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Biomedical subjects

P Ruszniewski

Publications and source records attributed to P Ruszniewski.

At least 19 recordsLinked to original sources

Influence of multiple endocrine neoplasia type 1 on gastric endocrine cells in patients with the Zollinger-Ellison syndrome.

The influences of multiple endocrine neoplasia type 1 (MEN 1), hypergastrinaemia, age, and sex on gastric endocrine cell densities were studied in 48 patients with the Zollinger-Ellison syndrome of either the sporadic type (n = 31) or associated with MEN 1 (n = 17). The mean fundic argyrophil cell density was higher in women (p < 0.05). It showed no appreciable difference between young and old women but it declined with age in men. The mean argyrophil cell density, when adjusted for sex, was higher (+48.5%, p = 0.06) in patients with Zollinger-Ellison syndrome associated with MEN 1 than in those with sporadic type disease. This measurement was not significantly different between the two groups of patients when antisecretory treatments were considered. In patients with sporadic type disease, fundic argyrophil cells showed a normal pattern (16%) or diffuse (71%) or linear (13%) hyperplasia. In patients with MEN 1 diffuse and linear hyperplasia were of the same order (53% and 47%). Furthermore, fundic argyrophil endocrine tumours developed in five of 17-that is, 29.5% of patients with associated MEN 1 while none was seen in patients with sporadic type disease. These tumours showed an exclusive or prominent enterochromaffin like cell population. Antral gastrin and somatostatin cell densities and fasting serum gastrin concentrations were similar in the two groups of patients with Zollinger-Ellison syndrome. Whatever the underlying mechanism for carcinoidosis, the risk of developing fundic enterochromaffin like cell tumours in Zollinger-Ellison syndrome patients who present with MEN 1 is probably higher than was initially estimated and suggests that regular follow up of these patients is necessary.

Adolescent

[Cost of fibroscopy in gastroduodenal ulcer].

The assessment of mean cost of upper GI endoscopy is of critical importance if one wants to perform pharmacoeconomic studies, especially in peptic ulcer disease (PUD). The aim of this work was to calculate such costs, based on an inquiry conducted in December 1991 in a representative sampling of 94 French gastroenterologists (GEs) (i.e. 4.3% of the whole population). Thirty-nine percent of GEs work in their office; 25% work in private and 26% in public hospitals. GEs performed 70 +/- 5 (mean +/- SEM) upper GI endoscopies per month. Fifty-nine % are performed to investigate epigastric pain; PUD was found in nearly one patient out of four. Fifteen % of the endoscopies were performed for follow-up of PUD. Upper GI endoscopy modalities varied greatly according to whether performed in GEs' office, private or public hospital. The proportion of investigations performed with biopsies was 66, 71 and 50%, respectively. Neuroleptanalgesia (or general anesthesia), was performed in 8, 49 and 4% of cases, respectively, and a 24-hour hospitalization was required in 0, 7 and 2% of cases, respectively. Sources of expenditure were evaluated according to the current fares of the French Health Care System (for GEs' office and private hospitals) and to real costs (for public hospitals). Taking into account the differences in place and modalities of realization, mean cost of upper GI endoscopy was evaluated at 1,084 FF. This cost could be used in future cost or cost/effectiveness studies of diagnostic or therapeutic strategies.

Duodenal Ulcer

[Economic analysis of maintenance treatment with ranitidine 150 mg in duodenal ulcer].

While it is well-established that ranitidine 150 mg/day is effective in preventing recurrence and complications of duodenal ulcer, the economic impact of maintenance therapy is unknown. Socio-economic data, allowing to calculate the costs and cost-effectiveness ratio of intermittent and maintenance therapy, were prospectively obtained from a therapeutic trial in 399 duodenal ulcer patients (Mignon et al, Gastroenterol Clin Biol 1990;14:732-8). Visits and endoscopy investigations, work days lost, duration of hospital stay and drug consumption were recorded in both placebo (n = 202) and ranitidine (n = 197) groups. Each source of expenditure was evaluated using current fares and sales prices, from the point of view of both the collectivity and the French Health Care System. The costs of ranitidine strategy were less than the costs of placebo strategy, for the collectivity (2,031 and 2,823 FF per patient for one year, respectively) as well as for the French Health Care System (1,541 and 2,426 FF per patient per year, respectively). In the ranitidine group, expenditures were principally due to the drug (71%) and endoscopy investigation (24%). In the placebo group, endoscopy and hospital stay accounted for 50 and 39% of the expenses, respectively. The latter were due to the occurrence of complications in the placebo group. Sensitivity analysis disclosed that the results were unsensitive to the variations in cost hypotheses of the main expenditure sources. Cost/effectiveness analysis defined as cost per patient successfully treated showed that the cost of a "ranitidine strategy" was 2-3 times less than a "placebo strategy". Maintenance therapy for duodenal ulcer with ranitidine 150 mg/day for one year is less expensive and more cost-effective than intermittent treatment.

Cost of Illness

[Intravenous chemotherapy with streptozotocin and 5 fluorouracil for hepatic metastases of Zollinger-Ellison syndrome. A prospective multicenter study in 21 patients].

Twenty-one patients with liver metastasis of gastrinoma received intravenous streptozotocin (STZ: 500 mg/sqm.day) and 5 fluorouracil (5 FU: 400 mg/sqm.day) during 5 consecutive days every 6 weeks. Variations in tumor mass (TM) on CT scan and in serum gastrin levels were assessed every two courses. Treatment was continued if TM decreased or remained unchanged, and if severe renal toxicity of STZ was not observed. Three patients had a minor (25-50 percent decrease in TM) and transient response. Only one patient (5 percent) presented an objective response (greater than 50 percent) which lasted 55 months. TM remained unchanged in 28 percent and increased in 65 percent of cases. Changes in serum gastrin levels did not parallel those of TM. Nausea and/or vomiting (66 percent) was easily controlled by symptomatic treatment. Renal toxicity (24 percent), including one case of acute and transient renal failure due to accidental overdosing, was observed in 24 percent of cases. This prospective study does not confirm the efficacy of combined STZ-5 FU as previously suggested by retrospective data.

Actuarial Analysis

[Intermittent treatment or preventive treatment of recurrence in duodenal ulcer disease? A controlled, double-blind study with 150 mg ranitidine daily for one year].

This 1-year study compared two pragmatic strategies in long-term management of duodenal ulcer: continuous treatment with ranitidine 150 mg after dinner and treatment of duodenal ulcer attacks with ranitidine 300 mg and placebo in the interval. A multicentric, randomized double-blind study was conducted in 399 patients, 197 in the ranitidine group and 202 in the placebo group. Efficacy was judged by the prevalence of ulcer-pain recurrences; secondary criteria were the prevalence of endoscopic recurrences, complications and the number of facultative visits, hospitalizations and days off work related to duodenal ulcer disease. Both groups were similar with regard to main epidemiologic features and number of drop-outs (10.5 percent). Fifty-two patients were withdrawn for symptomatic or endoscopic relapses: 6 in the ranitidine group, 46 in the placebo group (p less than 0.05). Sixty-six percent of the patients remained asymptomatic at one year in the ranitidine group versus 33 percent in the placebo group (p less than 0.001). Seventeen patients with ranitidine (8.6 percent) and 59 with placebo (29.2 percent) experienced at least one endoscopic recurrence (p less than 0.05). In the placebo group, 8 complications were observed (bleeding = 5, duodenal stenosis = 3), and none in the ranitidine group (p less than 0.005). Patients with ranitidine had significantly less facultative visits and endoscopies, number of days off work, and hospitalizations (p less than 0.05). Tolerance was good (5 percent side-effects, all minor) and identical in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Gastric endocrine cell behavior in Zollinger-Ellison patients upon long-term potent antisecretory treatment.

Serum gastrin and gastric endocrine cell numerical densities were examined in 22 patients with long-standing Zollinger-Ellison syndrome who were receiving either ranitidine, omeprazole, or other antisecretory drugs (SMS 201-995 or pirenzepine with or without ranitidine) for long periods of time. Fifteen patients had iterative biopsies. Twenty-one subjects with normal endoscopy, serum gastrin, and acid secretion served as controls. Individual fundic argyrophil cell density was above the highest control value in 77% of the patients, whatever the treatment. Argyrophil cell densities tended to be higher in women than in men. During the survey, fundic carcinoids developed in one ranitidine- and in one omeprazole-treated patient. Fundic argyrophil cell densities were correlated with serum gastrin levels (r' = 0.730, p less than 0.001). Antral somatostatin cell density was not modified in any patients as compared with controls, nor was antral gastrin cell density except in omeprazole-treated patients. In these patients, gastrin cell density and gastrin to somatostatin cell ratio were significantly higher than in all other patients or controls. Such increases may indicate true gastrin cell hyperplasia in relation to drug-induced profound acid inhibition.

Adult

Long-acting somatostatin (SMS 201-995) in the management of Zollinger-Ellison syndrome: evidence for sustained efficacy.

Five patients with Zollinger-Ellison syndrome (ZES) have been treated during 9-12 months with long-acting somatostatin (SMS 201-995). Basal acid output presented a sustained decrease in 4 of 5 cases, below 10 mmol/h in three patients, allowing ranitidine discontinuation. No escape phenomenon was observed. Maximal acid secretion progressively decreased, suggesting an SMS antitrophic effect. Serum gastrin level was affected in a greater extent, showing a mean 87% decrease throughout the treatment period. Thus three patients kept normal serum gastrin levels in the long-term; one escaped to SMS after 9 months. Associated endocrine neoplasia were poorly influenced by SMS. No convincing evidence of tumor size variation was noted. Tolerance of SMS was excellent in the five patients. SMS' antitrophic and antigastrin properties could be of great interest in long-term management of ZES.

Adult

Long acting somatostatin treatment of paraneoplastic Cushing's syndrome in a case of Zollinger-Ellison syndrome.

Cushing's syndrome, caused by ectopic ACTH production during Zollinger-Ellison syndrome, raises difficult therapeutic problems. We report a case of clinical and biological efficacy of long acting somatostatin (SMS) in this condition. In a short term study with 200 micrograms SMS bid, symptoms of hypercorticism disappeared while cortisol and ACTH serum concentrations fell below the normal values. Longterm treatment was instituted with 50 micrograms SMS bid. Excellent clinical efficacy as well as normal cortisol and ACTH serum concentrations were maintained during the nine month follow up. Lipotrophic hormone (LPH) serum concentration remained raised. No decrease in size of hepatic metastases was observed. Long acting somatostatin analogues may be useful in endocrine paraneoplastic syndromes.

ACTH Syndrome, Ectopic

Gastrin secretion by gastrinoma cells in long-term culture.

Gastrinoma cells from surgical specimens of a primary pancreatic tumor and an hepatic metastasis in two patients with a Zollinger-Ellison syndrome were grown and subcultured for 7 mo. Cultured cells displayed a strong reactivity to heptadecapeptide gastrin antibody and maintained an ultrastructural appearance resembling that of the original tumor cells with the presence of secretory granules of variable size and electron density. Cultured cells also showed the ability to secrete immunoreactive gastrin, and this secretion was further concentration-dependently stimulated by secretin (10(-10)-10(-6) M), carbachol (10(-6) M), and bombesin (10(-10)-10(-6) M). The latter peptide was the more potent stimulant with a maximal effect at 10(-9) M (460 +/- 20% of basal release; P less than 0.05). This stimulation occurred in the absence of extracellular Ca2+ and was potentiated by the addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP; 10(-3) M) into the culture medium. The somatostatin analogue, somatostatin-(201-995), did not alter basal gastrin release but inhibited secretin, carbachol, and bombesin stimulation. Moreover, DBcAMP (10(-3) M) and Ca2+ (1-3 mM) stimulated gastrin release; Ca2+ ionophore A23187 (6 micrograms/ml) enhanced gastrin response to Ca2+ in the early time intervals of incubation. Furthermore the phorbol ester derivative, 12-O-tetradecanoyl phorbol-13-acetate, dramatically stimulated gastrin release (10 times the basal value). We conclude that gastrinoma cells can be cultured over an extended period with maintenance of their capacity to secrete gastrin in response to various hormones and mediators.(ABSTRACT TRUNCATED AT 250 WORDS)

Bombesin