RESUMO
BACKGROUND: The frequency of cytomegalovirus (CMV) colitis in steroid-refractory inflammatory bowel disease has been reported to range from 15.8% to 34.0%. Infected patients are more likely to become hospitalized, have longer lengths of stay, and higher mortality rates. Current data are limited to small scale studies and showed conflicting result regarding the role of antiviral therapy. AIMS: (1) To investigate the role of antiviral treatment in ulcerative colitis (UC) patients with CMV infection. (2) To investigate the role of viremia in the outcomes of these patients. MATERIALS AND METHODS: The Cleveland Clinic pathology database identified 1478 patients who had colon biopsy and were tested for CMV during 1990 to 2013. After inclusion and exclusion, 41 UC patients were selected. Among them, 24 (58.5%) received treatment, 17 (41.5%) did not. A total of 14 demographic data and 4 clinical outcomes (surgery free survival, hospitalization, rehospitalization, and mortality) were compared between treated and nontreated patients. The same outcomes were also compared in patients who received treatment based on their viremia status. RESULTS: All demographic variables are similar between those treated and nontreated groups. Antiviral therapy significantly improved the surgery free survival within 30 days, and lasted 70 months (P<0.01). In contrast, hospitalization, rehospitalization, and mortality were comparable (P>0.05). No significant difference was observed in any of the clinical outcomes based on viremia status. CONCLUSIONS: Our small scale study demonstrates that antiviral treatment for colonic CMV infection significantly improves the surgery free survival short-term and long-term in patients with UC.
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Antivirais/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Infecções por Citomegalovirus/tratamento farmacológico , Estudos de Casos e Controles , Colectomia/estatística & dados numéricos , Colite Ulcerativa/complicações , Colite Ulcerativa/mortalidade , Colite Ulcerativa/cirurgia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/cirurgia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ohio , Estudos RetrospectivosRESUMO
The newborn heart adapts to postnatal life by shifting from a fetal glycolytic metabolism to a mitochondrial oxidative metabolism. Abcc9, an ATP-binding cassette family member, increases expression concomitant with this metabolic shift. Abcc9 encodes a membrane-associated receptor that partners with a potassium channel to become the major potassium-sensitive ATP channel in the heart. Abcc9 also encodes a smaller protein enriched in the mitochondria. We now deleted exon 5 of Abcc9 to ablate expression of both plasma membrane and mitochondria-associated Abcc9-encoded proteins, and found that the myocardium failed to acquire normal mature metabolism, resulting in neonatal cardiomyopathy. Unlike wild-type neonatal cardiomyocytes, mitochondria from Ex5 cardiomyocytes were unresponsive to the KATP agonist diazoxide, consistent with loss of KATP activity. When exposed to hydrogen peroxide to induce cell stress, Ex5 neonatal cardiomyocytes displayed a rapid collapse of mitochondria membrane potential, distinct from wild-type cardiomyocytes. Ex5 cardiomyocytes had reduced fatty acid oxidation, reduced oxygen consumption and reserve. Morphologically, Ex5 cardiac mitochondria exhibited an immature pattern with reduced cross-sectional area and intermitochondrial contacts. In the absence of Abcc9, the newborn heart fails to transition normally from fetal to mature myocardial metabolism.-Fahrenbach, J. P., Stoller, D., Kim, G., Aggarwal, N., Yerokun, B., Earley, J. U., Hadhazy, M., Shi, N.-Q., Makielski, J. C., McNally, E. M. Abcc9 is required for the transition to oxidative metabolism in the newborn heart.
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Coração/fisiologia , Miócitos Cardíacos/metabolismo , Consumo de Oxigênio/fisiologia , Receptores de Sulfonilureias/metabolismo , Animais , Animais Recém-Nascidos , Cardiomiopatias/congênito , Membrana Celular/metabolismo , Ácidos Graxos/metabolismo , Feminino , Canais KATP/metabolismo , Masculino , Potencial da Membrana Mitocondrial/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismoRESUMO
In pediatric out-of-hospital cardiac arrest (POHCA), cardiovascular monitoring tools have improved resuscitative endeavors and cardiovascular outcomes but with still poor neurologic outcomes. Regarding cardiac arrest in patients with congenital heart disease during surgery, the application of cerebral oximetry with blood volume index (BVI) during the resuscitation has shown significant results and prognostic significance. We present 2 POHCA patients who had cerebral oximetry with BVI monitoring during their arrest and postarrest phase in the emergency department and its potential prognostic aspect.Basic procedures include left and right cerebral oximetry with BVI monitoring at every 5-second interval during cardiac arrest, resuscitation, and postarrest in 2 POHCA patients in the pediatric emergency department.Regional cerebral tissue oxygen saturation (rSo2) with BVI readings in these 2 POHCA survivors demonstrated interesting cerebral physiology, blood flow, and potential prognostic outcome. In 1 patient, the reference range of cerebral rSo2 with positive blood flow during arrest and postarrest phases consistently occurred. This neurologic monitoring had its significance when the resuscitation effectiveness was used and end-tidal CO2 changes were lost. The other patient's cerebral rSo2 with simultaneous BVI readings and trending showed the effectiveness of the emergency medical services (EMS) resuscitation.Cerebral oximetry with cerebral blood flow index monitoring in these POHCA survivors demonstrates compelling periarrest and postarrest cerebral physiology information and prognostication. Cerebral oximetry with cerebral BVI monitoring during these arrest phases has potential as a neurologic monitor for the resuscitative intervention's effectiveness and its possible neurologic prognostic application in the pediatric OCHA patients.
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Circulação Cerebrovascular , Parada Cardíaca Extra-Hospitalar/sangue , Oximetria/métodos , Adolescente , Reanimação Cardiopulmonar , Feminino , Humanos , Masculino , Parada Cardíaca Extra-Hospitalar/terapia , Fluxo Sanguíneo RegionalRESUMO
AIM: We have recently shown an increase in cholecystectomies for biliary dyskinesia. Based on these results, we hypothesized that diagnostic criteria are less stringently applied which may contribute to ongoing resource utilization. METHODS: Using billing codes, patients seen for biliary dyskinesia were identified and data were extracted from the electronic medical record to confirm the diagnosis, obtain demographic and clinical data and assess resource utilization 1 year prior to and after cholecystectomy. RESULTS: A total of 972 patients were identified, with 894 undergoing cholecystectomy. In 259 patients, symptoms had started <3 months prior to evaluation. Functional gallbladder imaging revealed a mean gallbladder ejection fraction of 23.1 ± 0.7 %; of the patients undergoing surgery, 116 had a normal gallbladder ejection fraction. Sufficient up data for pre- and post-operative assessment of resource utilization was available for 368 patients. Emergency room (ER) visits decreased from 0.86 ± 0.07 to 0.69 ± 0.03 (P < 0.05), while hospitalization rates remained unchanged after surgery. Patients not meeting consensus criteria for the diagnosis of biliary dyskinesia were more likely to use opioids and have ER visits prior to and after cholecystectomy. Using multiple logistic regression benzodiazepine use, migraine history and prior ER visits independently predicted postoperative resource utilization. CONCLUSIONS: Our data demonstrate that a significant number of patients undergo cholecystectomy for biliary dyskinesia, even though they do not meet currently accepted diagnostic criteria. While healthcare resource utilization drops within the first year after surgery, ER visits and hospitalizations remain common, suggesting a more limited benefit of surgical approaches in these patients.
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Discinesia Biliar/diagnóstico , Discinesia Biliar/cirurgia , Colecistectomia/tendências , Dor Abdominal/diagnóstico , Adulto , Analgésicos Opioides/uso terapêutico , Discinesia Biliar/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Gastroenteropatias/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Doctoring is a 2-year preclinical course designed to teach medical students fundamental clinical skills. PURPOSE: We designed, implemented, and evaluated an innovative and cost-effective peer-mentoring program embedded within Doctoring. Our Teaching Academy (TA) included a formal orientation for teaching "Fellows." METHODS: During academic years 2008-09 and 2009-10, 2nd-year students were systematically selected by course faculty and then trained as TA Fellows to peer-mentor 1st-year students. Both TA Fellows and 1st-year medical students completed anonymous written surveys. RESULTS: Peer-mentors reported a significant increase of confidence in their ability to provide feedback (p < .001). First-year students reported a significant increase of confidence in their ability to conduct a medical interview and perform a physical exam (p < .001 for each). CONCLUSIONS: Student participation in a formal peer-mentor program embedded within a clinical skills course significantly increased, for both teachers and learners, confidence in their skills. Our program is easily transferrable to other courses and institutions.
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Mentores/educação , Grupo Associado , Desenvolvimento de Programas , Estudantes de Medicina , Educação de Graduação em Medicina , Humanos , Autoeficácia , Inquéritos e Questionários , Estados UnidosRESUMO
Lipomas of the oral cavity are uncommon. Here we report a case of 85 year old female presenting with a progressively increasing large growth in the oropharynx which was diagnosed as lipoma on histopathology. The clinicoradiological and histopathological findings are discussed. To the best of our knowledge; this is one of the largest intraoral lipoma reported in India till date. The present case highlights the need to be aware of intraoral lipomas which can present as large growths at this unusual site so as to avoid any unwarranted aggressive surgery.
RESUMO
Arachidonic acid (AA) metabolites function as EDHFs in arteries of many species. They mediate cyclooxygenase (COX)- and nitric oxide (NO)-independent relaxations to acetylcholine (ACh). However, the role of AA metabolites as relaxing factors in mouse arteries remains incompletely defined. ACh caused concentration-dependent relaxations of the mouse thoracic and abdominal aorta and carotid, femoral, and mesentery arteries (maximal relaxation: 57 ± 4%, 72 ± 4%, 82 ± 3%, 80 ± 3%, and 85 ± 3%, respectively). The NO synthase inhibitor nitro-L-arginine (L-NA; 30 µM) blocked relaxations in the thoracic aorta, and L-NA plus the COX inhibitor indomethacin (10 µM) inhibited relaxations in the abdominal aorta and carotid, femoral, and mesenteric arteries (maximal relaxation: 31 ± 10%, 33 ± 5%, 41 ± 8%, and 73 ± 3%, respectively). In mesenteric arteries, NO- and COX-independent relaxations to ACh were inhibited by the lipoxygenase (LO) inhibitors nordihydroguaiaretic acid (NDGA; 10 µM) and BW-755C (200 µM), the K(+) channel inhibitor apamin (1 µM), and 60 mM KCl and eliminated by endothelium removal. They were not altered by the cytochrome P-450 inhibitor N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (20 µM) or the epoxyeicosatrienoic acid antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (10 µM). AA relaxations were attenuated by NDGA or apamin and eliminated by 60 mM KCl. Reverse-phase HPLC analysis revealed arterial [(14)C]AA metabolites that comigrated with prostaglandins, trihydroxyeicosatrienoic acids (THETAs), hydroxyepoxyeicosatrienoic acids (HEETAs), and hydroxyeicosatetraenoic acids (HETEs). Epoxyeicosatrienoic acids were not observed. Mass spectrometry confirmed the identity of 6-keto-PGF(1α), PGE(2), 12-HETE, 15-HETE, HEETAs, 11,12,15-THETA, and 11,14,15-THETA. AA metabolism was blocked by NDGA and endothelium removal. 11(R),12(S),15(S)-THETA relaxations (maximal relaxation: 73 ± 3%) were endothelium independent and blocked by 60 mM KCl. Western immunoblot analysis and RT-PCR of the aorta and mesenteric arteries demonstrated protein and mRNA expression of leukocyte-type 12/15-LO. Thus, in mouse resistance arteries, 12/15-LO AA metabolites mediate endothelium-dependent relaxations to ACh and AA.
Assuntos
Acetilcolina/metabolismo , Araquidonato Lipoxigenases/metabolismo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/metabolismo , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/farmacologia , Amidas/farmacologia , Animais , Apamina/farmacologia , Artérias/metabolismo , Artérias/fisiopatologia , Feminino , Indometacina/farmacologia , Masculino , Masoprocol/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Nitroarginina/farmacologiaRESUMO
RATIONALE: Cardioprotective pathways may involve a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel but its composition is not fully understood. OBJECTIVE: We hypothesized that the mitoK(ATP) channel contains a sulfonylurea receptor (SUR)2 regulatory subunit and aimed to identify the molecular structure. METHODS AND RESULTS: Western blot analysis in cardiac mitochondria detected a 55-kDa mitochondrial SUR2 (mitoSUR2) short form, 2 additional short forms (28 and 68 kDa), and a 130-kDa long form. RACE (Rapid Amplification of cDNA Ends) identified a 1.5-Kb transcript, which was generated by a nonconventional intraexonic splicing (IES) event within the 4th and 29th exons of the SUR2 mRNA. The translated product matched the predicted size of the 55-kDa short form. In a knockout mouse (SUR2KO), in which the SUR2 gene was disrupted, the 130-kDa mitoSUR2 was absent, but the short forms remained expressed. Diazoxide failed to induce increased fluorescence of flavoprotein oxidation in SUR2KO cells, indicating that the diazoxide-sensitive mitoK(ATP) channel activity was associated with 130-kDa-based channels. However, SUR2KO mice displayed similar infarct sizes to preconditioned wild type, suggesting a protective role for the remaining short form-based channels. Heterologous coexpression of the SUR2 IES variant and Kir6.2 in a K(+) transport mutant Escherichia coli strain permitted improved cell growth under acidic pH conditions. The SUR2 IES variant was localized to mitochondria, and removal of a predicted mitochondrial targeting sequence allowed surface expression and detection of an ATP-sensitive current when coexpressed with Kir6.2. CONCLUSIONS: We identify a novel SUR2 IES variant in cardiac mitochondria and provide evidence that the variant-based channel can form an ATP-sensitive conductance and may contribute to cardioprotection.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Processamento Alternativo/fisiologia , Isquemia Miocárdica/genética , Miócitos Cardíacos/fisiologia , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Receptores de Droga/genética , Receptores de Droga/metabolismo , Animais , Células Cultivadas , Éxons/genética , Flavoproteínas/metabolismo , Biblioteca Gênica , Humanos , Camundongos , Camundongos Knockout , Mitocôndrias/fisiologia , Isquemia Miocárdica/metabolismo , Miócitos Cardíacos/citologia , Oxirredução , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Receptores de SulfonilureiasRESUMO
The sulfonylurea receptor-2 (SUR2) is a subunit of ATP-sensitive potassium channels (K(ATP)) in heart. Mice with the SUR2 gene disrupted (SUR2m) are constitutively protected from ischemia-reperfusion (I/R) cardiac injury. This was surprising because K(ATP), either sarcolemmal or mitochondrial or both, are thought to be important for cardioprotection. We hypothesized that SUR2m mice have an altered mitochondrial phenotype that protects against I/R. Mitochondrial membrane potential (ΔΨ(m)), tolerance to Ca(2+) load, and reactive oxygen species (ROS) generation were studied by fluorescence-based assays, and volumetric changes in response to K(+) were measured by light scattering in isolated mitochondria. For resting SUR2m mitochondria compared with wild type, the ΔΨ(m) was less polarized (46.1 ± 0.4 vs. 51.9 ± 0.6%), tolerance to Ca(2+) loading was increased (163 ± 2 vs. 116 ± 2 µM), and ROS generation was enhanced with complex I [8.5 ± 1.2 vs. 4.9 ± 0.2 arbitrary fluorescence units (afu)/s] or complex II (351 ± 51.3 vs. 166 ± 36.2 afu/s) substrates. SUR2m mitochondria had greater swelling in K(+) medium (30.2 ± 3.1%) compared with wild type (14.5 ± 0.6%), indicating greater K(+) influx. Additionally, ΔΨ(m) decreased and swelling increased in the absence of ATP in SUR2m, but the sensitivity to ATP was less compared with wild type. When the mitochondria were subjected to hypoxia-reoxygenation, the decrease in respiration rates and respiratory control index was less in SUR2m. ΔΨ(m) maintenance in the SUR2m intact myocytes was also more tolerant to metabolic inhibition. In conclusion, the cardioprotection observed in the SUR2m mice is associated with a protected mitochondrial phenotype resulting from enhanced K(+) conductance that partially dissipated ΔΨ(m). These results have implications for possible SUR2 participation in mitochondrial K(ATP).
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Metabolismo Energético , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Canais de Potássio/metabolismo , Receptores de Droga/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , Hipóxia Celular , Respiração Celular , Genótipo , Luz , Masculino , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Mutantes , Dilatação Mitocondrial , Traumatismo por Reperfusão Miocárdica/metabolismo , Fenótipo , Potássio/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/genética , Espécies Reativas de Oxigênio/metabolismo , Receptores de Droga/genética , Espalhamento de Radiação , Espectrometria de Fluorescência , Receptores de Sulfonilureias , Fatores de TempoRESUMO
Sulfonylurea receptor-containing ATP-sensitive potassium (K(ATP)) channels have been implicated in cardioprotection, but the cell type and constitution of channels responsible for this protection have not been clear. Mice deleted for the first nucleotide binding region of sulfonylurea receptor 2 (SUR2) are referred to as SUR2 null since they lack full-length SUR2 and glibenclamide-responsive K(ATP) channels in cardiac, skeletal, and smooth muscle. As previously reported, SUR2 null mice develop electrocardiographic changes of ST segment elevation that were shown to correlate with coronary artery vasospasm. Here we restored expression of the cardiomyocyte SUR2-K(ATP) channel in SUR2 null mice by generating transgenic mice with ventricular cardiomyocyte-restricted expression of SUR2A. Introduction of the cardiomyocyte SUR2A transgene into the SUR2 null background restored functional cardiac K(ATP) channels. Hearts isolated from rescued mice, referred to as MLC2A, had significantly reduced infarct size (27 ± 3% of area at risk) compared with SUR2 null mice (36 ± 3% of area at risk). Compared with SUR2 null hearts, MLC2A hearts exhibited significantly improved cardiac function during the postischemia reperfusion period primarily because of preservation of low diastolic pressures. Additionally, restoration of cardiac SUR2-K(ATP) channels significantly reduced the degree and frequency of ST segment elevation episodes in MLC2A mice. Therefore, cardioprotective mechanisms both dependent and independent of SUR2-K(ATP) channels contribute to cardiac function.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Eletrocardiografia , Canais KATP/metabolismo , Miócitos Cardíacos/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Receptores de Droga/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Membrana Celular/metabolismo , Vasoespasmo Coronário/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Modelos Animais , Infarto do Miocárdio/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/genética , Receptores de Droga/genética , Transdução de Sinais/fisiologia , Receptores de SulfonilureiasRESUMO
Endophytes are beneficial microbes that reside intercellularly inside the plants. Interaction of endophytes with the host plants and their function within their host are important to address ecological relevance of endophyte. Four endophytic bacteria OS-9, OS-10, OS-11, and OS-12 were isolated from healthy leaves of Ocimum sanctum. These isolated microbes were screened in dual culture against various phytopathogenic fungi viz. Rhizoctonia solani, Sclerotium rolfsii, Fusarium solani, Alternaria solani, and Colletotrichum lindemuthianum. Of these, strain OS-9 was found to be antagonistic to R. solani, A. solani, F. solani, and C. lindemuthianum while OS-11 was found antagonistic against A. solani only. The growth-promoting benefits of the endophytes were initially evaluated in the glasshouse by inoculated seeds of O. sanctum. Treatment with endophytes OS-10 and OS-11 resulted in significant enhancement of growth as revealed by increase in fresh as well as dry weight. Further, field trials involving two genotypes OS Purple and CIM-Angana were conducted with strains OS-10 and OS-11. The growth-promoting effect was visible on both the genotypes tested as the endophytes significantly enhanced fresh herbage yield (t/ha). Interestingly, these endophytes increased the content of essential oil particularly in cultivar OS Purple and thereby increasing the total oil yields. Molecular characterization of strain OS-11 indicated the strain to be highly related to the type strain of Bacillus subtilis.
Assuntos
Alternaria/isolamento & purificação , Colletotrichum/isolamento & purificação , Fusarium/isolamento & purificação , Ocimum/microbiologia , Doenças das Plantas/microbiologia , Rhizoctonia/isolamento & purificação , Alternaria/genética , Alternaria/crescimento & desenvolvimento , Colletotrichum/genética , Colletotrichum/crescimento & desenvolvimento , Fungos/genética , Fungos/crescimento & desenvolvimento , Fungos/isolamento & purificação , Fusarium/genética , Fusarium/crescimento & desenvolvimento , Ocimum/crescimento & desenvolvimento , Folhas de Planta/microbiologia , Rhizoctonia/genética , Rhizoctonia/crescimento & desenvolvimento , Sementes/microbiologiaRESUMO
Wilson's disease (WD) is an inherited disorder of copper metabolism. Despite being treatable, patients with WD suffer severe disabilities due to delay in initiation and difficulty in monitoring treatment. We propose a two tier, Global Assessment Scale for Wilson's Disease (GAS for WD) that grades the multisystemic manifestations of the disease. Tier 1 scores the global disability in four domains: Liver, Cognition and behavior, Motor, and Osseomuscular. Tier 2 is multidimensional scale for a fine grained evaluation of the neurological dysfunction. We prospectively validated this scale in 30 patients with WD. Both tiers had a high inter-rater reliability (Intraclass correlation coefficient ICC (A, 2) = 0.96-1.0). Tier 2 items were internally consistent (Cronbach's alpha = 0.89) and factorial analysis showed that 90.3% of the Tier 2 total score variance was determined by seven factors. Scores of both tiers were commensurate with the disease burden as assessed by standard disability scales (Child Pugh, UPDRS, SS3, and CGI) and satisfied criteria for validity. Longitudinal follow-up over 1.5 years showed that the scale was sensitive to clinical change. This suggests that GAS for WD is a practical tool with potential applications in management of patients, and in testing and comparison of treatment regimens.
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Avaliação da Deficiência , Degeneração Hepatolenticular/diagnóstico , Índice de Gravidade de Doença , Adolescente , Adulto , Sintomas Comportamentais/etiologia , Criança , Transtornos Cognitivos/etiologia , Feminino , Guias como Assunto , Degeneração Hepatolenticular/fisiopatologia , Degeneração Hepatolenticular/psicologia , Humanos , Estudos Longitudinais , Masculino , Atividade Motora/fisiologia , Exame Neurológico/métodos , Qualidade de Vida , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Arachidonic acid (AA) metabolites from 15-lipoxygenase-1 (15-LO-1), trihydroxyeicosatrienoic acid (THETA), and hydroxyepoxyeicosatrienoic acid (HEETA) relax arteries. We studied 15-LO-1 expression, THETA and HEETA synthesis, and their effect on arterial relaxations and blood pressure in hypercholesterolemic nonatherosclerotic rabbits. METHODS AND RESULTS: Immunoblots, RTPCR analysis, and (14)C-AA metabolism revealed that hypercholesterolemia increased 15-LO-1 expression in the endothelium and THETA and HEETA synthesis in the arteries. Isometric tension recording, in presence of nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibitors, showed greater relaxations to acetylcholine (ACH) and AA (max 76.0+/-4.6% and 79.5+/-2.4%, respectively) in aortas from hypercholesterolemic rabbits compared with normal rabbits (max 39.1+/-2.8% and 39.9+/-2.2%, respectively). AA induced greater hyperpolarization in the smooth muscle cells of hypercholesterolemic aortas (-45.85+/-3.0 mV) compared with normal aortas (-31.45+/-1.9 mV). The ACH- and AA-relaxations were inhibited by 15-LO-1 inhibitors. ACH induced hypotensive responses were greater in hypercholesterolemic rabbits in absence (-54.9+/-3.3%) or presence (-48.5+/-3.2%) of NOS and COX-inhibitors compared with control rabbits (-31.6+/-3.3% and -24.3+/-1.6%, respectively). BW755C reduced these responses in hypercholesterolemic rabbits to -29.3+/-2.3%. CONCLUSIONS: Hypercholesterolemia increases endothelial 15-LO-1 expression, THETA and HEETA synthesis and enhances vasorelaxation.
Assuntos
Araquidonato 15-Lipoxigenase/fisiologia , Hipercolesterolemia/fisiopatologia , Hipotensão/fisiopatologia , Vasodilatação/fisiologia , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/metabolismo , Acetilcolina/farmacologia , Animais , Aorta/metabolismo , Araquidonato 15-Lipoxigenase/genética , Ácido Araquidônico/metabolismo , Ácido Araquidônico/farmacologia , Artérias/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Hipercolesterolemia/genética , Hipotensão/etiologia , Hipotensão/genética , Técnicas In Vitro , Inibidores de Lipoxigenase/farmacologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coelhos , Vasodilatação/efeitos dos fármacosRESUMO
The relationship between schizophrenia and idiopathic Parkinson's disease is still not clear and rare when they coexist. Diagnosing coexisting schizophrenia and idiopathic Parkinson's disease is a chal-lenge, especially in developing countries due to lack of experts and advance imaging facilities. Treatment options are also limited. A 58- year- old male was admitted due to relapse of psychotic symptoms following non-compliance to antipsychotic medications. The patient was previously diag-nosed with schizophrenia and later developed Parkinson's disease while non-compliant to antipsy-chotic medications. While the patient was at our center, his detailed history was taken and general physical examination was done to distinguish Parkinson's disease from anti-psychotic induced ex-trapyramidal symptoms. All the routine investigations were within normal limits. This case report highlights the clinical factors that help make a distinction and help use appropriate drugs to manage schizophrenia with comorbid Parkinson's disease in developing countries, where lack of precise di-agnostic imaging modalities interferes in making a conclusive diagnosis.
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Objective: To assess the pattern of serum folate and vitamin B12 levels in psychiatric inpatients compared with nonpsychiatric controls. Methods: An observational cross-sectional study was conducted with 100 psychiatric inpatients diagnosed with psychiatric illness for the first time per ICD-10 criteria and their age-matched caregivers at a super-specialty center in northern India (from January 1, 2012, to December 31, 2012). Complete blood counts and serum levels of vitamin B12, folate, and homocysteine were measured in all patients and caregivers, who were sharing the same kitchen as that of the patients. Results: Twenty-five percent of the patients were found to have low levels of serum vitamin B12, which was significant compared with healthy controls (P < .001). Similarly, the difference in homocysteine levels between the patient and control groups was significant (35% vs 13%, P = .012). Conclusions: A significant proportion of psychiatric patients were found to be vitamin B12 deficient. In-depth studies are required to establish the cause-effect relationship between vitamin B12 deficiency and psychiatric illness and the effect of vitamin B12 replacement.
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Ácido Fólico/sangue , Transtornos Mentais/sangue , Deficiência de Vitamina B 12/sangue , Vitamina B 12/sangue , Adulto , Comorbidade , Estudos Transversais , Feminino , Homocisteína/sangue , Humanos , Índia , Pacientes Internados/estatística & dados numéricos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Deficiência de Vitamina B 12/epidemiologiaRESUMO
OBJECTIVE: To investigate the effectiveness of a modification of the retrosigmoid (RS) approach in reducing the rate of postoperative cerebrospinal fluid (CSF) leak after vestibular schwannoma surgery. PATIENTS: Of 1,499 vestibular schwannomas operated on at the Gruppo Otologico between April 1987 and July 2006, 84 cases have been selected, all of them treated through the RS approach. INTERVENTIONS: The classic approach was adopted in the first 21 cases, whereas a retrolabyrinthine bone removal was added in the last 56. MAIN OUTCOME MEASURE: Percentage of postoperative CSF leak. RESULTS: The overall percentage of postoperative CSF leak was 8.3%. However, the percentage decreased from 21.4 to 1.8% after the surgical modification, with a single leak recorded in the second group. The only drawback was an additional surgical time of 40 minutes. CONCLUSION: Extension of the classic RS that addressed retrolabyrinthine air cells is associated with a significant reduction in CSF leak manifesting rhinorrhea.
Assuntos
Rinorreia de Líquido Cefalorraquidiano/etiologia , Neuroma Acústico/cirurgia , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Feminino , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Studies suggest that Ineffective Esophageal Motility (IEM) is the manometric correlate of Functional Dysphagia (FD). Currently, there is no accepted therapy for either condition. Buspirone is a serotonin modulating medication and has been shown to augment esophageal peristaltic amplitude in healthy volunteers. We aimed to determine if buspirone improves manometric parameters and symptoms in patients with overlapping IEM/FD. METHODS: We performed a prospective, double-blind, placebo-controlled, crossover-style trial of 10 patients with IEM/FD. The study consisted of two 2-week treatment arms with a 2-week washout period. Outcomes measured at baseline, end of week 2, and week 6 include high resolution esophageal manometry (HREM), the Mayo Dysphagia Questionnaire-14 (MDQ-14), and the GERD-HRQL. RESULTS: The mean age of our 10 patients was 53 ± 9 years and 70% were female. After treatment with buspirone, 30% of patients had normalization of IEM on manometry; however, there was 30% normalization in the placebo group as well. Comparing buspirone to placebo, there was no statistically significant difference in the HREM parameters measured. There was also no statistically significant difference in symptom outcomes for buspirone compared to placebo. Of note, patients had a statistically significant decrease in the total GERD-HRQL total score when treated with placebo compared to baseline levels. DISCUSSION: Despite previous data demonstrating improved esophageal motility in healthy volunteers, our study shows no difference in terms of HREM parameters or symptom scores in IEM/FD patients treated with buspirone compared to placebo. Further research is necessary to identify novel agents for this condition.
Assuntos
Buspirona/uso terapêutico , Transtornos da Motilidade Esofágica/tratamento farmacológico , Agonistas do Receptor de Serotonina/uso terapêutico , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
The problem of determining the location and orientation of straight lines in images is of great importance in the fields of computer vision and image processing. Traditionally the Hough transform, (a special case of the Radon transform) has been widely used to solve this problem for binary images. In this paper, we pose the problem of detecting straight lines in gray-scale images as an inverse problem. Our formulation is based on use of the inverse Radon operator, which relates the parameters determining the location and orientation of the lines in the image to the noisy input image. The advantage of this formulation is that we can then approach the problem of line detection within a regularization framework and enhance the performance of the Hough-based line detector through the incorporation of prior information in the form of regularization. We discuss the type of regularizers that are useful for this problem and derive efficient computational schemes to solve the resulting optimization problems enabling their use in large applications. Finally, we show how our new approach can be alternatively viewed as one of finding an optimal representation of the noisy image in terms of elements chosen from a dictionary of lines. This interpretation relates the problem of Hough-based line finding to the body of work on adaptive signal representation.
Assuntos
Algoritmos , Inteligência Artificial , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Reconhecimento Automatizado de Padrão/métodos , Armazenamento e Recuperação da Informação/métodos , Análise Numérica Assistida por Computador , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
CONTEXT: The relationship between opioid use and sexual problems among males is complex one, as some are using opioids to increase their sexual performance while others are suffering from sexual problems due to its use. And research addressing this relationship is still limited. AIMS: The aim of the current study was to assess and evaluate sexual dysfunction in male subjects seeking treatment for opioid dependence and to compare it with healthy control group. METHODS AND MATERIAL: 60 male subjects with opioid dependence for more than one year (ICD-10 criteria) were compared to 120 healthy age & tobacco abuse matched control group (case: control=1:2) using standard questionnaires evaluating various domains of sexual dysfunction. RESULTS: Opioid dependents were found to have sexual dysfunction ranging from 53.3% to 81.7% which was significantly greater than the healthy control group (15.8% to 41.7%). CONCLUSIONS: Sexual dysfunctions are highly prevalent in opioid dependents and this should be addressed properly while assessing and treating a patient of opioid dependence.