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1.
BMJ Mil Health ; 167(6): 402-407, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32139417

RESUMO

INTRODUCTION: Venous thromboembolism (VTE) is a frequent complication of trauma associated with high mortality and morbidity. Clinicians lack appropriate tools for stratifying trauma patients for VTE, thus have yet to be able to predict when to intervene. We aimed to compare random forest (RF) and logistic regression (LR) predictive modelling for VTE using (1) clinical measures alone, (2) serum biomarkers alone and (3) clinical measures plus serum biomarkers. METHODS: Data were collected from 73 military casualties with at least one extremity wound and prospectively enrolled in an observational study between 2007 and 2012. Clinical and serum cytokine data were collected. Modelling was performed with RF and LR based on the presence or absence of deep vein thrombosis (DVT) and/or pulmonary embolism (PE). For comparison, LR was also performed on the final variables from the RF model. Sensitivity/specificity and area under the curve (AUC) were reported. RESULTS: Of the 73 patients (median Injury Severity Score=16), nine (12.3%) developed VTE, four (5.5%) with DVT, four (5.5%) with PE, and one (1.4%) with both DVT and PE. In all sets of predictive models, RF outperformed LR. The best RF model generated with clinical and serum biomarkers included five variables (interleukin-15, monokine induced by gamma, vascular endothelial growth factor, total blood products at resuscitation and presence of soft tissue injury) and had an AUC of 0.946, sensitivity of 0.992 and specificity of 0.838. CONCLUSIONS: VTE may be predicted by clinical and molecular biomarkers in trauma patients. This will allow the development of clinical decision support tools which can help inform the management of high-risk patients for VTE.


Assuntos
Militares , Tromboembolia Venosa , Trombose Venosa , Biomarcadores , Humanos , Fator A de Crescimento do Endotélio Vascular , Tromboembolia Venosa/diagnóstico , Trombose Venosa/diagnóstico
2.
Acta Parasitol ; 66(2): 406-415, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33037957

RESUMO

PURPOSE: Oxidative stress is an essential component of innate response against microbes. The oxidative impact has a very subtle connection with apoptosis. Our previous work indicated presumptive evidence of apoptosis by the chalcone derivatives against the human lymphatic filarial parasite. Evidence suggests the involvement of glutathione-S-transferase (GST) in the mechanism of action of chalcone drugs. In the present study, we explored the implications of redox status in apoptosis of the parasite by this drug. RESULTS: Treatment with the representative drug, 4t, significantly decreased GSH level and increased GST activity in the Brugia malayi microfilariae (Mf) in comparison to Mf without 4t treatment. Drug-induced loss of motility of the parasites was reversed by the treatment with GSH (41%) and NAC (19%). A significant fall in rGST activity was observed due to drug addition, which could be reversed by the addition of GSH co-substrate, but not with the re-addition of rGST, indicating a vital role of GSH. In silico study demonstrated a favorable drug-GST enzyme interaction. Oxidative stress was reflected by increased protein carbonylation and intracellular reactive oxygen species level, in the drug-treated parasite. Mitochondrial oxygen consumption was reduced by the drug, which was reversed on the addition of GSH. Mitochondrial dysfunction was confirmed by MTT and cytochrome c assay. Apoptosis was confirmed by the inhibition in PARP activity. CONCLUSION: We conclude that the depletion of GSH by chalcone with concomitant mitochondrial dysfunction revealed a novel rationale of apoptosis in the parasite. Such a mechanism might have wide therapeutic implications.


Assuntos
Apoptose , Brugia Malayi , Chalcona , Chalconas , Animais , Brugia Malayi/patogenicidade , Filariose/tratamento farmacológico , Glutationa , Humanos , Estresse Oxidativo
3.
Eur J Neurol ; 27(8): 1570-1577, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32359218

RESUMO

BACKGROUND AND PURPOSE: Epilepsy is most common in lower-income settings where access to electroencephalography (EEG) is generally poor. A low-cost tablet-based EEG device may be valuable, but the quality and reproducibility of the EEG output are not established. METHODS: Tablet-based EEG was deployed in a heterogeneous epilepsy cohort in the Republic of Guinea (2018-2019), consisting of a tablet wirelessly connected to a 14-electrode cap. Participants underwent EEG twice (EEG1 and EEG2), separated by a variable time interval. Recordings were scored remotely by experts in clinical neurophysiology as to data quality and clinical utility. RESULTS: There were 149 participants (41% female; median age 17.9 years; 66.6% ≤21 years of age; mean seizures per month 5.7 ± SD 15.5). The mean duration of EEG1 was 53 ± 12.3 min and that of EEG2 was 29.6 ± 12.8 min. The mean quality scores of EEG1 and EEG2 were 6.4 [range, 1 (low) to 10 (high); both medians 7.0]. A total of 44 (29.5%) participants had epileptiform discharges (EDs) at EEG1 and 25 (16.8%) had EDs at EEG2. EDs were focal/multifocal (rather than generalized) in 70.1% of EEG1 and 72.5% of EEG2 interpretations. A total of 39 (26.2%) were recommended for neuroimaging after EEG1 and 22 (14.8%) after EEG2. Of participants without EDs at EEG1 (n = 53, 55.8%), seven (13.2%) had EDs at EEG2. Of participants with detectable EDs on EEG1 (n = 23, 24.2%), 12 (52.1%) did not have EDs at EEG2. CONCLUSIONS: Tablet-based EEG had a reproducible quality level on repeat testing and was useful for the detection of EDs. The incremental yield of a second EEG in this setting was ~13%. The need for neuroimaging access was evident.


Assuntos
Epilepsia , Adolescente , Eletroencefalografia , Epilepsia/diagnóstico , Feminino , Guiné , Humanos , Masculino , Reprodutibilidade dos Testes , Convulsões/diagnóstico
4.
J Helminthol ; 91(5): 539-548, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27667321

RESUMO

Epidemiological and experimental evidence has supported the concept of using helminths as alternative bio-therapeutic agents in the treatment of type 1 diabetes (T1D). In the current study, two filarial proteins, recombinant Wuchereria bancrofti L2 (rWbL2) and Brugia malayi abundant larval transcript 2 (rBmALT-2) have been investigated, individually and in combination, for their therapeutic potential in streptozotocin (STZ)-induced T1D. The rWbL2 and rBmALT-2 proteins, when administered individually or in combination, have resulted in lowering of the blood glucose levels and reducing the incidence of T1D in mice. In addition, these proteins have led to reduced lymphocytic infiltration and decreased islet damage and inflammation. The curative effect was found to be associated with the suppression of release of tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and increased production of interleukin (IL)-4, IL-5 and IL-10 cytokines by the splenocytes of the diabetic mice. Insulin-specific IgG1 and antigen-specific IgE antibodies were found to be elevated in the sera of mice treated with rWbL2 and rBmALT-2 proteins. From the findings in this study, it can be envisaged that both of these filarial immunomodulatory proteins have the potential to ameliorate T1D by altering the regulatory immune responses.


Assuntos
Brugia Malayi/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Proteínas de Helminto/administração & dosagem , Fatores Imunológicos/administração & dosagem , Wuchereria bancrofti/química , Animais , Autoanticorpos/sangue , Proteínas de Helminto/isolamento & purificação , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Fatores Imunológicos/isolamento & purificação , Ilhotas Pancreáticas/patologia , Camundongos , Resultado do Tratamento
5.
Parasite Immunol ; 37(12): 624-34, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26434489

RESUMO

Understanding the modulation of the host-immune system by pathogens-like filarial parasites offers an alternate approach to prevent autoimmune diseases. In this study, we have shown that treatment with filarial proteins prior to or after the clinical onset of streptozotocin-induced type-1 diabetes (T1D) can ameliorate the severity of disease in BALB/c mice. Pre-treatment with Brugia malayi adult soluble (Bm A S) or microfilarial excretory-secretory (Bm mf ES) or microfilarial soluble (Bm mf S) antigens followed by induction of diabetes led to lowering of fasting blood glucose levels with as many as 57.5-62.5% of mice remaining nondiabetic. These proteins were more effective when they were used to treat the mice with established T1D as 62.5-71.5% of the mice turned to be nondiabetic. Histopathological examination of pancreas of treated mice showed minor inflammatory changes in pancreatic islet cell architecture. The therapeutic effect was found to be associated with the decreased production of cytokines TNF-α & IFN-γ and increased production of IL-10 in the culture supernatants of splenocytes of treated mice. A switch in the production of anti-insulin antibodies from IgG2a to IgG1 isotype was also seen. Together these results provide a proof towards utilizing the filarial derived proteins as novel anti-diabetic therapeutics.


Assuntos
Brugia Malayi/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Proteínas de Helminto/uso terapêutico , Animais , Antígenos de Helmintos/uso terapêutico , Brugia Malayi/imunologia , Feminino , Proteínas de Helminto/metabolismo , Interações Hospedeiro-Parasita , Sistema Imunitário , Imunoglobulina G/metabolismo , Ilhotas Pancreáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Microfilárias , Estreptozocina
6.
Scand J Immunol ; 82(4): 380-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26179420

RESUMO

Lymphatic filariasis, a mosquito-borne parasitic disease, affects more than 120 million people worldwide. Vaccination for filariasis by targeting different stages of the parasite will be a boon to the existing MDA efforts of WHO which required repeated administration of the drug to reduce the infection level and sustained transmission. Onset of a filaria-specific immune response achieved through antigen vaccines can act synergistically with these drugs to enhance the parasite killing. Multi-epitope vaccine approach has been proved to be successful against several parasitic diseases as it overcomes the limitations associated with the whole antigen vaccines. Earlier results from our group suggested the protective efficacy of multi-epitope vaccine comprising two immunodominant epitopes from Brugia malayi antioxidant thioredoxin (TRX), several epitopes from transglutaminase (TGA) and abundant larval transcript-2 (ALT-2). In this study, the prophylactic efficacy of the filarial epitope protein (FEP), a chimera of selective epitopes identified from our earlier study, was tested in a murine model (jird) of filariasis with L3 larvae. FEP conferred a significantly (P < 0.0001) high protection (69.5%) over the control in jirds. We also observed that the multi-epitope recombinant construct (FEP) induces multiple types of protective immune responses, thus ensuring the successful elimination of the parasite; this poses FEP as a potential vaccine candidate.


Assuntos
Filariose Linfática/prevenção & controle , Epitopos Imunodominantes/administração & dosagem , Vacinas Protozoárias/imunologia , Proteínas Recombinantes de Fusão/administração & dosagem , Animais , Anticorpos Anti-Helmínticos/imunologia , Anticorpos Antiprotozoários/sangue , Antígenos de Helmintos/imunologia , Brugia Malayi/imunologia , Brugia Malayi/patogenicidade , Modelos Animais de Doenças , Gerbillinae , Proteínas de Helminto/imunologia , Humanos , Epitopos Imunodominantes/imunologia , Masculino , Camundongos , Vacinas Protozoárias/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes/imunologia , Tiorredoxinas/imunologia , Transglutaminases/imunologia , Vacinação , Wuchereria bancrofti/patogenicidade
7.
Eur J Surg Oncol ; 41(5): 647-52, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25800934

RESUMO

BACKGROUND: In contrast to colon cancer, the implications of reduced lymph node retrieval in rectal cancer are unclear. METHODS: Using the California Cancer Registry, we performed a retrospective cohort study of 4790 patients with stage I - III rectal cancer diagnosed from 2000 to 2007 who underwent tri-modality therapy. Using multivariate Cox proportional hazards models adjusted for age, sex, race, socioeconomic status, T-stage, and lymph node numbers, we evaluated rectal cancer specific survival (RC-SS) in neoadjuvant and adjuvant cohorts in the overall population and amongst those without involved lymph nodes (pN0). RESULTS: Sixty one percent of evaluable patients were treated with neoadjuvant chemoradiation. Although there was no difference in RC-SS between neoadjuvant and adjuvant chemoradiation cohorts, the median number of lymph nodes examined was reduced after neoadjuvant therapy (8 vs. 11, p < 0.0001). Positive lymph nodes were associated with worse RC-SS regardless of sequence, although the effect was numerically stronger for residual lymph nodes in the neoadjuvant cohort. Compared to at least 12, eight or fewer lymph nodes retrieved was associated with worse outcome in both neoadjuvant and adjuvant cohorts. However, no association between reduced lymph nodes examined and RC-SS was seen in the neoadjuvant cohort when the analysis was restricted to pN0 patients. CONCLUSIONS: In this large cohort of rectal cancer patients treated with tri-modality therapy, reduced lymph node retrieval in node negative patients did not provide additional prognostic information in patients treated with neoadjuvant therapy.


Assuntos
Adenocarcinoma/terapia , Excisão de Linfonodo , Linfonodos/patologia , Neoplasias Retais/terapia , Reto/cirurgia , Sistema de Registros , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , California , Quimiorradioterapia , Quimiorradioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/patologia , Estudos Retrospectivos , Resultado do Tratamento
8.
Parasite Immunol ; 36(10): 475-84, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24888320

RESUMO

The chromadorea abundant larval transcript (ALT) family of proteins contains ALT one of the most studied putative vaccine candidate in experimental filariasis. This study reports the characterization of Wuchereria bancrofti 20/22 (Wb20/22) as a member of chromadorea, the ALT family of proteins from the L3 stage of W. bancrofti. The high reactivity with serum from the endemic normal (EN) population suggests that Wb20/22 could be a target of elicit protective immunity. The glutamic acid-rich region of Wb20/22 was predicted to harbour the longest linear B-cell epitope by insilico prediction tools. The significance of this region was revealed by studying the mutant form of Wb20/22, without acidic domain (WOAD) which was cloned, and the immune response was compared with Wb20/22. The signal sequence of Wb20/22 was also an immunodominant region, and mutant construct without signal sequence (WOSS) was cloned and characterized. The peak antibody titre elicited by WOAD was higher than Wb20/22 or WOSS, which pointed to the immunomodulatory role of glutamic acid-rich region. Wb20/22 elicited very high levels of IL-10 and diminished levels of IL-4 and IL-5 which could be the reason for low antibody titre. The prophylactic efficacy of WOAD conferred protection (62·26%) which was higher than Wb20/22 (49·82%) and WOSS (54·78%).


Assuntos
Antígenos de Helmintos/isolamento & purificação , Wuchereria bancrofti/genética , Sequência de Aminoácidos , Animais , Antígenos de Helmintos/química , Antígenos de Helmintos/genética , Clonagem Molecular , Citocinas/imunologia , Filariose/imunologia , Filariose/parasitologia , Humanos , Larva/imunologia , Dados de Sequência Molecular , Alinhamento de Sequência , Vacinas/imunologia , Wuchereria bancrofti/imunologia
9.
Minerva Chir ; 68(5): 479-87, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24101005

RESUMO

An update on the current status of robotic hepatobiliary surgery based on a review of the available literature. A literature search was performed using the PubMed database with search phrases "robotic hepatectomy", "robotic liver resection", "robotic liver surgery", "robotic hepatobiliary surgery", and "robotic biliary reconstruction". We selected articles with high volume case series or case controlled series. As a result of our literature search we will focus on the 9 major articles on robotic liver resection (RLR) with 235 patients undergoing RLR for a total of 244 liver resections. In addition a brief update on robotic biliary reconstruction will also be presented based on the above articles and recent review articles. Indications for robotic liver resection included both benign (N.=72, 29.5%) and malignant disease (N.=172, 70.5%). The most common indication was colorectal liver metastasis (N.=87, 50.6%) and hepatocellular carcinoma (N.=57, 33%). The most common type of resection was subsegmental (N.=55, 22.5%), with a significant number of major hepatectomies (N.=80, 32.8%). Overall conversion rate was 7.8%, with majority converted to open (N.=18) and one converted to hand assisted. The overall complication rate was 11.8% (N.=29). No perioperative mortality was reported. Preliminary results show that robotic assisted laparoscopic hepatobiliary surgery has materialized as a new technique that combines the advantages of laparoscopy with the dissection, suturing and articulation of robotics. This more closely approximates open surgery. The preliminary data demonstrates that RLR can be applied in major hepatobiliary centers safely. Future comparative studies are needed to determine if this is of significant benefit over current open techniques.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/métodos , Hepatectomia/métodos , Robótica/métodos , Perda Sanguínea Cirúrgica , Ensaios Clínicos como Assunto , Humanos , Laparotomia/métodos , Hepatopatias/cirurgia , Neoplasias Hepáticas/cirurgia , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos de Cirurgia Plástica/métodos , Resultado do Tratamento
10.
Eur J Surg Oncol ; 39(6): 627-33, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23523315

RESUMO

BACKGROUND DATA: Recent literature has suggested that completion axillary lymph node dissection (ALND) in breast carcinoma patients with positive SLN may not be necessary. However, a method for determining the risk of non-SLN or extranodal disease remains to be established. AIMS: To determine if pathological variables from primary tumors and sentinel lymph node (SLN) metastases could predict the probability of non-sentinel lymph node (NSLN) metastases and extranodal disease in patients with breast carcinoma and SLN metastases. METHODS: 84 women with T1-3 breast cancer and clinically-negative axillae underwent completion ALND. Maximum diameter and width of SLN metastases were measured to calculate metastatic area. When multiple SLNs contained metastases, areas were summed to calculate the Total Metastatic Area (TMA). Multiple linear regression models were used to identify predictive factors. RESULTS: Her-2/neu over-expression increased the odds of NSLN metastases (OR 4.3, p = 0.01) and extranodal disease (OR 7.9, p < 0.001). Independent SLN predictors were ≥1 positive SLN (OR, 7.35), maximum diameter and area of SLN metastases (OR 2.26, 1.85 respectively) and TMA (OR, 2.12). Maximum metastatic diameter/SLN diameter (OR 3.71, p = 0.04) and the area of metastases/SLN area (OR 3.4, p = 0.04) were predictive. For every 1 mm increase in diameter of SLN metastases, the odds of NSLN extranodal disease increased by 8.5% (p = 0.02). TMA >0.40 cm(2) was an independent predictor for NSLN metastases and extranodal disease. CONCLUSION: Her-2/neu over-expression and parameters assessing metastatic burden in the SLN, particularly TMA, predicted the presence of NSLN involvement and extranodal disease in patients with breast carcinoma and SLN metastases.


Assuntos
Neoplasias da Mama/química , Neoplasias da Mama/patologia , Linfonodos/patologia , Receptor ErbB-2/análise , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Axila , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/química , Carcinoma Lobular/patologia , Fatores de Confusão Epidemiológicos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Modelos Lineares , Linfonodos/cirurgia , Metástase Linfática/diagnóstico , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Regulação para Cima
11.
Eur J Surg Oncol ; 38(6): 531-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22459903

RESUMO

AIMS: Liver resection is indicated for several primary and secondary liver lesions. We follow up our earlier experience with the use of InLine Multichannel Radiofrequency Device (ILMRD, Resect Medical Inc., Fremont, CA) a device that produces coagulative necrosis along the transection plane. METHODS: The records of 68 consecutive patients who underwent liver resection for primary and metastatic liver tumors from August 2000 to December 2008 were reviewed. Data analyzed include demographic data as well as complexity of liver resection, intra-operative blood loss, use of portal triad clamping and transfusion of blood. Postoperative outcomes measured were morbidity, hospital and ICU length of stay. RESULTS: The median estimated blood loss was 150 mL in the ILMRD group compared to 400 mL in the non-ILMRD group (p < 0.0001). Median length of stay was decreased in the ILMRD group by a day (7 vs. 8 p < 0.003). There was a significant decrease in frequency of parenchymal clamp time (57% vs 84%, p < 0.001) and median total portal triad clamp time (2.5 vs 30 min p < 0.0001). We also noted a significant decrease in the median portal triad clamp time (0 vs 25 min, p < 0.001) used during the parenchymal transection phase. Furthermore, use of the ILMRD device allowed us to perform more complex hepatic resections. CONCLUSION: Use of ILMRD to perform radiofrequency-assisted hepatic resection was associated with a significant decrease in intra-operative blood loss and earlier discharge from the hospital despite increasing complexity of resections and decreased use of portal triad clamping.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue/estatística & dados numéricos , Hepatectomia/instrumentação , Tempo de Internação/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Ondas de Rádio , Adulto , Idoso , Neoplasias Colorretais/patologia , Fatores de Confusão Epidemiológicos , Feminino , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/secundário , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Terapia por Radiofrequência , Estudos Retrospectivos , Tamanho da Amostra , Viés de Seleção , Reação Transfusional , Resultado do Tratamento
12.
Somatosens Mot Res ; 27(3): 111-20, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20722492

RESUMO

Rodent whisking behavior generates two types of neural signals: one produced by whisker contact with objects; the other by movements in air. While kinematic signals generated by contact reliably activate neurons at all levels of the trigeminal neuraxis, the extent to which the kinematics of whisking in air are reliably encoded at each level remains unclear. Previously, we showed that the responses of trigeminal ganglion (TG) neurons in awake, head-fixed rats are correlated with whisking kinematic parameters, but that individual neurons may differ substantially in the reliability of their kinematic encoding. Here, we extend that analysis to neurons in the ventral posterior medial (VPM) nucleus. Three possible coding strategies were examined: (1) firing rate across an entire movement; (2) the probability of individual spikes as a function of the instantaneous movement trajectory; and (3) the coherence between spikes and whisking. While VPM neurons were clearly responsive to variations in whisker kinematics during whisking in air, the encoding of whisker kinematics by VPM neurons was less consistent than that of TG neurons. Furthermore, we found that, in VPM as in TG, movement direction is an important determinant of unit responsiveness during whisking in air.


Assuntos
Neurônios/fisiologia , Núcleos Ventrais do Tálamo/fisiologia , Vibrissas/fisiologia , Animais , Eletrofisiologia , Feminino , Estimulação Física , Ratos , Ratos Sprague-Dawley , Estatísticas não Paramétricas
13.
J Neurophysiol ; 101(4): 1836-46, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19109457

RESUMO

Active sensing requires the brain to distinguish signals produced by external inputs from those generated by the animal's own movements. Because the rodent whisker musculature lacks proprioceptors, we asked whether trigeminal ganglion neurons encode the kinematics of the rat's own whisker movements in air. By examining the role of kinematics, we have extended previous findings showing that many neurons that respond during such movements do not do so consistently. Nevertheless, the majority ( approximately 70%) of trigeminal ganglion neurons display significant correlations between firing rate and a kinematic parameter, and a subset, approximately 30%, represent kinematics with high reliability. Preferential firing to movement direction was observed but was strongly modulated by movement amplitude and speed. However, in contrast to the precise time-locking that occurs in response to active whisker contacts, whisker movements in air generate temporally dispersed responses that are not time-locked to the onset of either protractions or retractions.


Assuntos
Ar , Movimento/fisiologia , Neurônios/fisiologia , Gânglio Trigeminal/citologia , Vibrissas/inervação , Vigília , Potenciais de Ação/fisiologia , Animais , Fenômenos Biomecânicos/fisiologia , Condicionamento Operante/fisiologia , Feminino , Curva ROC , Ratos , Ratos Long-Evans , Esquema de Reforço , Estatística como Assunto
14.
J Neurophysiol ; 92(6): 3244-54, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15306632

RESUMO

Layer IV circuitry in the rodent whisker-to-barrel pathway transforms the thalamic input signal spatially and temporally. Excitatory and inhibitory barrel neurons display response properties that differ from each other and from their common thalamic inputs. Here we further examine thalamocortical response transformations by characterizing the responses of individual thalamic barreloid neurons and presumed excitatory and inhibitory cortical barrel neurons to periodic whisker deflections varying in frequency from 1 to 40 Hz. Both pulsatile and sinusoidal periodic stimulation of fixed deflection amplitude were used to assess stimulus-evoked adaptation of thalamocortical units (TCUs), fast-spike barrel units (FSUs: presumed inhibitory neurons), and regular-spike barrel units (RSUs: presumed excitatory neurons). Monotonic, frequency-dependent reductions in firing were observed in thalamic and cortical neurons to the second and subsequent stimuli in trains of high (pulsatile)- and low (sinusoidal)-velocity deflections. RSUs and FSUs adapted substantially more than their thalamic input neurons, and at all frequencies, FSUs fired at higher rates than the other two cell types. For example at 40 Hz, response magnitudes of TCUs decreased by 34%, FSUs by 72%, and RSUs by 78%. Across frequencies, RSUs and FSUs displayed more cycle-by-cycle entrainment and phase-locked responses for (high velocity) pulsatile than (lower velocity) sinusoidal deflections; for TCUs, phase-locking was equivalent for both stimuli, but entrainment was higher for sinusoidal deflections. Strong feed-forward inhibition, in conjunction with synaptic depression, renders the firing of barrel neurons sparse but temporally faithful to the occurrence of repetitive whisker deflections, especially when they are of high velocity.


Assuntos
Córtex Somatossensorial/fisiologia , Tálamo/fisiologia , Tato/fisiologia , Vibrissas/fisiologia , Potenciais de Ação/fisiologia , Adaptação Fisiológica/fisiologia , Animais , Feminino , Inibição Neural/fisiologia , Vias Neurais , Estimulação Física , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/citologia , Tálamo/citologia , Vibrissas/inervação
15.
Arch Surg ; 136(9): 990-4, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11529819

RESUMO

HYPOTHESIS: Stereotactic core biopsy (SCB) is more cost-effective than needle-localized biopsy (NLB) for evaluation and treatment of mammographic lesions. DESIGN: A computer-generated mathematical model was developed based on clinical outcome modeling to estimate costs accrued during evaluation and treatment of suspicious mammographic lesions. Total costs were determined for evaluation and subsequent treatment of cancer when either SCB or NLB was used as the initial biopsy method. Cost was estimated by the cumulative work relative value units accrued. The risk of malignancy based on the Breast Imaging Reporting Data System (BIRADS) score and mammographic suspicion of ductal carcinoma in situ were varied to simulate common clinical scenarios. MAIN OUTCOME MEASURES: Total cost accumulated during evaluation and subsequent surgical therapy (if required). RESULTS: Evaluation of BIRADS 5 lesions (highly suggestive, risk of malignancy = 90%) resulted in equivalent relative value units for both techniques (SCB, 15.54; NLB, 15.47). Evaluation of lesions highly suspicious for ductal carcinoma in situ yielded similar total treatment relative value units (SCB, 11.49; NLB, 10.17). Only for evaluation of BIRADS 4 lesions (suspicious abnormality, risk of malignancy = 34%) was SCB more cost-effective than NLB (SCB, 7.65 vs. NLB, 15.66). CONCLUSIONS: No difference in cost-benefit was found when lesions highly suggestive of malignancy (BIRADS 5) or those suspicious for ductal carcinoma in situ were evaluated initially with SCB vs. NLB, thereby disproving the hypothesis. Only for intermediate-risk lesions (BIRADS 4) did initial evaluation with SCB yield a greater cost savings than with NLB.


Assuntos
Biópsia/economia , Neoplasias da Mama/economia , Mamografia , Biópsia/métodos , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/economia , Carcinoma Intraductal não Infiltrante/terapia , Redução de Custos , Análise Custo-Benefício , Feminino , Humanos , Excisão de Linfonodo/economia , Mastectomia/economia , Mastectomia Segmentar/economia , Modelos Teóricos , Escalas de Valor Relativo , Técnicas Estereotáxicas
16.
Cancer ; 92(3): 471-8, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11505390

RESUMO

BACKGROUND: Although several refinements have been reported for breast magnetic resonance imaging (MRI), there has been no uniform agreement by researchers on the optimal method. The authors report a simple and effective MRI method that incorporated the best qualities of other breast MRI methods yet eliminated the complexity of dynamic sequences and computer subtraction. This new method used fat-suppression, a 3D technique, a dedicated breast coil, and quantitation of lesion enhancement. METHODS: Sixty-one mammographically suspicious lesions were evaluated with a fat-suppressed T1-weighted 3D FLASH sequence before and after administration of Gd-DTPA. Abnormalities were evaluated primarily by the degree of lesional enhancement; lesional morphology was assessed as a secondary criterion. For small or multiple lesions, the authors reformatted images to produce MRI findings that corresponded to the mammographic abnormality. To allow accurate pathologic correlation, all subjects underwent stereotactic or excisional biopsy of the suspicious lesions. RESULTS: Using this new method, all 15 breast carcinomas were enhanced with a signal intensity (SI) increase of > or = 180% (mean = 337%). No benign lesions enhanced at a SI of > 180%. The difference in degree of enhancement between malignant and benign lesions was statistically significant (P < 0.05). There were overlapping degrees of postcontrast enhancement among fibroadenomas (n = 13; mean SI = 70%) and atypical hyperplasias (n =; 11; mean SI = 82%), but morphologic characteristics allowed for discrimination between these two entities. In the remaining benign breast disease lesions, there was minimal enhancement. CONCLUSIONS: 3D fat-suppressed sequencing using this new MRI method accurately discriminated between benign and malignant mammographic abnormalities and eliminated the time-intensive and complex MRI methods without sacrificing accuracy.


Assuntos
Neoplasias da Mama/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Pessoa de Meia-Idade
17.
Ann Surg ; 233(2): 282-6, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11176136

RESUMO

OBJECTIVE: To validate the authors' published surface landmarks for gaining percutaneous access to the internal jugular vein (IJV), and to determine whether these surface landmarks were altered after neck surgery. SUMMARY BACKGROUND DATA: Carotid puncture and pneumothorax continue to be the most frequent mechanical complications of percutaneous IJV venipuncture, particularly when the anterior or posterior approaches are used. The authors' modified technique of IJV venipuncture was associated with a 0.6% complication rate; notably, there were no instances of carotid artery puncture. Determining the accuracy of this method using duplex ultrasound would enhance the technique's applicability and safety. The authors also hypothesized that previous neck surgery would alter the regional anatomy in relation to these surface landmarks for IJV venipuncture. METHODS: The authors prospectively evaluated 417 IJVs in 209 consecutive patients undergoing carotid duplex imaging before and after carotid endarterectomy (CEA). Patients who had undergone CEA were enrolled to investigate the effect of neck surgery on IJV anatomy. The opposite, nonoperated side of the neck served as a control for each patient. The position of the IJV in relation to the surface landmarks, the mobility of the IJV on neck rotation, and the size, patency, and relation of the IJV to the carotid artery were evaluated. RESULTS: Overall accuracy of the surface landmarks for locating the IJV percutaneously was 99% for the control group and 95% for the CEA group. With neck rotation, the IJV was located in a more lateral position in relation to the landmarks that would significantly reduce its accessibility. After neck rotation, it was also noted that the carotid artery moved behind the jugular vein in 85% of the patients in both groups. The mean size of the vein and its patency were similar in both groups. CONCLUSIONS: Duplex imaging validated the accuracy of the surface landmarks for IJV cannulation and documented the adverse effects of neck rotation. IJV anatomy is not altered after CEA.


Assuntos
Endarterectomia das Carótidas , Veias Jugulares/anatomia & histologia , Idoso , Feminino , Humanos , Veias Jugulares/diagnóstico por imagem , Masculino , Período Pós-Operatório , Estudos Prospectivos , Ultrassonografia Doppler Dupla
19.
Arch Surg ; 136(1): 60-4, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11146779

RESUMO

HYPOTHESIS: Surgical residents and staff oncologists (surgical, medical, and radiation therapy) have similar opinions on participation in physician-assisted death for patients with terminal cancer. DESIGN: Prospective survey. SETTING: Tertiary care referral center. PARTICIPANTS: Residents undergoing surgical training (n = 56) and faculty oncologists (n = 24) of all specialties (surgical, medical, and radiation therapy). MAIN OUTCOME MEASURES: Subjects were queried regarding previous experience and willingness to participate (either directly or indirectly) in assisted death for terminal cancer patients. RESULTS: Response rates were 39% (22 of 56) for the residents and 87% (21 of 24) for the oncologists. Of those who responded, 86% (19 of 22) of the residents would aid any of the hypothetical patients with assisted death, whereas only 19% (4 of 21) of the staff oncologists expressed willingness to perform the same service. Furthermore, 32% (7 of 22) of the residents reported previous involvement in a case of assisted death from any disease, whereas only 19% (4 of 21) of the staff oncologists reported previous direct experience with assisted death in the terminal cancer patient. CONCLUSIONS: Surgical residents tend to have more experience with assisted death and are much more willing than staff oncologists to aid terminal cancer patients with this procedure. These opinions and practices are probably not the result of medical education but are developed from personal values.


Assuntos
Atitude do Pessoal de Saúde , Internato e Residência , Neoplasias , Suicídio Assistido , Adulto , Coleta de Dados , Feminino , Cirurgia Geral/educação , Humanos , Masculino , Oncologia , Corpo Clínico Hospitalar , Estudos Prospectivos , Inquéritos e Questionários
20.
Dermatol Online J ; 7(2): 1, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12165217

RESUMO

Controversy still surrounds the recommendation for performing sentinel node biopsy (SLNB) in patients with primary melanoma 1mm or greater in thickness, but why? In the absence of widespread, metastatic disease, nodal status is the single most important prognostic factor which determines likelihood of survival. It allows early therapeutic removal of micrometastatic lymph node disease and identifies patients who are eligible for Interferon alfa-2b adjuvant therapy. SLNB is a requirement for current clinical trials.


Assuntos
Melanoma/patologia , Biópsia de Linfonodo Sentinela , Humanos , Melanoma/diagnóstico , Melanoma/secundário , Melanoma/terapia , Prognóstico , Biópsia de Linfonodo Sentinela/normas , Biópsia de Linfonodo Sentinela/estatística & dados numéricos
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