RESUMO
AIM: The antifungal activity was studied on sessile and persister cells (PCs) of Candida tropicalis biofilms of gold nanoparticles (AuNPs) stabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) and those conjugated with cysteine, in combination with Amphotericin B (AmB). MATERIALS/METHODS: The PC model was used and synergistic activity was tested by the checkerboard assay. Biofilms were studied by crystal violet and scanning electron microscopy. RESULTS/CONCLUSIONS: After the combination of both AuNPs and AmB the biofilm biomass was reduced, with significant differences in architecture being observed with a reduced biofilm matrix. In addition, the CTAB-AuNPs-AmB combination significantly reduced PCs. Understanding how these AuNPs aid in the fight against biofilms and the development of new approaches to eradicate PCs has relevance for chronic infection treatment.
Assuntos
Anfotericina B , Antifúngicos , Biofilmes , Candida tropicalis , Sinergismo Farmacológico , Ouro , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Candida tropicalis/efeitos dos fármacos , Ouro/química , Ouro/farmacologia , Biofilmes/efeitos dos fármacos , Anfotericina B/farmacologia , Anfotericina B/química , Nanopartículas Metálicas/química , Antifúngicos/farmacologia , Antifúngicos/química , Cetrimônio/química , Compostos de Cetrimônio/farmacologia , Compostos de Cetrimônio/químicaRESUMO
Brain states such as sleep, anesthesia, wakefulness, or coma are characterized by specific patterns of cortical activity dynamics, from local circuits to full-brain emergent properties. We previously demonstrated that full-spectrum signals, including the infraslow component (DC, direct current-coupled), can be recorded acutely in multiple sites using flexible arrays of graphene solution-gated field-effect transistors (gSGFETs). Here, we performed chronic implantation of 16-channel gSGFET arrays over the rat cerebral cortex and recorded full-band neuronal activity with two objectives: (1) to test the long-term stability of implanted devices; and (2) to investigate full-band activity during the transition across different levels of anesthesia. First, we demonstrate it is possible to record full-band signals with stability, fidelity, and spatiotemporal resolution for up to 5.5 months using chronic epicortical gSGFET implants. Second, brain states generated by progressive variation of levels of anesthesia could be identified as traditionally using the high-pass filtered (AC, alternating current-coupled) spectrogram: from synchronous slow oscillations in deep anesthesia through to asynchronous activity in the awake state. However, the DC signal introduced a highly significant improvement for brain-state discrimination: the DC band provided an almost linear information prediction of the depth of anesthesia, with about 85% precision, using a trained algorithm. This prediction rose to about 95% precision when the full-band (AC + DC) spectrogram was taken into account. We conclude that recording infraslow activity using gSGFET interfaces is superior for the identification of brain states, and further supports the preclinical and clinical use of graphene neural interfaces for long-term recordings of cortical activity.
Assuntos
Grafite , Ratos , Animais , Encéfalo , Córtex Cerebral/fisiologia , Neurônios/fisiologia , Vigília/fisiologiaRESUMO
Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms (SNPs) were tested in meta-analysis of 4 independent cohorts. One replication cohort was from the United States, and the others were from Germany, Finland, and Brazil, totaling 1,911 TMD cases and 6,903 controls. A locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in the discovery analysis ( P = 2.6 × 106) and replicated (i.e., 1-tailed P = 0.016) in the Brazilian cohort. In the discovery cohort, sex-stratified analysis identified 2 additional genome-wide significant loci in females. One lying upstream of the relaxin/insulin-like family peptide receptor 2 ( RXP2) (chromosome 13, rs60249166, odds ratio [OR] = 0.65, P = 3.6 × 10-8) was replicated among females in the meta-analysis (1-tailed P = 0.052). The other (chromosome 17, rs1531554, OR = 0.68, P = 2.9 × 10-8) was replicated among females (1-tailed P = 0.002), as well as replicated in meta-analysis of both sexes (1-tailed P = 0.021). A novel locus at genome-wide level of significance (rs73460075, OR = 0.56, P = 3.8 × 10-8) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 × 10-7) upstream of the Sp4 Transcription Factor ( SP4) gene were identified in the discovery cohort, but neither of these was replicated. The SGCA gene encodes SGCA, which is involved in the cellular structure of muscle fibers and, along with DMD, forms part of the dystrophin-glycoprotein complex. Functional annotation suggested that several of these variants reside in loci that regulate processes relevant to TMD pathobiologic processes.
Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Transtornos da Articulação Temporomandibular/genética , Brasil/epidemiologia , Estudos de Casos e Controles , Distrofina , Feminino , Finlândia/epidemiologia , Loci Gênicos , Predisposição Genética para Doença , Genótipo , Alemanha/epidemiologia , Hispânico ou Latino , Humanos , Masculino , Fenótipo , Prevalência , Receptores Acoplados a Proteínas G , Sarcoglicanas , Fator de Transcrição Sp4 , Inquéritos e Questionários , Transtornos da Articulação Temporomandibular/epidemiologia , Transtornos da Articulação Temporomandibular/etnologia , Estados Unidos/epidemiologiaRESUMO
Temporomandibular disorders (TMD) are a set of conditions characterized by pain and dysfunction in the temporomandibular joint and muscles of mastication. These pain conditions are associated with considerable morbidity, societal costs, and reduced quality of life. The prevalence varies between 4% and 10%, with females at higher risk, and a higher prevalence occurs during reproductive years. The increased prevalence of TMD in females and low prevalence in childhood reinforce that sex hormones, like estrogen, play an important, complex role in the pathophysiology of these disorders. The goal of this study was to determine whether women with TMD exhibit a monocytic hyperinflammatory response compared with control women, and to examine associations of monocytic inflammatory responses with clinical pain. Eighteen women, aged 18 to 35 y, were seen during their follicular menstrual phase. A blood sample was collected, a clinical questionnaire about pain history was administered, and a Research Diagnostic Criteria (RDC) exam was performed. Extracted monocytes were stimulated with the toll-like receptor (TLR)-4 ligand, lipopolysaccharide (LPS), in the presence and absence of estrogen, and the levels of IL6 expression evaluated. Women with TMD showed a systemic hyperinflammatory phenotype, manifested by an increased monocytic release of cytokines after an inflammatory insult, and this was further increased by estrogen. In addition, monocytes from participants who self-reported more pain on the VAS scale produced higher levels of IL6 compared with those from participants who self-reported lower pain sensitivity. These data suggest that an estrogen-induced hyperinflammatory phenotype in women with TMD may at least in part contribute to heightened clinical pain, perhaps via central sensitization.
Assuntos
Artralgia/imunologia , Artralgia/fisiopatologia , Estrogênios/farmacologia , Dor Facial/imunologia , Dor Facial/fisiopatologia , Monócitos/imunologia , Transtornos da Articulação Temporomandibular/imunologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Fase Folicular , Humanos , Interleucina-6/sangue , Lipopolissacarídeos , Medição da Dor , Fenótipo , Inquéritos e Questionários , Receptor 4 Toll-Like/sangueRESUMO
PURPOSE: The objective is to define the therapeutic role of antiplatelet agents in a triple-negative breast cancer (TNBC) population. METHODS: We performed retrospective analysis using the UTSW TNBC registry containing data from 222 Stage II-III TNBC patients treated between 1998 and 2016. Univariate analysis and multivariable logistic regression models were constructed to identify factors associated with disease-free survival (DFS), distant metastases rate (DMR), and overall survival outcomes. Antiplatelet drug use was determined by review of electronic medical records. RESULTS: A total of 65 patients used antiplatelet (AP) agents, and 157 patients did not use AP agents. Median follow-up for AP and non-AP groups was 41.3 and 40.9 months, respectively. There was an improvement in the AP group compared with the control group in 5-year DFS (80.4% at 5 years compared with 62.3% in the control group, p = 0.04) and 5-year DMR (8.8 vs. 31.9%, p = 0.007). In multivariate analysis, AP use was found to be significantly associated with improvements in DFS and DMR. CONCLUSIONS: We illustrate that antiplatelet agent use improves DMR and DFS among a stage II and III TNBC population despite our short follow-up evaluation. Longer follow-up evaluation will be required to determine additional outcome advantage for antiplatelet agent use. Our findings support consideration of investigation of antiplatelet therapy as an adjunctive therapy for TNBC at high risk for disease recurrence.
Assuntos
Aspirina/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aspirina/administração & dosagem , Neoplasias da Mama , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Inibidores da Agregação Plaquetária/administração & dosagem , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/diagnósticoRESUMO
PURPOSE: Studies comparing laparoscopic (LIHR) vs. open inguinal hernia repair (OIHR) have shown similar recurrence rates but have disagreed on perioperative outcomes and costs. The aim of this study is to compare laparoscopic vs. open outcomes and costs. METHODS: The National Surgical Quality Improvement Program (NSQIP) was used to compare durations of surgery, anesthesia time, and length of stay (LOS). The University HealthSystem Consortium (UHC) was used to review the cost and complications between approaches. Patients were matched on demographics, year of procedure and surgical approach between datasets for statistical analysis. RESULTS: A sample of 5468 patients undergoing OIHR (N = 4,693) or LIHR (N = 775) was selected from UHC from 2008-2011. An identical number of patients from NSQIP were matched to those from UHC resulting in a total of 10,936 records. LIHR patients had shorter duration of wait from admission to operation (p < 0.05). Conversely, LIHR patients had longer operating time (p < 0.05), duration of anesthesia (p < 0.05), and time in the operating room (p < 0.05).Overall complication rate was higher in open (3.1 vs. 1.8 %, p < 0.05). Cost favored open over LIHR ($4360 vs $5105). The cost discrepancy mainly stemmed from LIHR supplies ($1448 vs. $340; p < 0.05) and OR services ($1380 vs. $1080; p < 0.05). CONCLUSION: This study demonstrates the LOS and perioperative outcomes were superior in the LIHR group; however, the overall cost was higher due to the supplies. Advancement in technology, surgeons' skill level and preference of supplies are all factors in decreasing the overall cost of LIHR.
Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/economia , Herniorrafia/métodos , Laparoscopia/economia , Laparoscopia/métodos , Idoso , Anestesia , Redução de Custos , Análise Custo-Benefício , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to compare short-term outcomes between epidural analgesia and conventional intravenous analgesia for patients undergoing laparoscopic colectomy. This paper uses a large national database to add a current perspective on trends in analgesia and the outcomes associated with two analgesia options. Our evidence augments the opinions of recent randomized controlled trials. METHODS: The University HealthSystem Consortium, an alliance of more than 300 academic and affiliate institutions, was reviewed for the time period of October 2008 through September 2014. International Classification of Disease 9th Clinical Modification codes for laparoscopic colectomy and epidural catheter placement were used. RESULTS: A total of 29,429 patients met our criteria and underwent laparoscopic colectomy during the study period. One hundred and ten (0.374%) patients had an epidural catheter placed for analgesia. Baseline patient demographics were similar for the epidural and conventional analgesia groups. Total charges were significantly higher in the epidural group ($52,998 vs. $39,277; p < 0.001). Median length of stay was longer in the epidural group (6 vs. 5 days; p < 0.001). There was no statistical difference between the epidural and conventional analgesia groups in death (0 vs. 0.03%; p = 0.999), urinary tract infection (0 vs. 0.1%; p = 0.999), ileus (11.8 vs. 13.6%; p = 0.582), or readmission rate (9.1 vs. 9.3%; p = 0.942). CONCLUSION: Compared to conventional analgesic techniques, epidural analgesia does not reduce the rate of postoperative ileus, and it is associated with increased cost and increased length of stay. Based on our data, routine use of epidural analgesia for laparoscopic colectomy cannot be justified.
Assuntos
Administração Intravenosa/estatística & dados numéricos , Analgesia Epidural/estatística & dados numéricos , Analgésicos/administração & dosagem , Colectomia/estatística & dados numéricos , Manejo da Dor/métodos , Administração Intravenosa/efeitos adversos , Administração Intravenosa/economia , Adulto , Idoso , Analgesia Epidural/efeitos adversos , Analgesia Epidural/economia , Colectomia/métodos , Feminino , Preços Hospitalares/estatística & dados numéricos , Humanos , Íleus/epidemiologia , Íleus/etiologia , Laparoscopia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Manejo da Dor/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
The endocannabinoid system is a modulatory system that has been strongly associated with the regulation of functions as learning and memory, pain perception and sensory physiology in many areas of the central nervous system. However, although a role in sensory processing has been demonstrated at the level of the thalamus, the influence of the endocannabinoid system on thalamic rhythms and oscillations has been less studied, despite the fact that such activities are significant characteristics of the thalamic state. The present work aimed to characterize the role of anandamide (AEA) - one of the endogenous CB1 receptor agonists - and AM251 - a CB1 antagonist - in the modulation of burst firing and oscillatory activity present in the dLGN of the anesthetized rat. Administration of AEA (0.5mg/kg iv) increased the number of bursts in the majority of the cells tested and induced the appearance of a slow delta-like (1.5Hz) oscillatory activity. These effects were CB1-mediated, as demonstrated by the complete antagonism during the co-application of AM251 (0.5mg/kg iv). Thus, by demonstrating that the AEA-mediated activation of CB1 receptors increases spontaneous bursting and oscillatory activity in the thalamus our study infers that endocannabinoids could have a role in processes controlling the sleep-wake cycle and level of arousal.
Assuntos
Ácidos Araquidônicos/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Endocanabinoides/farmacologia , Corpos Geniculados/fisiologia , Neurônios/fisiologia , Alcamidas Poli-Insaturadas/farmacologia , Receptor CB1 de Canabinoide/agonistas , Animais , Antagonistas de Receptores de Canabinoides/farmacologia , Eletroencefalografia , Corpos Geniculados/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Receptor CB1 de Canabinoide/antagonistas & inibidores , Córtex Visual/fisiologiaRESUMO
The purpose of this study was to examine differences in heat pain threshold (HPTh) and heat pain tolerance (HPTo) between temporomandibular joint disorder (TMJD) patients and healthy controls. Using suprathreshold heat pain, this study also examined between-group (i.e. TMJD vs. healthy controls) differences in hyperalgesia and temporal summation (TS) of heat pain. Lastly, whether between-group differences in these heat pain outcomes were mediated by self-reported sleep quality was also tested. A total of 119 participants (41% TMJD) completed the current study. HPTh and HPTo responses were assessed at the ventral forearm with an ascending method of limits, while hyperalgesia and TS responses were assessed at the dorsal forearm at temperatures of 46, 48 and 50 °C. Prior to completion of heat pain procedures, participants completed the Pittsburgh Sleep Quality Index. Significant between-group differences in HPTh and HPTo were not observed. TMJD patients demonstrated significantly greater hyperalgesia than healthy controls at 46 °C only, but there were no differences for TS. Furthermore, TMJD patients reported significantly poorer sleep quality compared with healthy controls. Data analysis revealed a significant simple mediation effect whereby the presence of TMJD was strongly associated with poorer self-reported sleep quality, which, in turn, was related to enhanced hyperalgesia at 46 °C. These findings support the hypothesis that the thermal hyperalgesia demonstrated by TMJD patients may be related to poor quality of their self-reported sleep. The ability of interventions that improve sleep quality to also affect pain sensitivity is currently the topic of ongoing investigation.
Assuntos
Hiperalgesia/fisiopatologia , Limiar da Dor/fisiologia , Sono/fisiologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Adulto , Feminino , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Autorrelato , Inquéritos e QuestionáriosRESUMO
Pancreatic cancer is characterized by aggressive growth and resistance to treatment. Identification of unique biomarkers for diagnosis and prognosis is important for treatment of this disease. We investigated the expression patterns of mucin 1 (MUC1), mucin 2 (MUC2) and cytokeratin 17 (CK17) in both normal tissues and metastatic adenocarcinomas using immunohistochemistry (IHC). We have shown that MUC1 (pan-epithelial membrane mucin), MUC2 (intestinal-type secretory mucin) and CK17 can be used as a panel of markers to distinguish collectively pancreatobiliary carcinoma from other primary site carcinomas. Tumors originating in the pancreatobiliary system showed an expression pattern of MUC1 (+), MUC2 (-) and CK17 (+). By contrast, tumors arising from the colorectal region were MUC1 (-), MUC2 (+) and CK17 (-), while tumors originating from non-pancreatobiliary system tissue expressed a MUC1 (+), MUC2 (-) and CK17 (-) profile. More importantly, the MUC1 (+), MUC2 (-) and CK17 (+) result showed greater sensitivity than CA19-9 by IHC, which is the currently accepted and widely used pancreatic tumor marker for diagnosing pancreatic cancer. Thirteen of 51 cases (25%) of pancreatobiliary adenocarcinomas with the pattern MUC1 (+), MUC2 (-) and CK17 (+) showed no immunoreactivity for CA19-9, while 34/51 (67%) cases having MUC1 (+), MUC2 (-) and CK17 (+) were correlated with positive CA19-9 staining. Our data support using an antibody panel of MUC1, MUC2 and CK17 to enhance current methods for pancreatic cancer diagnosis by identifying specifically the primary tissue of origin.
Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Queratina-17/análise , Mucina-1/análise , Mucina-2/análise , Neoplasias Pancreáticas/química , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Antígeno CA-19-9/análise , Humanos , Imuno-Histoquímica , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/secundário , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND AIMS: Orthotopic liver transplantation (OLT) has been the standard treatment for end-stage acute and chronic liver disease. Ischemia-reperfusion (I/R) injury is one of the major causes of poor graft function early after OLT, and adversely influencing graft and patient survivals. It is unknown whether I/R injury influences liver fibrogenesis. MATERIALS AND METHODS: Livers from 25 adult male Wistar rats were randomly assigned into 5 experimental groups according to the preservation solution: saline solution (SS); University of Wisconsin (UW) solution; Fructose 1, 6-biphosphate (FBP); S-Nitroso-N-Acetylcysteine (SNAC): or UW+SNAC (SNAC+UW). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) were determined in preservation solution samples at 2, 4, and 6 hours. After 6 hours of cold ischemia, ex situ reperfusion was applied to the liver for 15 minutes. Serum AST, ALT, LDH, and renin levels were determined. Fresh liver slices were processed for histological studies, determination of thiobarbituric acid reactive substances, catalase, and glutathione, and expression of TGF-ß1 and angiotensin II AT1 receptor. RESULTS: AST was significantly lower during cold storage with UW than with the older media (P=.001); ALT was lower in the FBP group (P=.023) and LDH was lower in the FBP and SNAC groups (P=.007). After reperfusion, serum AST, ALT, LDH, and TBARS showed no significant differences among the groups. Catalase was significantly lower in the SS and FBP groups (P=.008 and P=.006, respectively). Compared with UW, glutathione concentrations were significantly higher in SS, FBP, and SNAC 200 (P=.004). Renin levels were significantly lower in the FBP group (P=.022). No histological signs of preservation injury were observed in the hepatic sample. No expressions were detected of TGF-ß1 or AT1 receptor. CONCLUSION: In this experimental model of early reperfusion injury, preservation changes related to higher levels of renin, which suggest its role in fibrogenesis. FBP was associated with lower renin levels than other solutions including UW.
Assuntos
Cirrose Hepática/prevenção & controle , Transplante de Fígado/efeitos adversos , Fígado/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Acetilcisteína/análogos & derivados , Acetilcisteína/farmacologia , Adenosina/farmacologia , Alanina Transaminase/sangue , Alopurinol/farmacologia , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Catalase/metabolismo , Modelos Animais de Doenças , Frutosedifosfatos/farmacologia , Glutationa/metabolismo , Glutationa/farmacologia , Insulina/farmacologia , L-Lactato Desidrogenase/sangue , Fígado/irrigação sanguínea , Fígado/metabolismo , Fígado/patologia , Fígado/cirurgia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Soluções para Preservação de Órgãos/química , Rafinose/farmacologia , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Renina/sangue , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Studies have demonstrated menstrual cycle influences on basal pain perception, but direct evidence of menstrual cycle influences on analgesic responses has not been reported in humans. Our aim was to determine whether the magnitude of morphine and pentazocine analgesia varied across the menstrual cycle. Sixty-five healthy women, 35 taking oral contraceptives (OC) and 30 normally cycling (NOC), underwent experimental pain assessment both before and after intravenous administration morphine (0.08mg/kg) or pentazocine (0.5mg/kg) compared to saline placebo. Both active drug and placebo were administered once during the follicular phase and once during the luteal phase. Measures of heat, ischemic, and pressure pain sensitivity were obtained before and after drug administration. Change scores in pain responses were computed to determine morphine and pentazocine analgesic responses, and medication side effects were recorded. The data were analyzed using mixed-model analyses of variance. NOC women showed slightly greater heat pain sensitivity in the follicular vs luteal phase, while the reverse pattern emerged for OC women (P=0.046). Also, OC women showed lower pressure pain thresholds compared to NOC women (P<0.05). Regarding analgesic responses, NOC women showed greater morphine analgesia for ischemic pain during the follicular vs the luteal phase (P=0.004). Likewise, side effects for morphine were significantly higher in NOC women in the follicular phase than in the luteal phase (P=0.02). These findings suggest that sex hormones may influence opioid responses; however, the effects vary across medications and pain modalities and are likely to be modest in magnitude. Limited menstrual cycle effects on baseline pain responses were observed; however, morphine analgesia and side effects were greater during the follicular phase.
Assuntos
Analgésicos Opioides/uso terapêutico , Hiperalgesia/tratamento farmacológico , Ciclo Menstrual/efeitos dos fármacos , Morfina/uso terapêutico , Limiar da Dor/efeitos dos fármacos , Pentazocina/uso terapêutico , Adolescente , Adulto , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Hiperalgesia/fisiopatologia , Medição da Dor/métodos , Estatística como Assunto , Adulto JovemRESUMO
Pain represents the major motivating factor for which individuals seek healthcare, and pain responses are characterized by substantial inter-individual differences. Increasing evidence suggests that genetic factors contribute significantly to individual differences in responses to both clinical and experimental pain. The purpose of this review article was to summarize the current literature regarding genetic contributions to pain, highlighting findings relevant to oral pain where available. A brief discussion of methodologic considerations is followed by a review of findings regarding genetic influences on clinical pain. Next, the literature examining genetic contributions to experimental pain responses is presented, emphasizing genetic associations that have been replicated in multiple cohorts. It is hoped that an enhanced understanding of genetic contributions to pain responses will ultimately improve diagnosis and treatment of clinical pain conditions.
Assuntos
Dor/genética , Doença Crônica , Dor Facial/genética , Genes , Humanos , Limiar da Dor/classificação , Fenótipo , Estudos em Gêmeos como Assunto , Gêmeos/genéticaRESUMO
Multiple endocrine neoplasia (MEN 2) is a rare disorder. Of this group, 42% develop a pheochromocytoma of which 60% will have bilateral involvement. Although the benefits of unilateral laparoscopic adrenalectomy have been well documented, fewer cases of simultaneous bilateral laparoscopic adrenalectomy have been reported. We present the cases of three patients with MEN 2 who underwent successful simultaneous bilateral laparoscopic adrenalectomy after their initial presentation with bilateral pheochromocytoma. Although the management of bilateral pheochromocytomas has traditionally been approached via open laparotomy or bilateral posterior incisions, the bilateral laparoscopic approach should be considered a viable alternative for patients requiring surgical intervention. Clinical outcomes and complications are similar to open laparotomy. Simultaneous bilateral laparoscopic adrenalectomy is a safe and effective procedure that results in a more rapid recovery and a shorter hospital stay for patients with bilateral pheochromocytomas originating from MEN 2.
Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia/métodos , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Neoplasia Endócrina Múltipla/cirurgia , Feocromocitoma/cirurgia , Humanos , Resultado do TratamentoRESUMO
The kinematic properties of a new dynamic external fixator device for treatment of distal radial fractures are described. Using a combination of data obtained from computed tomography scans and high-speed video images, a three-dimensional reconstruction of carpal motion was made. To describe carpal motion, the radiolunate, capitolunate, and scapholunate angles were measured during flexion and extension and during radioulnar deviation. During these types of motion, the device changed normal carpal kinematics to a limited extent although the differences in kinematic pattern with and without the device were small. The results for flexion and extension correspond with data from previously published studies with other dynamic external fixators. However, because the new device (Flexafix) allows flexion and extension and radioulnar deviation, in contrast to other dynamic external fixation devices, with its use normal carpal kinematics can be approached more closely.
Assuntos
Fixadores Externos , Fixação de Fratura/instrumentação , Articulação do Punho/fisiopatologia , Adulto , Fenômenos Biomecânicos , Cadáver , Feminino , Fixação de Fratura/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas do Rádio/cirurgia , Amplitude de Movimento Articular , Sensibilidade e Especificidade , Traumatismos do Punho/cirurgiaRESUMO
Upper extremity compression neuropathies are fairly rare in athletes. Initially, most can be managed conservatively. These conditions can follow direct contusion of the tissues that overlay these peripheral nerves or can result from vigorous, repetitive, athletic activity leading to tissue swelling and ischemia with nerve compression symptoms. A complete history and physical examination, including a neurologic examination, should be paramount when treating athletes with upper extremity injuries. Early diagnosis and treatment with conservative measures such as splinting, rest, activity modification, and medications can afford the athlete an earlier return to sports. Surgery can be employed when conservative treatment fails and a specific diagnosis has been ascertained.
Assuntos
Traumatismos em Atletas/fisiopatologia , Nervo Mediano/lesões , Síndromes de Compressão Nervosa/fisiopatologia , Nervo Radial/lesões , Nervo Ulnar/lesões , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/terapia , Humanos , Síndromes de Compressão Nervosa/diagnóstico , Síndromes de Compressão Nervosa/terapiaRESUMO
BACKGROUND: Disorders of kidney development represent a major cause of renal failure and end-stage renal disease in the pediatric population. To understand further the prenatal pathogenesis of obstructive renal dysplasia, a fetal monkey model was developed using ultrasound-guided techniques. METHODS: Ureteropelvic obstruction (N = 13) was induced during the early or late second trimester by the injection of purified guluronic alginate spheres. All fetuses were monitored sonographically, and then fetal tissues were removed at varying time points during the second and third trimesters. RESULTS: There was no evidence of oligohydramnios during the course of gestation, and the obstructed kidneys were typically progressively smaller than the contralateral (nonobstructed) kidneys when monitored sonographically over time. Obstructed kidneys displayed most features of renal dysplasia, including numerous cortical cysts of various sizes derived predominantly from collecting ducts and glomeruli. Mesenchymal changes included expansion of both the cortical and medullary interstitium, as well as mesenchymal-myocyte transformation, expressed as pericystic and peritubular fibromuscular collar formation. An important feature of this model was the disruption of normal glomerular development and architecture, associated with significant podocyte apoptosis, evident as early as the prevascularized S-shaped nephron. As in other models, collecting duct cell apoptosis was apparent, particularly in areas of cyst formation and cellular atrophy. CONCLUSIONS: These results demonstrate the importance of this nonhuman primate model for exploring the pathophysiology of congenital obstructive uropathy and highlight the potential role of podocyte injury in determining long-term renal function associated with this condition.
Assuntos
Obstrução Ureteral/patologia , Obstrução Ureteral/fisiopatologia , Animais , Apoptose , Divisão Celular , Modelos Animais de Doenças , Desenvolvimento Embrionário e Fetal , Feminino , Feto/fisiologia , Rim/diagnóstico por imagem , Rim/embriologia , Rim/patologia , Macaca mulatta/embriologia , Ultrassonografia Pré-Natal , Obstrução Ureteral/diagnóstico por imagemRESUMO
To evaluate anatomic variations and distribution of degenerative changes in the scaphotrapezio-trapezoidal (STT) joint, 165 embalmed cadaver wrists were examined. An interfacet ridge on the distal scaphoid was found in 81% of the wrists and the shape of the distal joint surface of the scaphoid was classified into 3 types. Underdevelopment of the capitate-trapezium ligament was found in 15% of the wrists. A new skeletal measurement for the inclination of the joint surface of the trapezium-trapezoid in the STT joint (TT inclination) was investigated anatomically and radiographically. Degenerative changes were found in 39% of the wrists. The most common location of degenerative changes was on its ulnar aspect on the distal scaphoid and on the radial and central aspect of the trapezoid on the TT side. The presence of degenerative changes had a significant correlation with a higher anatomic and/or radiographic TT inclination and/or underdevelopment of the capitate-trapezium ligament.
Assuntos
Ossos do Carpo/patologia , Osteoartrite/patologia , Osso Escafoide/patologia , Articulação do Punho/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Kinematics of the scaphotrapezio-trapezoidal joint during wrist flexion/extension motion (FEM) and radial/ulnar deviation (RUD) was investigated using a 3-dimensional dynamic motion analysis system. The scaphoid/trapezoid motion was found to be a rotational motion obliquely oriented relative to the sagittal plane of the wrist and described in an ulnoflexion/radial extension motion plane in both FEM and RUD of the wrist. The axis of rotation of the scaphoid/trapezoid motion during both FEM and RUD wrist motions was essentially the same and runs through the radiopalmar aspect of the distal scaphoid and the waist of the capitate. Motion analysis also revealed that the trapezium-trapezoid and trapezoid-capitate joints are essentially immobile. Hence, the scaphotrapezio-trapezoidal motion is considered to be a single degree of freedom that is essentially the same in both FEM and RUD of the wrist.
Assuntos
Ossos do Carpo/fisiopatologia , Osteoartrite/fisiopatologia , Amplitude de Movimento Articular/fisiologia , Osso Escafoide/fisiopatologia , Articulação do Punho/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Pessoa de Meia-IdadeRESUMO
We tested the hypothesis that the fracture location of scaphoid nonunions relates to the fracture displacement, development of dorsal intercalated segment instability (DISI) deformity, and changes in the contact area of the bones in the radiocarpal joint. Eleven patients with scaphoid nonunions were examined with 3-dimensional computed tomography and a new method of proximity mapping. Two different patterns of displacement of scaphoid nonunions were demonstrated, 1 volar and 1 dorsal. All patients with a volar pattern scaphoid nonunion had a DISI deformity. Only a few of the patients with a dorsal pattern scaphoid nonunion, mostly in longstanding nonunions, had a DISI deformity. The fracture line was generally distal to the dorsal apex of the ridge of the scaphoid in the volar-type fractures and proximal in the dorsal displaced fractures. The proximity map of the distal fragment of the scaphoid on the radius in the volar type shifts radial compared with normal; in the distal type it shifts dorsal. Neither of the patterns showed any significant changes of the proximity map in the radiocarpal joint at the proximal scaphoid fragment and the lunate. Whether the fracture line passes distal or proximal to the dorsal apex of the ridge of the scaphoid appears to determine the likelihood of subsequent fracture displacement, DISI deformity, and contact area of the bones in the radiocarpal joint.