Intra-arterial Infusion (intra-arterial + infusion)

Distribution by Scientific Domains

Selected Abstracts

Dual modulation of urinary bladder activity and urine flow by prostanoid EP3 receptors in the conscious rat

MJ Jugus
Background and purpose:, Cyclooxygenase inhibitors function to reduce levels of prostaglandin E2 (PGE2) and are broadly efficacious in models of bladder overactivity. We therefore investigated a regulation of urinary bladder function in conscious rats by modulation of the EP3 receptor for PGE2. Experimental approach:, The activity of the EP3 receptor agonist GR63799X, and EP3 receptor antagonists, CM9 and DG041, at recombinant EP3 receptors was evaluated in vitro. In vivo, intraduodenal dosing during conscious, continuous-filling cystometry of spontaneously hypertensive rats was utilized to determine the urodynamic effect of EP3 receptor modulation. Key results:, GR63799X dose-dependently (0.001,1 mg·kg,1) reduced bladder capacity, as indicated by a reduction in both the micturition interval and volume of urine per void. In contrast, CM9 (10 and 30 mg·kg,1) and DG041 (30 mg·kg,1) enhanced bladder capacity, as indicated by significantly longer micturition intervals and larger void volumes. CM9 and DG041 inhibited the responses to GR63799X supporting the in vivo activity of these pharmacological agents at the EP3 receptor. In addition to its effect on bladder capacity, GR63799X increased endogenous urine production. Intra-arterial infusion of saline mimicked the enhancement of urine flow observed with GR63799X, and the response was inhibited by CM9. Conclusions and implications:, These data support the EP3 receptor as a modulator of urinary bladder activity in the conscious rat, and in addition, indicate a role for EP3 receptor activity in regulating urine flow. [source]

Effects of short-term food deprivation on orexin-A-induced intestinal bicarbonate secretion in comparison with related secretagogues

G. Flemström
Abstract Studies of gastrointestinal physiology in humans and intact animals are usually conducted after overnight fast. We compared the effects of orexin-A, vasoactive intestinal polypeptide (VIP), melatonin, serotonin, uroguanylin, ghrelin and prostaglandin E2 (PGE2) on duodenal bicarbonate secretion in fed and overnight fasted animals. This review is a summary of our findings. Secretagogues were administered by intra-arterial infusion or luminally (PGE2). Enterocyte intracellular calcium ([Ca2+]i) signalling was studied by fluorescence imaging. Total RNA was extracted, reverse transcripted to cDNA and expression of orexin receptors measured by quantitative real-time PCR. Orexin-A stimulates the duodenal secretion in continuously fed animals but not in food-deprived animals. Similarly, short-term fasting causes a 100-fold decrease in the amount of the muscarinic agonist bethanechol required for stimulation of secretion. In contrast, fasting does not affect secretory responses to intra-arterial VIP, melatonin, serotonin, uroguanylin and ghrelin, or that to luminal PGE2. Orexin-A induces [Ca2+]i signalling in enterocytes from fed rats but no significant [Ca2+]i responses occur in enterocytes from fasted animals. In addition, overnight fasting decreases the expression of mucosal orexin receptors. Short-term food deprivation thus decreases duodenal expression of orexin receptors and abolishes the secretory response to orexin-A as well as orexin-A-induced [Ca2+]i signalling. Fasting, furthermore, decreases mucosal sensitivity to bethanechol. The absence of declines in secretory responses to other secretagogues tested strongly suggests that short-term fasting does not affect the secretory capacity of the duodenal mucosa in general. Studies of intestinal secretion require particular evaluation with respect to feeding status. [source]

The role of the ,-adrenergic receptor in the leg vasoconstrictor response to orthostatic stress

M. Kooijman
Abstract Aim:, The prompt increase in peripheral vascular resistance, mediated by sympathetic ,-adrenergic stimulation, is believed to be the key event in blood pressure control during postural stress. However, despite the absence of central sympathetic control of the leg vasculature, postural leg vasoconstriction is preserved in spinal cord-injured individuals (SCI). This study aimed at assessing the contribution of both central and local sympathetically induced ,-adrenergic leg vasoconstriction to head-up tilt (HUT) by including healthy individuals and SCI, who lack central sympathetic baroreflex control over the leg vascular bed. Methods:, In 10 controls and nine SCI the femoral artery was cannulated for drug infusion. Upper leg blood flow (LBF) was measured bilaterally using venous occlusion strain gauge plethysmography before and during 30° HUT throughout intra-arterial infusion of saline or the non-selective ,-adrenergic receptor antagonist phentolamine respectively. Additionally, in six controls the leg vascular response to the cold pressor test was assessed during continued infusion of phentolamine, in order to confirm complete ,-adrenergic blockade by phentolamine. Results:, During infusion of phentolamine HUT still caused vasoconstriction in both groups: leg vascular resistance (mean arterial pressure/LBF) increased by 10 ± 2 AU (compared with 12 ± 2 AU during saline infusion), and 13 ± 3 AU (compared with 7 ± 3 AU during saline infusion) in controls and SCI respectively. Conclusion:, Effective ,-adrenergic blockade did not reduce HUT-induced vasoconstriction, regardless of intact baroreflex control of the leg vasculature. Apparently, redundant mechanisms compensate for the absence of sympathetic ,-adrenoceptor leg vasoconstriction in response to postural stress. [source]

High-dose superselective intra-arterial cisplatin and concomitant radiation (radplat) for advanced head and neck cancer,

Alfons J. M. Balm MD
Abstract Background. The purpose of this study was to study the effect of intensive targeted chemoradiation in a group of patients with head and neck cancer with stage IV inoperable disease. Methods. We examined 79 patients with inoperable stage IV head and neck cancer receiving intra-arterial infusion of high-dose cisplatin (150 mg/m2) on days 2, 9, 16, and 23 concomitant with delivery of external beam radiotherapy (total dose, 70 Gy; 2 Gy, 35 fractions; 1 fraction/day for 7 weeks). Sodium thiosulfate was administered intravenously to provide effective cisplatin neutralization. Results. Four patients were not assessable. Complete local tumor response was achieved in 72 patients (91%) and a partial response in three patients. The complete response rate of neck node metastases was 90%. The 1- and 2-year locoregional control rates were 82% and 69%, respectively. The median overall survival time was 2.2 years, with a 3-year overall survival probability of 43%. Acute toxicities were as follows: grade III/IV hematologic toxicity (22%/16%), grade III/IV nephrotoxicity (0%), grade III mucositis (43%), grade III skin reactions (24%), grade III toxicity of the upper gastrointestinal tract (57%), grade III nausea (20%), and grade III subjective hearing loss (10%). Grade V toxicity (treatment-related deaths) was 3.8%. Six (18%) of 33 patients with complete remission needed tube feeding 2 years after treatment without intercurrent salvage surgery. Conclusions. Supradose superselective intra-arterial cisplatin and concomitant radiation is an effective organ-preserving therapy in an unfavorable group of patients. Our series confirms encouraging results reported previously. This regimen is justified in unresectable patients despite the substantial toxicity. © 2004 Wiley Periodicals, Inc. Head Neck26: 485,493, 2004 [source]

Evaluation of newly developed combination therapy of intra-arterial 5-fluorouracil and systemic pegylated interferon ,-2b for advanced hepatocellular carcinoma with portal venous invasion: preliminary results

Kazuhiro Kasai
Aim:, Prognosis is extremely poor for advanced hepatocellular carcinoma (HCC) in patients with portal invasion. The present study evaluated the efficacy of combined intra-arterial 5-fluorouracil (5-FU) and systemic pegylated interferon (PEG-IFN),-2b in patients with advanced HCC. Methods:, The subjects comprised nine HCC patients with portal vein thrombosis treated using subcutaneous administration of PEG-IFN,-2b (50,100 µg on day 1 of every week, for 4 weeks) and intra-arterial infusion of 5-FU (250 mg/day for 5 h on days 1,5 of every week, for 4 weeks). For four patients with hepatitis C virus (HCV) infection, oral administration of ribavirin (400,800 mg/day) was added. At the end of every cycle, response to therapy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Results:, Partial response (PR) was observed in seven of nine patients, with stable or progressive disease in the remaining two patients. Tumors were resectable in three patients displaying PR after treatment. Tumor markers decreased significantly after therapy. Serum HCV-RNA titers were markedly decreased and became undetectable in all patients with HCV infection. National Cancer Institute,Common Toxicity Criteria: version 3.0 (NCI-CTC) grade 3 thrombocytopenia was seen in one case at the end of treatment, but was resolved with cessation of treatment. Other adverse effects were manageable. Conclusion:, Combination therapy with intra-arterial 5-FU and systemic PEG-IFN,-2b may be useful as a palliative treatment for patients with advanced HCC. A prospective controlled trial using a larger population of patients with advanced HCC is needed to evaluate this new combination therapy. [source]

Ineffective Peripheral Tissue Perfusion: Clinical Validation in Patients With Hypertensive Cardiomiopathy

Rita de Cassia Gengo de Silva MS
PURPOSE.,To validate defining characteristics of ineffective peripheral tissue perfusion using vasomotor function assessment. METHODS.,Twenty-four patients with hypertensive cardiomiopathy were evaluated for 18 defining characteristics of ineffective peripheral tissue perfusion and underwent vasomotor function assessment with induction of reactive hyperemia, intra-arterial infusion of acetylcholine, and pulse wave velocity measurement. The Student's t test and Kruskall,Wallis test were used to assess the significance of relationships between defining characteristics and vasomotor function data. FINDINGS.,Diminished lower extremity pulses were associated with diminished forearm blood flow during acetylcholine infusion; left ventricular overload, intermittent claudication, and diminished skin moisture were associated with elevated pulse wave velocity values. CONCLUSION.,The defining characteristics of ineffective peripheral tissue perfusion were highly associated with vasomotor function data as "gold standards" for that diagnosis. PRACTICE IMPLICATIONS.,Nurses should be able to accurately assess diminished lower extremity pulses, intermittent claudication, and diminished skin moisture as relevant characteristics of ineffective peripheral tissue perfusion in patients with hypertensive cardiomiopathy. Irrigation Tissulaire Périphérique Inefficace: Validation Clinique Chez les Patients Atteints de Cardiomyopathie Hypertensive BUT.,Valider les caractéristiques de Irrigation tissulaire périphérique inefficace en utilisant l'évaluation de la fonction vasomotrice. MÉTHODES.,Vingt-quatre patients souffrant de cardiomyopathie hypertensive furent évalués au regard des 18 caractéristiques du diagnostic Irrigation vasculaire périphérique inefficace et de la fonction vasomotrice par induction d'une hyperémie réactionnelle, la perfusion intra-artérielle d'acétylcholine, et la mesure de la vélocité de l'onde du pouls. Les tests "Student t et Kruskall,Wallis" furent utilisés pour déterminer l'importance des liens entre les caractéristiques et les valeurs de la fonction vasomotrice. RÉSULTATS.,La diminution des pulsations périphériques des membres inférieurs fut associée à une diminution du flot sanguin pendant la perfusion d'acétylcholine; une surcharge ventriculaire gauche, de la claudication intermittente et une diminution de l'hydratation de la peau furent associées à des valeurs élevées de la vélocité de l'onde du pouls. CONCLUSION.,,Les caractéristiques de Irrigation tissulaire périphérique inefficace qui furent associées de manière significative à la fonction vasomotrice peuvent être considérées comme les "étalons or" de ce diagnostic. IMPLICATIONS POUR LA PRATIQUE.,Les infirmières devraient être capables d'évaluer correctement la diminution des pouls périphériques, la claudication intermittente, et la diminution de l'hydratation de la peau, car ce sont des caractéristiques pertinentes de l'irrigation tissulaire périphérique inefficace chez les patients atteints de cardiomyopathie hypertensive. Translation by Cécile Boisvert, MSN, RN Perfusão Tissular Periférica Ineficaz: Validação Clínica em Pacientes com Miocardiopatia Hipertensiva PROPÓSITO.,Validar as caraterísticas definidoras do diagnóstico de perfusão tissular periférica ineficaz usando a avaliação da função vasomotora. MÉTODO.,Vinte e quatro pacientes com miocardiopatia hipertensiva foram avaliados segundo 18 características definidoras de perfusão tissular periférica ineficaz e submetidos a avaliação da função vasomotora por indução de hiperemia reativa, infusão intra-arterial de acetilcolina e por mensuração da velocidade da onda de pulso. Testes T de Student e de Kruskall,Wallis foram aplicados para avaliar a significância das relações entre as características definidoras e os dados da função vasomotora. RESULTADOS.,Diminuição de pulso nas extremidades inferiores foi associada com o menor fluxo de sangue no antebraço durante a infusão de acetilcolina; sobrecarga ventricular esquerda, claudicação intermitente e diminuição da hidratação da pele foram associados com valores elevados de velocidade de onda de pulso. CONCLUSÃO.,Quatro características definidoras de perfusão tissular periférica ineficaz foram altamente associadas com função vasomotora alterada como "padrão ouro" para este diagnóstico. IMPLICAÇÕES PARA A PRÁTICA.,As enfermeiras devem ser capazes de avaliar com precisão a diminuição dos pulsos das extremidades inferiores, claudicação intermitente e diminuição na hidratação da pele como características definidoras relevantes da perfusão tissular periférica ineficaz em pacientes com miocardiopatia hipertensiva. Translation by Alba Leite de Barros, PhD, RN Perfusión Tisular Periférica Inefectiva: Validación Clínica en Pacientes que Presentan Miocardiopatía Hipertensiva PROPÓSITO.,Validar las características definitorias del diagnóstico Perfusión tisular periférica inefectiva utilizando una valoración de la función vasomotora. METODOLOGÍA.,Veinticuatro pacientes diagnosticados de Miocardiopatía Hipertensiva fueron evaluados con respecto a las 18 características definitorias del diagnóstico Perfusión tisular periférica inefectiva y sometidos a una valoración de la función vasomotora con inducción de Hiperemia reactiva, infusión intra-arterial de acetilcolina, y medida de la velocidad de la onda del pulso. Se utilizaron los análisis estadísticos de t-Student y Kruskall,Wallis para valorar el significado de las relaciones entre las características definitorias y los datos obtenidos de la valoración de la función vasomotora. HALLAZGOS.,Durante la infusión de acetilcolina se detectó disminución de los pulsos en la extremidad inferior relacionado con la disminución del volumen de sangre en el antebrazo; la sobrecarga ventricular izquierda, claudicación intermitente y disminución de la hidratación de la piel fueron asociadas con la elevación de los valores de la velocidad de la onda del pulso. CONCLUSIÓN.,Las características definitorias del diagnóstico Perfusión tisular periférica inefectiva estaban fuertemente asociadas a los datos procedentes de la valoración de la función vasomotora identificándose como "estándares fundamentales" para este diagnóstico. IMPLICACIONES PARA LA PRÁCTICA.,Las enfermeras deberían ser capaces de valorar cuidadosamente la presencia de pulsos disminuidos en las extremidades inferiores, y la disminución de la hidratación de la piel ya que son características relevantes del diagnóstico Perfusión tisular periférica inefectiva en pacientes que presentan Miocardiopatía Hipertensiva. Translation by Adolf Guirao, RN [source]

Intra-arterial therapy with cisplatin suspension in lipiodol and 5-fluorouracil for hepatocellular carcinoma with portal vein tumour thrombosis

H. Nagamatsu
Aliment Pharmacol Ther 2010; 32: 543,550 Summary Background, Portal vein tumour thrombosis is a negative prognostic factor for hepatocellular carcinoma (HCC). Aim, To assess the efficacy of cisplatin in lipiodol emulsion combined with 5-fluorouracil (5-FU) for patients with HCC and portal vein tumour thrombosis. Methods, The study subjects were 51 patients with the above-specified criteria who received injection of cisplatin suspension in lipiodol emulsion followed by intra-arterial infusion of 5-FU. The primary objective was to determine tumour response to the treatment, while the secondary objectives were safety and tolerability. Independent factors for survival were also assessed. Results, Ten patients had complete response and 34 patients had partial response (response rate, 86.3%). The median survival for all 51 patients was 33 months, while that for 10 complete response patients and 21 patients who showed disappearance of HCC following additional therapies was 39 months. The single factor that significantly influenced survival was therapeutic effect. Treatment was well tolerated and severe toxicity was infrequent, with only grade 3 toxicity (thrombocytopenia) in one patient. Conclusions, The present study demonstrated the efficacy of hepatic arterial infusion chemotherapy using cisplatin-lipiodol emulsion and 5-FU without serious adverse effects in patients with unresectable HCC and portal vein tumour thrombosis. [source]

Forearm blood flow in pre-eclampsia

Lucy Bowyer
Objective 1. To characterise the forearm vascular reactivity of women with pre-eclampsia in the third trimester of pregnancy and compare it with that in normal or gestational hypertensive pregnancies. 2. To document female sex steroid (oestradiol, progesterone, oestriol and ,hCG) levels in the three groups of women. Design Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of saline and vasoactive substances: angiotensin II, sodium nitroprusside, acetylcholine and NG -monomethyl- l -arginine (l -NMMA). Setting Research laboratory at St George Hospital, Kogarah, Sydney, Australia. Sample Fifteen non-pregnant women in the follicular phase of the menstrual cycle, 15 third trimester normal pregnant women, 13 women in the third trimester with gestational hypertension and 15 women with pre-eclampsia. Main outcome measures Changes in forearm blood flow in response to vasoactive substances. Results Normal pregnant women had higher baseline forearm blood flow than non-pregnant women, decreased vasodilator responses to sodium nitroprusside and reduced vasoconstrictor responses to angiotensin II. No difference in response to angiotensin II, sodium nitroprusside or l -NMMA was found among normal pregnant, pre-eclampsia or gestational hypertension women, but vasodilatory responses of pre-eclamptic women to acetylcholine were reduced compared with normal pregnant women. Higher serum progesterone levels were found in women with pre-eclampsia and gestational hypertension than in normal pregnancy. Conclusion The hyperdynamic circulation of normal pregnancy is characterised by refractoriness to angiotensin II but this is not altered in pre-eclampsia. Pre-eclamptic women demonstrate a reduced vasodilator response to acetylcholine which, in the absence of any alteration in response to l -NMMA, implies that factors other than nitric oxide deficiency mediate the vasoconstriction of pre-eclampsia. [source]

Repeatability of local forearm vasoconstriction to endothelin-1 measured by venous occlusion plethysmography

Fiona E. Strachan
Aims ,We ,investigated ,the ,repeatability ,of ,the ,forearm ,blood ,flow ,response ,to intra-arterial infusion of endothelin-1 (ET-1), assessed by venous occlusion ­plethysmography. Methods In eight healthy men (aged 18,50 years), on four separate occasions, ET-1 (2.5 or 10 pmol min,1) was infused for 120 min via a 27 SWG cannula sited in the brachial artery of the nondominant arm. Each dose level was administered twice on consecutive visits. The dose order was randomized. Results are expressed as percentage change from baseline at 120 min (mean ± s.e. mean). Results ET-1 caused significant vasoconstriction (P < 0.0001 anova) at both doses (38 ± 3%, 2.5 pmol min,1 and 62 ± 3%, 10 pmol min,1; mean visit 1 and 2). There was no difference in the response to either dose on repeated challenge. Responses appeared to be less variable when expressed as percentage change in the ratio of blood flow (infused:noninfused) in both arms than as percentage change in blood flow in the infused arm alone, as indicated by repeatability coefficients (15% vs 21%, 2.5 pmol min,1 and 11% vs 13%, 10 pmol min,1; ratio vs infused arm alone). Conclusions We have shown dose-dependent vasoconstriction in the forearm vascular bed to intra-arterial infusion of ET-1 and that this response is less variable when expressed as percentage change in the ratio of forearm blood flow than percentage change in the infused arm. These data should also provide useful information to determine the power of early clinical pharmacology studies investigating the activity of endothelin receptor antagonists. [source]

Different vasodilator responses of human arms and legs

Sean C. Newcomer
Forearm vascular responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators have been thoroughly characterized in humans. While the forearm is a well-established experimental model for studying human vascular function, it is of limited consequence to systemic cardiovascular control owing to its small muscle mass and blood flow requirements. In the present study we determined whether these responses could be generalized to the leg. Based upon blood pressure differences between the leg and arm during upright posture, we hypothesized that the responsiveness to endothelium-dependent vasodilators would be greater in the forearm than the leg. Brachial and femoral artery blood flow (Q, ultrasound Doppler) at rest and during intra-arterial infusions of endothelium-dependent (acetylcholine and substance P) and -independent (sodium nitroprusside) vasodilators were measured in eight healthy men (22,27 years old). Resting blood flows in the forearm before infusion of acetylcholine, substance P or sodium nitroprusside were 25 ± 4, 30 ± 7 and 29 ± 5 ml min,1, respectively, and in the leg were 370 ± 32, 409 ± 62 and 330 ± 30 ml min,1, respectively. At the highest infusion rate of acetylcholine (16 ,g (100 ml tissue),1 min,1) there was a greater (P < 0.05) increase in Q to the forearm (1864 ± 476%) than to the leg (569 ± 86%). Similarly, at the highest infusion rate of substance P (125 pg (100 ml tissue),1 min,1) there was a greater (P < 0.05) increase in Q to the forearm (911 ± 286%) than to the leg (243 ± 58%). The responses to sodium nitroprusside (1 ,g (100 ml tissue),1 min,1) were also greater (P < 0.05) in the forearm (925 ± 164%) than in the leg (326 ± 65%). These data indicate that vascular responses to both endothelium-dependent and -independent vasodilator agents are blunted in the leg compared to the forearm. [source]

Efficacy of Concomitant Chemoradiation and Surgical Salvage for N3 Nodal Disease Associated With Upper Aerodigestive Tract Carcinoma,

Khwaja A. Ahmed MD
Abstract Objectives/Hypothesis To determine whether an aggressive approach using trimodality therapy would improve the outcome in head and neck cancer patients with advanced (N3) nodal disease. Study Design In this retrospective, nonrandomized review, we analyzed a subset of patients who were treated in a targeted chemoradiation therapy protocol, consisting of 31 patients who received treatment between June 1993 and June 1997. Methods Patients received selective intra-arterial infusions of cisplatin (150 mg/m2/wk for 4 weeks) and concomitant radiation therapy (2 Gy/fraction × 35 daily fractions over a 7-wk period) to the primary and clinically positive nodal disease. The patients were re-evaluated 2 months later and underwent salvage neck dissections if there was any residual disease. Results Classification of disease in the primary site was as follows: T1 in 2 patients, T2 in 6 patients, T3 in 14 patients, and T4 in 9 patients. Among the 31 patients who were assessed for response at the nodal site, 4 of 31 (13%) had a complete response, 21 of 31 (68%) had a partial response, and 1 of 31 (3%) had no response. Excluding the 5 patients who could not be evaluated, 4 of 26 patients (15%) had a complete response, 21 of 26 (81%) had a partial response, and 1 of 26 (4%) had no response. Nineteen patients subsequently underwent neck dissection, and five patients had histological evidence of residual disease. The remaining seven patients included four who had a complete response in their necks and three who died of intercurrent disease before re-staging. Among the 23 patients who were rendered disease free, there were no recurrences within the neck, whereas 1 patient had recurrence at the primary site and 11 patients had recurrence at distant sites. With a median follow-up of 15 months (range, 4,41 mo), the 3-year overall survival and disease-specific survival were 41% and 43%, respectively. Conclusions Targeted chemoradiation therapy followed by surgical salvage is a highly effective approach for regional control of patients with N3 nodal disease, whereas additional strategies are required to address the problem of distant metastases. [source]