Effects Of Octreotide In Patients Research Articles

OCTREOTIDE-INDUCED ASYSTOLE IN A 70-YEAR-OLD WOMAN

OCTREOTIDE-INDUCED ASYSTOLE IN A 70-YEAR-OLD WOMAN

Effects of Octreotide in Patients With Lymphangioleiomyomatosis

Effects of Octreotide in Patients With Lymphangioleiomyomatosis

Octreotide for the treatment of systemic lupus erythematosus: Clinical effects and an in vitro study on its therapeutic mechanism

Increased serum growth hormone (GH), together with high expression of growth hormone receptor on peripheral blood mononuclear cells (PBMCs), correlates with systemic lupus erythematosus (SLE) activity, suggesting that modulation of GH signaling may affect SLE activity. We explored the effects of octreotide (OCT), an analog of somatostatin that suppresses the release of GH, in SLE. The objectives of the study were to investigate effects of OCT on the proliferative capacity and cytokine expression of PBMCs from patients with SLE and to investigate therapeutic effects of OCT in patients with SLE. PBMCs from 13 active/inactive SLE patients and 11 controls were pretreated with or without GH and cultured with OCT. The proliferation of PBMCs was assessed by MTT assay and cytokines were quantified by ELISA. We compared the clinical response of 12 patients with SLE treated with OCT (100 µg twice daily) with 12 patients treated with prednisone over three months. OCT inhibited PBMC proliferation in a dose-dependent manner and decreased the secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon-gamma (IFN-γ). Patients treated with OCT demonstrated improvements in SLEDAI, dsDNA titer, complement levels, and erythrocyte sedimentation rate (ESR). OCT inhibited PBMC proliferation and PBMC secretion of IL-6, IL-10 and IFN-γ stimulated by GH. Treatment of patients with OCT resulted in clinical improvement in SLE.

Effects of different octreotide dosages on splanchnic hemodynamics and glucagon in patients with TIPS.

The aim of this study was to evaluate the hemodynamic effects of octreotide in patients treated with transjugular intrahepatic portosystemic stent shunt in relation to plasma levels of octreotide and glucagon and the correlation between portal pressure and noninvasive Doppler parameters. In 15 fasting patients, we i.v. administered isotonic sodium chloride followed by octreotide 25 microg/h and 100 microg/h, each over 1 h. We measured portal pressure (PP) directly and portal vein blood flow velocity by Doppler ultrasound simultaneously and calculated portal vascular resistance (PVR) and portal venous flow (PVF). Blood samples were taken for glucagon and octreotide (mean +/- SE). Octreotide reduced PP (120': -7.7+/-2.2%, p < 0.01 vs baseline; 180': - 11.4+/-2.1%, p < 0.01 vs baseline) and PVF (120': -21.7+/-31.7%, p < 0.01 vs baseline; 180': -11.6+/-18.1%, p < 0.05 vs baseline). Glucagon decreased with the increase in octreotide levels and showed a correlation with the decrease in PP and with PVF. In patients with a high PVR, we found a close inverse correlation between PP and portal vein blood flow velocity (r = -0.83, p = 0.03) as well as Cl (r = 0.81, p = 0.05), whereas poor correlation was found in patients with low PVR. Octreotide caused a dose-related, moderate but sustained reduction in PP in patients with transjugular intrahepatic portosystemic stent shunt. PVR seems to be an important parameter that influences the efficacy of octreotide and the relation between PP and noninvasive Doppler parameters.

Effects of different octreotide dosages on splanchnic hemodynamics and glucagon in patients with TIPS

OBJECTIVE: The aim of this study was to evaluate the hemodynamic effects of octreotide in patients treated with transjugular intrahepatic portosystemic stent shunt in relation to plasma levels of octreotide and glucagon and the correlation between portal pressure and noninvasive Doppler parameters. METHODS: In 15 fasting patients, we i.v. administered isotonic sodium chloride followed by octreotide 25 μg/h and 100 μg/h, each over 1 h. We measured portal pressure (PP) directly and portal vein blood flow velocity by Doppler ultrasound simultaneously and calculated portal vascular resistance (PVR) and portal venous flow (PVF). Blood samples were taken for glucagon and octreotide (mean ± SE). RESULTS: Octreotide reduced PP (120′: −7.7 ± 2.2%, p < 0.01 vs baseline; 180′: −11.4 ± 2.1%, p < 0.01 vs baseline) and PVF (120′: −21.7 ± 31.7%, p < 0.01 vs baseline; 180′: −11.6 ± 18.1%, p < 0.05 vs baseline). Glucagon decreased with the increase in octreotide levels and showed a correlation with the decrease in PP and with PVF. In patients with a high PVR, we found a close inverse correlation between PP and portal vein blood flow velocity ( r = −0.83, p = 0.03) as well as CI ( r = 0.81, p = 0.05), whereas poor correlation was found in patients with low PVR. CONCLUSIONS: Octreotide caused a dose-related, moderate but sustained reduction in PP in patients with transjugular intrahepatic portosystemic stent shunt. PVR seems to be an important parameter that influences the efficacy of octreotide and the relation between PP and noninvasive Doppler parameters.

A phase II study of high-dose octreotide in patients with unresectable pancreatic carcinoma

This report describes the results of a phase II trial to evaluate the safety, feasibility and response of patients with irresectable, histologically proven, stage II–IV adenocarcinoma of the pancreas receiving high-dose octreotide treatment. Octreotide was self-adminstered subcutaneously (3×2000 μg per day) by 49 patients. Therapy was discontinued after progression of the disease. Due to the subseqment diagnosis of bile duct carcinoma and stage I disease, 2 patients were excluded, leaving 47 evaluable patients with measurable disease. The median Karnofsky score was 80%. 3 patients had stage II (6%), 19 stage III (40%), and 25 (53%) stage IV disease. Octreotide treatment resulted in stable disease in 9 patients (19%) for more than 12 weeks. No complete or partial response was observed. The median overall survival was 21.4 weeks and the median progression-free survival 9.0 weeks. Therapy with high-dose octreotide is feasible, well tolerated and might prolong survival. In a placebo-controlled phase III study the effects of octreotide in patients with pancreatic cancer will be confirmed.

Effects of octreotide in patients with hypertrophic obstructive cardiomyopathy.

Hypertrophic obstructive cardiomyopathy (HOCM), the cause of which is unknown, is a heart disease characterized by obstruction of the left ventricular outflow tract and an increase in interventricular septum thickness. Octreotide, a synthetic analogue of somatostatin, was administered subcutaneously to 15 patients for 6 months in order to determine its efficacy in HOCM. Echocardiographic examination was performed in each patient before we had initiated treatment and after treatment. Interventricular septum thickness, interventricular septum thickness/left ventricular posterior wall thickness, and subaortic gradient decreased significantly at the end of treatment. The ratio of the mitral valve E to A waves increased significantly. We observed that octreotide treatment caused a significant decrease in interventricular septum thickness and subaortic pressure gradient. Before and after therapy left ventricular enddiastolic diameter, left ventricular endsystolic diameter, ejection fraction and fractional shortening were not changed. No adverse effect was observed during the therapy. According to our results, octreotide has some beneficial effects on HOCM and it seems to be a new therapeutic approach for HOCM.

Hemodynamic effects of octreotide in patients with cirrhosis and portal hypertension

Describir la técnica utilizada para imputar la fecha de seroconversión al virus de la inmunodeficiencia humana (VIH) en cohortes de hemofílicos y validar su utilización en sujetos con fecha de seroconversión datada dentro de un intervalo de las cohortes del proyecto GEMES (Grupo Español Multicéntrico para el Estudio de Seroconvertores al VIH).Se dispone de 632 hemofílicos procedentes de tres unidades de hemofilia identificados como VIH+ entre 1983 y 1985 (fechas de las primeras pruebas VIH+) y 1.092 individuos procedentes de 5 cohortes del proyecto GEMES con una ventana de seroconversión (tiempo entre pruebas VIH– y VIH+) menor de 3 años en los que se asume el punto medio (PM) como fecha de seroconversión. Se imputa la fecha de seroconversión para los dos grupos a partir de la estimación de la distribución de probabilidad de seroconversión que se obtiene mediante el algoritmo EM. Se utilizan dos métodos de imputación: uno a partir del valor esperado de la distribución estimada y otro de la media geométrica de 5 muestras aleatorias de la distribución estimada. Las imputaciones se han validado en las cohortes de no hemofílicos al comparar con el PM y el tiempo libre de sida y la supervivencia con las diferentes estimaciones de seroconversión.La mediana de la seroconversión se sitúa en mayo de 1993 para los no hemofílicos y en 1982 para los hemofílicos. En las cohortes de no hemofílicos no se observan grandes diferencias entre las fechas de la seroconversión estimada como el punto medio y las medianas estimadas a partir de los dos métodos de imputación. Lo mismo ocurre en el caso de las cohortes de hemofílicos. No se observan diferencias en las estimaciones del tiempo libre de sida y supervivencia en ambos grupos de cohortes.La imputación de la media geométrica de varias muestras aleatorias y la imputación de valor esperado proporcionan una buena estimación de la fecha de seroconversión frente al VIH que puede ser utilizada para estimar el tiempo libre de sida y la supervivencia en una cohorte de hemofílicos para los que se desconoce la fecha de seroconversión.To describe the methods used to impute HIV seroconversion date in the haemophiliac cohorts from GEMES project and to validate its use.632 haemophiliacs coming from three hemophilia units identified as HIV+ and 1.092 individuals coming from 5 project GEMES cohorts with a seroconversion window (time among test HIV– and HIV+) less than 3 years where mid point (PM) was assumed as seroconversion date. For both groups, seroconversion date was imputed after estimating the probability distribution of seroconversion by means of the EM algorithm. Two imputation methods are used: one obtained from the expected value and the other from the geometric mean of 5 random samples. from the estimated distribution. Imputations have been validated in the non haemophiliacs cohorts comparing with the PM seroconversion date. Also AIDS free time and survival from the different seroconversion imputed dates were compared.Median seroconversion date is located in May of 1993 for the non haemophiliacs and in 1982 for the haemophiliacs. Not big differences are observed among the imputed seroconversion dates and the mid-point seroconversion date in the non-haemophiliac cohorts. Similar results are found for the haemophiliac cohorts. Also no differences are observed in the estimated AIDS-free time for both groups of cohorts.Geometric mean imputation from several random samples provides a good estimate of the HIV seroconversion date that can be used to estimate AIDS-free time and survival in haemophiliac cohorts where seroconversion date is ignored.

Somatostatin receptor scintigraphy and octreotide treatment in patients with thyroid eye disease

Octreotide, a potent long-acting synthetic somatostatin analogue, has been reported to have a beneficial effect in thyroid eye disease (TED), but the precise mechanism of action remains unexplained. 111In-DTPA-D-Phe1-octreotide (Octreoscan-111) has been used to localize a number of endocrine tumours and visualize somatostatin receptors in the retrobulbar tissue of patients with TED. Furthermore, this technique can predict the inhibitory effect of octreotide on hormone secretion by endocrine tumours, as there is a close relation between the clinically observed inhibition and visualization of the tumour using Octreoscan-111. The aims of the present study were to confirm the beneficial effect of octreotide in patients with TED, to investigate the presence of somatostatin receptors in the orbital area and also, if possible, to ascertain whether this technique could select those patients with TED who might benefit from treatment with octreotide. A prospective study. An endocrine clinic of a national hospital. Twenty treated thyrotoxic patients with TED, 5 treated thyrotoxic patients without TED and 5 normal individuals were studied. In 12 patients with TED, 5 without TED and 5 normal individuals, Octreoscan-111 scintigraphy of the orbits was performed. The remaining 8 patients with ophthalmopathy served as controls. In patients with TED who were investigated with Octreoscan-111, 300 micrograms octreotide daily was given for 12 weeks. Six patients in both eyes and one patient in one eye showed an improvement in ocular manifestations as assessed by clinical criteria and changes in the NOSPECS score, while the rest showed no improvement. The patients who showed an improvement had a high number of somatostatin receptors and positive orbital scans, while with one exception the patients who did not respond had a low number of receptors and negative orbital scans (P < 0.02). None of the 5 patients without TED nor the normal individuals had a positive orbital scan. Seven out of 8 control patients with TED showed no change in the disease during the trial, while 1 deteriorated. We conclude that octreotide has a beneficial effect in thyroid eye disease and that Octreoscan-111 could predict those patients with thyroid eye disease who might benefit from this treatment.

Cardiovascular effects of octreotide in patients with hepatic cirrhosis

Octreotide is thought to reduce splanchnic and variceal blood flow with minimal effects on the systemic circulation in cirrhotic patients with portal hypertension. However, we noticed significant bradycardia in some patients immediately after administration of bolus doses of octreotide. Therefore, we investigated the effect of intravenous octreotide on systemic hemodynamics in 59 patients with cirrhosis. In two double-blind, placebo-controlled protocols, 32 patients received a 25-micrograms bolus and 20 patients received an infusion of 50-micrograms/hr of octreotide/placebo. Immediately after the bolus dose of octreotide was administered, there were significant reductions in pulse rate (77 +/- 3 vs. 65 +/- 3 beats per minute, P < .01) and cardiac output (9.2 +/- 0.8 vs. 7.9 +/- 0.8 L/min; P < .01) and significant increases in mean arterial pressure (81 +/- 3 vs. 87 +/- 3 mm Hg; P < .05), mean pulmonary artery pressure (9.1 +/- 1.0 vs. 16.6 +/- 1.5 mm Hg; P < .01), right atrial pressure (3.8 +/- 0.8 vs. 6.6 +/- 1.0 mm Hg; P < .01), right ventricular pressure (7.1 +/- 0.6 vs. 12.5 +/- 1.3 mm Hg; P < .01), pulmonary capillary wedge pressure (4.8 +/- 0.8 vs. 11.2 +/- 1.4 mm Hg; P < .01), systemic vascular resistance, and pulmonary vascular resistance. Thirty minutes after the start of the infusion, there were significant increases in mean right atrial pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure. This study suggests that intravenous octreotide has significant effects on the systemic circulation in patients with cirrhosis and that these effects appear to be more marked after administration of bolus doses.

Cardiovascular effects of octreotide in patients with hepatic cirrhosis

Octreotide is thought to reduce splanchnic and variceal blood flow with minimal effects on the systemic circulation in cirrhotic patients with portal hypertension. However, we noticed significant bradycardia in some patients immediately after administration of bolus doses of octreotide. Therefore, we investigated the effect of intravenous octreotide on systemic hemodynamics in 59 patients with cirrhosis. In two double-blind, placebo-controlled protocols, 32 patients received a 25-μg bolus and 20 patients received an infusion of 50-μg/hr of octreotide/placebo. Immediately after the bolus dose of octreotide was administered, there were significant reductions in pulse rate (77 ± 3 vs. 65 ± 3 beats per minute, P < .01) and cardiac output (9.2 ± 0.8 vs. 7.9 ± 0.8 L/min; P < .01) and significant increases in mean arterial pressure (81 ± 3 vs. 87 ± 3 mm Hg; P < .05), mean pulmonary artery pressure (9.1 ± 1.0 vs. 16.6 ± 1.5 mm Hg; P < .01), right atrial pressure (3.8 ± 0.8 vs. 6.6 ± 1.0 mm Hg; P < .01), right ventricular pressure (7.1 ± 0.6 vs. 12.5 ± 1.3 mm Hg; P < .01), pulmonary capillary wedge pressure (4.8 ± 0.8 vs. 11.2 ± 1.4 mm Hg; P < .01), systemic vascular resistance, and pulmonary vascular resistance. Thirty minutes after the start of the infusion, there were significant increases in mean right atrial pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure. This study suggests that intravenous octreotide has significant effects on the systemic circulation in patients with cirrhosis and that these effects appear to be more marked after administration of bolus doses.

Octreotide in the Treatment of Acute Pancreatitis: Results of a Unicenter Prospective Trial with Three Different Octreotide Dosages

Acute necrotizing pancreatitis is still associated with high morbidity and mortality. In this prospective clinical trial, we analyzed the effect of octreotide in patients with acute pancreatitis. Eight patients received either 3 x 100, 3 x 200 or 3 x 500 micrograms octreotide subcutaneously per day over a period of 10 days. The complication rate was lower in the group of patients who received 3 x 200 or 3 x 500 micrograms octreotide than in the control group and the group of patients who received the dosis of 3 x 100 micrograms octreotide per day. The results of this study are promising and must be validated in a controlled clinical trial with octreotide in a larger patient population.

Acute and long-term effects of octreotide in patients with ACTH-dependent cushing's syndrome

purpose: Octreotide is of proven efficacy in the management of patients with acromegaly, thyrotropin-secreting pituitary adenomas, and certain gastrointestinal tumors, but its effect in Cushing's syndrome is less clear. patients and methods: We studied 10 patients who presented with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, 3 of whom were previously adrenalectomized. Serum cortisol or ACTH levels were measured before and during the administration of octreotide 50 to 500 μg every 8 hours for 24 to 72 hours. results: Treatment was effective in four patients: serum cortisol levels decreased to within or below the normal range in Patients 1,2, and 3, and ACTH levels were substantially lowered in Patient 4, who had previously been adrenalectomized for a metastatic islet cell tumor. These responses were sustained during long-term treatment for 2 to 72 weeks. All four patients showed no evidence of a pituitary tumor on computed tomographic or magnetic resonance imaging and had proven (Patients 3 and 4) or presumed ectopic disease. Of the six patients who did not respond, four had pituitary tumors and two had presumed ectopic ACTH production. conclusion: We conclude that a short trial of octreotide is warranted in patients with ACTHdependent Cushing's syndrome who have no demonstrable pituitary tumor. A response to treatment should alert the physician to the possibility of an ectopic ACTH source and will identify patients whose disease may be controllable using octreotide.

Hemodynamic effects of octreotide in patients with autonomic neuropathy.

The somatostatin analogue, ectrootide, is being used to treat postprandial hypotension in patients with autonomic neuropathy. Although the therapeutic effect of the drug is presumably secondary to a splanchnic vasoconstrictor action, its effect on splanchnic hemodynamics has never been characterized in patients with autonomic neuropathy. Moreover, it is unknown whether octreotide acts on other vascular beds in this group of patients or whether it affects cardiac output. We, therefore, measured splanchnic, forearm, and systemic vascular resistance and cardiac output before and after administering octreotide (0.4 microgram/kg s.c.) to patients with idiopathic autonomic neuropathy and diabetic autonomic neuropathy. Splanchnic blood flow was determined from the clearance of indocyanine green in seven patients. We observed that octreotide decreased splanchnic blood flow (from 850 +/- 77 to 664 +/- 48 ml/min, p less than 0.005), increased mean blood pressure (from 97 +/- 6 to 115 +/- 3 mm Hg, p less than 0.005), and increased splanchnic vascular resistance (from 0.118 +/- 0.012 to 0.18 +/- 0.018 mm Hg/ml/min, p less than 0.005). Forearm blood flow was measured by plethysmography in 13 patients. Octreotide increased forearm vascular resistance in patients with idiopathic autonomic neuropathy (n = 8) from 19.1 +/- 1.0 to 27.2 +/- 3.8 mm Hg/ml/min/100 ml forearm volume (p less than 0.01) and from 25.2 +/- 3.9 to 41.0 +/- 6.8 mm Hg/ml/min/100 ml (p less than 0.01) in patients with diabetic autonomic neuropathy (n = 5). Cardiac output was measured by two-dimensional echocardiography. Octreotide administration increased cardiac output in five of six patients with idiopathic autonomic neuropathy (from 4.4 +/- 0.4 to 5.0 +/- 0.5 l/min, p less than 0.02) and five of five patients with diabetic autonomic neuropathy (from 3.8 +/- 0.4 to 5.1 +/- 0.4 l/min, p less than 0.02). Systemic vascular resistance increased in patients with idiopathic autonomic neuropathy from 21.2 +/- 2 to 24.9 +/- 2.6 (p less than 0.05) but did not change in patients with diabetic autonomic neuropathy. The pressor effect of octreotide in patients with autonomic neuropathy is associated with increased splanchnic and forearm vascular resistance and with increased cardiac output.