A double-blind trial of perindopril and nitrendipine in incipient diabetic nephropathy.

UNLABELLED: We conducted a randomised, double-blind multicentre trial to compare the efficacy of the inhibitor of the angiotensin-converting enzyme (ACE) perindopril (P) with nitrendipine (N) in incipient diabetic nephropathy. METHODS: Forty-six patients with insulin-treated diabetes mellitus and mild-to-moderate hypertension and stable microalbuminuria were examined. P 4 or 8 mg once daily was compared to N 20 or 40 mg once daily; an optional open combination treatment with indapamide 2.5 mg once daily was given when needed. Main outcome measures were urinary albumin excretion rate, creatinine clearance and isotopic clearance measurements after 12 months. RESULTS: Baseline characteristics (blood pressure, HbA1, renal function) were highly comparable between groups. No serious adverse events occurred during the study period. Blood pressure was controlled (<140/90 mmHg) in all patients except for one in each group who dropped out. At the end of the study, albumin excretion rate was stabilized in both groups (P: 72% of baseline, N: 108%, NS). There were no significant differences found in radiometric clearance measurements. Creatinine clearance rose in patients treated with P by 10.0 ml/min on average, while it decreased by 9.8 m/min under N treatment (group effect: p<0.05). CONCLUSIONS: In this head-to-head comparison, P and N were effective in stabilising most parameters of renal function in incipient diabetic nephropathy.

Octreotide scintigraphy and catecholamine response to an octreotide challenge in malignant phaeochromocytoma.

OBJECTIVE: Octreotide scintigraphy has been reported to visualize chromaffine tumours. This study in patients with malignant phaeochromocytoma was designed to assess octreotide in comparison with standard m-iodobenzylguanidine (MIBG) scintigraphy and to study functional activity of somatostatin receptors. Finally, two cases of octreotide treatment are reported. DESIGN: Open, prospective clinical trial. PATIENTS: In 12 patients with histologically proven malignant phaeochromocytoma, 111In-octreotide scintigraphy, 123I-MIBG scintigraphy and computed tomography were performed. In ten patients plasma catecholamine response to a single dose of octreotide (200 micrograms i.v.) was monitored up to 5 hours after injection. Two patients were treated with octreotide over several months. MEASUREMENTS: Plasma catecholamines were measured by high performance liquid chromatography (HPLC). Scintigraphy was performed using a large field gamma camera and SPECT technique where appropriate. RESULTS: At least one metastatic lesion was visualized by octreotide scintigraphy in eight patients while the remaining four patients had negative findings. In total, 43 out of 54 known metastases (79.6%) were detected by MIBG, 24 (44.4%) by octreotide. Nevertheless, octreotide scintigraphy detected six metastases that were negative by MIBG. There was no correlation between the results of octreotide scintigraphy and catecholamine suppression after i.v. octreotide. In two patients on octreotide treatment, symptomatic improvement, but not mass reduction, could be documented. CONCLUSIONS: Octreotide scintigraphy behaves in part complementary to MIBG, thus, increasing diagnostic sensitivity. Presence of somatostatin receptors, as demonstrated by octreotide scintigraphy, does not necessarily predict functional activity or therapeutic response.

Real-time quantitative elemental analysis and mapping: microchemical imaging in cell physiology.

Recent advances in widely available microcomputers have made the acquisition and processing of digital quantitative X-ray maps of one to several cells readily feasible. Here we describe a system which uses a graphics-based microcomputer to acquire spectrally filtered X-ray elemental image maps that are fitted to standards, to display the image in real time, and to correct the post-acquisition image map with regard to specimen drift. Both high-resolution quantitative energy-dispersive X-ray images of freeze-dried cyrosections and low-dose quantitative bright-field images of frozen-hydrated sections can be acquired to obtain element and water content from the same intracellular regions. The software programs developed, together with the associated hardware, also allow static probe acquisition of data from selected cell regions with spectral processing and quantification performed on-line in real time. In addition, the unified design of the software program provides for off-line processing and analysing by several investigators at microcomputers remote from the microscope. The overall experimental strategy employs computer-aided imaging, combined with static probes, as an essential interactive tool of investigation for biological analysis. This type of microchemical microscopy facilitates studies in cell physiology and pathophysiology which focus on mechanisms of ionic (elemental) compartmentation, i.e. structure-function correlation at cellular and subcellular levels; it allows investigation of intracellular concentration gradients, of the heterogeneity of cell responses to stimuli, of certain fast physiological events in vivo at ultrastructural resolution, and of events occurring with low incidence or involving cell-to-cell interactions.