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1.
J Endourol ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39001824

RESUMO

Introduction: Several complications of retrograde intrarenal surgery have been attributed to inadvertent increases in intrarenal pressure. We recently described the development of an innovative isoprenaline-eluting guidewire (IsoWire). The objective of this study was to investigate the impact of this IsoWire on the intrarenal pressure and evaluate its safety. Materials and Methods: This study was performed in 17 renal units using a porcine model. As controls, the intrarenal pressure, heart rate, and mean arterial pressure were measured for a duration of six minutes with a standard guidewire placed in the renal pelvis. For the experiment, the conventional guidewire was substituted with the IsoWire and the same parameters were measured. Blood samples were taken at one-minute intervals to measure plasma isoprenaline levels. This procedure was repeated on the opposite side. Results: The mean intrarenal pressure reduction was 29% (95% CI: 13%-53%). The mean isoprenaline effect time was 174 seconds. No changes in heart rate (p = .908) or mean arterial pressure (p = .749) were recorded after IsoWire insertion. Plasma isoprenaline levels were below the quantitation threshold. Isoprenaline concentrations in the plasma were below the quantification threshold. Ureteroscopy revealed no ureteral lesions. Conclusions: The IsoWire demonstrated a safe and effective reduction of intrarenal pressure. Additional research is necessary to determine whether ureteral smooth muscle relaxation generated by isoprenaline facilitates easier insertion of a ureteral access sheath, decreases the incidence of ureteral access sheath related ureteral lesions, or even encourage the practice of sheathless retrograde intrarenal surgery.

2.
J Endourol ; 38(6): 590-597, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38468539

RESUMO

Introduction: Retrograde intrarenal surgery (RIRS) is associated with complications, many of which are related to the intrarenal pressure (IRP). We aim to describe the design of a novel isoprenaline-eluting guidewire ("IsoWire") and present the results from the first in vitro release studies and the first animal studies showing its effect on IRP. Materials and Methods: The IsoWire comprises a Nitinol core surrounded by a stainless-steel wire wound into a tight coil. The grooves created by this coil provided a reservoir for adding a hydrogel coating into which isoprenaline, a beta-agonist, was loaded. Animal studies were performed using a porcine model. For the control, IRP, heart rate (HR), and mean arterial pressure (MAP) were measured continuously for 6 minutes with a standard guidewire in place. For the experiment, the standard hydrophilic guidewire was removed, the IsoWire was inserted into the renal pelvis, and the same parameters were measured. Results: In vitro analysis of the isoprenaline release profile showed that most (63.9 ± 5.9%) of the loaded drug mass was released in the 1st minute, and almost all of the drug was released in the first 4 minutes exponentially. Porcine studies showed a 25.1% reduction in IRP in the IsoWire that released 10 µg in the 1st minute; however, there was a marked increase in HR. The average percentage reduction in IRP was 8.95% and 21.3% in the IsoWire that released 5 and 7.5 µg of isoprenaline, respectively, with no changes in HR or MAP. Conclusions: The IsoWire, which releases 5 and 7.5 µg of isoprenaline in the 1st minute, appears to be safe and effective in reducing the IRP. Further studies are needed to establish whether the isoprenaline-induced ureteral relaxation will render easier insertion of a ureteral access sheath, reduce IRP during sheathless RIRS, or even promote the practice of sheathless RIRS.


Assuntos
Isoproterenol , Animais , Projetos Piloto , Suínos , Isoproterenol/farmacologia , Desenho de Equipamento , Rim/cirurgia
3.
J Otolaryngol Head Neck Surg ; 37(5): 664-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19128673

RESUMO

INTRODUCTION: Gentamicin is one of the most extensively studied aminoglycoside antibiotics. The dogma of gentamicin ototoxicity theorizes that (1) the toxic effects of the drug are cumulative and dose dependent, despite clinical observations of ototoxicity after a single dose, and (2) gentamicin's ototoxic effects are irreversible, although clinicians have observed improvement in hearing over time. The objective of this study was to evaluate this basic dogma by examining the ototoxic differences between single-dose and 19-day daily dosing of gentamicin over a 60-day period. METHODS: Thirty-six C57 mice were randomly assigned to one of three treatment groups: (1) 19-day daily normal saline intraperitoneal injections (control; n = 10), (2) single-dose intraperitoneal 120 mg/kg gentamicin (n = 12), and (3) 19-day daily intraperitoneal 120 mg/kg gentamicin (n = 14). Pure-tone testing using auditory brainstem response was performed at frequencies of 6, 8, 12, 20, and 30 kHz. Hearing threshold was determined at each frequency by presenting stimuli from 90 dB to 5 dB using 10 dB decrements. Pure-tone testing was performed at days 1, 35, and 60 +/- 2 days. RESULTS: The results showed that hearing (1) improved between days 35 and 60 (p = .023) and (2) was not significantly different between a single dose versus 19 daily doses of gentamicin (p = .285). CONCLUSION: This study concurs with clinical observations that a single large dose of gentamicin may have ototoxic effects similar to those of multiple doses of gentamicin and that, over time, there is the potential for hearing recovery from gentamicin ototoxicity.


Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Gentamicinas/farmacologia , Gentamicinas/toxicidade , Perda Auditiva Neurossensorial/induzido quimicamente , Animais , Limiar Auditivo/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Injeções Intraperitoneais , Modelos Lineares , Camundongos , Camundongos Endogâmicos C57BL , Probabilidade , Distribuição Aleatória , Recuperação de Função Fisiológica , Fatores de Risco , Sensibilidade e Especificidade
4.
J Otolaryngol Head Neck Surg ; 37(5): 700-3, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19128679

RESUMO

OBJECTIVE: To illustrate some differences between humans and rodents in the dose-effect relationships for two ototoxic drugs. STUDY DESIGN: Controlled animal study using typical research regimens for gentamicin and cisplatin compared with human data from the clinical literature. METHODS: Auditory brainstem response testing was carried out over months in two groups of animals exposed to typical dose regimens for ototoxic drugs. In the first group, 30 guinea pigs received either 3 or 6 mg/kg of cisplatin on alternate days for 5 days (total dose 15 or 30 mg/kg). In the second group, 24 C57 mice received saline or 19 daily doses of gentamicin 120 mg/kg. The findings in rodents were contrasted with human toxicity in the literature. RESULTS: Cisplatin increased click thresholds (32 +/- 27 dB) in guinea pigs. Doses of 15 mg/kg caused less hearing loss than 30 mg/kg, but the higher dose was associated with greater mortality owing to renal insufficiency. These findings are comparable with expectations of similar doses of cisplatin in humans. In contrast, gentamicin produced less hearing loss in mice, although the dose employed was well above the lethal dose for humans. CONCLUSIONS: Ototoxic doses of cisplatin in guinea pigs are similar to those of humans, but C57 mice appear to be highly resistant to gentamicin-induced hearing loss compared to humans. Animal models of ototoxicity need to be considered carefully in translational research.


Assuntos
Cisplatino/toxicidade , Gentamicinas/toxicidade , Perda Auditiva Neurossensorial/induzido quimicamente , Animais , Limiar Auditivo/efeitos dos fármacos , Cisplatino/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Gentamicinas/farmacologia , Cobaias , Células Ciliadas Auditivas/efeitos dos fármacos , Perda Auditiva Neurossensorial/mortalidade , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Injeções Intraperitoneais , Modelos Lineares , Camundongos , Camundongos Endogâmicos C57BL , Probabilidade , Distribuição Aleatória , Valores de Referência , Medição de Risco , Especificidade da Espécie , Taxa de Sobrevida
5.
J Otolaryngol ; 31(3): 173-6, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12121023

RESUMO

Teratocarcinosarcoma, although a rare neoplastic entity, should be considered as a differential diagnosis in any middle-aged adult presenting with a history of intermittent unilateral epistaxis and nasal obstruction. Tissue biopsy may fail to reveal a full spectrum of histologic heterogeneity in these tumours, and definitive diagnosis is usually made with tumour resection. Aggressive treatment including surgery followed by adjuvant radiation therapy is advocated and confers a better rate of survival than radiotherapy alone. Our current report is unique in two respects. First, disease recurrence is usually manifested very early on, leading some authors to conclude that a neoplastic-free interval of 3 years or longer probably indicates a good chance of being cured. Our patient, in contrast, experienced a disease-free interval of 4 years before evidence of recurrence emerged. Second, intracranial extension with brain parenchymal involvement has not been previously reported despite the tumour's proximity to the anterior cranial fossa and its locally aggressive behaviour with frequent bony invasion. Despite intracranial invasion, our patient experienced a long disease-free interval. As such, even advanced disease should be treated aggressively.


Assuntos
Neoplasias Encefálicas/diagnóstico , Carcinossarcoma/diagnóstico , Neoplasias dos Seios Paranasais/diagnóstico , Teratoma/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/cirurgia , Teratoma/patologia , Teratoma/cirurgia
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