Three months of octreotide treatment decreases gastric acid secretion and argyrophil cell density in patients with Zollinger-Ellison syndrome and antral G-cell hyperfunction

Methods: The effects of three months of treatment with octreotide on gastric acid hypersecretion induced by hypergastrinaemia were investigated in patients with Zollinger-Ellison syndrome (n= 5) or antral G-cell hyperfunction (n= 4). Gastric acid secretion, fasting plasma gastrin concentrations and clinical findings were examined, and a morphometrical analysis of oxyntic endocrine cells was performed. Results: Administration of octreotide 100 meg b.d. subcutaneously significantly decreased the volume density of argyrophil cells (P < 0.05) as well as basal and pentagastrin-stimulated acid secretion (P < 0.05). Although partial or complete loss of inhibition was found in most patients after 3 months, gastrin levels were decreased during the first 2 months of treatment (P < 0.05). Fundic D-cells were not affected by treatment. Positive correlations were observed between volume density of argyrophil cells and basal acid output (r= 0.65); plasma gastrin and basal acid output (r= 0.74); plasma gastrin concentrations and volume density of argyrophil cells (r= 0.80). Conclusion: These results support the important role of the enterochromamn-like cell in maintaining acid secretion, and indicate a specific role for octreotide in the therapy of gastric acid hypersecretion associated with hypergastrinaemic diseases.     

Malignancy: Changes in Circulating Immature and Mature Dendritic Cells During IL-2 Cancer Immunotherapy and Their Relation with Lymphocyte Increase and Clinical Response

Lymphocytosis is the main biomarker predicting the efficacy of subcutaneous IL-2 anticancer immunotherapy. In addition, it has been demonstrated the fundamental role of dendritic cells (DC) in the generation of an effective anticancer immunity. However, the relation between IL-2 and DC system needs to be further understood. This preliminary study was performed in an attempt to analyze changes in circulating DC during IL-2 cancer immunotherapy in relation to lymphocyte variations and clinical efficacy of treatment. The study included 20 metastatic renal cell cancer patients, who underwent subcutaneous low-dose IL-2 immunotherapy (6.000.000 IU/day for 6 days/week for 4 weeks). To evaluate DC, venous blood samples were collected before and after 2 weeks of IL-2 injections, corresponding to the period of maximum lymphocytosis. Immature (CD123(+) ) and mature (CD11c(+) ) DC were measured by FACS and monoclonal antibodies. IL-2 induced a significant increase in the mean number of circulating mature DC, whereas no substantial change occurred in immature DC mean number. The increase in mature DC was associated with a control of disease, whereas no rise was observed in patients who had progressed on IL-2 immunotherapy. Moreover, the increase in mature DC mean number was significantly higher in patients showing evident lymphocytosis, with lymphocyte enhancement greater than 1000 cells/mmc, than in patients with less pronounced lymphocytosis, even though no significant correlation was seen in between mature DC and lymphocyte increase. This preliminary study would suggest that IL-2 may stimulate DC system and that the clinical anticancer efficacy of IL-2 is associated with the increase in circulating mature DC, which could be considered as a new favourable biomarker during IL-2 immunotherapy.     

SOMATOSTATIN AND OXYTOCIN INFUSION INHIBITS THE RISE OF PLASMA β-ENDORPHIN, β-LIPOTROPHIN AND CORTISOL INDUCED BY INSULIN HYPOGLYCAEMIA

The present study investigated the possible effect of somatostatin and oxytocin on the basal and stress-induced rise of beta-endorphin (beta-END), beta-lipotrophin (beta-LPH) and cortisol in the human. For this purpose somatostatin (4.1 micrograms/min for 120 min or oxytocin (0.4 micrograms/min for 120 min) was infused into two different groups of seven healthy subjects; 30 min after the start of the infusion, placebo or insulin (0.1 IU/kg body weight, B.W.) was injected on two different days. In a third experimental step, an insulin tolerance test was performed during saline infusion to evaluate stress-related effects on the different hormonal secretions under basal conditions. Plasma levels of beta-END, beta-LPH and cortisol were measured by radioimmunoassay. Extraction and chromatographic procedures preceded the assay for beta-END and beta-LPH. Neither somatostatin nor oxytocin significantly modified basal plasma levels of beta-END, beta-LPH and cortisol. However these treatments blunted the rise of the three hormones seen at 45 and 60 min during insulin-induced hypoglycaemia (P less than 0.01). These results indicate that somatostatin and oxytocin may influence the beta-END, beta-LPH and cortisol increase induced by stress in humans, without affecting their basal secretion.     

Fourier Analysis in Patients with Different Pacing Modes

The purpose of this study was to evaluate the usefulness of phase analysis in detecting the altered activation sequence induced by different pacing modes. Radionuclide ventriculography and planar gated blood pool scintigraphy were performed at rest in 56 patients with different pacemakers. This method permitted us to localize the pacemaker impulse site in the right ventricle and its diffusion in the heart. In patients with VVI pacemaker, this technique showed an evident asynchronism of contraction and relaxation of each ventricle and the standard deviation of phase angle (sigma), calculated by computer, is greater during pacing than sinus rhythm for left (LV) and right (RV) ventricles (LV sigma: 17 degrees +/- 4 vs 11 degrees +/- 3, less than 0.001; RV sigma: 31 degrees +/- 7 vs 14 degrees +/- 4, P less than 0.001). In the patients with VVI rate responsive pacemakers, the LV sigma changed from 18.5 +/- 3 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.001, while the RV sigma changed from 30 degrees +/- 8 to 14 degrees +/- 4, P less than 0.001. Instead in the patients with DDD pacemakers, the LV sigma changed from 15.5 degrees +/- 2 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.05, while the RV sigma changed from 29.1 degrees +/- 6 to 14 degrees +/- 4, P less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)     

New Cardiomechanic Pacing Lead Sensor Based on High Frequency Parameters: Experimental Studies in Sheep

Pacing Lead as a High Frequency Cardiomechanic Sensor . Introduction: The purpose of this study was to investigate the possibility of detecting and quantifying ventricular contraction in sheep utilizing the cardiomechanic sensor based upon the high frequency (HF) parameters measurements on bipolar cardiac pacing leads. Measurement of the HF reflection coefficient yields the lead‐bending signal (LBS) caused by myocardial contraction. The correlation between the lead‐bending acceleration (LBA) expressed as the rate of rise of LBS and LV dP/dt should reveal that LBS may be utilized as a cardiomechanic sensor in implantable cardiac electrotherapy devices. Methods and Results: We implanted 3 different pacing leads and tested the measurement system in 9 sheep (42 ± 6 kg) at baseline and during acute hemodynamic intervention with dobutamine infusion and tachycardia induced by VVI pacing at 200 bpm. A stable, consistent, and reproducible LBS was obtained in all sheep during the implantation procedure and 4 months after the implantation during different experimental conditions that included hemodynamic interventions. The dependence between LBA_max and LV dP/dt_max was found to be statistically significant and with high Pearson's correlation coefficient (r = 0.855, P <0.001). We could also observe the hemodynamic deterioration caused by fast ventricular pacing with the decrease of LV dp/dt and LBA compared with sinus rhythm. Conclusion: This study confirms the feasibility and efficacy of the hemodynamic sensor based upon HF lead parameters. Moreover, it was demonstrated that LBA_max is highly correlated to the ventricular contractility and, therefore, can be efficiently used as a hemodynamic and cardiomechanic sensor. (J Cardiovasc Electrophysiol, Vol. 24, pp. 338‐346, March 2013)     

Efficacy of long-term therapy with low doses of omeprazole in the control of gastric acid secretion in Zollinger-Ellison syndrome patients

Thirteen patients with Zollinger-Ellison syndrome were investigated: 8 without, and 5 with, previous gastric surgery. After 7–34 months of treatment with famotidine, 8 out of 13 patients were resistant to this drug. Omeprazole 60 mg/day was administered to these 8 patients; after one month, the dose was reduced to 40 mg/day, and after another month to 20 mg/day. Basal acid secretion was inhibited by every dose of omeprazole. The patients were then treated with a low dose (20 mg/day) of omeprazole for a longer period. Periodic clinical and endoscopic assessments, and measurement of basal acid secretion showed the efficacy of this low dose of omeprazole in our Zollinger-Ellison syndrome patients. The drug was discontinued after 12–32 months of omeprazole treatment, and gastric acid recovery was evaluated. Four patients recovered 50% of their ‘initial basal acid secretion’ after 5 days, while two patients who had been treated with omeprazole for a longer time (30–32 months) recovered only 38 and 40%, respectively, of their ‘initial basal acid secretion’ at the tenth day. Our results indicate that the omeprazole dosage to be used in the treatment of Zollinger-Ellison syndrome must be chosen principally on the basis of basal acid secretion determination. A low daily dose of omeprazole is able to control acid secretion in Zollinger-Ellison syndrome for a long period (10–30 months). The slow recovery of gastric secretory function demonstrates the prolonged inhibitory effects of omeprazole.     

Focal oxyntic gland atrophy with endocrine cell hyperplasia in Zollinger–Ellison syndrome during omeprazole treatment

Development of focal gland atrophy of the oxyntic mucosa was found in two patients with the Zollinger-Ellison syndrome undergoing long-term treatment with omeprazole. The atrophic areas revealed florid proliferation of endocrine cells in the form of both intraglandular crescents and micronodular hyperplasia. This proliferation was significantly more pronounced than in the remaining non-atrophic mucosa. The possible relationship of these changes to long-standing pharmacological therapy for gastric acid suppression is discussed.     

Risk factors for progression to gastric neoplastic lesions in patients with atrophic gastritis

Aliment Pharmacol Ther 31 , 1042–1050

Summary

Background Atrophic gastritis, involving the gastric body mucosa, predisposes to gastric neoplastic lesions (GNL). However, regular gastroscopic‐histological follow‐up for GNL is not recommended for patients with atrophic gastritis. Aim To evaluate risk factors for the progression to GNL in a cohort of patients with atrophic gastritis. Methods A total of 300 patients with atrophic gastritis [205 women, aged 54 (18–78) years] underwent gastroscopy with six gastric antrum and body biopsies. All patients had at least one follow‐up gastroscopy/histology at an interval of at least 1 year after the atrophic gastritis diagnosis. Baseline clinical and histological features were analysed as risk factors for the development of GNL by Cox‐regression. Results During a median follow‐up of 4.3 (1–16.5) years, 15 GNL were detected in 14 of the 300 patients with atrophic gastritis: three were gastric cancer, whereas 12 were non‐invasive neoplasia. The annual incidence for GNL was 1%. Cox‐regression analysis identified the following risk factors: age over 50 years (HR 8.8, 95%CI 1.2–68.4), atrophic pangastritis (HR 4.5, 95% CI 1.5–14.1) and severe intestinal metaplasia in the gastric body (HR 4.0, 95% CI 1.3–11.8). Conclusions Atrophic pangastritis, severe body intestinal metaplasia and/or age over 50 years increase the risk for developing GNL in patients with atrophic gastritis. In this subset of patients, an endoscopic‐histological follow‐up for GNL surveillance may be worthwhile.