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1.
J Vasc Access ; : 11297298241244509, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602233

RESUMO

INTRODUCTION: Pre-operative process optimization can expedite time-to-intervention and reduce overall health care costs. We hypothesized that the longest delay to hemodialysis (HD) access creation would be from pre-operative vessel mapping (mandatory in our practice), and that this would be correlated with increased catheter days. METHODS: One hundred thirty patients (24 inpatients, 106 outpatients) who received initial hemodialysis (HD) access from 01/01/2017 to 12/31/2021, at the Veterans Affairs Puget Sound, Seattle, Washington, were identified. Median time differences between pre-operative events were compared between inpatients and outpatients using the Mann-Whitney U test. Outpatients were then stratified by time of catheter-based HD initiation (no catheter, pre-referral catheter, post-referral catheter) and compared. The impacts of mapping-related delays on catheter use were evaluated using regression. RESULTS: Inpatients had shorter referral to access maturation times (125 days inpatient vs 146 days outpatient; p = 0.03). This was driven by shorter referral to mapping (2 days inpatient vs 27 days outpatient; p < 0.01) and mapping to pre-surgical evaluation (1-day inpatient vs 6 days outpatients; p < 0.01) times. Pre-surgical evaluation to OR times represented the longest pre-operative delay in both groups (51 days inpatient vs 29 days outpatient; p = 0.59). Among outpatients, tunneled catheter placement post-referral resulted in longer maturation times (74 days no catheter vs 67 days pre-referral vs 149 days post-referral; p < 0.01) but not additional pre-operative delays. No trend existed between increased mapping times and catheter-based dialysis duration (R2 = 0.08). CONCLUSION: Preoperative vein mapping contributed up to 21% of referral to maturation times but was not associated with increased tunneled catheter duration. While tunneled catheter placement impacted access maturation it did not cause additional pre-operative delays. Earlier referrals for access creation and reduction of outpatient wait-time from referral to OR and increased AV graft placement may minimize catheter days in our system thereby mitigating the added delays caused by pre-operative vein mapping.

2.
J Mech Behav Biomed Mater ; 152: 106402, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342023

RESUMO

Sub-zero (°C) additive manufacturing (AM) systems present a promising solution for the fabrication of hydrogel structures with complex external geometry or a heterogeneous internal structure. Polyvinyl alcohol cryogels (PVA-C) are promising tissue-mimicking materials, with mechanical properties that can be designed to satisfy a wide variety of soft tissues. However, the design of more complex mechanical properties into additively manufactured PVA-C samples, which can be enabled using the toolpath, is a largely unstudied area. This research project will investigate the effect of toolpath variation on the elastic and viscoelastic properties of PVA-C samples fabricated using a sinusoidal toolpath. Samples were fabricated using parametric variation of a sinusoidal toolpath, whilst retaining the same overall cross-sectional area, using a sub-zero AM system. To mechanically characterise the samples, they were tested under tension in uniaxial ramp tests, and through dynamic mechanical analysis (DMA). The elastic and viscoelastic moduli of the samples are presented. No correlations between the parametric variation of the design and the Young's modulus were observed. Analysis of the data shows high intra-sample repeatability, demonstrated robust testing protocols, and variable inter-sample repeatability, indicating differences in the printability and consistency of fabrication between sample sets. DMA of the wavelength samples, show a frequency-dependent loss moduli. The storage modulus demonstrates frequency independence, and a large increase in magnitude as the sample increases to 3 wavelengths.


Assuntos
Bioimpressão , Gastrópodes , Animais , Álcool de Polivinil , Criogéis , Módulo de Elasticidade
4.
J Cyst Fibros ; 22(6): 1002-1009, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37422432

RESUMO

BACKGROUND: Elexacaftor/Tezacaftor/Ivacaftor (ETI) modulator therapy is often associated with increased body mass index (BMI) in people with cystic fibrosis (CF). This is thought to reflect improved clinical stability and increased appetite and nutritional intake. We explored the change in BMI and nutritional intake following ETI modulator therapy in adults with CF. METHODS: Dietary intake, measured with myfood24®, and BMI were collected from adults with CF at baseline and follow-up as part of an observational study. Changes in BMI and nutritional intake in participants who commenced ETI therapy between time points were assessed. To contextualize findings, we also assessed changes in BMI and nutritional intake between study points in a group on no modulators. RESULTS: In the pre and post ETI threapy group (n = 40), BMI significantly increased from 23.0 kg/m2 (IQR 21.4, 25.3) at baseline to 24.6 kg/m2 (IQR 23.0, 26.7) at follow-up (p<0.001), with a median of 68 weeks between time points (range 20-94 weeks) and median duration of ETI therapy was 23 weeks (range 7-72 weeks). There was a significant decrease in energy intake from 2551 kcal/day (IQR 2107, 3115) to 2153 kcal/day (IQR 1648, 2606), p<0.001. In the no modulator group (n = 10), BMI and energy intake did not significantly change between time points (p>0.05), a median of 28 weeks apart (range 20-76 weeks). CONCLUSIONS: These findings tentatively suggest that the increase in BMI with ETI therapy may not simply be attributable to an increase in oral intake. Further exploration into the underlying aetiology of weight gain with ETI therapy is needed.


Assuntos
Fibrose Cística , Adulto , Humanos , Índice de Massa Corporal , Fibrose Cística/diagnóstico , Fibrose Cística/tratamento farmacológico , Ingestão de Alimentos , Regulador de Condutância Transmembrana em Fibrose Cística , Mutação , Benzodioxóis/efeitos adversos , Aminofenóis/efeitos adversos
5.
Ann Vasc Surg ; 95: 188-196, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37247835

RESUMO

BACKGROUND: We investigated the utility of both pre and perioperative vein mapping for evaluating vessel suitability for both arteriovenous fistula (AVF) and arteriovenous graft (AVG) creation. In our practice, we used both mapping methods to detect arterial issues and to maximize AVF creation. We hypothesized that the patients whose operative plan changed based on their perioperative mapping would ultimately benefit from more optimal access placement with maintained rates of maturation and functional patency. METHODS: We performed a retrospective chart review evaluating patients who received initial hemodialysis (HD) access from January 1, 2017, to December 31, 2021, at the Veterans Affairs (VA) Puget Sound in Seattle, Washington. Patients were separated by whether their final procedure was congruent with the best access predicted from the preoperative vein mapping or noncongruent. The primary outcome was fistula maturation. Secondary outcomes were functional patency and number of procedures required to achieve maturation or to maintain functional patency. Results were analyzed using Pearson's chi-squared, Moods median, Student's t-tests, and Kaplan-Meier curves. RESULTS: Preoperative vein mapping uncovered arterial issues in 42% of the patient population. Initial HD access was created in 130 patients (n = 69 congruent, n = 61 noncongruent). Perioperative ultrasound led to a change in the created access in 47% of patients. Within the noncongruent group, 74% received access creation at a more anatomically favorable site compared to their predicted access, 47% were changed to forearm fistula, 20% to brachiocephalic (BC) from previously planned brachiobasilic (BB) or graft, and 7% to BB from previously planned graft. Maturation rates were similar in both groups (congruent 86% and noncongruent 82%), and there were no significant differences in the duration of functional patency or the number of procedures needed to achieve maturation or maintain functional patency. CONCLUSIONS: Utilization of pre and perioperative ultrasound for all patients resulted in higher rates of native AVF, forearm placement, and one-stage operations, with maintained maturation rates and functional patency in patients who were otherwise unsuitable candidates based on preoperative vein mapping alone.


Assuntos
Derivação Arteriovenosa Cirúrgica , Humanos , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Grau de Desobstrução Vascular , Fatores de Risco , Diálise Renal , Artéria Braquial/cirurgia
6.
PLoS One ; 18(3): e0283736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37000822

RESUMO

In studies exploring the potential for nanosecond duration electric pulses to serve as a novel modality for neuromodulation, we found that a 5 ns pulse triggers an immediate rise in [Ca2+]i in isolated bovine adrenal chromaffin cells. To facilitate ongoing efforts to understand underlying mechanisms and to work toward carrying out investigations in cells in situ, we describe the suitability and advantages of using isolated murine adrenal chromaffin cells expressing, in a Cre-dependent manner, the genetically-encoded Ca2+indicator GCaMP6f. Initial experiments confirmed that Ca2+ responses evoked by a 5 ns pulse were similar between fluorescent Ca2+ indicator-loaded murine and bovine chromaffin cells, thereby establishing that 5 ns-elicited excitation of chromaffin cells occurs reproducibly across species. In GCaMP6f-expressing murine chromaffin cells, spontaneous Ca2+ activity as well as nicotinic receptor agonist- and 5 ns evoked-Ca2+ responses consistently displayed similar kinetic characteristics as those in dye-loaded cells but with two-twentyfold greater amplitudes and without photobleaching. The high signal-to-noise ratio of evoked Ca2+ responses as well as spontaneous Ca2+ activity was observed in cells derived from Sox10-Cre, conditional GCaMP6f mice or TH-Cre, conditional GCaMP6f mice, although the number of cells expressing GCaMP6f at sufficiently high levels for achieving high signal-to-noise ratios was greater in Sox10-Cre mice. As in bovine cells, Ca2+ responses elicited in murine GCaMP6f-expressing cells by a 5 ns pulse were mediated by the activation of voltage-gated Ca2+ channels but not tetrodotoxin-sensitive voltage-gated Na+ channels. We conclude that genetically targeting GCaMP6f expression to murine chromaffin cells represents a sensitive and valuable approach to investigate spontaneous, receptor agonist- and nanosecond electric pulse-induced Ca2+ responses in vitro. This approach will also facilitate future studies investigating the effects of ultrashort electric pulses on cells in ex vivo slices of adrenal gland, which will lay the foundation for using nanosecond electric pulses to stimulate neurosecretion in vivo.


Assuntos
Cálcio , Células Cromafins , Animais , Bovinos , Camundongos , Cálcio/metabolismo , Camundongos Transgênicos , Células Cromafins/fisiologia , Glândulas Suprarrenais/metabolismo , Eletricidade , Células Cultivadas
7.
JAMA Surg ; 157(9): e222935, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35947375

RESUMO

Importance: Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair. Objective: To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive. Design, Setting, and Participants: In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021. Interventions: Presurgical consultation using a decision aid vs usual care. Main Outcomes and Measures: The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios. Results: Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70). Conclusions and Relevance: Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT03115346.


Assuntos
Aneurisma da Aorta Abdominal , Procedimentos Endovasculares , Idoso , Aneurisma da Aorta Abdominal/cirurgia , Técnicas de Apoio para a Decisão , Procedimentos Endovasculares/métodos , Feminino , Humanos , Masculino , Preferência do Paciente
8.
Neurohospitalist ; 12(3): 541-543, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35755226

RESUMO

Acute neovascular glaucoma is an extremely rare complication following carotid artery revascularization that can lead to permanent vision loss. We describe an unusual case of acute glaucoma following carotid endarterectomy presenting with mechanical pupillary dilation and vivid visual hallucinations consistent with the Charles Bonnet Syndrome. This case highlights the importance of screening patients complaining of vision loss or eye pain for neovascular eye changes prior to carotid revascularization. These patients' eye health should be closely monitored peri-operatively.

9.
Arch Biochem Biophys ; 723: 109252, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35436445

RESUMO

In whole-cell voltage clamped bovine adrenal chromaffin cells maintained at a holding potential of -70 mV, a single 5 ns, 5 MV/m pulse elicited an inward current carried mainly by Na+ that displayed inward rectification and a reversal potential near -3 mV, a voltage consistent with a non-selective cation current. The broad-spectrum inhibitors of transient receptor potential (TRP) channels, La3+ (10 µM), Gd3+ (10 µM), SKF-96365 (50 µM) and 2-aminoethoxydiphenyl borane (2-APB; 100 µM), inhibited the current similarly by ∼72%, ∼83%, ∼68% and ∼76%, respectively. Depleting membrane cholesterol with methyl-ß-cyclodextrin (MßCD; 1-6 mg/ml) or inhibiting phosphatidylinositol 4,5-bisphosphate (PIP2) synthesis with wortmannin (20 and 40 µM) produced a similar level of inhibition on the NEP-induced conductance as the broad spectrum TRP channel inhibitors. Moreover, no additive inhibitory effect was detected by combining MßCD (3 mg/ml), wortmannin (20 µM) and La3+ (10 µM), suggesting that each agent targeted different levels of the same pathway to exert a full effect. RT-PCR experiments revealed robust expression at the mRNA level of TRPC4, TRPC5 and TRPM7 channels for which specific blockers were available. Whereas the TRPM7 blocker FTY720 had no effect, the TRPC4/5 channel inhibitor M084 (20 µM) blocked the conductance by ∼50%, indicating that TRPC4 and/or TRPC5 channel(s) may be partially involved in mediating the NEP-induced current. CP-96345 (20 µM), a specific blocker of the sodium leak current channel (NALCN), also reduced the NEP-induced current. The inhibition was ∼30% and additive to that caused by the TRPC4/5 blocker M084. RT-PCR experiments confirmed the expression of this channel at the mRNA level. Taken as a whole, these data provide evidence that a large fraction of the current evoked by a 5 ns pulse in adrenal chromaffin cells may be carried by both TRPC4/5 channels and the NALCN channel. Understanding the biophysical properties of the NEP-elicited conductance in a neural-type cell will be extremely valuable for the future development of NEP stimulation approaches for neuromodulation.


Assuntos
Células Cromafins , Canais de Cátion TRPM , Animais , Cátions/metabolismo , Bovinos , Células Cromafins/metabolismo , Potenciais da Membrana , RNA Mensageiro/metabolismo , Canais de Cátion TRPC/metabolismo , Canais de Cátion TRPM/metabolismo , Wortmanina/metabolismo , Wortmanina/farmacologia
10.
J Pharm Pract ; 35(4): 606-611, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33739190

RESUMO

OBJECTIVE: To evaluate the effect of a medication assistance program and the addition of pharmacist management on clinical outcomes in patients with hypertension and diabetes through an Advanced Pharmaceutical Care program. METHODS: This was a prospective quality improvement study on patients with hypertension and/or diabetes resistant to usual care. The primary outcomes were change in A1C, blood glucose, and blood pressure between 3 phases: usual care, free medications, and free medications plus pharmacist management. Secondary outcomes included achievement of A1C, blood glucose, and blood pressure goals as well as pharmacist interventions. RESULTS: Seven patients were included in the study. The mean A1C decreased from 11.3% to 8.3% with free medications (p = 0.28) and from 8.3% to 6.4% with pharmacist management (p = 0.119). Mean blood pressure during usual care, free medications, and pharmacist intervention was 150/87 mm Hg, 148/85 mm Hg, and 125/78 mm Hg, respectively. After pharmacist management, 75% of patients with type 2 diabetes were able to achieve A1C and blood glucose goals, and 71% of patients with hypertension achieved blood pressure <130/80 mm Hg. CONCLUSIONS: The Advanced Pharmaceutical Care program allowed pharmacists to identify and overcome patient-specific barriers to care, provide individualized disease state education, and optimize medication management. Medication assistance led to improvements in A1C and blood pressure, but did not affect achievement of disease state goals. Pharmacist involvement in hypertension and diabetes care led to clinically significant reductions in blood pressure and A1C and enabled patients to reach guideline-recommended blood pressure and glycemic goals.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Glicemia , Pressão Sanguínea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Humanos , Hipertensão/tratamento farmacológico , Farmacêuticos , Estudos Prospectivos
12.
Bioelectrochemistry ; 140: 107830, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33965669

RESUMO

Previously we reported that adrenal chromaffin cells exposed to a 5 ns, 5 MV/m pulse release the catecholamines norepinephrine (NE) and epinephrine (EPI) in a Ca2+-dependent manner. Here we determined that NE and EPI release increased with pulse number (one versus five and ten pulses at 1 Hz), established that release occurs by exocytosis, and characterized the exocytotic response in real-time. Evidence of an exocytotic mechanism was the appearance of dopamine-ß-hydroxylase on the plasma membrane, and the demonstration by total internal reflection fluorescence microscopy studies that a train of five or ten pulses at 1 Hz triggered the release of the fluorescent dye acridine orange from secretory granules. Release events were Ca2+-dependent, longer-lived relative to those evoked by nicotinic receptor stimulation, and occurred with a delay of several seconds despite an immediate rise in Ca2+. In complementary studies, cells labeled with the plasma membrane fluorescent dye FM 1-43 and exposed to a train of ten pulses at 1 Hz underwent Ca2+-dependent increases in FM 1-43 fluorescence indicative of granule fusion with the plasma membrane due to exocytosis. These results demonstrate the effectiveness of ultrashort electric pulses for stimulating catecholamine release, signifying their promise as a novel electrostimulation modality for neurosecretion.


Assuntos
Glândulas Suprarrenais/citologia , Cálcio/metabolismo , Catecolaminas/metabolismo , Células Cromafins/metabolismo , Eletricidade , Exocitose
13.
J Vis Exp ; (170)2021 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-33938886

RESUMO

Blood flow recovery is a critical outcome measure after experimental hindlimb ischemia or ischemia-reperfusion. Laser Doppler perfusion imaging (LDPI) is a common, noninvasive, repeatable method for assessing blood flow recovery. The technique calculates overall blood flow in the sampled tissue from the Doppler shift in frequency caused when a laser hits moving red blood cells. Measurements are expressed in arbitrary perfusion units, so the contralateral non-intervened upon leg is usually used to help control measurements. Measurement depth is in the range of 0.3-1 mm; for hindlimb ischemia, this means that dermal perfusion is assessed. Dermal perfusion is dependent on several factors-most importantly skin temperature and anesthetic agent, which must be carefully controlled to result in reliable readings. Furthermore, hair and skin pigmentation can alter the ability of the laser to either reach or penetrate to the dermis. This article demonstrates the technique of LDPI in the mouse hindlimb.


Assuntos
Membro Posterior/diagnóstico por imagem , Animais , Hemodinâmica , Membro Posterior/irrigação sanguínea , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Fluxometria por Laser-Doppler , Lasers , Camundongos , Perfusão/métodos , Fluxo Sanguíneo Regional , Reperfusão
14.
Biophys J ; 120(3): 556-567, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33359835

RESUMO

Cellular effects of nanosecond-pulsed electric field exposures can be attenuated by an electric field reversal, a phenomenon called bipolar pulse cancellation. Our investigations of this phenomenon in neuroendocrine adrenal chromaffin cells show that a single 2-ns, 16 MV/m unipolar pulse elicited a rapid, transient rise in intracellular Ca2+ levels due to Ca2+ influx through voltage-gated calcium channels. The response was eliminated by a 2-ns bipolar pulse with positive and negative phases of equal duration and amplitude and fully restored (unipolar-equivalent response) when the delay between each phase of the bipolar pulse was 30 ns. Longer interphase intervals evoked Ca2+ responses that were greater in magnitude than those evoked by a unipolar pulse (stimulation). Cancellation was also observed when the amplitude of the second (negative) phase of the bipolar pulse was half that of the first (positive) phase but progressively lost as the amplitude of the second phase was incrementally increased above that of the first phase. When the amplitude of the second phase was twice that of the first phase, there was stimulation. By comparing the experimental results for each manipulation of the bipolar pulse waveform with analytical calculations of capacitive membrane charging/discharging, also known as accelerated membrane discharge mechanism, we show that the transition from cancellation to unipolar-equivalent stimulation broadly agrees with this model. Taken as a whole, our results demonstrate that electrostimulation of adrenal chromaffin cells with ultrashort pulses can be modulated with interphase intervals of tens of nanoseconds, a prediction of the accelerated membrane discharge mechanism not previously observed in other bipolar pulse cancellation studies. Such modulation of Ca2+ responses in a neural-type cell is promising for the potential use of nanosecond bipolar pulse technologies for remote electrostimulation applications for neuromodulation.


Assuntos
Células Cromafins , Terapia por Estimulação Elétrica , Cálcio/metabolismo , Canais de Cálcio , Células Cromafins/metabolismo , Eletricidade
15.
Astrobiology ; 20(10): 1185-1211, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32700965

RESUMO

We used a deep-ultraviolet fluorescence mapping spectrometer, coupled to a drill system, to scan from the surface to 105 m depth into the Greenland ice sheet. The scan included firn and glacial ice and demonstrated that the instrument is able to determine small (mm) and large (cm) scale regions of organic matter concentration and discriminate spectral types of organic matter at high resolution. Both a linear point cloud scanning mode and a raster mapping mode were used to detect and localize microbial and organic matter "hotspots" embedded in the ice. Our instrument revealed diverse spectral signatures. Most hotspots were <20 mm in diameter, clearly isolated from other hotspots, and distributed stochastically; there was no evidence of layering in the ice at the fine scales examined (100 µm per pixel). The spectral signatures were consistent with organic matter fluorescence from microbes, lignins, fused-ring aromatic molecules, including polycyclic aromatic hydrocarbons, and biologically derived materials such as fulvic acids. In situ detection of organic matter hotspots in ice prevents loss of spatial information and signal dilution when compared with traditional bulk analysis of ice core meltwaters. Our methodology could be useful for detecting microbial and organic hotspots in terrestrial icy environments and on future missions to the Ocean Worlds of our Solar System.


Assuntos
Camada de Gelo , Sistema Solar , Groenlândia , Camada de Gelo/química , Camada de Gelo/microbiologia
16.
PLoS One ; 15(6): e0234114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516325

RESUMO

We previously reported that a single 5 ns high intensity electric pulse (NEP) caused an E-field-dependent decrease in peak inward voltage-gated Na+ current (INa) in isolated bovine adrenal chromaffin cells. This study explored the effects of a pair of 5 ns pulses on INa recorded in the same cell type, and how varying the E-field amplitude and interval between the pulses altered its response. Regardless of the E-field strength (5 to 10 MV/m), twin NEPs having interpulse intervals ≥ than 5 s caused the inhibition of TTX-sensitive INa to approximately double relative to that produced by a single pulse. However, reducing the interval from 1 s to 10 ms between twin NEPs at E-fields of 5 and 8 MV/m but not 10 MV/m decreased the magnitude of the additive inhibitory effect by the second pulse in a pair on INa. The enhanced inhibitory effects of twin vs single NEPs on INa were not due to a shift in the voltage-dependence of steady-state activation and inactivation but were associated with a reduction in maximal Na+ conductance. Paradoxically, reducing the interval between twin NEPs at 5 or 8 MV/m but not 10 MV/m led to a progressive interval-dependent recovery of INa, which after 9 min exceeded the level of INa reached following the application of a single NEP. Disrupting lipid rafts by depleting membrane cholesterol with methyl-ß-cyclodextrin enhanced the inhibitory effects of twin NEPs on INa and ablated the progressive recovery of this current at short twin pulse intervals, suggesting a complete dissociation of the inhibitory effects of twin NEPs on this current from their ability to stimulate its recovery. Our results suggest that in contrast to a single NEP, twin NEPs may influence membrane lipid rafts in a manner that enhances the trafficking of newly synthesized and/or recycling of endocytosed voltage-gated Na+ channels, thereby pointing to novel means to regulate ion channels in excitable cells.


Assuntos
Células Cromafins/fisiologia , Eletricidade , Glândulas Suprarrenais/citologia , Animais , Bovinos , Células Cultivadas , Células Cromafins/citologia , Potenciais da Membrana/efeitos dos fármacos , Técnicas de Patch-Clamp , Canais de Sódio Disparados por Voltagem/metabolismo , beta-Ciclodextrinas/farmacologia
17.
J Surg Res ; 253: 53-62, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32320897

RESUMO

BACKGROUND: Proteoglycan 4 (PRG4; lubricin) is a member of two gene co-expression network modules associated with human vein graft failure. However, little is known about PRG4 and the vascular system. Therefore, we have investigated the effects of recombinant human PRG4 (rhPRG4) on cell migration and proliferation in human veins. METHODS: Effects of rhPRG4 on cell migration, proliferation, and neointima formation were determined in human venous tissue and cultured venous smooth muscle cells (SMCs), adventitial cells, and endothelial cells. Expression of PRG4 by cultured human saphenous veins, failed vein grafts, and varicose veins was determined by immunostaining or Western blotting. RESULTS: Limited expression of PRG4 in fresh saphenous veins was dramatically increased around medial SMCs after culture ex vivo. rhPRG4 inhibited the migration of cultured SMCs, adventitial cells, and endothelial cells, as well as the proliferation of endothelial cells. rhPRG4 also inhibited the migration of SMCs and adventitial cells from tissue explants, but there was no effect on cell proliferation or neointima formation in ex vivo whole veins. Finally, PRG4 was largely absent in two examples of venous pathology, that is, failed human vein grafts and varicose veins. CONCLUSIONS: Although rhPRG4 can inhibit the migration of venous SMCs, endothelial cells, and adventitial cells, and the proliferation of endothelial cells, PRG4 was only increased around medial SMCs in veins after ex vivo culture. PRG4 was not observed around medial SMCs in failed human vein grafts and varicose veins, suggesting the possibility that a failure of PRG4 upregulation may promote these pathologies.


Assuntos
Rejeição de Enxerto/patologia , Neointima/patologia , Proteoglicanas/metabolismo , Veia Safena/transplante , Varizes/patologia , Movimento Celular , Proliferação de Células , Células Cultivadas , Células Endoteliais/patologia , Rejeição de Enxerto/etiologia , Humanos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/patologia , Neointima/etiologia , Técnicas de Cultura de Órgãos , Doença Arterial Periférica/cirurgia , Cultura Primária de Células , Proteoglicanas/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Veia Safena/citologia , Veia Safena/patologia , Técnicas de Cultura de Tecidos , Enxerto Vascular/efeitos adversos
19.
J Vasc Surg ; 71(2): 609-615, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31176639

RESUMO

BACKGROUND: During the past decade, the proportion of women within graduate medical education has increased. Correspondingly, the proportion of women in almost every specialty has increased, including surgical specialties. We sought to evaluate the effect of establishing vascular surgery integrated residencies (VSIRs) on the proportion of women in vascular surgery training programs. METHODS: Resident data were obtained from the Accreditation Council for Graduate Medical Education (ACGME) Data Resource Book for the academic years 2007 to 2016. Data were collected on overall ACGME residency numbers as well as on the following surgical subspecialties: vascular, general, thoracic, neurologic, orthopedic, otolaryngologic, and urologic surgery. The number and proportion of women per year in VSIRs and vascular surgery fellowships were compared with those in the other surgical specialties. RESULTS: During the study period, the proportion of women in ACGME-accredited residency programs increased from 0.41 (n = 43,695/107,851) to 0.44 (n = 57,130/129,720) of residents. Since the advent of the VSIR, the number of trainees within vascular surgery has increased by 56% from 221 to 501 trainees. The proportion of women in vascular surgery training programs has increased from 0.12 (n = 27/221) to 0.33 (n = 164/501) of trainees. This increase during the 9-year study period was greater than in any other surgical subspecialty and greatest within the VSIR. Compared with fellowship training programs, integrated surgical training programs within the same subspecialty had a higher proportion of women, although variability between surgical subspecialties remained notable. CONCLUSIONS: Although it is lower than the proportion of women within all graduate medical education training programs, an increasing proportion of women have entered vascular surgery training during the study period. This appears to be related to the introduction of VSIRs and exceeds the proportion of women entering almost all other surgical subspecialties at a rate of change faster than in all other surgical subspecialties. Further work to understand surgical specialty preferences and choice of careers after training is warranted.


Assuntos
Internato e Residência/organização & administração , Médicas/estatística & dados numéricos , Especialidades Cirúrgicas/educação , Procedimentos Cirúrgicos Vasculares/educação , Feminino , Humanos , Masculino , Distribuição por Sexo , Estados Unidos
20.
J Vasc Surg ; 71(2): 497-504, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31353272

RESUMO

OBJECTIVE: Shared medical decision making is most important when there are competing options for repair such as in treatment of abdominal aortic aneurysm (AAA). We sought to understand the sources of patients' pre-existing knowledge about AAA to better inform treating physicians about patients' needs for preoperative counseling. METHODS: We performed a multicenter survey of patients facing AAA repair at 20 Veterans Affairs hospitals across the United States as part of the Preferences for Open Versus Endovascular Repair of AAA study. A validated survey instrument was administered to examine the sources of information available and commonly used by patients to learn about their repair options. The survey was administered by study personnel before the patient had any interaction with the vascular surgeon because survey data were collected before the vascular clinic visit. RESULTS: Preliminary analysis of data from 99 patients showed that our cohort was primarily male (99%) and elderly (mean age 73 years). Patients commonly had a history of hypertension (86%), prior myocardial infarction (32%), diabetes (32%), and were overweight (58%). Patients arrived at their surgeon's office appointment with limited information. A majority of patients (52%) reported that they had not talked to their primary care physician at all about their options for AAA repair, and one-half (50%) reported that their view of the different surgical options had not been influenced by anyone. Slightly less than one-half of patients reported that they did not receive any information about open surgical aneurysm repair and endovascular aortic aneurysm repair (41% and 37%, respectively). Few patients indicated using the internet as their main source of information about open surgical aneurysm repair and endovascular aortic aneurysm repair (10% and 11%, respectively). CONCLUSIONS: Patients are commonly referred for AAA repair having little to no information regarding AAA pathology or repair options. Fewer than one in five patients searched the internet or had accessed other sources of information on their own. Most vascular surgeons should assume that patients will present to their first vascular surgery appointment with minimal understanding of the treatment options available to them.


Assuntos
Aneurisma da Aorta Abdominal , Conhecimentos, Atitudes e Prática em Saúde , Idoso , Aneurisma da Aorta Abdominal/cirurgia , Feminino , Humanos , Comportamento de Busca de Informação , Masculino , Estudos Prospectivos , Autorrelato
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