Pancreatic endocrine response to the first feed in term newborn infants

Blood glucose, insulin, C-peptide and glucagon were evaluated in 36 newborn term infants at birth, and before and 60 min after the first feed during the first day of life. Under basal conditions glycaemia diminished during the first day of life and glucagon increased, while insulin and C-peptide did not show any variation. The C-peptide: insulin molar ratio was higher in the newborn than in adults because of the longer half-life of C-peptide, probably due to reduced renal function in the neonatal period.The subjects were divided into two groups: 18 newborn infants were given a feed of commercially available milk powder reconstituted in water at 10% (5 ml/kg); the other 18 were given a feed of 5 ml/kg 10% glucose solution. In each group 6 were given the first feed after a fast of 6 h, 6 after a fast of 12 h, and 6 after a fast of 24 h from birth. After the first feed with milk, the average increase of glycaemia was 19.83 mg%, of insulin 6.06 U/ml, and of C-peptide 1.88 ng/ml. After the first feed with glucose the average increase of glycaemia was 13.59 mg%, of insulin 2.46 U/ml, and of C-peptide 0.59 ng/ml. Glucagon did not show significant changes after the first feed.     

The effects of non-painful transcutaneous electrical nerve stimulation on cutaneous pain threshold and muscular reflexes in normal men and in subjects with chronic pain

In healthy subjects and in subjects with chronic myofascial pain of one lower limb, the following was measured in both lower limbs: (i) sequential Hoffman (H) reflex, (ii) sequential Achilles tendon (T) reflex, (iii) cutaneous pain threshold determined with electrical stimuli, before, during and after transcutaneous electrical nerve stimulation (TENS).In healthy subjects no significant differences were observed between the pain thresholds of the two limbs. During and after TENS, changes of the reflexes were related to the pain thresholds.In the pathological subjects a significant difference of pain threshold was present between the affected limb and the contralateral one. An important difference between healthy and pathological subjects is not the quality but the quantity of the changes induced by TENS, in the sense that the levels of inhibition and facilitation of the reflexes are more evident in patients with pain. Indeed, TENS induces a reset of sensory and of motor system and a parallel long lasting effect both on sensory and on muscular function, with concomitant pain relief in the pathological subjects.     

Alterations in high-density lipoprotein subfractions during postprandial lipidaemia induced by fat with and without ethanol

1. Serum lipid and apolipoprotein levels, distribution and composition of high-density lipoprotein (HDL) subfractions and lecithin:cholesterol acryltransferase activity were analysed in nine normolipidaemic subjects, in whom a hypertriglyceridaemic state was induced by the acute administration of ethanol (40 g) plus fat (70 g) or of fat only. 2. Triglyceride (TG) levels increased by 180% 4-6 h after fat plus ethanol intake, the hypertriglyceridaemic response being inversely correlated with the basal HDL2 mass (r = -0.82). Serum apolipoprotein (apo) B levels rose by 8%, HDL-cholesterol decreased by 10% and HDL-TG increased by 57% at 6-8 h. 3. When ethanol was omitted, serum cholesterol and TG rose by 6% and 70%, respectively; both apo AI and apo B levels went up by 8%, whereas HDL-cholesterol rose progressively (15%) at 12 h. 4. The flotation rates of both HDL2 and HDL3 increased, reaching a maximum 6-8 h after ethanol plus fat intake. These changes were due to an increase in TG and phospholipid contents, whereas cholesteryl esters and proteins decreased. 5. The alterations in HDL are attributable to the increase in TG-rich lipoproteins, to the stimulated cholesterol esterification (+15%) and to an enhanced transfer of newly formed cholesteryl esters to apo-B-containing lipoproteins in exchange for TG. 6. Changes in HDL properties were evident only when ethanol was given concomitantly with fat. 7. These findings suggest that in the postprandial phase lipoprotein changes may occur, which facilitate an improved removal of cholesterol from tissues.     

Plasma protein glycation as measured by fructosamine assay

The fructosamine test for assessing control of glucose in blood has been extensively evaluated, but some questions remain regarding its validity. From the analytical and clinical evaluation we present here, we conclude that: the test is sensitive to variations in the composition of the sample protein; the fructosamine reaction is almost completely unaffected by labile fractions; the concentrations of fructosamine correlate well with the degree of glycation of total serum proteins, especially with glycated albumins and glycated immunoglobulins, as determined by affinity chromatography; the correlation with glycated hemoglobin (Hb A1c), measured as the stable fraction, is very poor, in diabetics treated with insulin (r = 0.373), or with oral hypoglycemic agents (r = 0.390); and (e) fructosamine and Hb A1c are, in fact, expressions of different periods of metabolic control and therefore have different clinical meanings.     

Incidence of lethal adverse drug reactions in the comprehensive hospital drug monitoring, a 20-year survey, 1974–1993, based on the data of Berne/St. Gallen

Objectives: Realising the limitations of spontaneous drug monitoring systems concerning the epidemiological aspects, a comprehensive program was founded. It was based on previous publications from the US, Canada and Northern Ireland, mainly those of the BCDSP (Boston Collaborative Drug Surveillance Programme). Methods: Drug monitoring was carried out by a group of physicians which included the medical head of each of the divisions of internal medicine, a statistician and an informatician. Only probable or definite drug event relationships were included. A probable event is defined as one in which the drug interaction was more likely to be the cause than any non-drug-related cause. The same criteria were valid for the lethal reactions. Results: In the present evaluation, we found 26 probable lethal adverse drug reactions out of a total of 48,005 patients consecutively admitted to the divisions of internal medicine of three Swiss teaching hospitals during the years 1974–1993, an incidence of 0.054%. The median age of the cohort was 68 years (range 11–103 years), of which 49% were women. The median hospital stay was 14 days and the median number of drugs was eight per patient. Conclusion: The patients with a lethal outcome were presented under the eight pharmacologic–therapeutic classes of drugs and the classification proposed by NS Irey. This is based on long histopathologic experience and helps to identify preventable risks. Received: 30 June 1999 / Accepted in revised form: 10 April 2000     

Losartan and prevention of atrial fibrillation recurrence in hypertensive patients

The aim of the study was to evaluate the effect of losartan as compared with amlodipine, both associated with amiodarone, in preventing the recurrence of atrial fibrillation (AF) in hypertensive patients with a history of recent paroxysmal atrial fibrillation. Two hundred and fifty mild hypertensive (SBP > 140 mm Hg and/or DBP > 90 < 100 mm Hg) outpatients in sinus rhythm but with at least two ECG-documented episodes of symptomatic atrial fibrillation in the previous 6 months and in treatment with amiodarone were randomized to losartan or amlodipine and were followed up for 1 year. Clinic blood pressure (BP) and a 24-hour ECG was evaluated every month; the patients were asked to report any episode of symptomatic atrial fibrillation and to perform an ECG as early as possible. Two hundred and thirteen patients completed the study, 107 in the losartan group and 106 in the amlodipine group. After 12 months the SBP/DBP mean values were significantly reduced by both losartan (from 151.4/95.6 to 135.5/83.7 mm Hg, P < 0.001 versus baseline) and amlodipine (from 152.3/96.5 to 135.2/83.4 mm Hg, P < 0.001 versus baseline), with no difference between the two treatments. At least one ECG-documented episode of atrial fibrillation was reported in 13% of the patients treated with losartan and in 39% of the patients treated with amlodipine. The use of losartan in combination with amiodarone seems more effective than amlodipine/amiodarone combination in preventing new episodes of atrial fibrillation in hypertensive patients with recurrent atrial fibrillation. This might be related to possible favorable impact of angiotensin II receptor blockers (ARB) on the atrial electrical and structural remodeling in this type of patients.     

Effects of amlodipine-atorvastatin combination on inflammation markers and insulin sensitivity in normocholesterolemic obese hypertensive patients

Objective The objective of this study was to assess the effect of amlodipine-atorvastatin combination on plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and insulin sensitivity in normocholesterolemic obese hypertensive patients.Materials and methods After a 4-week placebo wash-out period, 50 normocholesterolemic [total cholesterol (TC) <5.2 mmol/L], obese (BMI ≥30 kg/m²) hypertensive patients (DBP >90 and <105 mm Hg and SBP >140 and <180 mm Hg) were randomly treated with amlodipine (10 mg) or with amlodipine (10 mg) plus atorvastatin (20 mg) according to a cross-over design; each treatment had a 12-week duration. At the end of the placebo and of each treatment period, blood pressure (BP), TNF-α, IL-6, insulin resistance (IR) by homeostasis model assessment of IR index (HOMA-IR) and TC were evaluated.Results Amlodipine monotherapy decreased both SBP (−17.1 mm Hg, p=0.008 vs. placebo) and DBP (−14.3 mm Hg, p=0.008) as well as TNF-α (from 3.66±1.6 to 3.09±1.1 pg/ml, p=0.045) and HOMA-IR (from 4.58±0.7 to 3.88±0.6, p=0.007). The amlodipine-atorvastatin combination produced a decrease in SBP (−22.5 mm Hg, p=0.0007 vs. placebo, p=0.039 vs. amlodipine), DBP (−17.7 mm Hg, p=0.0007 vs. placebo; p=0.04 vs. amlodipine), TNF-α (2.59±0.9 pg/mL, p=0.007 vs. placebo and p=0.038 vs. amlodipine) and HOMA-IR (2.86±0.4, p=0.0008 vs. placebo and p=0.007 vs. amlodipine). The combination reduced IL-6 (from 7.93±1.9 to 5.59±1.2 pg/mL, p=0.008 vs. placebo and p=0.007 vs. amlodipine) and TC (from 4.3±0.5 to 3.6±0.4 mmol/L, p=0.008 vs. placebo and vs. amlodipine). HOMA-IR changes significantly correlated with TNF-α changes (r=0.38, p<0.05) during combination but not during amlodipine monotherapy. In normocholesterolemic, obese hypertensive patients, the amlodipine-atorvastatin combination decreased inflammatory markers and IR more than amlodipine monotherapy and produced a greater SBP and DBP reduction.     

Effect of benazepril amlodipine combination on fibrinolysis in hypertensive diabetic patients

Objective The aim of this study was to compare the effects of benazepril and amlodipine in monotherapy versus in combination with plasma t-PA and PAI-1 activity in hypertensive type-2 diabetic patients.Methods After an initial 6-week wash-out, single-blind placebo period, 38 patients, 17 men and 21 females, were randomly assigned to receive benazepril 10 mg o.d. or amlodipine 5 mg o.d. or their combination o.d. at the same dosage for 6 weeks in three crossover periods each separated by a 2-week placebo wash-out period (3×3 latin square). At the end of the placebo run-in period and of each treatment period, BP, plasma PAI-1 and tPA activity were evaluated.Results Both benazepril and amlodipine were similarly effective in reducing systolic blood pressure (SBP) (–17.6 mmHg with benazepril and –19.8 mmHg with amlodipine; P<0.001 versus placebo), and diastolic blood pressure (DBP) (–11.1 mmHg, –13.2 mmHg, respectively). Combination therapy produced greater reduction in SBP/DBP values (–28.3/–20.5 mmHg; P<0.001 versus placebo, P<0.01 versus benazepril and amlodipine). Benazepril monotherapy significantly decreased plasma PAI-1 activity (–8.4 IU/ml, P<0.05) while it did not influence t-PA activity (+0.02 IU/ml). Amlodipine monotherapy produced a significant increase in t-PA activity (+0.27 IU/ml, P<0.05) while it did not influence PAI-1 activity (+0.8 IU/ml). The amlodipine/benazepril combination produced both a significant decrease in plasma PAI-1 activity (–8.7 IU, P<0.05) and a significant increase in t-PA activity (+0.26 IU/ml, P<0.05).Conclusions These data suggest that in hypertensive type-2 diabetic patients, a population with an impaired fibrinolysis, the benazepril/amlodipine combination, may improve the fibrinolytic balance more than the single drugs.