Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST): a status report

The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery. Probucol is combined with cholestyramine and dietary management in hypercholesterolemic patients, and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique. A randomly selected control group is also being managed by dietary therapy and cholestyramine, but receives placebo instead of probucol. The treatment time in this double-blind trial is 3 years, and femoral angiography is performed yearly. Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals. The basic study design is described here, and some results from the open prerandomization phase of the study are presented.     

Oesophageal reflux tests, manometry, endoscopy, biopsy, and radiology in healthy subjects

The aim was to study the exposure time of acid during 24 h at two different oesophageal levels in 15 healthy subjects and its relation to other kinds of oesophageal findings. Five centimetres above the lower oesophageal sphincter the total reflux time was 0.2% (0-1.3%), and at the 15-cm level it was 0.1% (0-0.7%). A standardized compression test during manometry and radiologic examination showed that no subject had reflux. Hiatus hernia was provoked at the radiologic examination in four subjects, one of whom also had a widened hiatus. At endoscopy, one subject had a hiatus hernia and slightly granulated oesophageal mucosa. Biopsy specimens showed slight basal cell hyperplasia in one case. Bleeding in the dermal papillae or a few intraepithelial leukocytes were seen in eight cases, findings that might be due to endoscopic trauma. Without any history of gastrointestinal disorders, gastrooesophageal reflux was minimal under standardized conditions, although hiatus hernia and mild changes in biopsy specimens could be seen.     

Maintenance treatment with ranitidine compared with fundoplication in gastro-oesophageal reflux disease

The study comprises 31 patients with gastro-oesophageal reflux disease who received 8 weeks' treatment with ranitidine. Sixteen of the patients received in addition maintenance treatment with ranitidine (150 mg twice daily) for another 6 months, and fundoplication was performed on 15 patients. There was a significant improvement in endoscopic and histologic findings, a decrease in gastric acid secretion, and a reduction of symptoms during short-term treatment with ranitidine. No further improvement was seen in any of the factors after half a year of ranitidine. After surgery the total reflux time during 24 h decreased to practically zero, all patients had normal endoscopic findings and negative acid perfusion tests, and reflux symptoms had disappeared completely. Anti-reflux surgery was superior to treatment with ranitidine. Reflux oesophagitis is therefore not improved any further by a half year's treatment with ranitidine beyond what is achieved with short-term therapy.     

Differential effects of proinsulin C-peptide fragments on Na +, K +-ATPase activity of renal tubule segments

Summary Proinsulin C-peptide has been shown to stimulate the activity of Na ⁺ K ⁺ ATPase of rat renal tubule segments. Thirty-six peptides and amino acids, corresponding to parts of the intact rat C-peptide and suitable controls were screened for capacity to stimulate Na ⁺, K ⁺-ATPase in an attempt to determine potential active sites in the C-peptide molecule. The carboxy-terminal tetra and penta peptides were found to elicit 92–103 % of the intact molecule's activity, and the remaining segment, des-(27–31) C-peptide, did not possess stimulatory activity. Peptides from the middle C-peptide segment, however, centering around a GGPEAG sequence, stimulated Na ⁺, K ⁺-ATPase activity (36–80 % of the intact molecule's effect) but this effect was not balanced by corresponding inactivity of other parts. Furthermore, it was paralleled by activity of a non-native dipeptide d-form. It is concluded that the latter effect and that of the middle segment may represent complex interactions other than the apparently specific effects of the C-terminal segment. [Diabetologia (1998) 41: 287–291] Received: 31 July 1997 and in revised form: 30 October 1997     

Effects of hydrochlorothiazide,amiloride, and lisinopril on the metabolic response to adrenaline infusions in normal subjects

Summary Twelve healthy male volunteers were given adrenaline infusions, 0.05 g/kg body weight/min over 120 minutes in order to achieve serum adrenaline concentrations comparable with those seen in acute myocardial infarction. The infusions were given on four occasions, at intervals of at least 4 weeks. Before the infusions the subjects were given, in random order, 14 days of pretreatment with placebo, hydrochlorothiazide 50 mg once daily, amiloride 10 mg once daily, or lisinorpil 20 mg once daily. The adrenaline infusion induced a drop in serum potassium of the same magnitude in all four groups, with the lowest absolute value after hydrochlorothiazide because of the lowest pre-adrenaline level. The infusion-induced decreases in serum calcium and magnesium were of the same magnitude in all groups, with the absolute calcium being least low in the hydrochlorothiazide group because of the highest preinfusion value. Preinfusion serum urate was highest after hydrochlorothiazide and fell during the adrenaline infusion in all groups, although not significantly. Blood glucose increased during the adrenaline infusion in all groups, but significantly more after hydrochlorothiazide and amiloride than after lisinopril. Heart rate increased during the adrenaline infusion in all groups but least after lisinopril. QTc preinfusion was longer after hydrochlorothiazide than after amiloride and placebo, but the infusion-induced prolongation of QTc was of the same magnitude in all pretreatment groups. Since our results were obtained in short-term experiments in normal subjects, their clinical relevance is question-able, but they support the view that ACE inhibitors may have certain metabolic advantages over diuretics.     

C-peptide improves autonomic nerve function in IDDM patients

Summary In order to determine the possible influence of C-peptide on nerve function, 12 insulin-dependent diabetic (IDDM) patients with symptoms of diabetic polyneuropathy were studied twice under euglycaemic conditions. Tests of autonomic nerve function (respiratory heart rate variability, acceleration and brake index during tilting), quantitative sensory threshold determinations, nerve conduction studies and clinical neurological examination were carried out before and during a 3-h i. v. infusion of either C-peptide (6 pmol · kg^–1 · min^–1) or physiological saline solution in a double-blind study. Plasma C-peptide concentrations increased from 0.11±0.02 to 1.73±0.04 nmol/l during C-peptide infusion. Clinical neurological examination quantitative sensory threshold evaluations and nerve conduction measurements failed to detect significant changes between C-peptide and saline study periods. Respiratory heart rate variability increased significantly from 13±1 to 20±2% during C-peptide infusion (p<0.001), reaching normal values in five of the subjects; control studies with saline infusion did not alter the heart rate variability (basal, 14±2; saline, 15±2%). A reduced brake index value was found in seven patients and increased significantly during the C-peptide infusion period (4.6±1.0 to 10.3±2.2%, p<0.05) but not during saline infusion (5.9±2 to 4.1±1.1%, NS). It is concluded that short-term (3-h) infusion of C-peptide in physiological amounts may improve autonomic nerve function in patients with IDDM.Abbreviations IDDM Insulin-dependent diabetes mellitus - VT vibration perception threshold - CV conduction velocity - DL distal latency - CMAP compound action potential - S sensory amplitude - E/I ratio expiration/inspiration ratio     

A quantitative method of estimating inflammation in the rectal mucosa. IV. Ulcerative colitis in remission

Histological preparations of the rectal mucosa were analyzed quantitatively in 61 patients with ulcerative colitis in remission (UCR). Four histological variables were recorded: the diameter (minor axis) of the lumen of 10 consecutive (transversally cut) glands, the interglandular linear distance between 10 consecutive glands, the number of glands at high-power field examination, and the number of nuclei in 10 consecutive areas of lamina propria. The most important feature to differentiate UCR patients from non-colitic patients was the distance between glands and the number of glands per area. The sum of the values of the four variables demonstrated that 84% of the patients with UCR had scores of 22 or more, whereas only 1 of 124 non-colitic patients (that is, 0.8%) had similar scores.