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Biomedical subjects

C Zamboulis

Publications and source records attributed to C Zamboulis.

At least 19 recordsLinked to original sources

Inhibition of TNFalpha does not induce viral reactivation in patients with chronic hepatitis C infection: two cases.

Chronic infections, such as hepatitis C, in the setting of rheumatic disorders pose a potential hindrance to optimal management because of possible complications linked to the institution of immune suppression, as well as the high incidence of hepatotoxicity associated with many of the disease-modifying antirheumatic drugs included in the conventional therapeutic regimens. In the setting of hepatitis C, however, the effect of TNFalpha blockade may be potentially beneficial because TNFalpha appears to be involved in the pathogenesis of liver fibrosis through the stimulation of apoptotic pathways. Data related to this subject are, unfortunately, still limited and without detailed information regarding the clinical progression of the rheumatic disorder. We report the cases of two patients, one with ankylosing spondylitis and one with psoriatic arthritis, who were efficiently treated long-term with anti-TNF agents for their rheumatic disease without any evidence of reactivation or flaring of their hepatitis C infection or deterioration of their liver function. Our results indicate that TNFalpha blockade is a highly efficient and uncompromising therapy in hepatitis C-affected individuals with connective tissue disorders. However, systematic, large-scale studies addressing the issue of safety of these new efficient drugs, i.e., monoclonal antibodies targeted against TNFalpha, in patients with chronic hepatitis C will be needed to properly assess the risks and benefits of this treatment in analogous cases.

Adalimumab↗

Angiotensin converting enzyme gene polymorphism is not related to essential hypertension in a Greek population.

Studies in various ethnic groups have shown contradictory evidence on the association of the angiotensin converting enzyme (ACE) insertion/ deletion (I/D) polymorphism with essential hypertension. In addition, mistyping of the insertion allele in heterozygotes has been reported. We analyzed the ACE genotype of 98 hypertensive and 84 normotensive subjects of Greek origin. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers were flanking the polymorphic region in intron 16 of the ACE gene. To avoid mistyping of heterozygotes, samples with the DD genotype were also amplified with primers that detect only the insertion allele. The distribution of the DD, ID, and II ACE genotypes was 30, 45, and 23 in hypertensive patients and 29, 40, and 15 in normotensive subjects, respectively. The estimated frequency of the insertion allele was 0.45 in hypertensive and 0.42 in normotensive subjects. The difference was not statistically significant. The results indicate a lack of association between ACE I/D polymorphism and essential hypertension in this Greek population, suggesting that other genes must contribute to the pathogenesis of hypertension.

Alleles↗

Percutaneous transluminal renal angioplasty in patients with renovascular hypertension: long-term results.

This study evaluated the long-term effects of percutaneous transluminal renal angioplasty (PTRA) on blood pressure and renal function in patients with renovascular hypertension. Seventy-eight patients with hypertension and unilateral or bilateral stenoses of the renal arteries (16 with fibromuscular dysplasia and 62 with atherosclerosis) were studied. All patients with fibromuscular dysplasia (group A) had normal renal function, while 27 of the 62 patients with atherosclerosis (group B) presented with various degrees of renal failure. PTRA was technically successful in 87.5% patients of group A. The overall technical success rate (complete plus partial) was 72.3% (55/76 renal arteries) in group B. Mean follow-up (range) in months was 42 (12-108) for group A and 39 (13-106) for group B. After successful PTRA, the overall benefit rate (cure plus improved) for hypertension was 100% in group A; 10 of 14 patients were cured and 4 of 14 were improved. In group B, the overall benefit rate was 70.8%; 9 of 48 were cured and 25 of 48 were improved. PTRA was technically successful in 18 of 27 patients with renal failure. Renal function improved in 4 of 18 patients, remained stable in 9 of 18, and deteriorated in 5 of 18 patients. The above results suggest that PTRA is an effective method for the long-term management of patients with renovascular hypertension, although the results were less favorable in the presence of bilateral renal artery stenoses: in addition to improved control of blood pressure, PTRA might improve renal function or delay its progressive deterioration.

Adult↗

The relationship between the sympathetic nervous system and the renin-angiotensin system in renovascular hypertension.

UNLABELLED: The aim of this study is to evaluate and compare the activity of the sympathetic nervous system and the renin-angiotensin system in patients with unilateral or bilateral renovascular hypertension. Plasma noradrenaline (plNA) levels and plasma renin activity (PRA) were measured simultaneously in blood samples obtained both from a peripheral vein and from the renal veins, during catheterization of the venous cava system, in 17 patients with unilateral (group A) and in 9 patients with bilateral renal artery stenoses (group B). RESULTS: peripheral plNA levels were elevated in 6/17 patients of the group A and 3/9 patients of the group B, while in the remaining 11/17 and 6/9 were normal, respectively. The comparison of plNA levels between the renal veins showed that in both groups plNA levels were higher in the renal vein of the ischaemic (group A) or the more ischaemic kidney (group B), and the difference was statistically significant. Renal vein renin ratio was above 1.5 in both groups. Renin hypersecretion from the ischaemic or the more ischaemic kidney compared to renin suppression from the normal or the less ischaemic kidney showed statistically significant difference.

Humans↗

Effects of adrenaline infusion on serum thromboxane B2 and plasma beta-thromboglobulin levels in hypertensive and normotensive subjects.

Adrenaline was infused in incremental doses of 0.05 up to 0.1 microgram/kg/min over a 60-min period in nine patients with mild essential hypertension and six age-matched normotensive controls. Blood samples were drawn at preset time intervals and plasma adrenaline, platelet count, serum thromboxane B2 (TxB2) and plasma beta-thromboglobulin (beta-TG) were measured. Adrenaline levels (m +/- SEM) rose significantly, from 0.078 +/- 0.01 (baseline) to 0.902 +/- 0.03 ng/ml (60 min), in the hypertensive group; a similar increase was observed in the control group (from 0.049 +/- 0.007 to 0.877 +/- 0.03 ng/ml). Platelet count increased significantly at early time points and remained high throughout infusion in both groups (hypertensive from 250 +/- 25 to 305 +/- 24 x 10(3)/microliters, control from 219 +/- 16 to 260 +/- 18 x 10(3)/microliters). TxB2 levels likewise increased significantly from 15 minutes after initiation of infusion. In hypertensive subjects the mean resting value of 186 +/- 17 ng/ml rose to 312 +/- 42 ng/ml, while in control subjects the resting value of 174 +/- 29 ng/ml rose to 286 +/- 32 ng/ml. Baseline levels of TxB2 were found to be higher in the hypertensive patients but not significantly. beta-TG levels increased from an initial value of 43.84 +/- 3.69 ng/ml to 59.5 +/- 4.69 ng/ml at 60 min in the hypertensive group, while a similar change from 28.7 +/- 19.2 ng/ml to 40.36 +/- 3.16 ng/ml was observed in the control group. These changes were significant, as was the difference between basal values in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Changes of plasma noradrenaline levels in the renal and systemic circulation after successful percutaneous transluminal angioplasty in renovascular hypertension.

The sympathetic nervous system involvement in the pathogenesis of human renovascular hypertension was studied in 10 hypertensive patients with unilateral renal artery stenosis, who underwent percutaneous transluminal angioplasty (PTA). Before PTA, systolic/diastolic BP readings were 185.3 +/- 7.8/123.2 +/- 5.1 mmHg, peripheral PRA values were 8.63 +/- 2.27 ngAl/ml/h, the ratio RVRR was 2.15 +/- 0.27, the ratio V1-IVC/IVC was 1.00 +/- 0.23 (V1 = PRA from the renal vein of the stenotic side, IVC = PRA from the inferior vena cava) and the ratio V2-IVC/IVC was 0.04 +/- 0.02 (V2 = PRA from the renal vein of the non-stenotic side); 30 min after successful PTA the respective values of the above measured parameters were: 144.2 +/- 6.7/98.2 +/- 3.1 mmHg (p less than 0.01), 8.13 +/- 2.21 ngAl/ml/h (p less than 0.005), 1.79 +/- 0.19 (p less than 0.01), 0.68 +/- 0.18 (p less than 0.001) and 0.06 +/- 0.02 (p less than 0.005). Peripheral plasma noradrenaline levels (plNA) were 0.694 +/- 0.058 ng/ml, plNA levels from the renal vein of the stenotic side were 0.962 +/- 0.108 ng/ml and plNA levels from the renal vein of the non-stenotic side were 0.759 +/- 0.092 ng/ml; 30 min after successful PTA the respective values were 0.518 +/- 0.055 ng/ml (p less than 0.01), 0.681 +/- 0.078 ng/ml (p less than 0.005) and 0.510 +/- 0.063 ng/ml (p less than 0.005). It is suggested that the reversal of chronic renal ischaemia by PTA induced statistically significant changes in the sympathetic nervous system activity, parallel to the changes of renin secretion.

Adult↗

Changes of sympathetic activity during tooth extraction.

Urinary VMA excretion was studied in 3 groups of young and healthy subjects, before and 2 h after a standard tooth extraction. Local anaesthesia was either a solution of lignocaine 2% (1st group, n = 17) or a mixture of lignocaine 2% with noradrenaline bitartrate, 1250 micrograms/100 ml, (2nd group, n = 13) or lignocaine 2% with adrenaline hydrochloride 1250 micrograms/100 ml (3rd group, n = 10). Mean VMA excretion rose from 3.6 +/- 2.8 to 6.7 +/- 4.6 mg/g creatinine, in the first group. In the 2nd group, the mean VMA excretion was 2.3 +/- 1.2 and rose to 6.2 +/- 2.8, whereas in the 3rd it rose from 2.3 +/- 0.92 to 8.3 +/- 7.6 mg/g creatinine. The increase of VMA excretion after the tooth extraction was of the same order in the 3 groups studied and was not affected by the addition of noradrenaline and adrenaline in the anaesthetic solution.

Adolescent↗

Estimation of sympathetic activity in essential hypertension.

The estimation of sympathetic nervous activity by measurement of plasma norepinephrine (NE) concentration assumes a constant relation between this and the synaptic cleft concentration. This assumption would be incorrect if the clearance of plasma NE could be varied without affecting its removal from the synaptic cleft, so we compared the clearance of plasma NE in mild hypertensives and normal subjects by measurement of its plasma concentration during a 0.5-hr infusion at 0.07 microgram/kg/min; there were no differences. The simultaneous infusion of isoproterenol, 0.02 microgram/kg/min, led to an increase in heart rate and NE clearance. There was partial inhibition of catechol-O-methyltransferase by a single oral dose of alpha-methyldopa, 250 mg, which reduced the clearance of both catecholamines (CAs) by about 20%. After the end of the infusions containing isoproterenol, the tachycardia persisted for more than 1 hr and declined more slowly in the hypertensives than the normals. In contrast, plasma concentrations of both CAs returned to basal values within a few minutes. The persistent tachycardia may be due to rerelease of isoproterenol into the synaptic cleft, since stimulation of sympathetic activity by assumption of the erect posture was associated with an exaggerated increase in heart rate (by 48/min after infusion and 23/min before infusion). The study therefore suggests that synaptic cleft and plasma CA concentrations can be independently manipulated and the relation between them may be different in hypertensive patients and normal control subjects.

Blood Pressure↗

The role of presynaptic alpha-adrenoceptors in the regulation of blood pressure in the conscious rabbit.

1 Changes in mean arterial pressure, heart rate and plasma noradrenaline after alpha-adrenoceptor blockade with several alpha-adrenoceptor antagonists have been studied in the conscious rabbit in order to investigate the possible role of presynaptic alpha-adrenoceptors in cardiovascular regulation. 2 Prazosin (0.05-2 mg/kg) and phentolamine (0.5-20 mg/kg) produced dose-dependent falls in mean arterial pressure and rises in plasma noradrenaline. These changes were related to the degree of postsynaptic alpha-adrenoceptor blockade determined by the pressor response to intravenous phenylephrine. 3 Similar changes in mean arterial pressure and plasma noradrenaline were observed after administration of the direct vasodilators hydralazine (1-10 mg/kg) and nitroprusside (2.5-55 microgram kg-1 min-1). 4 After baroreceptor deafferentation by sinoaortic denervation the falls in mean arterial pressure were much greater and the rise in plasma noradrenaline was markedly attenuated. 5 Yohimbine (1 mg/kg) increased mean arterial pressure and plasma noradrenaline but it was not possible to exclude the possibility that central nervous effects of yohimbine underlay the increased sympathetic activity. 6 The magnitude of the baroreflex response to changes in pressure make it unlikely that the functional significance of the presynaptic alpha-adrenoceptor can be readily determined by measurement of plasma noradrenaline in intact animals.

Animals↗

Withdrawal of guanfacine after long-term treatment in essential hypertension. Observations on blood pressure and plasma and urinary noradrenaline.

1. Guanfacine (2-6 mg/day) a centrally acting antihypertensive drug, was effective in controlling blood pressure in 5 essential hypertensives and lowered plasma noradrenaline and urinary catecholamine excretion. 2. Withdrawal of guanfacine by blind substitution of identical placebo tablets under observation in hospital led to a gradual recovery of blood pressure over 2-4 days. 3. Salivary flow, which was reduced on guanfacine, returned to pretreatment levels by 2 days after withdrawal and significantly exceeded control for the next two days. 4. Urinary catecholamine excretion returned to pretreatment levels by 3 days but did not exceed control levels during the period of study. 5. Plasma noradrenaline returned gradually to pretreatment levels, and by day 4 significantly exceeded them. 6. No patient experienced symptoms suggesting catecholamine excess although four out of five reported a headache from the second day onwards. 7. Guanfacine, a centrally acting drug which pharmacologically resembles clonidine, has a slow offset of hypotensive effect over 2-3 days. Symptoms or biochemical evidence of catecholamine excess were not encountered within 48 h of withdrawal, possibly reflecting the longer duration of action and plasma half-life of guanfacine.

Blood Pressure↗

Absence of opiate and histamine H2 receptor-mediated effects of clonidine.

The possibility that clonidine might exert some of its effects via opiate or histamine H2 receptors has been suggested from observations in animals and man. We undertook a double-blind, randomized study in six normal subjects, comparing the effects of 0.2 mg intravenous clonidine after pretreatment with 300 mg cimetidine, 0.8 mg naloxone, and saline. There was no attenuation of the hypotension, bradycardia, sedation, inhibition of salivary flow, or reduction in plasma catecholamines after cimetidine and naloxone, but the fall in plasma catecholamines ater clonidine correlated with blood pressure, sedation, and salivary flow, suggesting a central adrenergic mechanism for these effects. It is not known whether cimetidine can cross the blood-brain barrier after short-term dosing. We conclude that in normotensive subjects the short-term effects of intravenous clonidine are probably not mediated by an action at peripheral histamine H2 or central opiate receptors.

Adult↗

Effects of single and multiple doses of guanfacine in essential hypertension.

The effects of oral guanfacine were examined in six patients with essential hypertension. Guanfacine caused a substantial fall in both lying and standing systolic and diastolic blood pressure. The fall in pressure was evident by 6 hr, maximal by 10 to 12 hr, and lasted as long as 36 hr. In four patients satisfactory blood pressure control throughout the day was achieved during inpatient administration with single daily doses of 2 to 4 mg in the evening. The other two patients required twice-daily dosing for optimal control of blood pressure. There was no evidence of tolerance to the hypotensive effect. Sedation and xerostomia were apparent after the first dose but did not limit dose titration. Guanfacine lowered lying and standing plasma norepinephrine; this continued on long-term dosing. Urinary catecholamines were reduced from 59.21 +/- 17.24 (mean +/- SEM) to 28.91 +/- 4.20 micrograms/24 hr after 7 days of treatment. The hemodynamic effects, side effects, and biochemical evidence of reduced sympathetic activity after guanfacine resembled the centrally acting antihypertensive clonidine, although guanfacine appeared to have a longer duration of action.

Antihypertensive Agents↗

Guanfacine: effects of long-term treatment and withdrawal.

1. Guanfacine 3-6 mg daily lowered blood pressure in five essential hypertensives and also reduced saliva production. 2. Plasma and urinary noradrenaline values were significantly reduced throughout the 8-10 weeks of treatment. 3. On substitution of placebo tablets for guanfacine, blood pressure increased over a 2-4 d period to reach but did not significantly exceed pretreatment levels. 4. After withdrawal of guanfacine plasma noradrenaline standing was significantly higher than the pretreatment level (P < 0.05) after 4 days. Saliva production was significantly higher than the pretreatment level on day 3 and day 4 of withdrawal. 5. Guanfacine is an effective antihypertensive drug with a spectrum of actions similar to clonidine. However, in abrupt withdrawal blood pressure returned to the pretreatment level over a 2-4 d period.

Antihypertensive Agents↗

The effects of desmethylimipramine on the pharmacological actions of alpha methyldopa in man.

The effect of pretreatment with the tricyclic antidepressant desmethylimipramine (DMI) 75 mg daily for 3 days on the action of oral methyldopa 750 mg was investigated in a double blind crossover design in volunteers. DMI pretreatment caused a small but not significant increase in supine systolic and diastolic blood pressure and heart rate. However, the effects of methyldopa on lying and standing blood pressure and heart rate were not markedly altered by pretreatment. In particular, the fall in standing blood pressure after methyldopa was present with and without DMI and the sedative action of methyldopa was similar. DMI alone reduced saliva production. No evidence was found that tricyclic antidepressant drugs significantly modify the hypotensive effect of methyldopa in man.

Adult↗