Randomised clinical trial: a 1-week, double-blind, placebo-controlled study of pancreatin 25 000 Ph. Eur. minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) often occurs following pancreatic surgery. AIM: To demonstrate the superior efficacy of pancreatin 25 000 minimicrospheres (Creon 25000 MMS; 9-15 capsules/day) over placebo in treating PEI after pancreatic resection. METHODS: A 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study with a 1-year, open-label extension (OLE). Subjects ≥18 years old with PEI after pancreatic resection, defined as baseline coefficient of fat absorption (CFA) <80%, were randomised to oral pancreatin or placebo (9-15 capsules/day: 3 with main meals, 2 with snacks). In the OLE, all subjects received pancreatin. The primary efficacy measure was least squares mean CFA change from baseline to end of double-blind treatment (ancova). RESULTS: All 58 subjects randomised (32 pancreatin, 26 placebo) completed double-blind treatment and entered the OLE; 51 completed the OLE. The least squares mean CFA change in the double-blind phase was significantly greater with pancreatin vs. placebo: 21.4% (95% CI: 13.7, 29.2) vs. -4.2% (-12.8, 4.5); difference 25.6% (13.9, 37.3), P < 0.001. The mean ± s.d. CFA increased from 53.6 ± 20.6% at baseline to 78.4 ± 20.7% at OLE end (P < 0.001). Treatment-emergent adverse events occurred in 37.5% subjects on pancreatin and 26.9% on placebo during double-blind treatment, with flatulence being the most common (pancreatin 12.5%, placebo 7.7%). Only two subjects discontinued due to treatment-emergent adverse events, both during the OLE. CONCLUSIONS: This study demonstrates superior efficacy of pancreatin 25 000 over placebo in patients with PEI after pancreatic surgery, measured by change in CFA. Pancreatin was generally well tolerated at the high dose administered (EudraCT registration number: 2005-004854-29).

Prediction of the effect of bisoprolol in dilated cardiomyopathy.

Survival improvement by beta-blocker treatment in patients with chronic heart failure appears to be related to the intermediate-term changes in left ventricular function. The therapeutic potential of beta blockade might be increased by early identification of patients in whom left ventricular function would deteriorate. We aimed at predicting the intermediate-term effect of bisoprolol on left ventricular systolic and diastolic function in patients with dilated cardiomyopathy. Twenty-five patients with symptomatic chronic heart failure treated with bisoprolol were investigated. As a background, tailored therapy with digitalis, diuretics and vasodilators was given. Prediction of the 6-month (intermediate-term) effect of bisoprolol was investigated, using baseline values and short-term (1-month) changes of simple, noninvasive parameters obtained at rest and during maximal exercise. Multivariate analysis resulted in reliable predictions, there was close correlation between the observed and predicted changes of left atrial filling pressure (R = 0.87) and left ventricular ejection fraction (R = 0.74). The baseline value of left ventricular ejection fraction, short-term changes of the pulse amplitude and the double product proved independent predictors of intermediate-term changes of left ventricular ejection fraction. The baseline value of mean pulmonary capillary wedge pressure, heart rate, and increase in heart rate during maximal exercise were predictors of the intermediate-term changes in mean pulmonary capillary wedge pressure. In dilated cardiomyopathy, the intermediate-term effects of bisoprolol on left ventricular ejection fraction and mean pulmonary capillary wedge pressure can be predicted reliably by simple noninvasive variables in the early treatment phase.

[Prognostic value of exercise parameters and simple non-invasive variables of left ventricular function in dilated cardiomyopathy]. / Terheléses vizsgálati paraméterek és egyszerü, noninvazív bal kamra funkciós változók prognosztikus értéke dilatatív cardiomyopathiában.

Authors assessed the prognostic value of some simple, routinely used non-invasive parameters in dilated cardiomyopathy. Fifty patients, 43 male and 7 female, mean NYHA class 2.3, treated with digitalis, diuretics and vasodilators, were tested. Mean follow up time was 24 months. The evaluated parameters were as follows: maximal exercise capacity, heart rate, systolic blood pressure, as well as rate-pressure product at peak exercise, their increase during the test, fractional shortening measured by M-mode echocardiography, mean pulmonary capillary wedge pressure estimated by apexcardiography and clinical grade of heart failure (NYHA class). Exercise test was multistage, symptom limited, maximal upright bicycle ergometer test. Both one-way and multivariate analysis showed that except of fractional shortening all of the evaluated parameters related significantly to the survival. According to the one-way analysis maximal exercise capacity, rate-pressure product and systolic blood pressure at peak exercise as well as the estimated value of mean pulmonary capillary wedge pressure proved to be the strongest prognosticators. Multivariate analysis showed that the prognostic value of the rate-pressure product at peak exercise and that of the estimated mean pulmonary capillary wedge pressure proved to be additive, their combined consideration resulted in the highest accuracy of prediction.

Prognostic value of simple exercise test parameters in patients with dilated cardiomyopathy.

The prognostic value of maximal exercise capacity as well as that of the simple exercise systolic blood pressure and heart rate variables were evaluated in 50 patients with dilated cardiomyopathy. Patients were treated beside digitalis and/or diuretics with vasodilators aggressively. Exercise was performed on an upright bicycle ergometer. Continuous, multistage, symptom limited, maximal tests were carried out. Patients were followed up for 23.5 +/- 15.2 months. Both one-way and multivariate analyses of data showed, that not only the maximal exercise capacity related significantly to the survival, but the several simple systolic blood pressure and heart rate variables (their values at peak exercise and their increase during the test) did so as well. Considering parameters separately, maximal exercise capacity was found the strongest predictor of survival, though the power of the calculated rate-pressure product at peak exercise, that of the systolic blood pressure at peak exercise as well as that of the increase in heart rate during the test proved nearly as strong as the maximal exercise capacity did. Anyway, the multivariate analysis showed that the former parameters were dependent on maximal exercise capacity. Some parameters with individual prognostic value proved independent from each other. Combined consideration of the systolic blood pressure at peak exercise and the increase of heart rate during exercise resulted in the highest predictive power which exceeded even the power of maximal exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

[Experience with long-term atrial pacing]. / Tartós pitvari pacemaker kezeléssel szerzett tapasztalataink.

The aim of this study was to evaluate the long term results of atrial pacing. There were 27 atrial pacemaker implantations and 26 out of them were followed for an average of 47, 04 months. Lead dislodgement occurred in two cases, which made necessary a ventricular pacing. Three other patients developed chronic atrial fibrillation. The late results of the remaining 21 patients were very good. No AV-block occurred during the follow-up period. The atrial pacing in selected patients is safe and reliable, and financial restraints makes it advantageous for economic reason.

Site of gamma-aminobutyric acid (GABA)-mediated inhibition of growth hormone secretion in the rat.

The effect of altering gamma-aminobutyric acid (GABA) activity on growth hormone (GH) secretion of freely moving chronically cannulated male rats was studied. Systemic injection of the GABA agonist muscimol (2 mg/kg i.v.) inhibited the anticipated secretory episode. Increasing brain GABA levels by gamma-acetylenic-GABA (50 mg/kg i.v.) also inhibited the expected GH rise. When injected before the expected secretory episode, the GABA receptor antagonist bicuculline methiodide (2 mg/kg i.v.) triggered an early secretory peak. GABA and muscimol failed to change GH secretion by cultured anterior pituitary cells. When the somatostatin input to the stalk-median eminence region was interrupted by an anterolateral cut around the medial basal hypothalamus, the GH level was steadily increased and muscimol injections caused a prompt decrease of plasma GH levels. These results are consistent with the hypothesis that GABAergic tonic inhibition participates in the control of GH secretion and that GABA inhibits spontaneous GH release by inhibiting the secretion of a GH-releasing factor.

Lack of episodic growth hormone secretion in rats with anterolateral deafferentation of the medial-basal hypothalamus.

Growth hormone secretory dynamics were studied in rats sampled through chronic indwelling right atrial cannulae at time-intervals ranging from 2 days to 2 months after placing an anterolateral cut (ALC) around the medial-basal hypothalamus (MBH). The episodic secretion normally occurring in the control animals could not be seen in the rats with an ALC. Instead of the usual high bursts and low trough levels occurring between 09.00 and 13.00 h in the controls, the operated animals had fairly constant plasma GH levels with only minor fluctuations at all postoperative time-points studied. These results suggest that (1) the isolated MBH is incapable of maintaining the episodic secretion of GH and (2) the pulsatile hormone release is dependent on neural pathways entering the MBH from an anterolateral direction.

Possible inhibitory influence of gamma-aminobutyric acid on growth hormone secretion in the rat.

Increasing the levels of endogenous gamma-aminobutyric acid (GABA) by treating rats with GABA-transaminase inhibitors (ethanolamine-O-sulphate and gamma acetylenic GABA) resulted in a decrease in plasma levels of GH. Diminishing GABAergic activity by inhibiting GABA synthesis with 3-mercaptopropionic acid or by blocking GABA receptors with bicuculline increased plasma concentration of GH. The presence of GABA was without effect on the basal, somatostatin-inhibited or high K+-stimulated secretion of GH by hemipituitary glands in vitro. The results suggest that GABA inhibits secretion of GH under the given experimental circumstances.