in children. Usually diagnosed incidentally on histologic investigation following appendectomy for acute apendicitis. To investigate the significance of the diagnosis of appendiceal carcinoid tumors in children, we conducted a retrospective study in our institution. Between 1990 and 2007 a total of 1158 appendectomy were done. In four patients the diagnosis was appendiceal carcinoid. We studied treatment, follow-up and prognosis of this patients. Indicacion for appendectomy was acute pain in lower right quadrant. The median tumor diameter was lower than 1 cm and the appropriate treatment was appendectomy. The prognosis was excellent in all the patients.