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Biomedical subjects

M Uusitupa

Publications and source records attributed to M Uusitupa.

At least 181 records · Page 10Linked to original sources
PubMed1988

First human studies on the safety and antitussive activity of vadocaine hydrochloride.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) is a new anilide derivative which resembles lidocaine in chemical structure. The safety and antitussive effects of this new compound were studied in 6 healthy male volunteers in the first Phase I clinical trial. Vadocaine was administered in single doses of 5, 10, 15, 20, 30 and 50 mg. At these dose levels vadocaine had no effects on the cardiovascular system, the haematological variables, blood biochemistry or urinary sediment examined as safety evaluation. The antitussive properties of the compound were studied using inhaled citric acid for induction of the cough response. The antitussive properties of vadocaine were most effective at a dose of 15 mg, although no statistical significance was found. Neither was any dose-response relationship noted. However, at this dose level vadocaine is apparently safe and its antitussive properties seem promising enough for further evaluation.

Adult↗
PubMed1988

Pharmacokinetics of graded single doses of the novel antitussive compound vadocaine hydrochloride in healthy male volunteers.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) is an anilide derivative with antitussive and local anaesthetic properties. The pharmacokinetics of this new compound were studied in two Phase I clinical trials during safety evaluation. 6 (Part I) and 8 (Part II) healthy male volunteers participated in these studies. The pharmacokinetics were studied after single oral doses of 5, 10, 15, 20, 30 and 50 mg (Part I) and 100, 200, 300, 400 and 500 mg (Part II) of vadocaine in aqueous solution. Vadocaine was rapidly absorbed at each dose level. The AUCo----infinity value and 24-h urinary recovery of intact compound increased linearly as functions of the dose. The elimination half-life varied from 2.2 +/- 0.2 h to 3.7 +/- 1.6 h in a dose range from 5 to 50 mg, and from 2.7 +/- 0.3 h to 4.0 +/- 1.0 h in a dose range from 100 to 500 mg. The peak concentration of vadocaine after the highest dose was 2317.3 +/- 31.5 ng/ml at 1 h. When higher doses were used renal clearance did not change, although total body clearance seemed to diminish. Over 90% of vadocaine is metabolized, and the metabolic pathways may become saturated at a dose of 400 mg.

Adult↗
PubMed1988

Assessment of the safety margin of vadocaine hydrochloride in man.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) is an anilide derivative with antitussive and local anaesthetic action. The safety of this new compound was studied in 8 healthy male volunteers in a Phase I clinical trial. Vadocaine was administered orally as a single dose of 50, 100, 200, 300, 400 and 500 mg. At the two highest dose levels used, 400 and 500 mg, vadocaine induced side-effects originating in the central nervous system; ECG analysis revealed small prolongations in the P-Q interval and QRS complex after 400 and 500 mg. At a dose of 500 mg the P-Q interval was prolonged by a maximum of 38% (184 ms at 0.5 h; 134 ms pre-dose). The compound had no effect on blood and urinary parameters measured for safety evaluation. On the basis of these results, a 300 mg dose of vadocaine appears to be safe in man in all respects. This dose level is 10 times the therapeutic dose (30 mg). Vadocaine is sufficiently safe for future clinical trials in patients with cough.

Adult↗
PubMed1987

Diabetes and atherosclerosis: an epidemiologic view.

Diabetes is associated with changes in plasma lipids and lipoproteins into atherogenic direction. In IDDM these changes are small or absent if good metabolic control can be maintained. Diabetic nephropathy is, however, associated with the appearance of dyslipoproteinemia. In NIDDM plasma total and VLDL triglyceride levels are elevated, and HDL-cholesterol level is decreased, and this pattern of dyslipoproteinemia does not always respond to improved control of hyperglycemia. Abnormalities of lipoprotein metabolism, not reflected in conventional plasma lipid and lipoprotein level measurements, and glucosylation of lipoproteins and resulting alterations in lipoprotein catabolism may be of importance in the enhanced atherogenesis in diabetes. Both IDDM and NIDDM are associated with an increased frequency of hypertension, but the underlying mechanisms appear to be different. In IDDM hypertension is usually associated with the development of diabetic nephropathy and thus with a long duration of the disease. In NIDDM hypertension is often present already at the time of diagnosis, and also in IGT, the precursor stage of NIDDM, the prevalence of hypertension is already increased. Obesity explains only in part the high prevalence of hypertension in patients with NIDDM. Diabetes is known to be associated with multiple abnormalities in hemostatic factors and, although these abnormalities may contribute importantly to the increased risk of ASVD in diabetic patients, information about their real role is scanty and conflicting. The impact of general major risk factors for ASVD, elevated plasma cholesterol, elevated blood pressure, and smoking, on the risk of ASVD appears to be similar in diabetics and nondiabetics. Only a relatively small proportion of the excessive occurrence of ASVD in diabetics can, however, be explained by the effects of diabetes on the levels of general risk factors for ASVD. This proportion mediated through the effects of diabetes on risk factors is larger in female diabetics than in male diabetics. The major proportion of the excess of ASVD in diabetics remains, however, unexplained and must be due to effects of diabetes itself through mechanisms that are incompletely understood.

Arteriosclerosis↗
PubMed1987

Lack of effect of hepatic enzyme induction on metabolic control in patients with type 2 (non-insulin-dependent) diabetes.

A placebo-controlled, double-blind crossover study was carried out in 11 non-insulin-dependent (type 2) diabetic patients to find out the effects of a hepatic enzyme inducer (phenobarbital, 100 mg/day for 2 months) on the metabolic control, plasma C-peptide, insulin, serum, and lipoprotein lipid levels. Phenobarbital induced a significant increase in hepatic antipyrine metabolizing activity, but no significant changes were found in fasting or postload blood glucose, plasma C-peptide, or insulin levels during the study. There was a significant increase in serum total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, as well as in serum total and very low-density lipoprotein triglycerides, during phenobarbital treatment as compared with placebo.

Adult↗
PubMed1987

Efficacy of dietary instructions in newly diagnosed non-insulin-dependent diabetic patients. Comparison of two different patient education regimens.

Eighty consecutive newly diagnosed non-insulin-dependent diabetic patients were randomly allocated into two groups to compare two different patient education regimens. One group received individual dietary instructions by a nurse and the other a short, written leaflet given by a doctor. The principal aim of the dietary instructions was weight reduction. A significant weight loss and improvement in the control of diabetes occurred in both groups, and these changes were similar in the two groups. At the end of one year's follow-up, however, only 25% of the patients were satisfactorily controlled (fasting blood glucose less than or equal to 6.0 mmol/l). The degree of weight loss correlated only weakly with the improvement in the metabolic control. The degree of obesity and insulin secretion capacity as measured at the beginning of the study did not predict the improvement of glycaemic control during the study. At the end of the study a significant improvement was observed in serum lipids of patients with good control (fasting blood glucose less than or equal to 6.0 mmol/l) or weight loss (greater than 5 kg). In conclusion, both brief, written and individual dietary instructions induced a significant weight loss as well as improved glucose and lipid metabolism in newly diagnosed non-insulin-dependent diabetic patients, but satisfactory metabolic control was achieved only in a minority of the patients.

Blood Glucose↗
PubMed1987

Aortic calcifications and their relationship to coronary heart disease and cardiovascular risk factors in patients with newly diagnosed non-insulin-dependent diabetes and in nondiabetic subjects.

The prevalence of radiologically detectable aortic calcifications, the cross-sectional area of the aortic arch, pulse wave velocity and cardiovascular risk factors were examined in 133 newly diagnosed non-insulin-dependent diabetic patients aged 45-64 years and in 144 randomly selected control subjects of the same age. In addition, the relationship between aortic calcifications and coronary heart disease was examined. Diabetic men tended to have more frequently calcifications in the abdominal aorta than nondiabetic men, whereas such a difference was not found between diabetic and nondiabetic women. No difference was observed between diabetic and nondiabetic subjects in the prevalence of calcifications of the aortic arch. Among cardiovascular risk factors, smoking was associated with calcifications of the abdominal aorta in diabetic and nondiabetic men. Ischemic ECG abnormalities at rest showed a statistically significant association with the presence of abdominal aortic calcifications in diabetic men. The cross-sectional area of the aortic arch increased with age in both in diabetic and in nondiabetic subjects and was larger in diabetic than in nondiabetic men. Diabetes did not show any significant effect on pulse wave velocity. An increased frequency of calcifications of the abdominal aorta and a dilatation of the aortic arch in newly diagnosed non-insulin-dependent men as compared with nondiabetic men is compatible with the view that an accelerated development of atherosclerotic lesions of large arteries starts already in an early, asymptomatic phase of this type of diabetes.

Aorta, Abdominal↗
PubMed1987

Macrovascular complications in relation to hyperinsulinaemia in non-insulin-dependent diabetes mellitus.

Despite suggestive evidence from studies on experimental pathology and cell biology of the arterial wall and from clinical and epidemiological studies on non-diabetic subjects indicating that hyperinsulinaemia might be associated with an increased risk of atherosclerotic vascular disease (ASVD) information concerning the role of hyperinsulinaemia as a risk factor of ASVD in diabetic patients still is circumstantial. A few cross-sectional and still fewer prospective studies in patients with non-insulin-dependent diabetes (NIDDM), including two ongoing studies carried out by our own research group, have shown associations between hyperinsulinaemia and the occurrence of ASVD, but these data still are far from consistent and conclusive. Further studies applying combined clinical and epidemiological approach, building upon the results of experimental research concerning possible mechanisms, are needed for better clarification of the role of hyperinsulinaemia as a risk factor of ASVD in NIDDM.

Adult↗
PubMed1987

Hyperinsulinemia and hypertension in patients with newly diagnosed non-insulin-dependent diabetes.

An increased occurrence of hypertension was observed in a group of patients (N = 133) with newly diagnosed non-insulin-dependent diabetes as compared to non-diabetic control subjects (N = 144). In men the excessive occurrence of hypertension in diabetics seemed to be mainly confined to obese subjects, whereas in women it occurred both in obese and non-obese subjects. Fasting or postglucose serum insulin levels showed a positive correlation with blood pressure levels in non-diabetic men and in diabetic and non-diabetic women even after adjustment of insulin for obesity.

Analysis of Variance↗
PubMed1987

Relationship of blood pressure and left ventricular mass to serum insulin levels in newly diagnosed non-insulin-dependent (type 2) diabetic patients and in non-diabetic subjects.

The relationship of blood pressure to fasting and postglucose serum insulin and lipid levels was examined in 133 (70 men, 63 women) newly diagnosed, non-insulin-dependent diabetic patients and 144 (62 men, 82 women) non-diabetic control subjects. In addition, the frequency of left ventricular hypertrophy by ECG criteria and left ventricular mass determined by M-mode echocardiography in diabetic patients were compared to that in non-diabetic subjects. Fasting serum insulin showed a significant correlation with systolic and diastolic blood pressure levels in male non-diabetic subjects, but not in male and female diabetic or in female non-diabetic subjects. Postglucose serum insulin levels showed no significant correlations with systolic or diastolic blood pressure levels in men, but in female diabetic and non-diabetic subjects significant correlations were found in particular with systolic blood pressure level. The correlations between serum insulin and blood pressure levels could not be accounted for by obesity. In male and female diabetic subjects serum triglycerides correlated positively with systolic and diastolic blood pressure levels even after adjustment for obesity. No significant difference was found in the prevalence of left ventricular hypertrophy based on ECG criteria between diabetic and non-diabetic subjects, but female diabetic subjects showed in echocardiography an increased left ventricular mass related to body surface area compared to their non-diabetic counterparts. Elevated systolic blood pressure and high postglucose serum insulin levels showed an independent, significant association with left ventricular mass in female diabetic subjects.

Adult↗
PubMed1986

The effect of sorbinil treatment on red cell sorbitol levels and clinical and electrophysiological parameters of diabetic neuropathy.

A randomized placebo-controlled double-blind cross-over study was conducted in order to examine the effect of an aldose reductase inhibitor, sorbinil (100 mg daily for 4 weeks), on red cell sorbitol concentration and clinical and electrophysiological parameters of diabetic neuropathy. A total of 31 diabetic patients with either clinically or electrophysiologically verified diabetic neuropathy were studied. Red cell sorbitol levels decreased significantly to the levels reported in non-diabetic subjects, but there were no significant changes in symptoms, signs, vibration perception thresholds or nerve conduction variables. One patient had transient skin rash, fever, myalgia and leucopenia, but no other significant adverse effects were found.

Adult↗
PubMed1986

Peripheral arterial disease and its relationship to cardiovascular risk factors and coronary heart disease in newly diagnosed non-insulin-dependent diabetics.

The prevalence of peripheral arterial disease and its relationship to cardiovascular risk factors was investigated in 133 patients aged 45-64 years with newly diagnosed non-insulin-dependent diabetes and in 144 randomly selected non-diabetic subjects of the same age. History of intermittent claudication, absent foot pulses, decreased ankle-arm blood pressure ratio (less than 0.9) and radiologically detectable arterial calcifications of the lower limbs were used as indicators of the presence of peripheral arterial disease. Peripheral arterial disease tended to be somewhat more common in men with newly diagnosed non-insulin-dependent diabetes than in non-diabetic men, whereas no difference was found in prevalence of peripheral arterial disease between diabetic and non-diabetic women. The association of various indicators of peripheral arterial disease with cardiovascular risk factors and coronary heart disease was low or absent.

Arteriosclerosis↗
PubMed1985

Prevalence of coronary heart disease, left ventricular failure and hypertension in middle-aged, newly diagnosed type 2 (non-insulin-dependent) diabetic subjects.

The prevalence of coronary heart disease, left ventricular failure and hypertension was examined in a representative group of 133 newly diagnosed Type 2 (non-insulin-dependent) diabetic subjects (70 men, 63 women), aged 45 to 64 years, and in a group of 144 randomly selected non-diabetic control subjects (62 men, 82 women) of the same age group. The prevalence of previous myocardial infarction (major Q-QS abnormalities in resting ECG and/or myocardial infarction verified at hospital) was increased 1.7-fold in male (NS) and 4.4-fold in female (p = 0.007) diabetic patients compared with that found in non-diabetic subjects. Chest pain symptoms and ischaemic ECG abnormalities were about twice as common among diabetic than among non-diabetic subjects. The frequency of coronary heart disease defined by chest pain symptoms and ECG abnormalities was 3.5 times higher in male (p = 0.001) and 3.1 times higher in female (p = 0.001) diabetic patients than in the respective non-diabetic subjects. The frequency of current digitalis therapy was increased 3.3-fold in male (p = 0.006) and 3.9-fold in female (p = 0.001) diabetic patients suggesting an increased frequency of left ventricular failure among diabetic subjects. The prevalence of hypertension, based on the elevated blood pressure levels and/or current use of antihypertensive drugs, was increased 1.6-1.7-fold among the diabetic patients.

Body Weight↗
PubMed1985

The relationship of cardiovascular risk factors to the prevalence of coronary heart disease in newly diagnosed type 2 (non-insulin-dependent) diabetes.

The relationship of cardiovascular risk factors to the prevalence of coronary heart disease was examined in 133 newly diagnosed Type 2 (non-insulin-dependent) diabetic patients (70 men, 63 women) aged from 45 to 64 years and in 144 randomly selected non-diabetic control subjects (62 men, 82 women) of the same age. The prevalence of coronary heart disease in diabetic patients, defined by symptoms and ischaemic ECG abnormalities in resting or exercise ECG, was more than threefold that in non-diabetic subjects. In multiple logistic analyses (including age, history of smoking, hypertension (+/-), serum cholesterol, HDL-cholesterol, triglycerides, 2-h post-glucose serum insulin, body mass index and diabetes (+/-] carried out separately for men and women, diabetes showed an independent, significant association to coronary heart disease in both sexes. In addition, age and hypertension had a borderline association to coronary heart disease in men, whereas smoking and high 2-h post-glucose serum insulin level showed a significant association in women.

Blood Glucose↗
PubMed1985

Left ventricular function in newly diagnosed non-insulin-dependent (type 2) diabetics evaluated by systolic time intervals and echocardiography.

Systolic time intervals (STI) and echocardiography were recorded in 133 (70 men, 63 women) newly diagnosed non-insulin-dependent diabetics aged 45-64 years and in 144 (62 men, 82 women) non-diabetic control subjects of the same age. Both male and female diabetics had significantly increased pre-ejection period/left ventricular ejection time ratio (PEP/LVET) in STI as compared with the respective non-diabetic control subjects. Male diabetics showed a reduced ejection fraction (EF) in echocardiography, but no significant difference was found in this respect between female diabetics and controls. A significant negative correlation was found between 2-hour postglucose serum insulin level and EF in male and female diabetics. After adjusting for the effect of age, coronary heart disease, hypertension, obesity and haemoglobin concentration, male diabetics still had a higher PEP/LVET ratio and a lower EF than male controls. In women, no significant differences were found between diabetics and controls in the PEP/LVET ratio or EF adjusted for the above factors. The results of this study are compatible with the view that impaired left ventricular function may be an early phenomenon in the clinical course of non-insulin-dependent diabetes.

Coronary Disease↗