Contraception after breast cancer: a retrospective review of the practice among French gynecologists in the 2000's.

PURPOSE OF INVESTIGATION: To describe the French practices regarding contraception after breast cancer in the 2000's. MATERIALS AND METHODS: A total of 2,500 forms were sent to gynecologists practicing in France. Inclusion criteria were premenopausal patients who had a history of breast cancer and who had been prescribed contraception after diagnosis. Between June 1, 2002 and January 1, 2003, 197 evaluable responses were retrieved. RESULTS: The median age of the sample was 38.5 years. The most commonly used form of contraception was an intrauterine device (n = 144, 73.1%). Hormonal contraception was prescribed for 42 patients (21.3%), and other methods were used in 29 patients (14.7%) (Condoms n = 14, tubal sterilization n = 7, and others n = 8). Recurrence occurred in 27 patients (13%); 2.9% in the progestin group, 16.3% in the IUD group, and 14.8% with the other methods). CONCLUSIONS: It is necessary to evaluate current contraception practices after breast cancer to evaluate the efficacy and safety of contraception in these patients.

BI-RADS categorisation of 2,708 consecutive nonpalpable breast lesions in patients referred to a dedicated breast care unit.

OBJECTIVES: To determine the malignancy rate of nonpalpable breast lesions, categorised according to the Breast Imaging Reporting and Data System (BI-RADS) classification in the setting of a Breast Care Unit. METHODS: All nonpalpable breast lesions from consecutive patients referred to a dedicated Breast Care Unit were prospectively reviewed and classified into 5 BI-RADS assessment categories (0, 2, 3, 4, and 5). RESULTS: A total of 2708 lesions were diagnosed by mammography (71.6%), ultrasound (8.7%), mammography and ultrasound (19.5%), or MRI (0.2%). The distribution of the lesions by BI-RADS category was: 152 in category 0 (5.6%), 56 in category 2 (2.1%), 742 in category 3 (27.4%), 1523 in category 4 (56.2%) and 235 in category 5 (8.7%). Histology revealed 570 malignant lesions (32.9%), 152 high-risk lesions (8.8%), and 1010 benign lesions (58.3%). Malignancy was detected in 17 (2.3%) category 3 lesions, 364 (23.9%) category 4 lesions and 185 (78.7%) category 5 lesions. Median follow-up was 36.9 months. CONCLUSION: This pragmatic study reflects the assessment and management of breast impalpable abnormalities referred for care to a specialized Breast Unit. Multidisciplinary evaluation with BI-RADS classification accurately predicts malignancy, and reflects the quality of management. This assessment should be encouraged in community practice appraisal.

Influence of long term oral anticoagulants upon prothrombin fragment 1 + 2, thrombin-antithrombin III complex and D-Dimer levels in patients affected by proximal deep vein thrombosis.

We have investigated the influence of long term oral anticoagulants (OAC) upon the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-Dimer in 20 patients affected by a proximal deep vein thrombosis (DVT) diagnosed by ultrasonic duplex scanning. Patients (63 +/- 17 years, mean +/- SD) were sampled at the beginning of the OAC treatment (day 1), which was started 1 to 6 days after diagnosis confirmation and full heparinization, and then 8, 35 and 92 days after. The results were compared to those obtained in a blood donor population (39 +/- 10 years) and to an age-matched healthy population (63 +/- 19 years). The mean INR determined on days 8, 35 and 92 were almost identical (2.8 +/- 0.7, 2.9 +/- 0.9 and 2.8 +/- 0.6 respectively). In contrast, highly significant variations of the three markers were recorded during the observation period. Eight days after the beginning of OAC, increased levels of TAT complexes were associated with subnormal levels of F1 + 2 suggesting persistence of a hypercoagulable state. On the further sampling times, TAT complexes were in the normal range while F1 + 2 were far below the normal range. Between day 1 and day 92, the levels of D-Dimer continuously decreased reflecting a long-term fibrinolytic process. This study clearly indicates that high INR are not systematically associated with very low F1 + 2 levels, particularly in the acute phase of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of roxatidine acetate on 24-hour gastric acidity. Early evening versus bedtime administration in healthy subjects.

The gastric antisecretory activity of roxatidine acetate was studied on 24-hour intragastric pH in 12 healthy male volunteers. The study was randomised, double-blind and double-dummy where either roxatidine acetate 150 mg as a slow release granulated formulation or placebo were administered at 7.30 pm or 10 pm. Roxatidine acetate 150 mg produced a significant decrease in the number of hours during which gastric acidity ranged between pH 1.5 and 4.0 which was consistent with the pharmacokinetic profile of the drug. There was no significant difference between the median intragastric pH values for early evening and bedtime administration of roxatidine acetate. The present data confirm that roxatidine acetate 150 mg inhibits gastric acid secretion but while a single evening dose is effective in controlling intragastric pH the results suggest there is no clear advantage in an early evening dose compared with a bedtime dose.

Intragastric pH profile during acute respiratory failure in patients with chronic obstructive pulmonary disease. Effect of ranitidine and enteral feeding.

The ability of H2 receptor antagonists and continuous enteral alimentation to maintain high intragastric pH in patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation was evaluated by continuously monitoring intragastric pH prior to and following sequential addition of ranitidine or continuous enteral alimentation (or both) to their therapeutic regimen. Prior to therapy, intragastric pH was less than 4.0 for 75 +/- 10 percent of the time, but never less than 1.0. Nevertheless, this moderate gastric acidity was associated with evidence of mucosal injury. Ranitidine failed to continuously maintain a high intragastric pH (pH less than 4.0 for 35 +/- 11 percent of the time; p greater than 0.2 compared to patients treated with placebo). Following administration of continuous enteral alimentation, intragastric pH fell, and ranitidine therapy only partially blocked this increase in gastric acidity induced by continuous enteral alimentation. We conclude that without treatment, patients with COPD who have acute respiratory failure may develop gastric mucosal injury despite the presence of only moderate intragastric acidity; however, ranitidine and continuous enteral alimentation are not effective in maintaining a high intragastric pH.

Antral gastrin- and somatostatin-producing cells and intraluminal peptide secretion in normal subjects and duodenal ulcer patients with and without vagotomy.

The behaviour of gastrin (G) cells and somatostatin (D) cells in endoscopic antral biopsies and that of intraluminal gastrin (ILG) and somatostatin (ILS) release in the gastric juice were investigated in three groups of patients: control subjects, duodenal ulcer (DU) patients and DU patients treated by a superselective vagotomy (SSV). G and D cell densities were correlated in the three groups of subjects. The G/D cell ratio was significantly increased in SSV patients (P less than 0.001) as compared to control and DU patients. No correlation was found between gastrin or somatostatin cell densities and basal intraluminal levels of the two peptides. ILG output was significantly higher in DU patients than in control or SSV patients (P less than 0.001). ILS output was also higher in DU patients than in controls (P less than 0.001) and in SSV patients (P less than 0.05). It was also significantly augmented in SSV (P less than 0.001) as compared to control patients. ILG and ILS concentrations were only correlated in controls. Within each of the three groups of subjects, ILG and ILS release varied in function of the gastric juice pH. Our results emphasize the necessity to consider the intragastric pH as well as the physiological or pathological state to study intraluminal peptides in man.

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.

Clinical, anatomical, and evolutive features of patients with the Zollinger-Ellison syndrome combined with type I multiple endocrine neoplasia.

The clinical evolution of type I multiple endocrine neoplasia (MEN I) was studied in 45 patients among a consecutive series of 172 with Zollinger-Ellison syndrome (ZES). These 172 patients were seen in our hospital between 1959 and 1989. Diarrhea was half as frequent in ZES-MEN I as in sporadic ZES cases. At diagnosis, mean basal acid output and serum gastrin levels in MEN I patients (28.8 +/- 6.6 mmol/h and 587 +/- 487 pg/ml, respectively) were not different from those observed in the others with sporadic ZES. Laparotomy was performed in all 36 patients with no diffuse liver involvement to attempt the removal of gastrinomas. Twenty-nine patients had adenomas, located in the pancreas in 21, in the duodenal wall in 3, and in both in 5. Adenomas were multiple in 23 cases (78%). No tumor was found in seven patients. Twenty-nine of the 36 operated patients were tumor-free after surgery; 7 died in the postoperative period between 1959 and 1970. Median follow-up of the 38 other patients was 95 months (range 17-278 months). Among the 24 patients without residual tumor at discharge (group I), biological and/or morphological evidence of a persistent or recurrent source of gastrin was obtained in 22. Among the 14 patients with residual tumor (group II), an increase in tumor size was seen in 5 after a median of 27 months (range 9-36 months), while no change occurred in 9 after 54 months (3-100 months). Actuarial survival curves were not different, either in group I versus group II patients (67 and 72% at 5-year follow-up, respectively) or in MEN I versus sporadic ZES patients. Apparently, complete resection of primary tumor did not reduce the incidence of subsequent liver metastases. In all, 21 of the 45 patients had malignant gastrinomas (47%), consisting of liver metastases in 14 (31%), metastatic lymph nodes in 11 (24%), and lung metastases in 2 (4%). Monitoring of fundic argyrophil cells disclosed hyperplasia in 13 of the 14 MEN I patients (92%), and 5 had invasive carcinoid tumors. Taken together, these results prompt us to recommend that in ZES-MEN I patients, surgery should be avoided and oxyntic mucosa regularly monitored.

Quantification of lipoprotein X and its relationship to plasma lipid profile during different types of parenteral nutrition.

An abnormal lipoprotein (LP), detected in plasma during total parenteral nutrition, has been shown to be similar to LPX observed in cholestasis and in familial lecithin-cholesterol-acyl-transferase (LCAT) deficiency. However, the conditions which facilitate the appearance of LPX during total parenteral nutrition are unclear; potential determining factors could be lipid input, plasma lipid levels, and/or inhibition of LCAT activity. An investigation was conducted on 12 patients receiving total parenteral nutrition for 3 wk by simultaneously evaluating plasma LPX (via a quantitative method) as well as total cholesterol, phospholipids (PL), triglycerides (TG), apolipoprotein B, and LCAT activity. Daily total nonprotein calories (40 kcal/kg body weight) and nitrogen input (250 mg/kg body weight) were fixed in this study. Three 7-day periods were defined: during periods 1 and 3, lipid emulsion (10 or 20% Intralipid) and glucose were given as nonprotein calories (glucose-lipid periods); in period 2, glucose was administered alone as the sole source of nonprotein energy (glucose period) so that the total energy input was not modified. During periods 1 and 3, the patients were randomly assigned to receive either 9 g (period 1) and 12 g (period 3) of PL/day for 7 days, or 12 and 9 g of PL/day. By infusing either 10 or 20% Intralipid, TG input was varied concomitantly so that the subjects received 75, 100, or 150 g/day in periods 1 and 3. During the glucose-lipid periods, plasma LPX was measurable from the 2nd day and increased progressively. Its increment was closely related to a rise in unesterified cholesterol and PL (r = 0.7; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Small bowel and plasma gastrin rhythms in cats.

The purpose of this experiment was to study the possible role of the gastric antrum and small bowel in the rhythm(s) of plasma gastrin. The cat was used as the laboratory animal. Three groups of cats were provided with a gastric fistula for the study of gastric acid and plasma gastrin rhythms. The first group (N = 7) served as controls. A second group (N = 3) was antrectomized and later subjected to a 80% small bowel resection. Gastric acid secretions were collected every 30 min from 0800 to 2400. Blood samples for determination of gastrin were drawn every 2 hr from 0800 to 2400. In control animals a circadian (i.e. approximately 24 hr) and 3 ultradian (i.e. less than 24 hr) rhythms were detected for acid output. In the antrectomized cats, circadian and ultradian rhythms were documented. After small bowel resection circadian and ultradian rhythms in gastric acid secretion were observed. For plasma gastrin, circadian and ultradian rhythms were found in the control cats. In the antrectomized cats no rhythms were observed. After small bowel resection an ultradian rhythm reappeared in these antrectomized cats. Removal of the antrum in the cat induces disappearance of circadian and ultradian rhythms of plasma gastrin but fails to modify the acid rhythms. Small bowel resection results in the reappearance of an ultradian rhythm for plasma gastrin and a shift in acrophase for the circadian rhythm in acid secretion.

[Role of antral histamine and gastrin in gastric acid secretion: experimental facts and hypotheses]. / Rôle de l'histamine antrale et de la gastrine dans la sécrétion acide gastrique: réalités expérimentales et hypothèses.

Histamine isolated from the gastric antral mucosa probably potentiates the secretory activity of gastrin by suppression of the inhibitory effect of somatostatin on gastrin. In dogs with gastric fistula and Heindenhain pouch, acid secretion was obtained in response to exogenous gastrin, antral histamine or various combinations of both stimulants. Acid output was expressed by graphic representation: the administered doses of gastrin and antral histamine were reported respectively, on the X and Y axis, the acid output values were plotted on the intersection of the stimulant dosages used, and curves of equal acid outputs were drawn. This representation was used to approach the physiological and physiopathological mechanisms of gastric secretion, considering that gastrin and antral histamine could be the main parameters. It also seems possible that an histaminic factor could be involved in secretion processes. Excess or lack of one of the other stimulants could be responsible for an increased or a decreased secretory response: these facts can be related to the curves of high acid output or low acid output observed in the animal. Thus, histamine, especially of antral origin, might be an important component of the secretion mechanism, by modulation of gastrin activity; both substances could be the main mediators of somatostatin-induced inhibition.

[Idiopathic ulcerative proctitis. Clinical presentation and endoscopic outcome]. / Rectites hémorragiques non spécifiques. Aspects symptomatiques et évolution endoscopique.

Endoscopic information was obtained for 52 patients with ulcerative proctitis (23 F, 29 H) seen during a ten-year period. The median follow-up was 68 +/- 8 months. During the first referral period (38 patients experienced a first attack), endoscopic particularities were available: inflammation involved the anal mucosa above the dental line (n = 16), the whole circumference of rectal mucosa (n = 19) or the anterior wall exclusively (n = 33). The upper limit was 12.2 +/- 0.6 cm from the anal verge. Inflammatory lesions were higher in circumferencial conditions, when patients were older (late onset disease) but sex and ethnic state did not influence results of endoscopic presentation. Exulcerations or superficial ulcers were visualized in 16 and spontaneous bleeding in 43. Forty-five patients achieved clinical accuracy after 9.4 +/- 1 ms, but 32 only a complete endoscopic remission. Mean number of relapses was 3.6 +/- 0.4; 13 patients experienced a single attack. During relapses, inflammation was stable in 11 of 38 patients. Extension to the rectum in rectosigmoid junction, and sigmoid and above by 6, 14, and 7 patients respectively. After 5 years follow-up, the cumulative risk of further extension was 37 percent and 13 percent, respectively. Low abdominal pain, an family history of ulcerative colitis, and high inflammatory lesions at referral were significantly associated with a higher risk of extension. Cancer did not occur and not surgery was necessary during the follow-up. Idiopathic proctitis is perhaps at the "benign end" of the spectrum of ulcerative colitis. Nevertheless, its endoscopic particularities should be noticed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Histologic aspect of the human gastric mucosa: relation to gastrin and somatostatin cells and the intraluminal secretion of these peptides]. / Aspect histologique de la muqueuse gastrique humaine: relations avec les cellules à gastrine et à somatostatine et la sécrétion intraluminale de ces peptides.

Fifty-eight subjects including controls, patients with duodenal ulcer, non-operated or treated with a superselective vagotomy underwent endoscopic fundic and antral biopsies. Histologic classification of the two mucosae was performed. We examined the relationship between the histologic grade of gastritis in the two mucosae, then between the histologic aspect of the antral mucosa and antral gastrin-and somatostatin-cell densities, the basal intraluminal secretion of gastrin and somatostatin. There was a significant correlation between the histologic aspect of fundic or antral mucosa and the age of patients, except in the case of vagotomized patients. Fundic and antral histologic patterns were also correlated in each patient, except for vagotomized. Gastrin and somatostatin cell densities showed no variation in function of the degree of inflammation of non atrophic gastritis. These cell densities showed a tendency to decrease in atrophic gastritis, especially when intestinal metaplasia was present. Intraluminal gastrin secretion was increased in patients with mild atrophic gastritis (p less than 0.05 to p less than 0.02) in comparison with those whose histology was roughly normal. It was also increased in severe atrophic gastritis. The highest intraluminal secretion of somatostatin was observed in patients with mild atrophic gastritis while this secretion fell noticeably in those showing severe atrophic gastritis, as compared to the other groups. This work seems to suggest a relationship between intraluminal peptides and the evolution of gastritis. While results are still preliminary, they do not indicate that these peptides, thus released, play any pathophysiologic role.

Sensitivity, specificity and predictive values of the secretin infusion test in the diagnosis of gastrinoma.

From 1974 to 1981, 55 patients, 18 with Zollinger-Ellison syndrome (ZES) histologically confirmed and 37 patients with duodenal ulcer (DU) without pylorostenosis were followed for a minimal period of 5 years. The diagnostic values of a) basal acid output (BAO mEq/h); b) 60 min acid output after secretin infusion, 3 CU-GIH/kg, (MAO-SE mEq/h); c) basal serum gastrin (BSG pg/ml: mean of 4 gastrin determinations) and d) serum gastrin after secretin (SG-SE pg/ml: mean of 4 gastrin determinations during secretin infusion) were calculated. Cut off point values of 100 p. 100 specificity (i. e. no DU patient reached these values) with a positive predictive value of 100 p. 100 (i. e. probability for gastrinoma when this cut off point was attained) were BAO greater than 26 mEq/h, MAO-SE greater than 18 mEq/h, BSG greater than 221 pg/ml, SG-SE greater than 186 pg/ml. The sensitivities of these parameters (i. e. percent of ZES which reached the given cut off point) were respectively (p. 100): 39, 78, 72 and 94. Ranking these parameters according to their own discriminative value expressed by R2 (square correlation coefficient) gave SG-SE, R2 = 0.559; BSG, R2 = 0.508; MAO-SE, R2 = 0.456; BAO, R2 = 0.414. The most discriminative association of 2 variables was SG-SE and MAO-SE (R2 = 0.650). Association of SG-SE, MAO-SE and BAO or BSG (or BAO and BSG) did not increase significantly the discrimination between ZES and DU (R2 = 0.672).

[Treatment of gastric acid hypersecretion in the Zollinger-Ellison syndrome with a thioamide derivative (40749 RP). Comparison with ranitidine]. / Traitement de l'hypersécrétion gastrique acide du syndrome de Zollinger-Ellison par un dérivé des thioamides (40749 RP). Comparaison avec la ranitidine.

The efficacy of a new gastric antisecretory drug, 40749 RP, was studied in five cases of Zollinger-Ellison syndrome. Daily oral dosage was 2 mg/kg bw b.d. Clinical results and tolerance were excellent in all five cases (follow-up 1 to 16 months). In two cases, chronic duodenitis disappeared with 40749 RP only. Antisecretory activity was evaluated on basal acid output and 24 h pH profile. During 24 h period, the mean number of hours at or below pH 1.5, 2 and 3 obtained with 40749 RP in the five cases was 5, 9 and 12 h versus 13, 14 and 19 h with ranitidine. In all cases, basal acid output measured during one hour before fractional intake of 40749 RP was below 7 mmol/h during the first month of treatment. Clinical and biological results obtained with 40749 RP are similar to those obtained with omeprazole.

[Plasma pharmacokinetics of roxatidine in the healthy man: correlation with gastric antisecretory effect]. / Pharmacocinétique plasmatique de la roxatidine chez l'homme sain: corrélation avec l'effet antisécrétoire gastrique.

Inhibitory effects of roxatidine acetate upon human gastric secretion have been shown to be dose-related after oral administration. In order to correlate this effect with drug pharmacokinetics, blood concentration of the active metabolite, roxatidine, was assessed in 10 healthy volunteers, each receiving in random order 75, 150, 300, 600 mg of roxatidine acetate and placebo. Blood was drawn for roxatidine measurement at T 0 (time of drug intake) T 75, 90, 120, 150, 210, 240 and 300 min. Meal-induced gastric secretion was studied by intragastric titration (IGT) at 15 min intervals, from T 150 to T 240. Mean peak of blood concentration occurred at T 150 with significant correlation with the administered dosage. Gastric secretion inhibition over the 90 min of IGT correlated with peak concentration exclusively for the subpopulation with peak occurrence at T 150. Beyond the peak, decrease in roxatidine concentrations was slow, as expected from a known 6-h half-life. However, overall results showed that mean blood concentration was correlated with gastric secretion inhibition from T 180 on. The last IGT sample also correlated with the peak. Interpretation of these results would be different whether roxatidine concentration variations are appreciated as exhibiting a significant decrease or not. Infusion studies of roxatidine would be a valuable technique for further analysis and comparison of blood-concentration/efficacy relationships as compared with other H2-antagonists.

[How to express results of 24-hour gastric pH measurement? Choice of a mode of expression in 27 healthy subjects]. / Comment exprimer les résultats de la pH-métrie gastrique sur 24 heures? Choix d'un mode d'expression chez 27 sujets sains.

Twenty-four hour intragastric acidity was studied in 27 healthy subjects (mean age = 29 yrs) by continuous recording in standardized conditions. Data obtained were expressed according to several analytical methods as used extensively elsewhere. In our study, there was a wide discrepancy in results from one subject to another. The use of median values of pH was more appropriate than mean values to express half-hour acidity levels for 24 hours. The median value of H+ concentration is recommended as well. The median value of pH varied from 1 to 4.8 with a slight rise during the second half of the night. During the postprandial period, increase of pH values was prolonged over 2 h 30 in 50 p. 100 of subjects. Profile of pH allowed to demonstrate the distribution of pH value without excluding the extreme values. Both periodicity of pH measurement (30 or 60 min) and parameters used to quantify acidity (percentage of time or pH value at or below threshold values) did not modify results. As measured over a 24 hours period, the percentage of time (mean +/- SEM) at or below pH 1.5 and 3.5 was 54 +/- 3 p. 100 and 85 +/- 2 p. 100, respectively. Daytime and night-time profiles were similar. Mean 24 h H+ concentration (mean +/- SEM) was 47 +/- 35 mmol/l, with, once again, similarity between day and night-time values. The mean 24 h pH values underestimated true acidity with respect to median values.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistence of circadian rhythms in gastric acid, gastrin, and pancreatic polypeptide secretions despite loss of cortisol and body temperature rhythms in man under stress.

During organic stress, severe dysfunctions of fundamental biological phenomena, such as modification of vagal tone, have been described. These dysfunctions could induce changes in the rhythm of acid secretion and/or its hormonal control. We therefore analyzed the effects of acute respiratory failure on the 24 h variations in intragastric pH, serum gastrin, and pancreatic polypeptide levels, taken as a marker of vagal tone. Body temperature and plasma cortisol circadian rhythms were used as marker rhythms. Twelve patients with chronic obstructive pulmonary disease complicated with acute respiratory failure were studied before and during continuous enteral nutrition; half of the patients received ranitidine, a H2 blocker. During the 3 days of the study, intragastric pH was below 2.5 for only one third of the time. No difference was observed between the placebo and the ranitidine groups. Plasma pancreatic polypeptide was within normal ranges despite increased cortisol levels. Gastrin levels reflected changes in intragastric pH over the 24 h time frame and were noted to increase during ranitidine and enteral nutrition. Despite the loss of cortisol and body temperature circadian rhythmicity all throughout the study, circadian rhythms were maintained or restored during the different therapeutic regimens for intragastric pH, serum gastrin, and pancreatic polypeptide levels. Moreover, an ultradian rhythm for gastrin before any treatment, a circadian rhythm for intragastric pH on enteral nutrition, a circadian rhythm for intragastric pH, plasma gastrin and plasma pancreatic polypeptide on ranitidine regimen were observed. Thus during acute respiratory failure, certain physiological circadian rhythms persisted despite the disappearance of "marker" rhythms. Furthermore, these rhythms for digestive secretions could be pharmacologically restored.

[Gastric secretory, ultrastructural and pH changes during prolonged treatment with omeprazole in a severe form of Zollinger-Ellison syndrome]. / Modifications sécrétoires, pHmétriques, et ultrastructurales gastriques au cours d'un traitement prolongé par l'oméprazole dans une forme sévère de syndrome de Zollinger-Ellison.

Omeprazole, a powerful and long-lasting gastric anti-secretory benziimidazole derivative has been used to treat a particularly severe case of Zollinger-Ellison syndrome with familial type I multiple endocrine involvement. Before treatment with omeprazole, the patient's basal acid secretion, ranging from 50 to 100 mmol/h, had been poorly controlled by cimetidine (doses of up to 2,400 mg/d), ranitidine (doses of up to 1,200 mg/d) and even by ranitidine (1,200 mg/d) combined with pirenzepine (150 mg/d). Upon oral administration of four 20-mg capsules of omeprazole twice daily, rapid healing of the diffuse mucosal ulcerations of the upper GI tract as well as control of diarrhea were achieved. Clinical benefit accompagnied dramatic and sustained reductions in gastric acid secretion as demonstrated by repeated basal output measurements and 24-hour intragastric pH recording. The biodisponibility of omeprazole improved as gastric intraluminal acidity was reduced. The effects of omeprazole on pepsin output appeared to be mainly related to the reduction of gastric secretory volume. After more than one year of treatment, neither clinical nor biological side-effects were noted. However, repeated ultrastructural studies of fundic gastric mucosa revealed two types of alterations: a) a pattern of hyper-stimulated parietal cells with turgescent intra-cellular micro-canalicus invested by numerous microvilli; b) in about a fourth of the parietal cells, cytoplasmic modifications resembling auto-phagosomia and mitochondrial reduction in number and morphological transformation. Poorly understood to date, these alterations call for regular histological control of the gastric mucosa in patients with Zollinger-Ellison syndrome submitted to long-term administration of large doses of omeprazole.

[Relation of the kinetics of the antisecretory effect and kinetics of blood concentration in man. Comparing cimetidine and ranitidine]. / Rapports entre cinétique de l'effet antisécrétoire et cinétique de la concentration sanguine chez l'homme. Comparaison cimétidine-ranitidine.

The time course of antisecretory effects of ranitidine and cimetidine and their relationship to plasma concentration were studied in 4 healthy volunteers. Placebo, cimetidine (266 mg) or ranitidine (100 mg) were infused during one hour preceding the 90 minute assessment of food-stimulated gastric acid secretion (intragastric titration); cimetidine and ranitidine blood levels and gastric acid outputs were measured at 15 min intervals. For each test a significant (p less than or equal to 0.01) correlation was found between concentration and effect. The half-life effect of ranitidine (t1/2 E) was significantly (p less than or equal to 0.05) greater than t1/2 E of cimetidine whereas their plasma half-lives (t1/2) were similar. The ratio t1/2 E/t1/2 was significantly (p less than or equal to 0.05) lower with cimetidine than with ranitidine. Explanations for this discrepancy are analyzed according to various hypotheses. The determination of t1/2 E seems to be a good approach to the duration of action of H2-antagonists. Our results show that the ratio t1/2 E/t1/2 and the t1/2 E might be important pharmacokinetic parameters to compare various H2-receptor antagonists.