Amphiphilic perfluoroalkyl carbohydrates as new tools for liver imaging.

The synthesis of three molecules containing a fluorocarbon chain (either C(6)F(13), C(8)F(17) or C(10)F(21)), a sugar moiety (derived from lactobionic acid) and a chelate (derived from DTPA) is reported. These molecules (C(6)F(13)-Gal-DTPA, C(8)F(17)-Gal-DTPA or C(10)F(21)-Gal-DTPA) have been dispersed in water and their critical micellar concentration (CMC) as well as their size were determined. Their interaction with serum was weak as evaluated by time resolved fluorimetry of europium complexes. The presence of sugar on the surface of the nanoparticles was confirmed by the agglutination test using ricin. Conditions of pH and concentrations were optimised for in vivo studies. Finally, the nanoparticles formed with C(10)F(21)-Gal-DTPA have been complexed with (99m)Tc and injected to rats in order to follow their biodistribution by scintigraphy while following their stability by transmission electronic microscopy. A majority of the compound was found in the liver post-bolus injection.

Hyperosmolarity causes inflammation through the methylation of protein phosphatase 2A.

OBJECTIVE AND DESIGN: We evaluated the role of the osmolarity in the pro-inflammatory responses of epithelial cells. MATERIAL: Twenty-five female Wistar rats and colorectal (HT-29) and bladder (T24) cell lines were used. TREATMENTS: Rats and cells were exposed for 48 hours to hyperosmotic solutions. METHODS: Interleukin-8 (IL-8) production was measured by Enzyme Linked ImmunoSorbent Assay, mRNA transcription of pro-inflammatory cytokines by microarrays or RNase Protection Assay. Nuclear factor-kappa B (NF-kappaB) pathway and Protein Phosphatase 2A (PP2A) activations were measured. Myeloperoxydase (MPO) activation and Macrophage-Inflammatory Protein-2 (MIP-2) transcription were monitored. RESULTS: The exposure to hyperosmotic solutions enhanced the production of IL-8 and induced pro-inflammatory cytokines transcription. In vivo, MPO enhanced activity accompanied by an increased MIP-2 transcription was observed. In vitro, NF-kappaB activation is accompanied by an inhibitor of kappa B-alpha degradation and inhibitor of kappa B kinase (IKK gamma) activation. We demonstrated the induction of IKK gamma after methylation and activation of PP2A. Cytokine induction was inhibited by okadaic acid and calyculin A and stimulated by xylitol. CONCLUSION: Hyperosmolarity can induce pro-inflammatory cytokine responses in colorectal and bladder epithelial cells. Inflammation appears to be the simple consequence of a shift of methylation of PP2A which in turn activates NF-kappaB.

Reinforced interferon alpha-2b and ribavirin is more effective than standard combination therapy in the retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial.

Interferon-alpha (IFN) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a standard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were randomized. The reinforced group (n = 114) received IFN-2b 6 million units (MU) thrice weekly (TIW) and ribavirin for 48 weeks, and the nonreinforced group (n = 117) received IFN-2b 3 MU TIW and ribavirin for 24 weeks. The main outcome measure was a sustained virological response, defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment. This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group. At the end of follow-up, a sustained virological response was observed in 29 of the 98 patients (29.6%) in the reinforced group vs 16 of the 105 patients (15.2%) in the nonreinforced group (P = 0.014). In multivariate analysis, factors associated with a sustained virological response were treated with a reinforced regimen [odds ratio (OR) 2.9; P = 0.06] and genotype 2 or 3 (OR 8.8; P < 0.0002). A total of 160 patients had paired biopsies before and after treatment. Histological activity improvement was observed in 32 of 80 patients (40%) and fibrosis worsening in 26 of 80 patients (33%) in the reinforced group vs 13 of 80 (16%) and 19 of 80 (24%) in the nonreinforced group (P = 0.30 and 0.20, respectively). Hence in nonresponders, a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only.

Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontané; FFAACS).

BACKGROUND: A combination of low-dose aspirin with anticoagulants may provide better protection against thromboembolic events compared to anticoagulants alone in high-risk patients with atrial fibrillation. OBJECTIVE: Evaluation of the preventive efficacy against nonfatal thromboembolic events and vascular deaths of the combination of the oral anticoagulant fluindione and aspirin (100 mg) in patients with high-risk atrial fibrillation. METHODS: A multicenter, placebo-controlled, double-blind, randomized trial was conducted at 49 investigating centers in France. Atrial fibrillation patients with a previous thromboembolic event or older than 65 years and with either a history of hypertension, a recent episode of heart failure or decreased left ventricular function were included in the study. Patients were treated with fluindione plus placebo (i.e. anticoagulant alone) or fluindione plus aspirin (i.e. combination therapy), with an international normalized ratio target of between 2 and 2.6. The combined primary endpoint was stroke (ischemic or hemorrhagic), myocardial infarction, systemic arterial emboli or vascular death. The secondary endpoint was the incidence of hemorrhagic complications. RESULTS: The 157 participants (average age 74 years; 52% women; 42% with paroxysmal atrial fibrillation) were followed for an average of 0.84 years. Three nonfatal thromboembolic events were observed (1 in the anticoagulation group, 2 in the combination group) and 6 patients died (3 in the anticoagulation group, 3 in the combination group), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe hemorrhagic complications (1 in the anticoagulation group, 2 in the combination group). Nonfatal hemorrhagic complications occurred more often in the combination group (n = 10, 13.1%) compared to the anticoagulation group (n = 1, 1.2%) (p = 0.003). CONCLUSION: The combination of aspirin with anticoagulant is associated with increased bleeding in elderly atrial fibrillation patients. The effect on thromboembolism and the overall balance of benefit to risk could not be accurately assessed in this study due to the limited number of ischemic events.

Induction of labour with a viable infant: a randomised clinical trial comparing intravaginal misoprostol and intravaginal dinoprostone.

OBJECTIVE: To compare the efficacy and safety of vaginal misoprostol (50 microg) with vaginal dinoprostone. DESIGN: Double-blind randomised trial. SETTING: Obstetrics Department, Poissy Hospital, France. PARTICIPANTS: 370 patients with medical indications for induction of labour. OUTCOME MEASURES: Vaginal deliveries within 24 hours, as well as time to vaginal deliveries, caesarean rates, costs, and fetal, neonatal and maternal condition. RESULTS: Compared with vaginal dinoprostone, vaginal misoprostol resulted in greater efficacy in several areas: vaginal delivery within 24 hours; time to vaginal delivery; and vaginal delivery within 12 hours. There was a non-significant increase in the caesarean section rate for fetal distress in the misoprostol group, but fewer caesarean sections for failed induction. Fetal tolerance was similar in the two groups, although significantly more neonates had a cord pH <7.20 and (non-significantly) none had meconium stained amniotic fluid in the misoprostol group. The incidence of poor neonatal outcome was similar in both groups. Subgroup analysis by indication for induction showed that the higher rates of arterial cord pH <7.20 and of meconium-stained amniotic fluid with misoprostol persisted only in possible fetal compromise. Poor neonatal outcome was less frequent in the misoprostol group in cases of induction for non-fetal indications. CONCLUSIONS: Vaginal misoprostol resulted in successful and earlier induction of labour more often than dinoprostone, but the safety of misoprostol raises some concern in potentially compromised infants. Misoprostol should be preferred to dinoprostone in cases of induction for non-fetal indications.

French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group.

The effect of amiloride, a sodium channel blocker, has been evaluated in a multicenter randomized double-blind placebo-controlled trial in cystic fibrosis patients more than 5-years-old (n = 137) whose forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and forced mid-expiratory flow (FEF(25-75)) were not below 50%, 50%, and 30% of reference values, respectively. Patients were randomly allocated to two parallel groups. Sixty-four patients were chronically colonized with Pseudomonas aeruginosa; they received either amiloride or placebo as a nebulized solution three times daily for 6 months. Routine treatments were continued. Patients chronically colonized with Pseudomonas received nebulized colimycine twice a day for a month during the third and sixth months of treatment. Bronchopulmonary exacerbations were treated in the usual way. The effects of the amiloride treatment were assessed at the end of the 6-month treatment period. The effects on FVC and secondarily on FEV(1), FEF(25-75), the number of days on antibiotic therapy, the Shwachman score, a nutritional index (weight/height(2)), the change in sputum bacterial flora, and nocturnal cough were assessed. For the patients not chronically colonized with Pseudomonas, the effect of the treatment was also evaluated by counting chronic colonizations with pathogens appearing during the trial period. The present study failed to demonstrate any significant benefit of amiloride over placebo on FVC, FEV(1), and the other secondary endpoints in the studied population. Neither the chronically colonized, nor the noncolonized patients benefited. The confidence intervals of the differences between treatment groups indicated small differences that were most likely of no clinical significance. Complementary analyses taking into account the gender, the type of mutation, the subpopulations whose FVC and FEV(1) were below 80% of normal values at the beginning of the study, and also patients less than 10 years old, did not show any statistically or clinically significant improvements following amiloride therapy.

[Study of combined anticoagulant (fluindione)-aspirin therapy in patients with atrial fibrillation at high risk for thromboembolic complications. A randomized trial (FFAACS)]. / Etude de l'association anticoagulant (fluindione)-aspirine, chez les patients en fibrillation auriculaire à haut risque de complications thrombo-emboliques. Une étude randomisée (FFAACS).

BACKGROUND: A combination of low-dose aspirin (A) and anticoagulation (AC) may provide better protection against thromboembolic events compared with AC alone in high-risk patients with atrial fibrillation (AF). METHODS: We performed a multicentric placebo-controlled double blind-trial to test the preventive efficacy against thromboembolic events of the addition of aspirin (A) (100 mg) or placebo (P) to anticoagulant treatment in patients with high-risk atrial fibrillation. A total of 157 patients were included, with atrial fibrillation and previous thromboembolic event or older than 65 years with either a history of hypertension, a recent episode of heart failure or a left ventricular dysfunction. All patients received fluindione (F) and P or F and A, with an INR target between 2 and 2.6. The primary endpoint was a combined endpoint of stroke (ischaemic or haemorrhagic), myocardial infarction, systemic arterial emboli or vascular death. RESULTS: The study had to be stopped prematurely owing to a too low recruitment rate. During follow-up (0.84 years) 3 non-fatal thromboembolic events were recorded (1P, 2A) and 6 patients died (3P, 3A), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe haemorrhagic complications (1P, 2A). Non-fatal haemorrhagic complications occurred more often in group A (n = 10, 13.1 pour cent) compared with group P (n = 1, 1.2 pour cent), p = 0.003. CONCLUSION: The FFAACS study was not able to show any therapeutic benefit from the addition of aspirin to anticoagulant in patients with high-risk AF. Such a combination increased the incidence rate of bleeding complications, which therefore greatly reduces its potential overall benefit.

Prognostic value of the soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alfa. Multicenter GER-CYT 04 Group.

BACKGROUND/AIMS: High serum levels of the soluble interleukin 2 receptor (sIL-2R) have been reported in patients with chronic hepatitis C. The aims of this study were to determine the evolution of sIL-2R considered as an indicator of activation of T cells in patients with hepatitis C virus (HCV) treated with IFN-alpha and to correlate sIL-2R serum levels with parameters reflecting ongoing liver disease and with outcome of interferon treatment. METHODS: In a case-control study, we studied patients enrolled in a multicenter randomized clinical trial which had demonstrated the benefit of a reinforced regimen of interferon alpha. Each of the 26 sustained virological responders (SVR) was paired for treatment regimen with two non-responders (NR). RESULTS: Prior to treatment, higher levels of sIL-2R were found in the sera of 78 patients compared with healthy controls (3791+/-210 pg/ml versus 956+/-88 pg/ml (p<0.001)). In the 78 patients after 4 weeks of treatment, the levels of sIL-2R were higher than pretreatment levels (4308+/-206 pg/ml (p<0.01)). In the NR, levels of sIL-2R increased significantly after 4 weeks of treatment compared with pretreatment levels (p<0.01), and levels of sIL-2R at week 72 were not significantly different from those at pretreatment. Conversely, in the SVR, levels of sIL-2R at week 4 did not significantly increase compared to pretreatment values, and thereafter gradually decreased. At week 72, levels of sIL-2R were significantly lower than before treatment (p<0.001). The difference between levels of sIL-2R at week 4 and before initiation of treatment (delta s IL-2R) was smaller in the SVR than in the NR (142+/-219 pg/ml versus 704+/-107 pg/ml (p<0.02). The disappearance of HCV RNA from the serum at week 4 showed a sensitivity of 92% (95% confidence interval 86-98) and a specificity of 60% (95% confidence interval 49-71), delta sIL-2R had a sensitivity of 42% (95% confidence interval 31-53) and a specificity of 81% (95% confidence interval 79-90) for the prediction of a sustained virological response 6 months after stopping treatment. The disappearance of HCV RNA from serum at week 4 and delta sIL-2R were independent and early predictive factors for a sustained virological response 6 months after stopping treatment. CONCLUSIONS: At week 4, delta sIL-2R may be a more specific parameter than the disappearance of HCV RNA for assessing total, and hence more sustained, elimination of HCV infection 6 months after stopping treatment.

A study of the relative bioavailability of cysteamine hydrochloride, cysteamine bitartrate and phosphocysteamine in healthy adult male volunteers.

AIMS: Cysteamine, the only drug available for the treatment of cystinosis in paediatric patients, is available as the hydrochloride, the bitartrate and as sodium phosphocysteamine salts. It has been suggested that cysteamine bitartrate and phosphocysteamine are better tolerated and may have a better bioavailability than cysteamine hydrochloride. This has, however, never been demonstrated. METHODS: We compared the pharmacokinetics and tolerance of these three formulations of cysteamine in 18 healthy adult male volunteers in a double-blind, latin-square, three-period, single oral dose cross-over relative bioavailability study. RESULTS: No statistical difference was found between relative bioavailabilities, AUC (0, infinity) (geometric mean and s.d. in micromol l(-1) h: 169+/-51, 158+/-46, 173+/-49 with cysteamine hydrochloride, phosphocysteamine and cysteamine bitartrate respectively), Cmax (geometric mean and s.d. in micromol l(-1); 66+/-25.5, 59+/-12, 63+/-20) and tmax (median and range in h: 0.88 (0.25-2), 1.25 (0.25-2), 0.88 (0.25-2)) with each of the three forms of cysteamine tested. Bioequivalence statistics (90% confidence intervals) showed non equivalence of Cmax of cysteamine base as the only non equivalence of pharmacokinetics between the three formulations: 90% CI for Cmax relative ratios to cysteamine hydrochloride were [75.6-105.81 for phosphocysteamine and [74.2-124.2] for cysteamine bitartrate. The only significant adverse event was vomiting whose frequency was inversely correlated with body weight (Spearman's r=-0.76, P<0.001). The nature of the salt tested did not influence vomiting. CONCLUSIONS: While none of the three forms of cysteamine tested has a clear advantage over the others in terms of pharmacokinetics and tolerance profile, this should now however be addressed in patients treated for cystinosis during repeat administrations.

Reinforced regimen of interferon alfa-2a reduces the incidence of cirrhosis in patients with chronic hepatitis C: a multicentre randomised trial. Multicentre GER-CYT-04 Group.

BACKGROUND/AIMS: Our aim was to assess and compare the long-term effect of interferon at standard (6 months) and reinforced dose and duration regimens in chronic hepatitis C. METHODS: A multicentre institutional trial included 244 previously untreated patients with chronic hepatitis C, without cirrhosis, who were randomly allocated to either standard (3 MU thrice a week for 24 weeks; n=120) or reinforced (6 MU daily for 12 days, 6 MU thrice a week for 22 weeks, 3 MU thrice a week for 24 weeks; n=124) regimens. The main endpoint was sustained ALT response at 72 weeks (18 months); secondary end-points were virological (branched DNA and PCR) and histological responses (incidence of cirrhosis) at month 18. RESULTS: Sustained ALT response was observed in five patients (4%, 95% confidence interval 0-8%) in the standard group and in 21 patients (18%, 95% confidence interval 11-25%), from the reinforced group (p=0.002), in agreement with virological response in 21 (81%) patients. Cirrhosis at month 18 was observed in ten (10%) patients in the standard group and one (1%) in the reinforced group (p=0.004). CONCLUSIONS: The standard regimen of interferon, in chronic hepatitis C, confers a minimal sustained response rate at 18 months and may not prevent the occurrence of cirrhosis. Reinforced regimens allow sustained response to be reached in a limited number of patients and reduce the risk of cirrhosis during 18 months of follow-up.

A prospective multicenter trial of octreotide in 24 patients with visual defects caused by nonfunctioning and gonadotropin-secreting pituitary adenomas. French Multicenter Octreotide Study Group.

OBJECTIVE: The somatostatin analog octreotide has been demonstrated to improve optic tract compression caused by pituitary macroadenomas within hours of its administration and/or reduce tumor size in some patients. We report the results of a prospective multicenter study of the effects of octreotide on visual function and tumor size in patients with nonfunctioning pituitary adenomas or gonadotropin-secreting adenomas. METHODS: Twenty-four patients with visual defects caused by histologically confirmed macroadenomas were administered octreotide via continuous subcutaneous infusion, as follows: 100 micrograms the 1st day and, if necessary, 200 micrograms the 2nd and then 100 or 200 micrograms three times daily if visual function improved. Vision was assessed after 4 days, 1 month, and 2 months, including tumor size evaluation. Visual improvement was defined by a net gain of at least 2/10 in acuity and/or of more than 20% of the surface of one isopter (a reduction in tumor volume of > or = 20% of the initial measurement); opposite changes were defined as deterioration. RESULTS: Visual improvement was noted in 13 of 24 patients, 10 of 23 patients and 9 of 22 patients, and was not noted in 11 of 24 patients, 14 of 23 patients, and 13 of 22 patients after 4 days, 1 month, and 2 months, respectively. After 2 months, three adenomas had shrunk, three had not changed in size, and one had increased; visual function improved in the seven patients with these adenomas. Octreotide was discontinued in 13 patients for lack of efficacy. CONCLUSION: The incidence of visual improvement and tumor shrinkage noted in this study was higher than previously reported. Our data suggest that early onset of visual improvement might help in deciding which patients profit from octreotide. However, concomitant gain in visual acuity with deterioration in visual fields or visual improvement with an increase (moderate) in tumor size can occur.

[Essential elements of quality assurance of clinical trials in hospital environment]. / Eléments essentiels de l'assurance de qualité des essais cliniques en milieu hospitalier.

This round table discussion was devoted to describing the present status of clinical trials in the hospital setting, analysing common difficulties in conducting quality clinical research, and proposing realistic solutions to solve or attenuate those difficulties. This analysis was performed on five critical topics: personnel, laboratory tests and investigations, drug supplies, source documents and investigator's procedures.

[Parlodel in early combination with levodopa in the treatment of Parkinson disease. Comparison of 2 dosage forms]. / Introduction du Parlodel en association précoce à la lévodopa dans le traitement de la maladie de Parkinson. Comparaison de deux progressions posologiques.

In order to compare two titrations of Parlodel in early combination with levodopa in the treatment of Parkinson's disease a multicentre randomized open study was performed with a fast titration in group A (15 mg/day for 3 weeks) and slow in group B (15 mg/day for 5 weeks). 153 patients were included: 77 in group A and 76 in group B. The recommended titration was observed in 76% in group A and 88% in group B, the difference was not significant. The efficacy assessed by the Webster Scale was remarkable and similar in the two groups. This study confirms the additive benefit of bromocriptine on the symptoms and long term complications of levodopa therapy, but no absolute conclusion can be drawn regarding the best titration.

[Therapeutic trials in Alzheimer disease. Selection--recruitment and stratification]. / Essais thérapeutiques dans la maladie d'Alzheimer. Sélection--recrutement et stratification.

Therapeutic trials conducted in Alzheimer's disease have benefited from the standardization of diagnostic criteria based on internationally recognized scales (DSM III-R, NINCDS-ADRDA) which ensure more valid inclusions. Well specified exclusion criteria are also of the utmost importance, in particular depression, vascular dementia and concomitant psychotropic drugs. Cognitive and/or functional scales allow an appreciation of the severity of the disease. Due to the heterogeneity of Alzheimer's disease stratification methods on identified prognostic factors i.e. aphasia, extrapyramidal symptoms should be performed. Selection of responders during an enrichment phase has still to be discussed. Multicentric studies become imperative because of the large number of patients required and the difficulties in selecting the adequate patients. These raise the issues of investigators' experience, coordination and between center variability.

Residential care and risk of proximal femur fracture.

The risk of hip fracture is higher among persons living in long-term care than among persons living at home. The aim of this study was to explain the difference in risk between the two types of residence by identifying differences in the respective risk factor profiles. Information from the Mediterranean osteoporosis (MEDOS) study questionnaire was used for statistical analyses of 107 non-demented female cases and 225 neighbourhood controls matched for age, sex, and residential area. The statistical analyses incorporated adjustments of the risk estimates by unconditional multivariate logistic regression. Urban background, activity, and morbidity were found to differ between the two types of residence. The detected differences in risk factor profiles were, however, not considered to be sufficient as an explanation for the difference in risk of fracture.

[Clozapine (Leponex) in France]. / La clozapine (Leponex) en France.

Leponex (clozapine) is an atypical neuroleptic indicated in severe schizophrenia, launched in France in December 1991. The safety and efficacy data pertaining to 1,062 patients treated on a compassionate needs basis between May 1989 and December 1991 constitute the first French experience on the drug. The results of an interim analysis pertaining to 602 patients, i.e. available data on 03-15-1992, generally collected on a retrospective basis, by means of a specific questionnaire are reviewed. The population included patients with severe and long-standing schizophrenia i.e. 15.71 +/- 9.3 years, resistant to usual neuroleptic therapy (90.86% of cases), and rarely with a history of intolerance to this class (2.49%). The indication was in the majority of the cases a paranoid schizophrenia (67.2%). The mean maintenance daily dose was 419 mg/d (+/- 152). Overall, with respect to associated drugs, neuroleptics were recorded in 16.4%, another psychotropic drug in 44.7% and symptomatic treatments for extrapyramidal disorders in 21.3% of patients. Of interest is the fact that, for those patients started on Leponex more recently, the drug is more often prescribed on a single basis. Leponex was stopped in 24.3% for the following reasons: adverse events 10.6%, lack of efficacy 6%, non compliance 3.8%, other reasons 3.8%. The adverse event profile is consistent with the literature data, taking into account the fact that certain adverse events were more commonly described: fatigue of lower limbs 11.8%, leucocytosis 19.8% and eosinophilia 4.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Nicardipine in the prevention of spasm-induced neurological deficits after subarachnoid hemorrhage: a dose-ranging study.

The tolerability of four doses of intravenous nicardipine (0.03, 0.08, 0.11, and 0.15 mg/kg/h) was assessed in this randomized multicenter, parallel-group study. Fifty-two patients with Hunt and Hess grade I-III aneurysmal subarachnoid hemorrhage were treated with intravenous nicardipine beginning within 4 days of bleeding, for a mean duration of 12.6 days; this treatment was followed by administration of oral nicardipine 90-120 mg until day 30. Hypotension was the main side effect, and it occurred only in the two groups that received the highest doses. However, it was possible to continue nicardipine in all cases at lower doses or even without modification, and hypotension was never responsible for any deleterious clinical effect.

[Use of octreotide in the treatment of digestive endocrine tumors. A French multicenter study]. / Utilisation de l'octréotide dans les tumeurs endocrines digestives. Etude française multicentrique.

Morbidity and mortality in endocrine gastro-enteropancreatic (GEP) tumours are mainly related to the clinical consequences of tumoral peptide hypersecretion. Surgical resection at an early stage is the only curative treatment. However, most tumours are detected only when the hypersecretory state reflects the presence of metastases; surgery and chemotherapy then give only palliative results counterbalanced by serious side-effects. Somatostatin inhibits most endocrine secretions of the GEP tract and thus can alleviate invalidating symptoms. Its use is limited by its short half-life (2 min), the necessity of i.v. infusion and the possibility of a rebound phenomenon. Octreotide, a synthetic somatostatin analogue with a long duration of action, is administered subcutaneously and allows ambulatory treatment. In our series of 78 patients we observed about 80 percent of excellent or good clinical results, enabling the patients to resume normal life. Only minor and transient side-effects were noted. The overall tolerance of the drug was considered excellent or good. Prolonged administration of octreotide is a safe and effective symptomatic treatment in patients without any restriction of anti-tumoral procedures. Furthermore, it prevents the severe carcinoid crises that occur during surgery or embolization in patients with carcinoid syndromes.