Early results of the studies of the effect of cimetidine on selected parameters of humoral and cellular immunity in patients with peptic ulcer

The study aimed at evaluating an early effect of cimetidine on the blood IgG, IgA, IgM, number and functioning of T-cells in peripheral blood of patients with ulcerative disease. The study involved 27 patients (9 women and 8 men), aged between 27 and 70 years (mean 52.6 +/- 10.9 years). Nine of these patients suffered from the peptic ulcer and 8--from duodenal ulcer. Cell-mediated and humoral immunity were evaluated simultaneously in all patients prior to and after a 4-week treatment with cimetidine administered orally in the dose of 200 mg four times daily. Rosette test with theophylline and leukocyte migration test were used to assess cell-mediated immunity. It was found that cimetidine significantly increases blood serum IgG (p less than .01), the number of theophylline-resistant lymphocytes in TRFC-TR (P less than 0.01), and T-cell response to higher mitogen concentrations (PHA and Con-A) (p less than .005 and p less than .001, respectively).     

Effects of ACTH on plasma levels of adrenal steroids in essential hypertension.

Plasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F) and aldosterone (A) in 8 control subjects (mean age: 40.5 years) and 10 patients with essential hypertension (EH) (mean age: 48.5 years) were determined before, 4 and 8 hours after an infusion of ACTH at a rate of 25 units per 8 hours. Secretion rates (SR) of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured 24 hours before and again on the day of ACTH infusion. All subjects were studied on the fourth day of a diet containing 135 mEq of sodium and 90 mEq of potassium. There was no statistically significant difference between 8 control subjects and 10 patients with EH in the 7 plasma steroid levels and the SR of 18-OH DOC before ACTH infusion. The mean plasma P response to ACTH was slightly lower in controls than in patients with EH, while that of 17-OH P (in male subjects) was slightly higher. The mean plasma B response was significantly lower after 4 hours of ACTH infusion (p less than 0.01), while that of DOC was significantly higher after 8 hours of ACTH infusion (p less than 0.05) in patients with EH. The mean plasma S rose significantly more in patients with EH (p less than 0.025) at 4 and 8 hours after ACTH infusion. The mean plasma F response to ACTH infusion was slightly lower in patients with EH than in controls. The mean response of 18-OH DOC SR to ACTH infusion was slightly higher in patients with EH than in controls. The mean plasma A response was significantly higher in patients with EH than in controls 4 (p less than 0.05) and 8 hour (p less than 0.001) after an ACTH infusion. These results could be explained in part by abnormalities in the 17- and 11-hydroxylase systems, and that the abnormality in 11-hydroxylation was more pronounced than that in the 17-position. Furthermore, we suspect that the sensitivity of adrenal aldosterone to ACTH might be increased or another accelerated pathway to aldosterone biosynthesis might exist in patients with EH.     

The pharmacokinetics of H2 receptor blocking agents in compensated liver cirrhosis

The bioavailability of oral and intravenous cimetidine and ranitidine was studied in patients with compensated liver cirrhosis. Single doses of 200 and 400 mg cimetidine were used for both administration routes, while ranitidine was administered in doses of 150 mg orally or 50 mg i.v. Plasma concentrations and urinary recovery were determined by the HPLC method. The pharmacokinetics of both of these drugs in the cirrhotic patients did not differ from those found in normal subjects. The two doses of cimetidine given i.v. gave rise to the same plasma concentrations, while after oral administration, 400 mg produced higher plasma concentrations than 200 mg. As to the pharmacokinetic parameters, neither cimetidine nor ranitidine administered i.v. offered any further advantages compared to the oral route. The urinary recovery of both cimetidine and ranitidine was higher after intravenous than after oral administration. It is concluded therefore that the pharmacokinetics of cimetidine and ranitidine is not altered in compensated liver cirrhosis.     

Influence of intrinsic sympathomimetic activity on respiratory function during chronic beta blockade: comparison of propranolol and pindolol.

The long term effect of beta blockers and the influence of intrinsic sympathomimetic activity on respiratory function were assessed in patients with chronic stable angina pectoris randomised to receive treatment with propranolol (n = 21) or pindolol (n = 19) for one year. Forced expiratory volume in one second (FEV1) had fallen by a mean of 240 ml after one year (p less than 0.001) in those treated with propranolol compared with 120 ml in those treated with pindolol (p less than 0.05). The difference between the groups was significant (p less than 0.01). Vital capacity fell significantly only in those treated with propranolol (p less than 0.05 at one year). In those in whom the basal ratio of FEV1 to forced vital capacity was low (less than 70%) propranolol, but not pindolol, caused a significant (p less than 0.05) fall in FEV1 throughout treatment. Long term administration of pindolol has a less adverse effect on respiratory function than propranolol, which results in a progressive deterioration in respiratory function over one year.     

Ambulatory blood pressure during once-daily randomised double-blind administration of atenolol,metoprolol, pindolol,and slow-release propranolol

Intra-arterial ambulatory blood pressure was measured over 24 hours, in 34 patients with newly diagnosed hypertension, both before and after double-blind randomisation to treatment with atenolol (n=9), metoprolol (n=9), pindolol (n=9), or propranolol in its slow-release form (n=7). The dosage of each drug was adjusted at monthly clinic visits until satisfactory control of blood pressure was achieved (140/90 mm Hg or less by cuff) or the maximum dose in the study protocol was reached. A second intra-arterial recording was made after these drugs had been taken once daily at 0800 for three to eight months (mean 5·0±SD 1·4) and was started four hours after the last dose.At the end of the 24-hour recordings blood pressure was significantly lower with all four drugs. The extent to which the drugs reduced blood pressure, however, differed over the 24 hours. Atenolol lowered mean arterial pressure significantly throughout all 24 recorded hours, metoprolol for 12 hours, pindolol for 15 hours, and slow-release propranolol for 22 hours. Neither metoprolol nor pindolol lowered blood pressure during sleep. A significant reduction in heart rate was observed over 20 hours with atenolol, 20 hours with metoprolol, 10 hours with pindolol, and 24 hours with slow-release propranolol. Atenolol, metoprolol, and slow-release propranolol continued to slow the heart rate 24 hours after the last tablet was taken; this effect on heart rate, however, was not sustained throughout the second morning in those patients taking atenolol. Pindolol, the only drug studied that has intrinsic sympathomimetic activity, increased heart rate and did not lower blood pressure during sleep.Atenolol and slow-release propranolol are effective as antihypertensive agents over 24 hours when taken once daily, whereas metoprolol and pindolol may need to be taken more frequently. At times of low sympathetic tone, however, such as during sleep, beta-blockers with intrinsic sympathomimetic activity may raise heart rate and attenuate the fall in blood pressure with treatment.     

Vitamin A toxicity and hypercalcaemia in chronic renal failure.

Serum vitamin A concentrations were measured in 38 patients undergoing haemodialysis, 24 of whom were taking multivitamin preparations containing vitamin A. Vitamin A concentrations were significantly higher in patients undergoing haemodialysis than in 28 normal controls (p less than 0.001). Patients taking vitamin A supplements had significantly higher vitamin A concentrations than those not taking them (p less than 0.05), and hypercalcaemic patients had higher concentrations than normocalcaemic patients (p less than 0.005). Withdrawal of vitamin A supplements in seven patients caused significant falls in serum vitamin A concentrations and plasma calcium concentrations (p less than 0.01 at two and three months in both cases) and in plasma alkaline phosphatase concentrations (p less than 0.01 at two months). Vitamin A toxicity can contribute to hypercalcaemia in patients undergoing haemodialysis, probably by an osteolytic effect. Multivitamin preparations containing vitamin A should therefore be prescribed with caution in these patients.     

Changes of serum angiotensin-I-converting enzyme in patients with thyroid disorders

In 149 subjects (63 euthyroid, 21 hyperthyroid, 26 with autonomous nodules, subdivided into 20 euthyroid and 6 hyperthyroid, 17 hypothyroid subjects and 22 women taking estrogens) the serum angiotensin-I-converting enzyme (SACE) was spectrophotometrically measured and correlated with age, systolic and diastolic blood pressure, free thyroid hormones (FT4, FT3) and delta TSH level. In patients with diffuse hyperthyroidism and with regional autonomy, systolic blood pressure was elevated. The highest values for FT4 and FT3 were found in patients with hyperthyroidism and hyperthyroid autonomous nodules. SACE correlated with age for the euthyroid control group (p less than 0.05). In this group, SACE levels were higher in men than in women (p less than 0.02). Regarding all 149 subjects together, significant linear correlations between SACE and systolic blood pressure as well as with FT4 and FT3 concentrations could be demonstrated (p less than 0.01-0.001). Among the individual groups the mean SACE activities were significantly elevated in hyperthyroid patients (p less than 0.01). No significant differences could be observed between controls and euthyroid subjects with autonomous nodules as well as in hypothyroid cases. In comparison to euthyroid patients the mean SACE levels of hyperthyroid patients with autonomy were significantly (p less than 0.05) elevated. The SACE activities of women taking estrogens for contraception did not differ significantly from SACE in age-matched female controls.     

Comparison of high fibre diets,basal insulin supplements,and flexible insulin treatment for non-insulin dependent (type II) diabetics poorly controlled with sulphonylureas.

OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months'' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.     

Additive antianginal effect of verapamil in patients receiving propranolol

Ten men with stable angina pectoris not fully relieved by optimal doses of propranolol (mean 218 mg daily) were given a single oral dose of 120 mg verapamil or a placebo on alternate mornings; the order of treatment was double blind. Patients had trained in a protocol that precipitated angina after three to six minutes of exercise on a bicycle ergometer. On test days, and with continued propranolol treatment, bicycle exercise was performed just before the administration of verapamil or placebo and hourly thereafter for eight hours. Mean exercise tolerance was 118 seconds greater one hour after verapamil than one hour after placebo (p <0·001), and a significant though somewhat diminished difference of 66 seconds was still present at six hours (p <0·01). Verapamil lowered resting systolic blood pressure by 12 mm Hg (p <0·01) without changing heart rate. None of the 10 patients showed adverse effects from the verapamil-propranolol combination.The results of this study suggest that verapamil is a highly effective antianginal supplement to propranolol.     

MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party.

The main aim of the trial was to determine whether drug treatment of mild hypertension (phase V diastolic pressure 90-109 mm Hg) reduced the rates of stroke, of death due to hypertension, and of coronary events in men and women aged 35-64 years. Subsidiary aims were: to compare the course of blood pressure in two groups, one taking bendrofluazide and one taking propranolol, and to compare the incidence of suspected adverse reactions to these two drugs. The study was single blind and based almost entirely in general practices; 17 354 patients were recruited, and 85 572 patient years of observation have accrued. Patients were randomly allocated at entry to take bendrofluazide or propranolol or placebo tablets. The primary results were as follows. The stroke rate was reduced on active treatment: 60 strokes occurred in the treated group and 109 in the placebo group, giving rates of 1.4 and 2.6 per 1000 patient years of observation respectively (p less than 0.01 on sequential analysis). Treatment made no difference, however, to the overall rates of coronary events: 222 events occurred on active treatment and 234 in the placebo group (5.2 and 5.5 per 1000 patient years respectively). The incidence of all cardiovascular events was reduced on active treatment: 286 events occurred in the treated group and 352 in the placebo group, giving rates of 6.7 and 8.2 per 1000 patient years respectively (p less than 0.05 on sequential analysis). For mortality from all causes treatment made no difference to the rates. There were 248 deaths in the treated group and 253 in the placebo group (rates 5.8 and 5.9 per 1000 patient years respectively). Several post hoc analyses of subgroup results were also performed but they require very cautious interpretation. The all cause mortality was reduced in men on active treatment (157 deaths versus 181 in the placebo group; 7.1 and 8.2 per 1000 patient years respectively) but increased in women on active treatment (91 deaths versus 72; 4.4 and 3.5 per 1000 patient years respectively). The difference between the sexes in their response to treatment was significant (p = 0.05). Comparison of the two active drugs showed that the reduction in stroke rate on bendrofluazide was greater than that on propranolol (p = 0.002). The stroke rate was reduced in both smokers and non-smokers taking bendrofluazide but only in non-smokers taking propranolol. This difference between the responses to the two drugs was significant (p = 0.03).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of cimetidine on upper gastrointestinal bleeding after renal transplantation: a prospective study.

In 97 consecutive patients undergoing renal transplantation the incidence of upper gastrointestinal bleeding was registered over 180 days after allocation to treatment with either cimetidine or placebo. Bleeding episodes occurred in 12 patients, 11 of whom were receiving placebo and only one cimetidine (p less than 0.01). All bleeding episodes occurred during the first month after allotransplantation. Treatment with cimetidine did not lead to an increased incidence of rejection of the allograft. It is concluded that cimetidine is effective and safe in protecting against upper gastrointestinal bleeding after renal transplantation.     

Propranolol withdrawal-induced supersensitivity to the chronotropic effects of isoproterenol in the conscious rabbit

The present study was undertaken to determine if chronic administration and abrupt withdrawal of propranolol would induce supersensitivity to the chronotropic effects of isoproterenol in the conscious rabbit. Eight rabbits were pretreated with propranolol (40 mg/kg/day, i.p.) for one week. Dose-response curves were obtained one week prior to pretreatment and 24, 48, 72 and 168 hours after the last dose of propranolol. Isoproterenol (0.01 to 10 ωg/kg) was injected via the marginal ear vein and heart rate was monitored continuously by recording the ECG. During the withdrawal period no significant rebound increase in basal heart rate was noted. Geometric mean ED₅₀ values and their corresponding 95% confidence intervals were calculated and used as an index of potency. Twenty-four hours after withdrawal of propranolol pretreatment, the ED₅₀ value for isoproterenol was significantly greater than control indicating continued surmountable β-adrenoceptor blockade. In contrast, 72 hours after withdrawal, the geometric mean ED₅₀ value was significantly less than control. The maximum chronotropic response to isoproterenol was not found to be different from control at any time during the withdrawal period indicating that a change in responsiveness was not induced. These data are interpreted as evidence of a true supersensitivity to the chronotropic effects of isoproterenol in the conscious rabbit following propranolol withdrawal.     

Therapeutic effect of cimetidine in patients undergoing haemodialysis.

Blood concentrations of cimetidine were measured and the therapeutic effect of the drug assessed patients undergoing maintenance haemodialysis. Thirteen patients were given a single oral 200-mg dose of cimetidine a mean of 2.7 hours before the start of dialysis. Dialysing for 6--12-6 m2 hours led to a mean fall of 71% in blood cimetidine concentration during haemodialysis. Nine patients with various upper gastrointestinal lesions diagnosed endoscopically were treated for up to six weeks with a reduced cimetidine dose of 200 mg 12-hourly; two patients received two courses of treatment. Repeat endoscopy after treatment disclosed satisfactory healing, and the drug did not accumulate. This lower dose regimen is recommended for patients receiving dialysis who develop upper gastrointestinal lesions for which a histamine H2-receptor antagonist is indicated.     

Correlation between manifestations of digoxin toxicity and serum digoxin,calcium, potassium,and magnesium concentrations and arterial pH.

In 18 patients with gastrointestinal manifestations of digoxin toxicity the mean serum digoxin concentration (+/- SEM) was 3.16 micrograms/l (+/- 0.25), the calcium to potassium ratio 0.31 (+/- 0.01), and the mean arterial pH 7.406 (+/- 0.017). In contrast 19 patients with digoxin induced automaticity had a mean serum digoxin concentration of 1.24 micrograms/l (+/- 0.15; p less than 0.001), a calcium to potassium ratio of 0.38 (+/- 0.01; p less than 0.01), and an arterial pH of 7.498 (+/- 0.008; p less than 0.001). Eight out of 13 patients with digoxin induced cardiotoxicity had serum concentrations of the drug within the therapeutic range (0.8-2.0 micrograms/l). The calcium to potassium ratio, however, was lower than in the patients with automaticity (0.31 +/- 0.02; p less than 0.01) and the arterial pH was 7.370 (+/- 0.033; p less than 0.05). Serum magnesium concentrations were similar in all groups. In this study patients with digoxin induced gastrointestinal symptoms had high serum concentrations of the drug, whereas those with drug induced automaticity had therapeutic concentrations. This second group, however, was identified by their higher calcium to potassium ratios and higher pH values.     

Psychiatric morbidity among spouses of patients with stroke.

The medium term psychiatric morbidity of spouses of patients with stroke was evaluated one to three years after the event. Compared with a control group the spouses were more likely to be depressed (p less than 0.005) and had more physical symptoms (p less than 0.01). Depression increased with the severity of the stroke in the spouse (p less than 0.05) and with time during the three years. Regular contact with friends and neighbours protected spouses (p less than 0.005). Depressed spouses were more likely to be taking tranquillisers than non-depressed spouses (p less than 0.0001) but no more likely to be taking antidepressants. Social rehabilitation after stroke was less successful when the spouse was depressed. Proper attention paid to spouses of patients with stroke might improve the prospects of these patients.     

Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study)

ABSTRACT: BACKGROUND: No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. METHODS: Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (+/- standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level [greater than or equal to]180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured. RESULTS: The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 +/- 35.5 vs. 153.2 +/- 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 +/- 33.5 vs. 129.4 +/- 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 +/- 40.2 vs. 223.2 +/- 43.5 mg/dL; p = 0.015), the AUC ([greater than or equal to]180 mg/dL) within 3 hours was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 +/- 41.6 vs. 85.2 +/- 39.9 mug/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. CONCLUSIONS: CGM showed that mean 24-hour blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. Trial registration UMIN000007687 KEYWORDS: Vildagliptin; Sitagliptin; Continuous glucose monitoring (CGM); Brain natriuretic peptide (BNP); plasminogen activator inhibitor-1 (PAI-1).     

Chemoprophylaxis with oral amoxycillin against bacterial endocarditis: when should second doses be administered after dentistry?

The adequacy of serum bactericidal activity after oral amoxycillin given as prophylaxis against infective endocarditis was studied using a double blind randomised protocol in healthy volunteers having dentistry. One hour before their procedure 38 patients received 3 g amoxycillin syrup and 12 received matching placebo. Venous blood samples were drawn before and one and nine hours after dosing and serum amoxycillin concentrations determined using a standard bioassay. Samples containing amoxycillin had inhibitory titres measured against two reference isolates of viridans streptococci known to have caused infective endocarditis. The susceptibility to amoxycillin of one strain was high and the other low, respective minimal bactericidal and inhibitory concentrations being 0.08 and 0.04 mumol/l (0.03 and 0.015 microgram/ml) and 2.74 and 1.37 mumol/l (1 and 0.5 microgram/ml). Amoxycillin was detected in only post-treatment samples of patients given the active drug. There were no significant correlations between one or nine hour drug concentrations and age or physical characteristics, nor was there any relation to preceding food consumption. Correlations between drug concentrations at one and nine hours were weak (r = 0.34; p less than 0.05), but between corresponding drug concentrations and serum inhibitory titres there were consistent correlations (r = 0.46-0.48; p less than 0.005). Against the low susceptibility reference isolate bactericidal amoxycillin concentrations were encountered in only 20 of the 38 nine hour samples (95% confidence limits 34% and 66%). When repeat doses of amoxycillin are indicated after dentistry they should be given about four hours later, not eight hours later as commonly practised.     

Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria.

STUDY OBJECTIVE--To assess the effectiveness of inhibition of angiotensin converting enzyme in preventing diabetic nephropathy. DESIGN--Randomised follow up study of normotensive diabetics with persistent microalbuminuria (30-300 mg/24 hours) treated with enalapril or its matched placebo for one year. Double blind for first six months, single blind for last six months. SETTING--Diabetic clinic in tertiary referral centre. PATIENTS--Treatment group and placebo group each comprised 10 normotensive diabetics with persistent microalbuminuria. INTERVENTIONS--Treatment group was given enalapril 20 mg daily and controls matched placebo. Patients were given antihypertensive treatment after one year. END POINT--Albumin excretion, arterial pressure, and renal function. MAIN RESULTS--In last three months of trial three of 10 patients taking placebo had diabetic nephropathy (albumin excretion greater than 300 mg/24 hours). No patients taking enalapril developed nephropathy and five showed normal albumin excretion (less than 30 mg/24 hours) (p = 0.005, Mann-Whitney test). Mean arterial pressure was reduced by enalapril throughout study (p less than 0.005) but increased linearly with placebo (p less than 0.05). Albumin excretion decreased linearly with enalapril but not placebo. An increase in albumin excretion with placebo was positively related to the increase in mean arterial pressure (r = 0.709, p less than 0.05, Spearman''s rank test). With enalapril total renal resistances and fractional albumin clearances improved progressively (time effect, p = 0.0001). CONCLUSION--Inhibition of angiotensin converting enzyme prevents development of nephropathy in normotensive diabetics with persistent microalbuminuria. This may be due to reduction in intraglomerular pressure and to prevention of increased systemic blood pressure. Future studies should compare long term effects of inhibitors of converting enzyme with other antihypertensive drugs.     

Interaction between cigarettes and propranolol in treatment of angina pectoris.

To determine whether cigarette smoking interferes with the medical management of angina pectoris, 10 patients with angina pectoris who smoked at least 10 cigarettes a day were studied before, during, and after a standardised maximal exercise test. This was done at the end of four randomly allocated one-week treatment periods during which the patients took glyceryl trinitrate while not smoking, took glyceryl trinitrate while smoking, took glycerly trinitrate and propranolol (380 mg/day) while not smoking, and took glyceryl trinitrate and propranolol while smoking. Carboxyhaemoglobin was measured to ensure compliance. Smoking was associated with a significantly higher heart rate, blood pressure, number of positions with ST-segment depression, and total ST-segment depression after exercise than non-smoking (p < 0.01) whether or not the patients were taking propranolol. These results suggest that smoking aggravates the simple haemodynamic variables used to assess myocardial oxygen requirements and the exercise-induced precordial electrocardiographic signs of myocardial ischaemia. These effects were still evident after treatment with propranolol and represent a hindrance to the effective medical treatment of angina pectoris.     

Effect of intravenous administration of cimetidine on renal excretion of calcium, phosphates, magnesium and adenosine cyclic monophosphate

An effect of cimetidine on parathyroid glands functioning in healthy subjects was evaluated. Serum calcium, phosphate, and magnesium concentrations together with renal excretion++ of these ions in healthy subjects as well as cAMP excretion++ in selected individuals were determined before and following intravenous administration of cimetidine (Altratmet Lek Ljublijana) in total dose of 500 mg (50 mg injected rapidly as a bolus following with 450 mg in an intravenous infusion during 60 minutes). No significant changes in serum calcium, phosphates, and magnesium concentrations were noted. Renal clearance of calcium and magnesium remained unchanged whereas renal phosphate excretion++ increased from 10.69 +/- 4.9 mL/min to 15.1 +/- 5.41 mL/min (p less than 0.02). Excretion++ of 3.5 cAMP increased from 2.65 +/- 2.19 nM/min to 5.16 +/- 2.0 nM/min (p less than 05). The obtained results do not exclude stimulating effect of intravenous cimetidine on parathyroid glands. Cimetidine given intravenously in the bleeding gastric or duodenal ulcers in the course of the primary hyperparathyroidism+ may decrease serum phosphate levels due to increased exretion of this ion with the urine.