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1.
Surg Endosc ; 37(3): 2239-2246, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35902405

RESUMEN

BACKGROUND: Controversy exists over the use of mesh, its type and configuration in repair of hiatal hernia. We have used biological mesh for large or recurrent hiatal hernias. We have developed a mesh configuration to better enhance the tensile strength of the hiatus by folding the mesh over the edge of the hiatus-entitled the "starburst" configuration. We report our experience with the starburst configuration, comparing it to our results with the keyhole configuration. METHODS: Medical records of all patients undergoing either the keyhole or starburst mesh configuration hiatal hernia repair were reviewed between 2017 and 2021. Data gathered included age, sex, type of hernia (sliding, paraesophageal, or recurrent), fundoplication type (none, Nissen, Toupet, Dor, Collis-Nissen, Collis-Toupet, or magnetic sphincter augmentation [MSA]), 30-day complications, and long-term outcomes (hiatal hernia recurrence, reflux-symptom recurrence, dysphagia, dilations, reoperations). RESULTS: From 7/2017 to 8/2019, 51 cases using the keyhole mesh were completed. Sliding hiatal hernia comprised 4%, paraesophageal hernia (PEH) 64% and recurrent hiatal hernia (RHH) 34% of cases. Distribution of fundoplication type: 2% none, 41% Nissen, 41% Toupet, 8% Dor, 2% Collis-Nissen, and 6% Collis-Toupet. 30-day complication rate 31%. Long-term outcomes: recurrent hiatal hernia 16%, dysphagia 12%, dysphagia requiring dilation(s) 10%, recurrent GERD symptoms 4%, and reoperation 14%. From 10/2020 to 8/2021, 58 cases using the starburst configuration were completed. PEH comprised 60% and RHH 40%. Distribution of fundoplication type: 10% none, 40% Nissen, 43% Toupet, 5% MSA, 2% Collis-Toupet. 30-day complication rate 16%. Long-term outcomes: recurrent hiatal hernia 19%, dysphagia 14%, dilations 5%, recurrent GERD symptoms 9%, and reoperations 3%. CONCLUSION: The starburst mesh configuration compares favorably with the keyhole configuration with respect to postoperative dysphagia, need for esophageal dilation, and GERD symptom recurrence, with similar recurrence rates. We are continuing to further refine this technique and study the long-term outcomes.


Asunto(s)
Trastornos de Deglución , Reflujo Gastroesofágico , Hernia Hiatal , Laparoscopía , Humanos , Hernia Hiatal/cirugía , Hernia Hiatal/complicaciones , Resultado del Tratamiento , Trastornos de Deglución/cirugía , Herniorrafia/métodos , Mallas Quirúrgicas/efectos adversos , Laparoscopía/métodos , Reflujo Gastroesofágico/cirugía , Reflujo Gastroesofágico/complicaciones , Fundoplicación/métodos , Estudios Retrospectivos , Recurrencia
2.
Surg Endosc ; 35(10): 5613-5619, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33048228

RESUMEN

BACKGROUND: Myotomy length for per-oral endoscopic myotomy (POEM) is standardized for type I and II achalasia. However, for type III achalasia, jackhammer esophagus, diffuse esophageal spasms and esophagogastric junction outflow obstruction, there is no standard. Determining myotomy length based on the high-pressure zone found during high-resolution manometry (HRM) and spastic length found during esophagography may be used to determine adequate myotomy length without excess muscle destruction. METHODS: The records of patients who have undergone POEM procedures at our institution had the following data gleaned: age, sex, esophageal spastic diagnosis, length of high-pressure zone and lower esophageal sphincter (LES) position by HRM, length of spastic esophagus by esophagography, position of the z-line by esophagoscopy and length of myotomy performed. Outcomes were assessed based on patient symptomatic improvement and need for re-intervention. RESULTS: 71 patients were evaluated for POEM, with 67 completing POEM. There was an average difference in LES position by HRM and z-line position by esophagoscopy of 3.9 ± 3.0 cm. There was an average difference in high-pressure zone by HRM and spastic length by esophagography of 4.9 ± 3.2 cm. Overall, with a median of 20 months follow-up, 74% achieved long-term symptomatic improvement, with 17 patients requiring re-intervention. CONCLUSIONS: Discordance among HRM, esophagography and esophagoscopy can be significant. Caution should be employed with using these methods to determine myotomy length in POEM.


Asunto(s)
Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Acalasia del Esófago/diagnóstico por imagen , Acalasia del Esófago/cirugía , Esfínter Esofágico Inferior/diagnóstico por imagen , Esfínter Esofágico Inferior/cirugía , Esofagoscopía , Humanos , Manometría , Espasticidad Muscular , Resultado del Tratamiento
3.
Curr Opin Gastroenterol ; 35(4): 371-378, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31033771

RESUMEN

PURPOSE OF REVIEW: To examine current trends and research in nonmedical approaches to the treatment of gastroesophageal reflux disease (GERD). RECENT FINDINGS: Long-term studies of GERD patients treated with transoral incisionless fundoplication (TIF) have found that a large portion of patients resume proton pump inhibitor therapy. In patients with uncomplicated GERD, magnetic sphincter augmentation (MSA) shows excellent short-term results in both patient satisfaction and physiologic measures of GERD, with fewer postoperative side-effects than fundoplication, although dysphagia can be problematic. SUMMARY: Fundoplication remains the standard of care for patients with GERD complicated by hiatal hernias more than 2 cm, Barrett's esophagus and/or grade C and D erosive esophagitis. For the patient with uncomplicated GERD, MSA appears to be a viable alternative that has greater technical standardization and fewer postoperative side-effects than fundoplication. TIF remains an option for patients with refractory GERD who refuse surgical intervention.


Asunto(s)
Reflujo Gastroesofágico , Laparoscopía , Fundoplicación , Reflujo Gastroesofágico/cirugía , Humanos , Fenómenos Magnéticos , Satisfacción del Paciente , Resultado del Tratamiento
4.
J Am Coll Surg ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38497555

RESUMEN

BACKGROUND: Laparoscopic surgery remains the mainstay of treating foregut pathologies. Several studies have shown improved outcomes with the robotic approach. A systematic review and meta-analysis comparing outcomes of robotic and laparoscopic hiatal hernia repairs (HHR) and Heller myotomy (HM) repairs is needed. STUDY DESIGN: PubMed, Embase and Scopus databases were searched for studies published between January 2010 and November 2022. The risk of bias was assessed using the Cochrane ROBINS-I tool. Assessed outcomes included intra- and post-operative outcomes. We pooled the dichotomous data using the Mantel-Haenszel random effects model to report odds ratio (OR) and 95% confidence intervals (95% CIs) and continuous data to report mean difference (MD) and 95% CIs. RESULTS: Twenty-two comparative studies enrolling 196,339 patients were included. Thirteen (13,426 robotic, 168,335 laparoscopic patients) studies assessed HHR outcomes, while nine (2,384 robotic, 12,225 laparoscopic patients) assessed HM outcomes. Robotic HHR had a non-significantly shorter length of hospital stay (LOS) [MD -0.41 (95% CI -0.87, -0.05)], fewer conversions to open [OR 0.22 (95% CI 0.03, 1.49)], and lower morbidity rates [OR 0.76 (95% CI 0.47, 1.23)]. Robotic HM led to significantly fewer esophageal perforations [OR 0.36 (95% CI 0.15, 0.83)], reinterventions [OR 0.18 (95% CI 0.07, 0.47)] a non-significantly shorter LOS [MD -0.31 (95% CI -0.62, 0.00)]. Both robotic HM and HHR had significantly longer operative times. CONCLUSIONS: Laparoscopic and robotic HHR and HM repairs have similar safety profiles and perioperative outcomes. Randomized controlled trials are warranted to compare the two methods, given the low to moderate quality of included studies.

5.
J Robot Surg ; 18(1): 82, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38367193

RESUMEN

Robotic surgery may decrease surgeon stress compared to laparoscopic. To evaluate intraoperative surgeon stress, we measured salivary alpha-amylase and cortisol. We hypothesized robotic elicited lower increases in surgeon salivary amylase and cortisol than laparoscopic. Surgical faculty (n = 7) performing laparoscopic and robotic operations participated. Demographics: age, years in practice, time using laparoscopic vs robotic, comfort level and enthusiasm for each. Operative data included operative time, WRVU (surgical "effort"), resident year. Saliva was collected using passive drool collection system at beginning, middle and end of each case; amylase and cortisol measured using ELISA. Standard values were created using 7-minute exercise (HIIT), collecting saliva pre- and post-workout. Linear regression and Student's t test used for statistical analysis; p values < 0.05 were significant. Ninety-four cases (56 robotic, 38 laparoscopic) were collected (April-October 2022). Standardized change in amylase was 8.4 ± 4.5 (p < 0.001). Among operations, raw maximum amylase change in laparoscopic and robotic was 23.4 ± 11.5 and 22.2 ± 13.4; raw maximum cortisol change was 44.21 ± 46.57 and 53.21 ± 50.36, respectively. Values normalized to individual surgeon HIIT response, WRVU, and operative time, showing 40% decrease in amylase in robotic: 0.095 ± 0.12, vs laparoscopic: 0.164 ± 0.16 (p < 0.02). Normalized change in cortisol was: laparoscopic 0.30 ± 0.44, robotic 0.22 ± 0.4 (p = NS). On linear regression (p < 0.001), surgeons comfortable with complex laparoscopic cases had lower change in normalized amylase (p < 0.01); comfort with complex robotic was not significant. Robotic may be less physiologically stressful, eliciting less increase in salivary amylase than laparoscopic. Comfort with complex laparoscopic decreased stress in robotic, suggesting laparoscopic experience is valuable prior to robotic.


Asunto(s)
Laparoscopía , Procedimientos Quirúrgicos Robotizados , Cirujanos , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Hidrocortisona/análisis , Amilasas
6.
J Gastrointest Surg ; 27(12): 2718-2723, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37932593

RESUMEN

BACKGROUND: Spinal deformities such as kyphosis, lordosis, and scoliosis have demonstrated a possible association between these deformities. Our hypothesis is that the presence of spinal deformities will increase the risk of hiatal hernia recurrence after repair. METHODS: The following data was retrospectively gleaned for patients undergoing hiatal hernia repair (1997-2022): age, sex, date of hiatal hernia repair, presence and type of spinal deformity, Cobb angle, type of hiatal hernia and size, type of hiatal hernia repair, recurrence and size, time to recurrence, reoperation, type of reoperation, and time to reoperation. RESULTS: Spinal deformities were present in 15.8% of 546 patients undergoing hiatal hernia repair, with a distribution of 21.8% kyphosis, 2.3% lordosis, 58.6% scoliosis, and 17.2% multiple. There was no difference in sex or age between groups. Spinal deformity patients were more likely to have types III and IV hiatal hernias (52.3% vs. 38.9%, p = 0.02) and larger hernias (median 5 [3-8] vs. 4 [2-6], p = 0.01). There was no difference in access, fundoplication use, or mesh use between groups. However, these patients had a higher recurrence rate (47.7% vs 30.0%, p = 0.001) and a shorter time to recurrence (months) (10.3 [5.6-25.1] vs 19.2 [9.8-51.0], p = 0.02). Cobb angle did not affect recurrence. CONCLUSIONS: Spinal deformity patients were more likely to have more complex and larger hiatal hernias. They were at higher risk of hiatal hernia recurrence after repair with shorter times to recurrence. This is a group that requires special attention with additional preoperative counseling and possibly use of surgical adjuncts in repair.


Asunto(s)
Hernia Hiatal , Cifosis , Laparoscopía , Lordosis , Escoliosis , Humanos , Hernia Hiatal/complicaciones , Hernia Hiatal/cirugía , Estudios Retrospectivos , Lordosis/etiología , Lordosis/cirugía , Escoliosis/etiología , Escoliosis/cirugía , Herniorrafia , Fundoplicación/efectos adversos , Recurrencia , Mallas Quirúrgicas , Cifosis/etiología , Cifosis/cirugía , Resultado del Tratamiento
7.
J Am Coll Surg ; 230(6): 999-1007, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32217191

RESUMEN

BACKGROUND: Recurrence after hiatal hernia repair is common. The causes are uncertain. Our observation is the site of recurrence is primarily the nonsutured or nonreinforced anterior-left lateral portion of the hiatus. Our aim was to assess the distribution of hiatal hernia recurrence location as a basis for developing a theory of recurrence. METHODS: Consecutive patients who underwent repair of recurrent hiatal hernias from March 2012 to December 2019 were reviewed. Data collected included age, sex, date of operation, location of hiatal hernia recurrence, operative approach, method of hiatal hernia repair, fundoplication performed, need for gastrectomy, and additional procedures. RESULTS: One hundred and eight consecutive patients were studied. The distribution of recurrence locations was as follows: anterior 67%, posterior 12%, and circumferential 21%. Foreshortened esophagus was a contributing factor in 12%. Median time from the original repair to recurrence was 1.5 years (interquartile range 0.9 to 3.75 years) for posterior recurrences, 2.75 years (interquartile range 1.15 to 8.5 years) for circumferential recurrences, and 3.25 years (interquartile range 1.38 to 10 years) for anterior recurrences. Recurrences were repaired in a variety of techniques, depending on the clinical circumstances. CONCLUSIONS: Hiatal hernia recurrences due to failure of the crural closure were less common, but early, recurrences. The majority of recurrences were due to stretching of the hiatus anterior and to the left of the esophagus. We theorize that the pathophysiology of late hiatal hernia recurrence is widening of the anterior and left lateral portion of the hiatus secondary to repeated stress from differential pressures that eventually overcomes the tensile strength of the hiatus.


Asunto(s)
Hernia Hiatal/etiología , Hernia Hiatal/patología , Herniorrafia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Hernia Hiatal/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Insuficiencia del Tratamiento , Adulto Joven
8.
Surg Laparosc Endosc Percutan Tech ; 30(4): 339-344, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32287112

RESUMEN

BACKGROUND: Paraesophageal hernia (PEH) and recurrent hiatal hernia (RHH) are prone to recurrences. One adjunct used to reduce recurrences is mesh reinforcement. The optimal configuration is yet to be determined. We present our evolution from the U-shaped to the keyhole pattern. METHODS: All patients undergoing PEH/RHH repair with mesh between 2013 and 2019 were reviewed for demographic information, perioperative/intraoperative details, postoperative complications, and recurrences. RESULTS: Of patients undergoing PEH/RHH repair between 2013 and 2019, 138 were repaired using mesh. Of these, 88 were repaired using the U-shaped configuration and 50 using the keyhole configuration. The U-shaped configuration was used for PEH in 72% and RHH in 28%, while the keyhole configuration was used for PEH in 66% and RHH in 34%. Thirty patients suffered postoperative complications, although there was no difference between the groups. Overall, 28 patients in the U-shaped configuration group (31.8%) had a recurrence of their hiatal hernia identified, compared with 7 patients (14.6%) in the keyhole group (P=0.039). The median time to last follow-up was 21 months (range: 1 to 85) in the U-shaped group and 8 months (range: 1 to 23) in the keyhole group. There was no difference in median time to recurrence, postoperative dysphagia, dilations, or strictures. CONCLUSIONS: The keyhole pattern mesh was not associated with a higher complication rate compared with the U-shape pattern. Although this study was not a direct comparison between the configurations, it does suggest that the keyhole pattern may lead to fewer recurrences.


Asunto(s)
Hernia Hiatal/epidemiología , Hernia Hiatal/cirugía , Herniorrafia/instrumentación , Complicaciones Posoperatorias/epidemiología , Mallas Quirúrgicas , Anciano , Femenino , Hernia Hiatal/diagnóstico , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
9.
J Laparoendosc Adv Surg Tech A ; 30(2): 110-116, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31237487

RESUMEN

Background: Achalasia and other esophageal motility disorders are incurable diseases for which palliation and symptom relief are the goals. One of the many ways these diseases are treated is with either a Heller myotomy or, now more commonly, per-oral endoscopic myotomy (POEM). Unfortunately, symptoms persistence or recurrence is common. This review presents our current approach to these complex patients. Methods: Review of the literature pertaining to approaches to recurrent or persistent symptoms after myotomy for esophageal motility disorders and elucidation of our multidisciplinary approach to this patient group. Results: There are a myriad of causes of recurrent or persistent symptoms. These include incomplete myotomy, periesophageal scarring, reflux-induced stricture, obstructing fundoplication, functional dysphagia, and end-stage achalasia. Therapeutic options include redo myotomy (either Heller or POEM), botulinum toxin injection, pneumatic, balloon or Savary dilation, adhesiolysis, and fundoplication reversal or esophagectomy. Choice of approach is best done through multidisciplinary consensus. Conclusions: A multidisciplinary approach to patients with persistent and recurrent symptoms after myotomy can best tailor the therapeutic approach based on symptom causation.


Asunto(s)
Dilatación/métodos , Acalasia del Esófago/cirugía , Fundoplicación/métodos , Miotomía de Heller/métodos , Miotomía/métodos , Reoperación/métodos , Bario , Diagnóstico por Imagen , Esofagectomía , Reflujo Gastroesofágico/cirugía , Humanos , Laparoscopía/métodos , Recurrencia , Resultado del Tratamiento
10.
J Gastrointest Surg ; 24(5): 991-999, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31147973

RESUMEN

BACKGROUND: Recurrent/persistent symptoms of achalasia occur in 10-20% of individuals after Heller myotomy. The causes and treatment outcomes are ambiguous. Our aim is to assess the causes and outcomes of a multidisciplinary approach to this patient population. METHODS: All patients undergoing revisional operations after a Heller myotomy were reviewed retrospectively. DATA COLLECTED: demographics, date of initial Heller myotomy, preoperative evaluation, etiology of recurrent symptoms, date of revisional operation, and surgical outcomes. RESULTS: A total of 34 patients underwent 37 revisional operations. Operations were tailored based on preoperative multidisciplinary evaluation. Causes of symptoms: periesophageal/perihiatal fibrosis 11 (27%), obstructing fundoplication 11 (27%), incomplete myotomy 8 (20%), progression of disease 9 (22%), and epiphrenic diverticulum 1 (2%). Operations performed: reversal/no creation of fundoplication with or without re-do myotomy 22 (59%), revision/creation of fundoplication with or without myotomy 6 (16%), and esophagectomy 9 (24%). Ten patients in the 37 operations (27%) developed postoperative complications. Of 33 patients for 36 operations with follow-up, 25 patient-operations (69%) resulted in resolution or improved dysphagia. Although there was variation in symptomatic improvement by cause and operation type, none reached statistical significance. CONCLUSION: There are several causes of dysphagia after Heller myotomy and a thoughtful evaluation is required. Complication rates are higher than first-time operations. Symptomatic improvement occurs in the majority of cases, but a significant minority will have persistent dysphagia. Although an individualized approach to dysphagia after Heller myotomy may improve symptoms and passage of food, the perception of dysphagia may persist in patients.


Asunto(s)
Trastornos de Deglución , Acalasia del Esófago , Miotomía de Heller , Laparoscopía , Trastornos de Deglución/etiología , Trastornos de Deglución/cirugía , Acalasia del Esófago/cirugía , Fundoplicación , Miotomía de Heller/efectos adversos , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
12.
Cureus ; 10(11): e3559, 2018 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-30648091

RESUMEN

Background General surgery chief residents are typically well equipped for board examinations but poorly trained to deal with the business challenges of surgical practice. We began a business leadership course to better prepare them for their careers. Methods Chief residents were given one-hour lectures with topics that included: Differences between private/academic practice, personal finances, contracts, practice management, legal issues and health law, and time management. Results Initial evaluations revealed that the topics covered and the presentations were well received. Subsequently, the course was moved to earlier in the academic year to prepare them for contract negotiations and then to Sunday nights to decrease interruptions and allow spouse participation. Conclusions The course evolved into a program that the chief residents feel is an important addition to their education. Moving the meetings to a weekend evening improved attendance, decreased interruptions, and allowed participation by spouses and significant others.

13.
16.
J Appl Physiol (1985) ; 94(3): 930-4, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12571128

RESUMEN

To test for a diurnal difference in the vasoconstrictor control of the cutaneous circulation, we performed whole body skin cooling (water-perfused suits) at 0600 (AM) and 1600 (PM). After whole body skin temperature (T(sk)) was controlled at 35 degrees C for 10 min, it was progressively lowered to 32 degrees C over 18-20 min. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry at three control sites and at a site that had been pretreated with bretylium by iontophoresis to block noradrenergic vasoconstriction. After whole body skin cooling, maximal cutaneous vascular conductance (CVC) was measured by locally warming the sites of SkBF measurement to 42 degrees C for 30 min. Before whole body skin cooling, sublingual temperature (T(or)) in the PM was significantly higher than that in the AM (P < 0.05), but CVC, expressed as a percentage of maximal CVC (%CVC(max)), was not statistically different between AM and PM. During whole body skin cooling, %CVC(max) levels at bretylium-treated sites in AM or PM were not significantly reduced from baseline. In the PM, %CVC(max) at control sites fell significantly at T(sk) of 34.3 +/- 0.01 degrees C and lower (P < 0.05). In contrast, in the AM %CVC(max) at control sites was not significantly reduced from baseline until T(sk) reached 32.3 +/- 0.01 degrees C and lower (P < 0.05). Furthermore, the decrease in %CVC(max) in the PM was significantly greater than that in AM at T(sk) of 33.3 +/- 0.01 degrees C and lower (P < 0.05). Integrative analysis of the CVC response with respect to both T(or) and T(sk) showed that the cutaneous vasoconstrictor response was shifted to higher internal temperatures in the PM. These findings suggest that during whole body skin cooling the reflex control of the cutaneous vasoconstrictor system is shifted to a higher internal temperature in the PM. Furthermore, the slope of the relationship between CVC and T(sk) is steeper in the PM compared with that in the AM.


Asunto(s)
Ritmo Circadiano/fisiología , Fenómenos Fisiológicos de la Piel , Temperatura Cutánea/fisiología , Vasoconstricción/fisiología , Adolescente , Adulto , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Compuestos de Bretilio/administración & dosificación , Compuestos de Bretilio/farmacología , Frío , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Iontoforesis , Masculino , Reflejo/fisiología , Estrés Fisiológico/fisiopatología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología
17.
Int J Pharm ; 384(1-2): 46-52, 2010 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-19782740

RESUMEN

Lung transplantation animal models have been well established and enabled the investigation of a variety of new pharmacotherapeutic strategies for prevention of lung allograft rejection. Direct administration of immunosuppressive agents to the lung is a commonly investigated approach; however, can prove challenging due to the poor solubility of the drug molecule, the tortuous pathways of the lung periphery, and the limited number of excipients approved for inhalation. In this study, we aimed to evaluate a solubility enhancing formulation of tacrolimus for localized therapy in a lung transplanted rat model and determine the extent of drug absorption into systemic circulation. Characterization of the nebulized tacrolimus dispersion for nebulization showed a fine particle fraction (FPF) of 46.1% and a mass median aerodynamic diameter (MMAD) of 4.06 microm. After single dose administration to transplanted and non-transplanted rats, a mean peak transplanted lung concentration of 399.8+/-29.2 ng/g and mean peak blood concentration of 4.88+/-1.6 ng/mL were achieved. It is theorized that enhanced lung retention of tacrolimus is due to lipophilic associations with bronchial tissue and phospholipid surfactants in lung fluid. These findings indicate that tacrolimus dispersion for nebulization can achieve highly localized therapy for lung transplant recipients.


Asunto(s)
Trasplante de Pulmón , Pulmón/metabolismo , Modelos Animales , Nebulizadores y Vaporizadores , Tacrolimus/farmacocinética , Animales , Rechazo de Injerto/metabolismo , Rechazo de Injerto/prevención & control , Pulmón/efectos de los fármacos , Trasplante de Pulmón/métodos , Masculino , Tamaño de la Partícula , Ratas , Ratas Endogámicas Lew , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Distribución Tisular/efectos de los fármacos , Distribución Tisular/fisiología
18.
Am J Physiol Heart Circ Physiol ; 287(3): H1404-9, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15165988

RESUMEN

Previous studies have provided evidence of a non-noradrenergic contributor to reflex cutaneous vasoconstriction in humans but did not identify the transmitter responsible. To test whether neuropeptide Y (NPY) has a role, in two series of experiments we slowly reduced whole body skin temperature (TSK) from 34.5 to 31.7 degrees C. In protocol 1, Ringer solution and the NPY receptor antagonist BIBP-3226 alone were delivered intradermally via microdialysis. In protocol 2, yohimbine plus propranolol (Yoh + Pro), Yoh + Pro in combination with BIBP-3226, and Ringer solution were delivered to antagonize locally the vasomotor effects of NPY and norepinephrine. Blood flow was measured by laser Doppler flowmetry (LDF). Mean arterial blood pressure (MAP) was monitored at the finger (Finapres). In protocol 1, cutaneous vascular conductance (CVC) fell by 45%, to 55.1 +/- 5.6% of baseline at control sites (P < 0.05). At BIBP-3226-treated sites, CVC fell by 34.1% to 65.9 +/- 5.0% (P < 0.05; P < 0.05 between sites). In protocol 2, during body cooling, CVC at control sites fell by 32.6%, to 67.4 +/- 4.3% of baseline; at sites treated with Yoh + Pro, CVC fell by 18.7%, to 81.3 +/- 4.4% of baseline (P < 0.05 vs. baseline; P < 0.05 vs. control) and did not fall significantly at sites treated with BIBP-3226 + Yoh + Pro (P > 0.05; P < 0.05 vs. other sites). After cooling, exogenous norepinephrine induced vasoconstriction at control sites (P < 0.05) but not at sites treated with Yoh + Pro + BIBP-3226 (P > 0.05). These results indicate that NPY participates in sympathetically mediated cutaneous vasoconstriction in humans during whole body cooling.


Asunto(s)
Arginina/análogos & derivados , Neuropéptido Y/fisiología , Reflejo/fisiología , Fenómenos Fisiológicos de la Piel , Piel/irrigación sanguínea , Vasoconstricción/fisiología , Adulto , Arginina/farmacología , Vasos Sanguíneos/efectos de los fármacos , Frío , Combinación de Medicamentos , Dedos , Humanos , Soluciones Isotónicas , Masculino , Neuropéptido Y/antagonistas & inhibidores , Norepinefrina/antagonistas & inhibidores , Norepinefrina/farmacología , Norepinefrina/fisiología , Propranolol/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Solución de Ringer , Piel/inervación , Temperatura Cutánea , Sistema Nervioso Simpático/fisiología , Vasoconstrictores/antagonistas & inhibidores , Vasoconstrictores/metabolismo , Vasoconstrictores/farmacología , Vasodilatadores/farmacología , Sistema Vasomotor/efectos de los fármacos , Sistema Vasomotor/fisiología , Yohimbina/farmacología
19.
J Physiol ; 552(Pt 1): 223-32, 2003 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-12847205

RESUMEN

Active vasodilatation (AVD) in human, non-glabrous skin depends on functional cholinergic fibres but not on acetylcholine (ACh). We tested whether AVD is a redundant system in which ACh and vasoactive intestinal polypeptide (VIP) are co-released from cholinergic nerves. (1) We administered VIP by intradermal microdialysis to four discrete areas of skin in the presence of different levels of the VIP receptor antagonist, VIP(10-28), also delivered by microdialysis. Skin blood flow (SkBF) was continuously monitored by laser Doppler flowmetry (LDF). Mean arterial pressure (MAP) was measured non-invasively and cutaneous vascular conductance (CVC) calculated as LDF/MAP. Subjects were supine and wore water-perfused suits to control whole-body skin temperature (Tsk) at 34 degrees C. Concentrations of 54 microM, 107 microM, or 214 microM VIP(10-28) were perfused via intradermal microdialysis at 2 microl min-1 for approximately 1 h. Then 7.5 microM VIP was added to the perfusate containing VIP(10-28) at the three concentrations or Ringer solution and perfusion was continued for 45-60 min. At the control site, this level of VIP caused approximately the vasodilatation typical of heat stress. All VIP(10-28)-treated sites displayed an attenuated dilatation in response to the VIP. The greatest attenuation was observed at the site that received 214 microM VIP(10-28) (P < 0.01). (2) We used 214 microM VIP(10-28) alone and with the iontophoretically administered muscarinic receptor antagonist atropine (400 microA cm-2, 45 s, 10 mM) in heated subjects to test the roles of VIP and ACh in AVD. Ringer solution and 214 microM VIP(10-28) were each perfused at two sites, one of which in each case was pretreated with atropine. After 1 h of VIP(10-28) treatment, individuals underwent 45-60 min of whole-body heating (Tsk to 38.5 degrees C). VIP(10-28), alone or in combination with atropine, attenuated the increase in CVC during heat stress, suggesting an important role for VIP in AVD.


Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Trastornos de Estrés por Calor/fisiopatología , Fragmentos de Péptidos/administración & dosificación , Piel/irrigación sanguínea , Péptido Intestinal Vasoactivo/administración & dosificación , Vasodilatación/efectos de los fármacos , Adulto , Atropina/farmacología , Fibras Colinérgicas/efectos de los fármacos , Fibras Colinérgicas/fisiología , Femenino , Humanos , Flujometría por Láser-Doppler , Masculino , Microdiálisis , Parasimpatolíticos/farmacología , Fragmentos de Péptidos/fisiología , Piel/inervación , Temperatura Cutánea/efectos de los fármacos , Temperatura Cutánea/fisiología
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