Biomedical subjects
Publications and source records attributed to M Candito.
A five-year-old child presented with a large undifferentiated sarcoma in the right lung. Urinary catecholamines were assayed as tumor markers. A short-lived but significant rise in urinary norepinephrine and dopamine followed by rises in urinary levels of corresponding breakdown products were evidenced.
The purpose of this study was to investigate circadian changes in noradrenaline (norepinephrine) levels in patients presenting with congestive heart failure. Eighteen patients were investigated with a group mean age of 66 years, 12 in NYHA class III and 6 in class IV. The cause of the heart failure was ischemia in 7 cases, valvular in 1 case and idiopathic in the other 10 cases. The mean follow-up time of the disease was 3.9 years. Six healthy volunteers were investigated following the same protocol. Blood samples were taken while the patient was lying down over a period of 24 hours, after installing a peripheral venous catheter. The assay was carried out by means of high performance liquid chromatography with electrochemical detection. In the controls, the mean noradrenaline level (norepinephrine) was 220 +/- 62 pg/ml, with daytime peaks. The heart failure patients showed a high mean level (230 +/- 404 pg/ml), with less daytime variability than the controls (92% vs 127%; p < 0.05). The 8 a.m. value was reproducible, and there was close correlation between this value and the mean value for the 24 hours (p < 0.001). Thus, the morning sample provides a good estimation of the levels over the 24 hours.
Because pruritus, erythema and tachycardia are observed in some patients during chemonucleolysis, a prospective study was designed to investigate the plasma levels of histamine and catecholamines occurring after an injection of chymopapain. Thirteen patients (11 men and 2 women), mean age 38 +/- 11 years, were studied. They all had negative prick skin tests, human basophil degranulation tests (HBDT) and radio-absorbent tests (RAST) to chymopapain. The patients were premedicated with 100 mg hydroxyzine and 3 g tranexamic acid. Sedation was carried out using 0.1 mg.kg-1 droperidol and 0.02 mg.kg-1 phenoperidine. The nucleosus pulposus was visualized with 3 ml of contrast medium (lopamiron 300); 2 ml of chymopapain were then injected. Blood samples were obtained at T1 (after the contrast medium, but before the chymopapain), and then 5, 10, 15, 20 and 30 minutes after the chymopapain. The usual haemodynamic parameters were recorded at the same times. Four patients had clinical signs (group I), whereas the other nine (group II) did not. There was an increase in histamine levels in three patients from group 1, as well as in two in group II (up to 33 nmol.l-1). However, mean histamine and catecholamines levels were comparable in both groups at all times, and between times, of sampling. There therefore was no relationship between clinical signs and the release of histamine or catecholamines. The premedication with an antihistamine may have protected the patients, but the signs reported by four patients may also be due to the chymopapain itself.
1. The effect of exercise testing and beta-blockade on plasma norepinephrine (PNE), and secretion of its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), was assessed in 28 mild-to-moderate hypertensives before and after the administration of dilevalol, a new beta-blocker with beta 2-agonism. 2. This double blind, placebo-controlled study consisted of two successive submaximal exercise tests before and after the administration of a single oral dose of dilevalol (200 mg, 400 mg or 600 mg). Plasma norepinephrine levels were determined at rest, at 100 watts step of exercise and at maximal effort (Emax). 3. During the control test, mean PNE levels increased from 1.73 +/- 0.52 nmol/L (resting value) to 8.01 +/- 4.01 nmol/L at Emax (P less than 0.01) as MHPG levels increased from 11.18 +/- 1.33 nmol/L (rest) to 17.50 +/- 1.15 nmol/L (Emax, P less than 0.01). After dilevalol, PNE increased significantly as compared to controls (P less than 0.05), from 2.32 +/- 0.99 to 12.42 +/- 5.97 nmol/L (P less than 0.01). PNE and MHPG levels were correlated, both at rest and during exercise. PNE levels after beta-blockade were linearly related to the dose of beta-blocker administered. MHPG levels were unaltered by the administration of dilevalol, both before and after exercise. 4. The increase in MHPG that occurs during bicycle exercise is largely generated from an increase in central nervous system noradrenergic activity. While dilevalol increases the peripheral sympathetic nervous system, both at rest and during exercise (which is reflected by increases in PNE levels) the drug does not alter resting central nervous system noradrenergic activity nor amplify the increase in central noradrenergic activity that occurs during exercise.
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The case of a young woman with clinical and biological manifestations suggestive of a pheochromocytoma primarily producing dopamine is reported. Whether endogenous production of dopamine was due to a tumor or to a metabolic abnormality remained unclear.
Dilevalol is a vasodilating beta-blocker with proven antihypertensive activity. In this study, 28 patients with mild-to-moderate uncomplicated hypertension underwent 2 submaximal exercise tests, each consisting of progressive steps of 20 watts for 2 minutes or up to 85% theoretical maximum heart rate. Five minutes after the first test, patients received either placebo or dilevalol 200 mg, 400 mg or 600 mg. The second exercise test was performed 3 hours later. Diastolic blood pressure, systolic blood pressure, heart rate and norepinephrine plasma levels were assessed before and after exercise. Dilevalol at all doses caused a significant decrease in heart rate and blood pressure both at rest and during exercise, compared to placebo. Dilevalol 600 mg had a greater effect on diastolic blood pressure than dilevalol 200 mg and 400 mg. Administration of dilevalol 200 mg and 400 mg enabled 42% of patients to increase their maximal exercise level by 20 to 60 watts. Dilevalol increased plasma norepinephrine levels at the 100 watts exercise levels from 5.1 +/- 4.0 nmol/l to 7.6 +/- 4.3 nmol/l (p less than 0.05). No adverse effects were observed during dilevalol treatment. This study shows that dilevalol is an effective antihypertensive agent that blunts heart rate and blood pressure risings during exercise.
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Circadian rhythms of total tryptophan were investigated by assays of hourly blood samples over 25 h. The study population consisted of four endogenously depressed patients investigated in the absence of any treatment and six healthy controls. The abnormalities detected by statistical analyses in untreated depression consisted mainly of amplitude reduction; the phase positions of the depressed patients were similar to those of the controls.
Enzymoimmunoassays have been developed as alternatives to radioimmunoassays because they obviate the need for labelled compounds yet offering comparable specificity. The authors used an enzymoimmunoassay to investigate hourly serum cortisol levels over 24 hours in 6 patients (aged over 40 years) with endogenous depression (4 unipolar depressions, under antidepressor treatment and 2 bipolar depressions, without medication) and in 2 controls, aged 20 and 47 years. In agreement with literature data, a clear circadian rhythm was observed in controls and in the depressed patients, and hypercorticism was noted in one depressed patient. A trend towards phase advance in depression was seen in both the treated and untreated patients.
Circadian rhythms of body temperature, plasma cortisol, norepinephrine (NE), thyroid stimulating hormone (TSH), and melatonin were compared in 16 endogenously depressed, 15 recovered (after 3 weeks of anti-depressant treatment), and 16 normal subjects. The depressed patients showed clear circadian rhythm abnormalities, consisting mainly in amplitude reduction. This amplitude reduction was significantly correlated with the patients' Hamilton depression scores. Normal circadian profiles were restored after recovery when amplitude, in particular, was increased. Features of the circadian rhythms observed in remission may be associated with antidepressant drug effects, whereas those observed in depression resemble the circadian rhythms observed in normal subjects living under conditions of temporal isolation and those of blind subjects. Our findings suggest that depression may be related both to a weakening of the coupling processes between internal pacemakers and to an abnormal sensitivity to environmental information.
Dilevalol (R,R'-isomer of labetalol) is an antihypertensive agent combining non-specific beta blockade with peripheral vasodilatation due to beta 2-receptor agonism. The aim of this study was to determine the effects of chronic dilevalol administration on lymphocyte beta 2-adrenoceptor density. The investigation was conducted as a double-blind, placebo-controlled comparison. Ten days of chronic dilevalol (400 mg) or placebo treatment was administered to 12 healthy normotensive volunteers. Clinical and biochemical parameters: heart rate (HR) systolic and diastolic blood pressure (SBP, DBP), electrocardiogram, norepinephrine (NE), epinephrine (E), MHPG (3-methoxy-4-hydroxyphenylethylene glycol; one of the major brain metabolites of NE) were analysed on the first day (D1) before (H0) and 3 h after oral treatment (H3) and on the tenth day (D10). Clinical results showed no significant changes in HR, DBP, SBP in the two groups (placebo, n = 6; dilevalol, n = 6). NE increased 3 h after the first oral dilevalol intake (p less than 0.05). This increase is greater than that due to the circadian variation observed in the placebo group. Acute dilevalol treatment seems to increase the plasma circulating NE level, which returns to normal values after 10 days of chronic treatment. Binding assays were performed before and after 10 days of treatment. In the placebo group, no change in beta-adrenoceptor density was observed (36.6 +/- 8.3 versus 38.3 +/- 9.4 femtomol/mg of protein). Lymphocyte beta-adrenoceptor density (Bmax) significantly decreased after 10 days of dilevalol treatment without any changes in affinity (KD). Results were 40.3 +/- 11.6 (D1) and 30 +/- 7.6 (D10) (p less than 0.05). It was concluded that dilevalol down-regulated lymphocyte beta 2-adrenoceptor density, suggesting that beta 2 agonism of dilevalol is predominant.
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Eighty-two children, class ASA I, between four months and 14 years of age, all undergoing elective subumbilical surgery, were randomly assigned to two groups: a control "halothane anesthesia" group (n = 35) and a 0.25% bupivacaine "caudal anaesthesia" group (n = 47). In the control group, there was a significant peroperative increase in heart rate, respiratory rate, systolic blood pressure and plasma adrenaline levels (p less than 0.05). There was no significant difference in the noradrenaline levels. In the "caudal anaesthesia" group, the haemodynamic response was less pronounced, this being concomitant with a decrease in adrenaline and noradrenaline levels (p less than 0.05 and p less than 0.001, respectively). During surgery, there were significant differences between the groups in heart rate, respiratory rate, noradrenaline levels (3 +/- 0,30 nmol X l-1 vs 1.68 +/- 0.18 nmol X l-1; p less than 0.001) and adrenaline levels (1.67 +/- 0,28 nmol X l-1 vs 0.78 +/- 0.08 nmol X l-1; p less than 0.01). It is concluded that the catecholamine response in children undergoing minor abdominal surgery has been blocked by caudal anaesthesia.
The circadian rhythm of plasma norepinephrine (NE) was investigated in the depressed (major affective disorder, DSM III; n = 12), recovered (after 3 weeks of treatment using usual antidepressant drugs; n = 12) and normal (volunteers, age and sex matched; n = 10) states. Data analysis (based on the evaluation of circadian parameters, on the chronogram method and on the chronobiological analysis) revealed a clear NE circadian rhythm in normal subjects, a rhythm which was disturbed in depression, with amplitude reduction and abnormal phase position. These abnormalities tended to disappear during recovery since circadian parameters were similar to those of controls. These circadian abnormalities could be linked to the impairment of the peripheral and central catecholaminergic systems. They may also support the chronobiological hypothesis of affective disorders.
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Both aqueous standards and plasmas spiked with standards are used for assays of plasma constituents. In a previous study, high-performance liquid chromatographic (HPLC) assays of plasma norepinephrine, epinephrine, and dopamine performed with spiked plasma reference solutions resulted in lower thresholds and thus gave higher concentrations. To verify the hypothesis that spiked catecholamines bind to plasma proteins (like physiological catecholamines) and thus escape extraction by alumina prior to HPLC, the recovery of standards in human albumin solution was compared with similar investigations using aqueous standards. Our findings confirm that (a) albumin is responsible to a great extent for the drop in recovery and (b) calibration by extraction of aqueous standards is preferable to calibration by spiked plasma for free catecholamine assays.