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Biomedical subjects

P Smits

Publications and source records attributed to P Smits.

At least 181 records · Page 10Linked to original sources
PubMed1989

The effect of alpha-human atrial natriuretic peptide on the incidence of acute renal failure in cadaveric kidney transplantation.

In previous studies in humans, mannitol (20%, 250 ml) has been shown to reduce the incidence of acute renal failure (ARF) after transplantation from 54% to 19%. In rats, atrial natriuretic peptide appears to prevent ischemia-induced ARF. We therefore decided to evaluate the effects of alpha-human atrial natriuretic peptide (alpha-h-ANP) both alone and combined with mannitol during transplantation in humans. First, we demonstrated that systemic alpha-h-ANP infusion during kidney transplantation was safe in dosages up to 0.08 micrograms/kg per minute. In these patients the calculated metabolic clearance rate of alpha-h-ANP was relatively low ranging from 0.68 to 1.80 l/min. In a second study of 11 renal graft recipients, no mannitol was used and alpha-h-ANP (0.05 micrograms/kg per minute) was infused into the donor kidney artery during transplantation for 46 +/- 2 min, followed by IV administration for 71 +/- 2 min. Our aim was to reduce the incidence of ARF. Nevertheless, ARF occurred immediately after surgery in four of the patients (36%) in this group and, as a result, mannitol was reintroduced. A third group of nine renal graft recipients received alpha-h-ANP (total dose 400 micrograms) as five IV injections within 90 min after transplantation. ARF occurred in four of these patients (44%). We conclude that alpha-h-ANP, administered according to the aforementioned protocols in such small groups of patients, does not seem to be of value in the prevention of ARF after transplantation.

Acute Kidney Injury↗
PubMed1989

Nicotine enhances the circulatory effects of adenosine in human beings.

A randomized, double-blind, and placebo-controlled study was performed in 10 healthy volunteers to evaluate a possible interaction between adenosine and nicotine in human beings. The infusion of adenosine alone (0.07 mg/kg/min) induced an increase in heart rate of 4.7 beats/min versus 0.2 beats/min after placebo administration (p less than 0.02). The infusion of adenosine alone induced a decrease in finger skin temperature compared with placebo administration (-1.0 degrees versus 0.0 degrees C, p less than 0.01). When compared with baseline values, nicotine gum chewing increased systolic and diastolic blood pressures by 6.2 and 7.0 mm Hg, respectively (p less than 0.001), heart rate by 5.5 beats/min (p less than 0.01), and plasma adrenaline levels by 0.03 nmol/L (p less than 0.025), whereas skin temperatures fell by 1.3 degrees C (p less than 0.001). The nicotine-induced increase in heart rate was larger during adenosine infusion than during placebo administration (14.9 versus 5.5 beats/min, p less than 0.001), whereas the increment of diastolic blood pressure was lower (1.1 versus 4.0 mm Hg, p less than 0.05). The increment in systolic blood pressure was not altered by concomitant adenosine infusion. The rise in plasma noradrenaline levels during the combined administration of nicotine and adenosine differed significantly from the response to nicotine alone (+ 0.23 versus -0.05 nmol/L, p less than 0.02). We concluded that, in human beings, the characteristic hemodynamic response to adenosine infusion is enhanced by nicotine.

Adenosine↗
PubMed1989

Cardiovascular effects of two xanthines and the relation to adenosine antagonism.

We hypothesize that the hemodynamic effects of xanthine derivatives depend on their ability to antagonize the vasodilating effects of endogenous adenosine. In a randomized, double-blind, and placebo-controlled study of 10 normotensive volunteers caffeine, a xanthine with in vitro adenosine antagonistic properties, increased mean arterial pressure by 5.6 +/- 0.9 mm Hg and lowered heart rate by 5.3 +/- 1.1 beats/min. After administration of enprofylline, a xanthine without adenosine antagonism, forearm vascular resistance decreased by 5.6 +/- 3.4 IU, heart rate increased by 10.6 +/- 2.6 beats/min, and plasma adrenaline, plasma noradrenaline, and renin activity increased by 178 +/- 86%, 14 +/- 8%, and 36 +/- 13%, respectively. Adenosine infusion alone induced a dose-related increase in pulse pressure and heart rate, and it increased plasma adrenaline and noradrenaline by 186 +/- 77% and 132 +/- 55%, respectively. This response to adenosine was reduced by pretreatment with caffeine but not enprofyline. Thus opposite circulatory responses to caffeine and enprofylline occurred, with signs of vasoconstriction and vasodilation, respectively. In addition, caffeine, but not enprofylline, reduced the cardiovascular response to exogenous adenosine.

Adenosine↗
PubMed1989

Effect of decaffeinated versus regular coffee on blood pressure. A 12-week, double-blind trial.

The effect of decaffeinated versus regular coffee on blood pressure and heart rate was investigated. In a randomized double-blind, crossover trial, 45 healthy volunteers (23 women and 22 men, 25-45 years old) with a habitual intake of 4-6 cups coffee/day received 5 cups of regular coffee each day for a period of 6 weeks, and 5 cups of decaffeinated coffee for the next 6 weeks or vice versa. The background diet was kept constant. The total amount of caffeine ingested was 40 mg during the decaffeinated coffee period and 445 mg during the regular coffee period. Use of decaffeinated coffee led to a significant but small decrease in systolic (mean +/- SEM, -1.5 +/- 0.4 mm Hg; p = 0.002) and diastolic (-1.0 +/- 0.4 mm Hg; p = 0.017) ambulant blood pressure and to a small increase in ambulant heart rate (+1.3 +/- 0.6 beats/min; p = 0.031). Individual differences in rate of caffeine metabolism did not explain differences in long-term response of blood pressure to caffeine. We conclude that in normotensive adults replacement of regular by decaffeinated coffee leads to a real but small fall in blood pressure. However, it remains to be established whether a mass switch from regular to decaffeinated coffee would significantly reduce the total incidence of hypertension-related disorders.

Adolescent↗
PubMed1989

Diabetes insipidus associated with leukaemia.

Three cases of leukaemia complicated by pituitary diabetes insipidus are presented. In one patient diabetes insipidus developed five months before acute myelomonocytic leukaemia became apparent. The two other patients suffered from acute myelomonocytic leukaemia and from a blastic transformation of chronic myeloid leukaemia. In one case a transient cure of diabetes insipidus was obtained after intrathecal chemotherapy and irradiation of the skull.

Adult↗
PubMed1989

Caffeine reduces dipyridamole-induced myocardial ischemia.

The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-201Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed no, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging.

Caffeine↗
PubMed1988

The effects of caffeine on the postprandial fall of blood pressure in the elderly.

In a double-blind placebo-controlled study, we examined the effect of caffeine pretreatment on the haemodynamic and humoral changes after a standardized breakfast in 15 healthy elderly subjects (mean age 75.4 +/- 6.6 years). After placebo, the preprandial blood pressure did not change and the postprandial blood pressure declined by a maximum of 6.1%. After oral ingestion of 250 mg caffeine, 60 min before breakfast, the preprandial blood pressure increased by 12.5%. Although the decrease of the postprandial blood pressure was not altered, blood pressure remained above its basal value. The increase in plasma noradrenaline after the meal was similar in the placebo and the caffeine tests. Plasma adrenaline decreased after placebo (-19%) but did not change after caffeine. Thus, despite the unchanged decrease of the postprandial blood pressure, the preprandial pressor effect of caffeine prevented the decline of the postprandial blood pressure below its baseline value. The clinical relevance of this finding has still to be determined.

Aged↗
PubMed1987

Prognostic factors in adult patients with acute leukemia at first relapse.

The case histories of 252 adolescent and adult patients with acute leukemia diagnosed and treated between 1975 and 1985 are analyzed with special attention to prognostic factors determining the second complete remission (CR) rate. A first CR was achieved in 65% of cases, 60% for acute myelogenous leukemia (AML), and 75% for lymphoblastic leukemia (ALL). In 86 patients a relapse occurred (50 AML, 36 ALL), and 50% of them entered a second CR after reinduction therapy. Median survival after first relapse of these reinduction-responders was significantly prolonged in comparison to the reinduction-nonresponders for both AML (15 versus 2 months) and ALL (11 versus 3 months). Median duration of the first CR of the reinduction-responders was significantly longer than that of the second CR (13 versus 6 months). The major determinant for the probability to obtain a second CR after reinduction therapy was the duration of the first CR. The latter was significantly longer in the reinduction-responders than in the nonresponding group (13 versus 5 months). Furthermore patients younger than 40 years, and those who relapsed after ending the maintenance therapy, tended to have better chances to achieve a second CR. Rapid achievement of the first CR, and sex of the patients seemed not to be of predictive value. The authors conclude that aiming for a second CR is worthwhile in young patients who relapse after a long first CR.

Adolescent↗
PubMed1987

Evidence for an antagonism between caffeine and adenosine in the human cardiovascular system.

A randomized, double-blind and placebo-controlled study was performed in 10 normotensive male subjects to analyze a possible antagonism between caffeine and adenosine with respect to their effects on the cardiovascular system in humans. Caffeine alone, 250 mg intravenously (i.v.), increased blood pressure by 9/12 mm Hg, and resulted in a fall of heart rate (HR) of 3 beats/min. Plasma epinephrine (E) rose by 114% after caffeine. Adenosine alone, in an increasing dose of 0.04-0.16 mg/kg/min, induced an increase in systolic blood pressure (SBP) (17 mm Hg), and HR (33 beats/min), a moderate fall in diastolic blood pressure (DBP) (-4 mm Hg), and no change of mean arterial pressure (MAP). At the highest adenosine infusion rate, forearm blood flow, skin temperature (ST), and transcutaneous oxygen tension were lowered, whereas plasma (nor)epinephrine was increased 227.2 and 215.9%, respectively. Adenosine infusion after caffeine induced comparable effects, but the fractional adenosine-induced changes of SBP, HR, plasma catecholamines, plasma renin activity (PRA), and aldosterone all were significantly reduced by previous administration of caffeine. Our results indicate an antagonism between caffeine and adenosine in humans, which may support the suggestion that some circulatory effects of caffeine are caused by an interaction with endogenous adenosine.

Adenosine↗
PubMed1987

Respiratory stimulant effects of adenosine in man after caffeine and enprofylline.

In a double-blind and randomized study the respiratory stimulant effect of continuous intravenous adenosine infusion was studied after previous administration of caffeine, placebo and enprofylline in 10 healthy young volunteers. After placebo, adenosine induced an increase of minute ventilation (from 6.3 to 12.5 l min-1), tidal volume (from 0.60 to 0.96 l), and breathing rate (from 11.0 to 14.8 min-1). Venous pCO2 fell and pH rose after adenosine. Caffeine significantly reduced the adenosine-induced changes of minute ventilation, tidal volume, venous pCO2 and pH, whereas no changes occurred after enprofylline. Our results suggest that adenosine stimulates respiration in man by binding with specific P1-purinoceptors, which can be blocked by caffeine, but not by enprofylline.

Adenosine↗
PubMed1986

Influence of slow calcium-channel blockade on the cardiovascular effects of coffee.

An increase in blood pressure after coffee and caffeine has recently been reported. A possible pharmacological mechanism for this pressor response is a rise in the intracellular calcium concentration, caused by an increase in calcium influx due to a direct effect of caffeine. Accordingly, the cardiovascular effects of drinking coffee after placebo and verapamil 3 X 80 mg in 1 day in 10 normotensive volunteers have been examined in a single-blind study. After placebo, coffee led to an increase in blood pressure (7/14 mm Hg), and a fall in heart rate (-7 beats/min); forearm blood flow did not change. Plasma epinephrine rose (257%), plasma norepinephrine did not change and the plasma renin activity fell significantly. The haemodynamic and humoral changes after coffee were not altered by pretreatment with verapamil. It is concluded that increased transmembrane calcium influx after caffeine does not appear to be an important pharmacological mechanism for the circulatory effects of coffee.

Adult↗
PubMed1986

The role of epinephrine in the circulatory effects of coffee.

The circulatory response to coffee was studied in 10 normotensive, 10 bilaterally adrenalectomized, and 10 hypertensive subjects. In the normotensive group, drinking coffee exerted a rise in blood pressure (+5.1/+11.5 mm Hg), a fall in heart rate (-6.0 bpm), a rise in plasma epinephrine (+257.2%), and no change in plasma norepinephrine. The response to coffee in the hypertensive group was similar or even enhanced. In the patients who had undergone adrenalectomy, the coffee-induced rise of diastolic blood pressure was attenuated (+7.9 mm Hg; P less than 0.05), whereas plasma norepinephrine showed a fall (-20.8%) and plasma epinephrine remained undetectable throughout all tests. Additionally, a fall of plasma renin activity after coffee was observed in all three groups. We conclude that the pressor response to coffee is not purely a result of circulating epinephrine or to stimulation of the renin-angiotensin-aldosterone system. On the other hand, the coffee-induced increase of plasma epinephrine may increase the pressor response to coffee.

Adrenalectomy↗
PubMed1985

Circulatory effects of coffee in relation to the pharmacokinetics of caffeine.

Drinking coffee results in an increase in blood pressure (BP) after an interval of caffeine abstinence. During chronic caffeine intake this pressor response disappears and adaptation to the circulatory effects of caffeine develops. This study was designed to determine whether a pressor response to coffee occurs during chronic caffeine intake if low basal plasma caffeine levels are achieved by a period of caffeine abstinence, defined by individual plasma caffeine half-life. In 8 normotensive subjects, circulatory measurements were studied after ingestion of coffee in 2 strengths, decaffeinated coffee and hot water after a caffeine abstinence of 4.5 times individual caffeine half-life. These measurements were compared to the same protocol without intervention. Coffee of both strengths resulted in a similar increase in BP (diastolic BP +/- 15%). The coffee-induced increase in forearm blood flow and plasma epinephrine levels were less pronounced. Decaffeinated coffee induced a smaller increase of diastolic BP, and after water, no changes were observed. Additionally, a negative correlation was found between the coffee-induced BP increase and basal plasma caffeine level in a group of 30 normotensive subjects (r = -0.71, p less than 0.001). During chronic caffeine intake, subjects with short plasma caffeine half-life are exposed to a pressor response after drinking coffee, despite the phenomenon of adaptation.

Adult↗
PubMed1985

The cardiovascular effects of regular and decaffeinated coffee.

In a single-blind study the effects of drinking two cups of regular or decaffeinated coffee on blood pressure, heart rate, forearm blood flow and plasma concentrations of caffeine, renin and catecholamines were studied in 12 normotensive subjects. Drinking regular coffee led to a rise of blood pressure, a fall of heart rate and an increase of plasma catecholamines. Decaffeinated coffee induced a smaller increase of diastolic blood pressure without changing other parameters. This study shows that the cardiovascular effects of drinking coffee are mainly the result of its caffeine content.

Adult↗
PubMed1983

Hemodynamic and humoral effects of coffee after beta 1-selective and nonselective beta-blockade.

Several studies report a substantial rise in plasma catecholamines after caffeine. Epinephrine infusion induces a pressor response after nonselective beta-blockade. We studied the hemodynamic and humoral effects of drinking coffee after placebo and after both nonselective (propranolol) and beta 1-selective (metoprolol) blockade in 12 normotensive subjects. After placebo, coffee induced a rise in systolic and diastolic blood pressure and a fall in heart rate, whereas forearm blood flow did not change. Plasma catecholamines, especially epinephrine (+150%), rose and plasma renin activity, fell after drinking coffee. The effects of coffee on blood pressure, forearm blood flow, and all humoral parameters were not altered by pretreatment with propranolol or metoprolol. The fall in heart rate after coffee, however, seemed to be greater during propranolol. We conclude that the rise in plasma epinephrine after coffee was too small to reveal differences in reaction in propranolol- and metoprolol-pretreated subjects.

Adolescent↗
PubMed1980

Heat-induced association of beta-lactoglobulin and casein micelles.

Heat-induced association of beta-lactoglobulin (beta-lg) and casein micelles, mainly at 85--90 degrees C, was studied by means of preparative ultracentrifugation, using [3H]-labelled beta-lg. Qualitative aspects were studied by gel electrophoresis and electron microscopy. In this association, the formation of intermolecular S-S bonds between beta-lg and kappa-casein plays a role, but hydrophobic bonds are also involved. After heating mixtures containing 25 g/kg casein and 4 g/kg beta-lg at 90 degrees C for 20 min, the amount of beta-lg sedimented with the casein micelles by ultracentrifugation decreased by approximately 30% when the milk salt buffer system was reduced to 0.25 of its normal concentration; it decreased by about 20% when the pH was increased from 6.8 to 7.3 and increased by 15% when the pH was reduced from 6.8 to 5.8. When the beta-lg concentration was decreased from 4 to 2 g/kg, the amount of sedimented beta-lg decreased by 25% after heating at 90 degrees C for 6 min. After heating in milk salt buffer, the amount of sedimented beta-lg was 15% higher than after heating in salt solution which contained neither Ca nor citrate ions. Although alpha-lactalbumin (alpha-la) is involved in the heat-association of beta-lg and casein micelles, no influence of alpha-la on the amount of associated beta-lg was found. In addition to the heat-association product of beta-lg and whole casein micelles, an association product consisting mainly of beta-lg and kappa-casein was also formed. This product was observed by electron microscopy as noodle-like particles. The size of these particles depended on the beta-lg/kappa-casein ratio.

Animals↗
PubMed1980

The primary structure of the phosphatidylcholine-exchange protein from bovine liver. Isolation and characterization of the staphylococcal protease peptides and the amino-acid sequence of the N-terminal half (residues 1--122).

The phosphatidylcholine exchange protein from bovine liver consists of a single polypeptide chain and has a blocked N terminus. The protein contains an estimated 244 amino acid residues in accordance with a determined molecular weight of 28000. The protease from mouse submaxillaris gland cleaved the citraconylated and S-carboxymethylated derivative of the exchange protein at one specific site (Arg14-Glu15) close to the N terminus. Analysis of the two resulting peptides showed that N-acetyl-methionine was the N-terminal residue and gave the sequence of the first 41 residues. The modified protein was also fragmented with the protease from Staphylococcus aureus. The peptides isolated represented 88% of the protein; their sequences were determined by manual and automated Edman degradation. Alignment of a number of these peptides gave the complex sequence of the N-terminal half up to position 122.

Amino Acid Sequence↗