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Gastric motility is coordinated by underlying bioelectrical slow waves. Gastric dysrhythmias occur in gastrointestinal (GI) motility disorders, but there are no validated methods for eliminating dysrhythmias. We hypothesized that targeted ablation could eliminate pacemaker sites in the stomach, including dysrhythmic ectopic pacemaker sites. In vivo high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was applied to localize normal and ectopic gastric pacemaker sites in 13 anesthetized pigs. Radiofrequency ablation was performed in a square formation surrounding the pacemaker site. Postablation high-resolution mapping revealed that ablation successfully induced localized conduction blocks after 18 min (SD 5). Normal gastric pacemaker sites were eliminated by ablation (n = 6), resulting in the emergence of a new pacemaker site immediately distal to the original site in all cases. Ectopic pacemaker sites were similarly eliminated by ablation in all cases (n = 7), and the surrounding mapped area was then entrained by normal antegrade activity in five of those cases. Histological analysis showed that ablation lesions extended through the entire depth of the muscle layer. Immunohistochemical staining confirmed localized interruption of the interstitial cell of Cajal (ICC) network through the ablation lesions. This study demonstrates that targeted gastric ablation can effectively modulate gastric electrical activation, including eliminating ectopic sites of slow wave activation underlying gastric dysrhythmias, without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.NEW & NOTEWORTHY This study presents gastric ablation as a novel tool for modulating gastric bioelectrical activation, including eliminating the normal gastric pacemaker site as well as abnormal ectopic pacemaker sites underlying gastric dysrhythmias. Targeted application of radiofrequency ablation was able to eliminate these pacemaker sites without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.
Assuntos
Ablação por Cateter , Gastroenteropatias , Células Intersticiais de Cajal , Animais , Motilidade Gastrointestinal/fisiologia , Células Intersticiais de Cajal/fisiologia , Membrana Serosa , Estômago/fisiologia , SuínosRESUMO
Gastric ablation has demonstrated potential to induce conduction blocks and correct abnormal electrical activity (i.e., ectopic slow-wave propagation) in acute, intraoperative in vivo studies. This study aimed to evaluate the safety and feasibility of gastric ablation to modulate slow-wave conduction after 2 wk of healing. Chronic in vivo experiments were performed in weaner pigs (n = 6). Animals were randomly divided into two groups: sham-ablation (n = 3, control group; no power delivery, room temperature, 5 s/point) and radiofrequency (RF) ablation (n = 3; temperature-control mode, 65°C, 5 s/point). In the initial surgery, high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was performed to define the baseline slow-wave activation profile. Ablation (sham/RF) was then performed in the mid-corpus, in a line around the circumferential axis of the stomach, followed by acute postablation mapping. All animals recovered from the procedure, with no sign of perforation or other complications. Two weeks later, intraoperative high-resolution mapping was repeated. High-resolution mapping showed that ablation successfully induced sustained conduction blocks in all cases in the RF-ablation group at both the acute and 2 wk time points, whereas all sham-controls had no conduction block. Histological and immunohistochemical evaluation showed that after 2 wk of healing, the lesions were in the inflammation and early proliferation phase, and interstitial cells of Cajal (ICC) were depleted and/or deformed within the ablation lesions. This safety and feasibility study demonstrates that gastric ablation can safely and effectively induce a sustained localized conduction block in the stomach without disrupting the surrounding slow-wave conduction capability.NEW & NOTEWORTHY Ablation has recently emerged as a tool for modulating gastric electrical activation and may hold interventional potential for disorders of gastric function. However, previous studies have been limited to the acute intraoperative setting. This study now presents the safety of gastric ablation after postsurgical recovery and healing. Localized electrical conduction blocks created by ablation remained after 2 wk of healing, and no perforation or other complications were observed over the postsurgical period.
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Ablação por Cateter , Células Intersticiais de Cajal , Animais , Ablação por Cateter/efeitos adversos , Estudos de Viabilidade , Células Intersticiais de Cajal/fisiologia , Membrana Serosa , Estômago/fisiologia , SuínosRESUMO
Gastric motility is coordinated by underlying bioelectrical "slow wave" activity. Slow wave dysrhythmias are associated with motility disorders, including gastroparesis, offering an underexplored potential therapeutic target. Although ablation is widely used to treat cardiac arrhythmias, this approach has not yet been trialed for gastric electrical abnormalities. We hypothesized that ablation can create localized conduction blocks and modulate slow wave activation. Radiofrequency ablation was performed on the porcine serosa in vivo, encompassing a range of parameters (55-85°C, adjacent points forming a line, 5-10 s/point). High-resolution electrical mapping (16 × 16 electrodes; 6 × 6 cm) was applied to define baseline and acute postablation activation patterns. Tissue damage was evaluated by hematoxylin and eosin and c-Kit stains. Results demonstrated that RF ablation successfully induced complete conduction block and a full thickness lesion in the muscle layer at energy doses of 65-75°C for 5-10 s/point. Gastric ablation may hold therapeutic potential for gastric electrical abnormalities in the future.NEW & NOTEWORTHY This study presents gastric ablation as a new method for modulating slow wave activation and propagation in vivo, by creating localized electrical conduction blocks in the stomach, validated by high-resolution electrical mapping and histological tissue analysis. The results define the effective energy dose range for creating conduction blocks, while maintaining the mucosal and submucosal integrity, and demonstrate the electrophysiological effects of ablation. In future, gastric ablation can now be translated toward disrupting dysrhythmic slow wave activation.
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Relógios Biológicos , Ablação por Cateter , Gastroparesia/cirurgia , Células Intersticiais de Cajal/patologia , Estômago/cirurgia , Animais , Condutividade Elétrica , Feminino , Motilidade Gastrointestinal , Gastroparesia/metabolismo , Gastroparesia/patologia , Gastroparesia/fisiopatologia , Células Intersticiais de Cajal/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Estômago/patologia , Estômago/fisiopatologia , Sus scrofa , Fatores de TempoRESUMO
DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs) facilitate methylation and hydroxymethylation of DNA, respectively. DNMTs are widely studied with conflicting results on their regulation in the endometrium. While the role of TETs in the endometrium remains relatively unexplored. Deregulated expression of TETs and DNMTs are associated with endometrial pathologies. The aim of this study is to characterize the temporal TET expression in endometrium and to determine the hormonal regulation of TETs in comparison to DNMTs. mRNA expressions were quantified by real-time PCR in endometrial tissues from cycling women and localization was determined by immunohistochemistry. Hormonal regulation was investigated in endometrial epithelial and stromal cell lines following a 24 and 48 h treatment cycle. TET1 and 3 mRNA expressions were significantly upregulated in the mid-secretory phase. TET protein expression was ubiquitous in endometrial epithelium throughout the menstrual cycle except during the late-secretory phase, while stromal staining was scattered. TET1 mRNA was significantly upregulated in response to estrogen in stromal cells. Transcriptions of all three TETs were induced in response to progesterone treatment in epithelial cells. Only DNMT3b in epithelial cells and DNMT1 in stromal cells were significantly upregulated upon 24-h estrogen exposure following a significant decrease of DNMT1 when treated with 24 h of estrogen and progesterone. This study suggests that TETs are expressed in a cell-specific, dynamic manner in the endometrium and are responsive to steroid hormones. Investigating the role of TETs individually and with respect to DNMTs, will help to elucidate gene regulatory mechanisms in endometrial biology and pathologies.
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Endométrio/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios Esteroides Gonadais/farmacologia , Células Cultivadas , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA Metiltransferase 3A , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dioxigenases/genética , Dioxigenases/metabolismo , Endométrio/efeitos dos fármacos , Feminino , Humanos , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , DNA Metiltransferase 3BRESUMO
Peroxynitrite-induced nitration of cellular proteins has been shown to associate with various human pathologies. The expression of pancreatic nitrotyrosine and its cellular source relative to insulitis were analysed in cases with increasing duration of type 1 diabetes and compared with non-diabetic autoantibody-negative and -positive cases. Pancreatic tail sections from non-diabetic autoantibody-negative cases (Group 1; n = 7), non-diabetic autoantibody-positive cases (Group 2; n = 6), recently diagnosed cases (Group 3; n = 6), 0.25-5 years of diabetes (Group 4; n = 8) and 7-12 years of diabetes (Group 5; n = 6) were immunostained sequentially for nitrotyrosine, insulin and leucocytes. Nitrotyrosine expression was observed in selective beta cells only. In group 1, the percentage of insulin-positive islets with nitrotyrosine ranged from 7.6 to 58.8%. In group 2, it was minimally expressed in 2 cases and was present in 4.7-19.3% of insulin-positive islets in 3 cases and in all islets in 1 case. In group 3, it was absent in 1 case and in the remaining 5 cases, the values were 17.4-85.7%. In group 4, nitrotyrosine was absent in 6 cases and positive in 1.8 and 22.2% of insulin-positive islets in 2 cases. In group 5, the values were 60% (1 case) and 100% (2 cases), being absent in 3 cases, consistent with insulin-negativity. This case analysis shows that nitrotyrosine immunostaining is independent of the presence and severity of insulitis. Variable nitrotyrosine expression is present in some non-diabetic cases. Its increased expression in beta cells of recent-onset and long-standing disease requires further studies to determine whether beta cell nitration plays a pathogenic role during T1D.
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Diabetes Mellitus Tipo 1/metabolismo , Ilhotas Pancreáticas/química , Tirosina/análogos & derivados , Adolescente , Adulto , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Ilhotas Pancreáticas/metabolismo , Masculino , Tirosina/análise , Tirosina/biossíntese , Adulto JovemRESUMO
Heart failure is characterized by the loss of sympathetic innervation to the ventricles, contributing to impaired cardiac function and arrhythmogenesis. We hypothesized that renal denervation (RDx) would reverse this loss. Male Wistar rats underwent myocardial infarction (MI) or sham surgery and progressed into heart failure for 4 wk before receiving bilateral RDx or sham RDx. After additional 3 wk, left ventricular (LV) function was assessed, and ventricular sympathetic nerve fiber density was determined via histology. Post-MI heart failure rats displayed significant reductions in ventricular sympathetic innervation and tissue norepinephrine content (nerve fiber density in the LV of MI+sham RDx hearts was 0.31 ± 0.05% vs. 1.00 ± 0.10% in sham MI+sham RDx group, P < 0.05), and RDx significantly increased ventricular sympathetic innervation (0.76 ± 0.14%, P < 0.05) and tissue norepinephrine content. MI was associated with an increase in fibrosis of the noninfarcted ventricular myocardium, which was attenuated by RDx. RDx improved LV ejection fraction and end-systolic and -diastolic areas when compared with pre-RDx levels. This is the first study to show an interaction between renal nerve activity and cardiac sympathetic nerve innervation in heart failure. Our findings show denervating the renal nerves improves cardiac sympathetic innervation and function in the post-MI failing heart.
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Insuficiência Cardíaca/cirurgia , Ventrículos do Coração/inervação , Rim/inervação , Simpatectomia/métodos , Disfunção Ventricular Esquerda/prevenção & controle , Disfunção Ventricular Esquerda/fisiopatologia , Animais , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Rim/cirurgia , Masculino , Ratos , Ratos Wistar , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologiaRESUMO
Higher psychological stress is associated with slower dermal wound healing, but the immunological mechanisms behind this effect are only partially understood. This paper aims to investigate whether immune cells present in the skin prior to wounding can affect subsequent healing in high-stress and low-stress participants. Two studies are presented in which skin biopsies were analysed using immunohistochemistry for numbers of macrophages and Langerhans cells, and immune cell activation (Study 2 only). Immune cells were related to perceived stress levels and subsequent healing. Study 1 included 19 healthy older adults and showed that higher stress was associated with significantly fewer macrophages in the skin. Study 2 included 22 younger adults and showed that higher stress was associated with significantly lower activation of immune cells in the skin. Furthermore, lower activation of immune cells (as measured by human leukocyte antigen (HLA expression)) and fewer Langerhans cells were associated with slower healing. Together these studies show the first preliminary evidence that the number and activation of immune cells in the skin prior to wounding are affected by stress and can impact healing. Larger studies are needed to confirm these effects.
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Pele/imunologia , Pele/lesões , Estresse Psicológico/imunologia , Cicatrização/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Células de Langerhans/imunologia , Macrófagos/imunologia , Masculino , Pele/patologiaRESUMO
Rectal drug administration could offer advantages in the delivery of medicines for children by avoiding swallowability issues, improving stability and enabling administration by caregivers. This study aimed to evaluate the rectal bioavailability of hollow-type suppositories (HTS) and understand the effect of two chemical forms of amoxicillin: amoxicillin sodium (AS) or amoxicillin trihydrate (AMT). HTS were prepared by incorporating a lipophilic core containing the antibiotic with a polyethylene glycol (PEG) shell. Formulations were characterised in vitro, and the absolute bioavailability was determined in a rabbit model, while drug-base interactions were evaluated using X-ray diffraction crystallography (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy. The in vitro amoxicillin release from AMT HTS was delayed, taking 27.3 ± 4.9 h to release 50% drug compared with 1.7 h for the AS HTS, likely due to solubility differences between AMT and AS. The presence of orthorhombic AMT and anhydrous AS crystals in respective HTS was confirmed via XRD and DSC. PEG shells were able to protect the drug chemical stability when stored at 25 °C/60% RH. Despite the difference in their in vitro release rates, a similar rectal bioavailability was found in both forms of amoxicillin (absolute bioavailability 68.2 ± 6.6% vs. 72.8 ± 32.2% for AMT HTS and AS HTS, respectively; p = 0.9682). Both HTS formulations showed little or no irritation to the rectal mucosa following a single dose.
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Corneal confocal microscopy has not previously been performed in penguins, despite recognition of its unusually flat shape. To identify features that the penguin shares with other birds and or mammals and those specific to penguins, we undertook confocal microscopic examination of two little (Eudyptula minor), four gentoo (Pygoscelis papua) and five king (Aptenodytes patagonicus) penguin corneas. Transmission electron microscopy was performed on one gentoo and one king penguin, for finer details. Features shared with other higher vertebrates included a five-layered cornea and a similar limbus. Typically avian were a lower density of stromal cells, a more regular arrangement of collagen bands and an absent basal nerve plexus. Features unique to penguins included a flattened superficial epithelium (king penguin), stromal myofibroblasts (all) and an irregular endothelium (little penguin). Other features uniquely identified by confocal microscopy in birds include epithelial and stromal nerves, guttata and stromal imprints on Descemet's membrane. Transmission electron microscopy identified a lack of wing cells (king penguin), greater posterior collagen lamellae thickness (gentoo penguin) and significantly less interlacing of collagen lamellae in the central cornea (king and gentoo). Most of these unique features are yet to be explained, but some could be adaptations to diving.
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Discoid lupus erythematosus (DLE) is the most common form of cutaneous lupus1. It can cause permanent scarring. The pathophysiology of is not fully understood. Plasmacytoid dendritic cells are found in close association with apoptotic keratinocytes inferring close cellular signalling. Matrix Associated Laser Desorption Ionisation (MALDI) combined with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR-MS) is an exquisitely sensitive combination to examine disease processes at the cellular and molecular level. Active areas of discoid lupus erythematosus were compared with normal perilesional skin using MALDI combined with FT-ICR-MS. A unique set of biomarkers, including epidermal lipids is identified in active discoid lupus. These were assigned as sphingomyelins, phospholipids and ceramides. Additionally, increased levels of proteins from the keratin, and small proline rich family, and aromatic amino acids (tryptophan, phenylalanine, and tyrosine) in the epidermis are observed. These techniques, applied to punch biopsies of the skin, have shown a distinctive lipid profile of active discoid lupus. This profile may indicate specific lipid signalling pathways. Lipid rich microdomains (known as lipid rafts) are involved in cell signalling and lipid abnormalities have been described with systemic lupus erythematosus which correlate with disease activity.
Assuntos
Lúpus Eritematoso Discoide , Lúpus Eritematoso Sistêmico , Humanos , Análise Espectral Raman , Lúpus Eritematoso Discoide/metabolismo , Epiderme/metabolismo , Espectrometria de Massas , LipídeosRESUMO
Prostate cancer (PCa) is a significant healthcare problem worldwide. Current diagnosis and treatment methods are limited by a lack of precise in vivo tissue analysis methods. Real-time cancer identification and grading could dramatically improve current protocols. Here, we report the testing of a thin optical probe using Raman spectroscopy (RS) and classification methods to detect and grade PCa accurately in real-time. We present the first clinical trial on fresh ex vivo biopsy cores from an 84 patient cohort. Findings from 2395 spectra measured on 599 biopsy cores show high accuracy for diagnosing and grading PCa. We can detect clinically significant PCa from benign and clinically insignificant PCa with 90% sensitivity and 80.2% specificity. We also demonstrate the ability to differentiate cancer grades with 90% sensitivity and specificity ≥82.8%. This work demonstrates the utility of RS for real-time PCa detection and grading during routine transrectal biopsy appointments.
Assuntos
Neoplasias da Próstata , Análise Espectral Raman , Humanos , Masculino , Biópsia , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Sensibilidade e EspecificidadeRESUMO
In this paper, rectal absorption and tissue tolerance of amoxicillin sodium (AS) suppositories prepared in a hydrophilic base, polyethylene glycol (PEG) or lipophilic base, Suppocire® NA 15 (SNA 15), were investigated. Following in vitro characterization, including drug distribution in the suppository bases, drug-base interactions and drug release, pharmacokinetics were investigated in rabbits to determine absolute bioavailability (F) at two dose levels (100 mg and 200 mg). Both types of suppositories were found uniform in weight and content. Powder X-ray diffraction (XRD) and differential scanning calorimetry indicated that AS existed as solid dispersion or anhydrous crystalline dispersion in both suppositories at different ratios without changing melting points of the bases. This was supported by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy conjugated with energy dispersive X-ray (SEM/EDX). In dissolution medium, melting and spreading of SNA 15 and dissolution of PEG suppositories accounted for their different drug release kinetics and mean dissolution time (MDT). A rapid and complete amoxicillin absorption (F close to 100%) with a double peak pharmacokinetic profile was observed alongside minimal signs of tissue irritation in rabbits treated with SNA 15 suppositories at both dose levels. In contrast, the F of amoxicillin from PEG suppositories was 59%, increasing to 77.3% as AS dose doubled from 100 mg to 200 mg, reflected in the slower release predominately controlled by erosion of the base. An in vitro - in vivo correlation was observed (MDT vs F; p < 0.01). AS was stable in SNA 15 suppositories at least for three months at 20 ± 0.2 °C. This research highlighted the advantages of SNA 15 suppositories over the PEG suppositories in providing rapid and complete rectal absorption of AS and tissue compatibility.
Assuntos
Amoxicilina , Reto , Amoxicilina/metabolismo , Animais , Disponibilidade Biológica , Liberação Controlada de Fármacos , Coelhos , Reto/metabolismo , SupositóriosRESUMO
The purpose of this review is to summarise contemporary knowledge of sinonasal tissue remodelling during chronic rhinosinusitis (CRS), a chronic disease involving long-term inflammation of the paranasal sinuses and nasal passage. The concept of tissue remodelling has significant clinical relevance because of its potential to cause irreversibility in chronic airway tissues. Recent studies have indicated that early surgical treatment of CRS may improve clinical outcome. Tissue remodelling has been described in the literature extensively with no consensus on how remodelling is defined. This review describes various factors implicated in establishing remodelling in sinonasal tissues with a special mention of asthma as a comorbid condition. Some of the main histological features of remodelling include basement membrane thickening and collagen modulation. This may be an avenue of research with regard to targeted therapy against remodelling in CRS.
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Pele/imunologia , Pele/lesões , Estresse Psicológico/imunologia , Cicatrização/imunologia , Feminino , Humanos , MasculinoRESUMO
Transcutaneous energy transfer (TET) systems use magnetic fields to transfer power across the skin without direct electrical connectivity. This offers the prospect of lifetime operation and overcomes risk of infection associated with wires passing through the skin. Previous attempts at this technology have not proved suitable due to poor efficiency, large size, or tissue damage. We have developed a novel approach utilizing frequency control that allows for wide tolerance in the alignment between internal and external coils for coupling variations of 10 to 20 mm, and relatively small size (50 mm diameter, 5 mm thickness). Using a sheep experimental model, the secondary coil was implanted under the skin in six sheep, and the system was operated to deliver a stable power output to a 15 W load continuously over 4 weeks. The maximum surface temperature of the secondary coil increased by a mean value of 3.4 +/- 0.4 degrees C (+/-SEM). The highest absolute mean temperature was 38.3 degrees C. The mean temperature rise 20 mm from the secondary coil was 0.8 +/- 0.1 degrees C. The efficiency of the system exceeded 80% across a wide range of coil orientations. Histological analysis revealed no evidence of tissue necrosis or damage after four weeks of operation. We conclude that this technology is able to offer robust transfer of power to implantable devices without excess heating causing tissue damage.
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Coração Auxiliar , Animais , Temperatura Baixa , Desenho de Equipamento , Ovinos , Pele/ultraestruturaRESUMO
Lingual frenotomy has become an increasingly common surgical procedure, performed for a broad range of indications from birth through adulthood. This study utilizes histology to define the structure and tissue composition of the lingual frenulum and floor of mouth (FOM) fascia. En bloc specimens of anterior tongue, lingual frenulum, and FOM tissues were harvested from ten embalmed adult cadavers. An additional three fresh tissue cadaveric specimens were frozen with the tongue supported in an elevated position, to enable harvesting and paraffin embedding of the elevated lingual frenulum as a discrete specimen. All 13 specimens were prepared as ten-micron coronal sections using stains to determine the general morphology of the lingual frenulum, its relationship to neighbouring structures (Mason's Trichrome), presence of elastin fibers (Verhoeff-van Gieson), and collagen typing (Picrosirius Red). Our results have shown a submucosal layer of fascia spanning horizontally across the FOM was present in all specimens, with variability in fascial thickness and histologic composition. This FOM fascia suspends the sublingual glands, vessels, and genioglossus from its deep surface. The elevated lingual frenulum is formed by a central fold of this FOM fascia together with the overlying oral mucosa with variability in fascial thickness and composition. With tongue elevation, the fascia mobilizes to a variable extent into the fold forming the frenulum, providing a structural explanation for the individual variability in lingual frenulum morphology seen in clinical practice.
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Gastric motility disorders are associated with bioelectrical abnormalities in the stomach. Recently, gastric ablation has emerged as a potential therapy to correct gastric dysrhythmias. However, the tissue-level effects of gastric ablation have not yet been evaluated. In this study, radiofrequency ablation was performed in vivo in pigs (n=7) at temperature-control mode (55-80°C, 5-10 s per point). The tissue was excised from the ablation site and routine H&E staining protocol was performed. In order to assess tissue damage, we developed an automated technique using a fully convolutional neural network to segment healthy tissue and ablated lesion sites within the muscle and mucosa layers of the stomach. The tissue segmentation achieved an overall Dice score accuracy of 96.18 ± 1.0 %, and Jacquard score of 92.77 ± 1.9 %, after 5-fold cross validation. The ablation lesion was detected with an overall Dice score of 94.16 ± 0.2 %. This method can be used in combination with high-resolution electrical mapping to define the optimal ablation dose for gastric ablation.Clinical Relevance-This work presents an automated method to quantify the ablation lesion in the stomach, which can be applied to determine optimal energy doses for gastric ablation, to enable clinical translation of this promising emerging therapy.
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Aprendizado Profundo , Redes Neurais de Computação , Animais , Músculos , Estômago/diagnóstico por imagem , Suínos , VíscerasRESUMO
Appropriate management of post-operative pain is an ongoing challenge in surgical practice. At present, systemic opioid administration is routinely used for analgesia in the post-operative setting. However, due to significant adverse effects and potential for misuse, there is a perceived need for the development of alternative, opioid-sparing treatment modalities. Continuous infusion of local anesthetic into the peritoneum after major abdominal surgery reduces pain and opioid consumption, and enhances recovery from surgery. Here we describe a non-opioid, poly(ethylene-co-vinyl-acetate) intraperitoneal implant for the sustained delivery of local anesthetic following major abdominal surgery. A radio-opaque core had the required mechanical strength to facilitate placement and removal procedures. This core was enclosed by an outer shell containing an evenly dispersed local anesthetic, lidocaine. Sustained release of lidocaine was observed in an ovine model over days and the movement modelled between peritoneal fluid and circulating plasma. While desirably high levels of lidocaine were achieved in the peritoneal space these were several orders of magnitude higher than blood levels, which remained well below toxic levels. A pharmacokinetic model is presented that incorporates in vitro release data to describe lidocaine concentrations in both peritoneal and plasma compartments, predicting similar release to that suggested by lidocaine concentrations remaining in the device after 3 and 7 days in situ. Histological analysis revealed similar inflammatory responses following implantation of the co-extruded implant and a commercially used silicone drain after three days. This non-opioid analgesic implant provides sustained release of lidocaine in an ovine model and is suitable for moving onto first in human trials.
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Analgésicos não Narcóticos , Lidocaína , Analgésicos Opioides , Anestésicos Locais , Animais , Humanos , Dor Pós-Operatória/tratamento farmacológico , OvinosRESUMO
We apply three optical coherence tomography (OCT) image analysis techniques to extract morphometric information from OCT images obtained on peripheral nerves of rat. The accuracy of each technique is evaluated against histological measurements accurate to + / - 1 µm. The three OCT techniques are: (1) average depth-resolved profile (ADRP), (2) autoregressive spectral estimation (AR-SE), and (3) correlation of the derivative spectral estimation (CoD-SE). We introduce a scanning window to the ADRP technique, which provides transverse resolution and improves epineurium thickness estimates-with the number of analyzed images showing agreement with histology increasing from 2 / 10 to 5 / 10 (Kruskal-Wallis test, α = 0.05). A method of estimating epineurium thickness, using the AR-SE technique, showed agreement with histology in 6 / 10 analyzed images (Kruskal-Wallis test, α = 0.05). Using a tissue sample in which histology identified two fascicles with an estimated difference in mean fiber diameter of 4 µm, the AR-SE and CoD-SE techniques both correctly identified the fascicle with larger fiber diameter distribution but incorrectly estimated the magnitude of this difference as 0.5 µm. The ability of the OCT signal analysis techniques to extract accurate morphometric details from peripheral nerves is promising but restricted in depth by scattering in adipose and neural tissues.