[Absence of HIV 1/HTLV I "autochtonous" coinfection in the region of Nice].
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
P Ferrari
Publications and source records attributed to P Ferrari.
Na+/K+/Cl- cotransport in resealed ghosts from erythrocytes of the Milan hypertensive rats.
The erythrocytes (RBC) of the Milan hypertensive rats (MHS) have a smaller volume and faster Na+/K+/Cl- cotransport than RBC from normotensive controls (MNS). The difference in Na+/K+/Cl- cotransport is no longer present in inside-out Vesicles (IOV) of RBC membrane. To differentiate between cytoplasmic or membrane skeleton abnormalities as possible causes of these differences. Resealed ghosts (RG) were used to measure ion transport systems. The following results have been obtained: (1) RG from MHS have a smaller volume than MNS (mean +/- S.E. 20.7 +/- 0.45 vs. 22.09 +/- 0.42 fl, P < 0.05). (2) RG showed a bumetanide-sensitive Na efflux that retains the characteristics of the Na+/K+/Cl- cotransport of the original RBC: it is K(+)- and Cl(-)-sensitive and dependent on the intracellular Na+ concentration. (3) The Na+/K+/Cl- cotransport was faster in RG from MHS than in those from MNS (mean +/- S.E. 0.095 +/- 0.01 vs. 0.066 +/- 0.01 rate constant h-1, P < 0.01). These results, together with those of IOV, support the hypothesis that an abnormality in the membrane skeletal proteins may play a role in the different Na+/K+/Cl- cotransport modulation between MHS and MNS erythrocytes.
Animals↗
[Diagnostic value of ambulatory daily blood pressure profile: comparison with measurements performed by a laboratory technician].
Office blood pressure measured by a physician is often higher than under the usual ambulatory conditions. Therefore, alternative methods such as self-assessment of blood pressure and ambulatory blood pressure measurements are increasingly promoted. The purposes of this study, covering 613 referred patients, were (1) compare office blood pressure with continuous ambulatory blood pressure measurements, (2) compare office blood pressure with blood pressure values recorded by a trained technician in the absence of a physician and (3) analyze the interpretation of the blood pressure profiles by the referring physicians. Office blood pressure exceeded average ambulatory blood pressure in 94% of the patients and also the blood pressure values recorded by a technician in 88%. According to the office blood pressure there were 523 patients with elevated blood pressure, 20 with isolated increased systolic blood pressure and 70 with normal blood pressure. Office blood pressure was higher (systolic +17 +/- 18 and diastolic +9 +/- 12 mm Hg, p less than 0.0001) than the average value of the ambulatory blood pressure profile, whereas the latter did not differ significantly from blood pressure values measured by the technician (systolic -1 +/- 12 and diastolic -2 +/- 9 mm Hg). 190 of the 523 (36%) patients had white-coat hypertension according to the ambulatory blood pressure measurements. Conventional blood pressure measurements by the technician yielded a high sensitivity (84%) and specificity (87%) for distinguishing white coat hypertension. Analysis of the questionnaires showed that opinions about normal limits of ambulatory blood pressure vary considerably.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Pressure Determination↗
Na+,2Cl-,K+ cotransport system as a marker of antihypertensive activity of new torasemide derivatives.
A series of compounds related to torasemide, a loop diuretic, were synthesized and examined for their diuretic potency and inhibitory activity on the erythrocyte and renal medullary thick ascending limb vesicle Na+,2Cl-,K+ cotransport in Milan hypertensive (MHS) and normotensive (MNS) rat strains, where previous studies had demonstrated an alteration of the cotransport system genetically related to hypertension. From the results of the screening, structure-activity relationships were drawn and two compounds, JDL 961 and C 2921 were selected. Their IC50 on renal vesicle cotransport were similar in the two strains (JDL 961: MHS = 1.8 microM; MNS = 1.2 microM; C 2921: MHS = 4 microM; MNS = 3.8 microM), and were 4-8 times lower than those of torasemide (MHS = 13 microM; MNS = 31 microM, P less than 0.01) and 50-60 times lower than those of bumetanide (MHS = 145 microM; MNS = 206 microM, P less than 0.05) taken as reference compounds. Their ability to reduce the development rate of hypertension was tested both in MHS and in Okamoto spontaneously hypertensive rats (SHR) strain, in which cotransport alterations are opposite to those of MHS. Both torasemide derivatives (7.5 mg.kg-1 os per day) prevented development of hypertension in the two strains. The time course of this hypotensive activity was faster and the percentage of blood pressure fall greater in MHS (20-25%) than in SHR rats (12-15%), even though the absolute value of blood pressure fall was similar in MHS (JDL 961 = -17 mm Hg; C 2921 = -30 mm Hg) and SHR (JDL 961 = -25 mm Hg; C 2921 = -20 mm Hg). A superimposable effect of bumetanide was observed in the two strains, but at 8 times higher daily dose (60 mg.kg-1). These results suggest that new loop diuretics can be selected for their antihypertensive activity on the basis of their in vitro potency in inhibiting the Na+,2Cl-,K+.
Animals↗
[Rational assessment procedure in hypertension].
Diagnosis of hypertension is based on a classification of blood-pressure values, determined by multiple blood-pressure measurements over a period of several weeks or months. However, possibility of a so-called 'white coat effect' has to be considered, i.e. a marked increase of blood-pressure values in the presence of medical persons. Multiple control-measurements by the patient himself or an ambulatory day profile may clarify the situation in suspicious cases. In the case of pure 'white coat' hypertension, no further investigation is necessary, since cardiovascular complications only correlate with the 'usual' ambulatory blood pressure. Persons with borderline (141-159/91-94 mmHg and intermittently lower, according to the WHO) or established hypertension usually present with further cardiovascular risk factors, like lack of physical exercise, smoking, hypercholesterolemia (elevated total cholesterol/HDL-cholesterol), alone or accompanied by hypertriglyceridemia, disturbed tolerance of glucose or diabetes mellitus, or hypertrophy of the left ventricle. Therefore, in borderline as well as in established hypertension these additional risk factors have to be evaluated. Considering left ventricular hypertrophy electrocardiogram and chest X-ray are insensitive with regard to diagnosis and prognosis of this important and serious risk factor. Echocardiography that can meet both these criteria is for capacity reasons still limited to selected cases. In contrast to the investigation of the risk profile, only few patients will profit from an investigation of etiology of hypertension. It should be tailored to individual features and after thorough evaluation of all consequences, such as costs for the patient, chances for a positive result and possible therapeutical consequences. Usually, careful history taking, clinical investigation and routine laboratory provide an appropriate basis for further rational investigative procedures. Hypertension is a common and important risk factor. The challenge for the public health is great because prognosis can markedly be influenced by early diagnosis and therapy. Insufficient distinction between efficient diagnostic and therapeutical efforts and those that may be superfluous may not only influence psyche and somatic well-being of the patient but also socio-economic balance.
Adrenal Gland Neoplasms↗
[Symptomatic mixed cryoglobulinemia containing the anti-HCV antibody].
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Chronic Disease↗
[Acute pulmonary embolism with negative D-dimers].
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Aged↗
Effect of amiloride analogues on sodium transport in renal brush border membrane vesicles from Milan hypertensive rats.
The effect of ethylisopropyl-amiloride (EIPA) and phenamil on sodium uptake in renal brush border membrane vesicles from prehypertensive rats of the Milan strain (MHS) and their normotensive controls (MNS) was investigated. In the presence of both a membrane potential and a pH gradient a differential effect of EIPA and phenamil was evidenced between the two rat strains. In the absence of a pH gradient, but in the presence of a membrane potential, EIPA was about two-fold more potent than phenamil in inhibiting sodium transport in both rat strains, excluding the presence of epithelial sodium channels in our BBMV preparations. Taken together these results support the hypothesis that a structurally different Na+/H+ exchanger located on the brush border membrane may be involved in the increased tubular sodium reabsorption observed in vivo in hypertensive rats.
Amiloride↗
[Antihypertensive therapy in the nineties].
The risk for cardiovascular complications is already substantially increased in persons with borderline elevation of arterial pressure (141-159/90-94 mmHg and transiently below). It increases progressively with higher grades of hypertension. The main aim of treatment is thus a significant improvement in survival for the patient. Persons with raised blood pressure (BP) have often additional cardiovascular risk factors such as deranged carbohydrate metabolism, dyslipidemia, left ventricular hypertrophy, smoking and others. Treatment of hypertensive patients should thus not only normalize BP but should at the same time reduce associated risk factors or at least not increase them. Conventional antihypertensive treatment based on thiazides in high doses or beta-blocking agents led to marked reduction of strokes and heart failure, but did not satisfactorily reduce coronary heart disease or sudden cardiac death. It has been suspected that other cardiac risk factors are insufficiently influenced or eventually even deteriorated by conventional therapy, thus counteracting partly a beneficial effect of lowered BP. Beta-blockers however have at least a secondary preventive effect after myocardial infarction. Newer antihypertensive drugs such as ACE-inhibitors, calcium antagonists and alpha 1-blockers reduce left ventricular hypertrophy and are at least neutral with regard to metabolism of lipids and carbohydrates. The non-thiazide diuretic indapamide and the serotonin (S2-) blocker ketanserin likewise are neutral with regard to glucose and lipid metabolism. The efficacy of these new drugs regarding long term survival is as yet undetermined. Persisting borderline or established hypertension should as a rule always be approached with basic non-pharmacologic measures: loss of overweight, reduction of alcohol intake, exercise, avoidance of high salt foods, abstention from smoking and withdrawal of BP-raising drugs. If antihypertensive medication is indicated, potential first line drugs are ACE-inhibitors, calcium antagonists, beta-blockers, thiazides at low dose, indapamide, ketanserin, the alpha 1-blocker prazosin and others; initially as monotherapy, if needed in combinations of 2 or 3. Older patients or those will with additional disturbances such as diabetes, hypercholesterolemia, nephropathy, heart failure, ischemic heart disease, arrhythmias, claudication, asthma and others need problem-adjusted modifications of treatment.
Antihypertensive Agents↗
Insulin sensitivity in normotensive subjects during angiotensin converting enzyme inhibition with fosinopril.
The effect of the new ACE-inhibitor, fosinopril, on insulin sensitivity (SI), glucose homoeostasis and lipid profile has been examined in 24 young, healthy, normotensive men. SI, fasting plasma glucose and insulin, serum total triglycerides (Tg) and lipoprotein cholesterol (C) fractions, and ACE activity were assessed after subjects had taken placebo for 1 week and after 3 further weeks either on placebo (12 subjects) or fosinopril 20 mg daily (12 subjects), administered in a double-blind, randomized order. Measurements were made after 3 days on a standard diet (2500 kcal/d, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared with control values at the end of the run-in placebo phase, fosinopril reduced plasma ACE activity (from 106 to 24 nmol.ml-1.min-1), Significantly increased plasma potassium and lowered upright systolic blood pressure. It also improved the k-value of the glucose disappearance rate after glucose load (from -1.70 to -1.88%.min-1) and tended to increase SI slightly although not significantly (from 10.2 to 12.0.10(-4).min-1.microU-1.ml-1). Fasting plasma glucose, insulin, serum total, high-, low-, and very-low density lipoprotein cholesterol fractions and total triglycerides were unchanged following fosinopril and placebo. The findings indicate that in healthy lean humans, ACE inhibition with fosinopril is neutral with regard to lipoprotein and carbohydrate metabolism, and that it may slightly enhance cellular glucose disposal. This calls for further evaluation in individuals at high risk of developing insulin resistance and in patients with impaired insulin sensitivity related to hypertension, obesity, decreased glucose tolerance and diabetes mellitus.
Adult↗
Plasma insulin during physiological and pathophysiological changes in atrial natriuretic factor.
Changes in plasma insulin in response to a physiological or pathophysiological elevation in circulating atrial natriuretic factor (ANF) have been investigated. Plasma insulin, glucose, immunoreactive (ir) ANF, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), absolute and fractional excretion of sodium (FENa), have been measured in 14 volunteers before and during infusion of low doses of ANF or vehicle (V). Each subject received single-blind in a randomized sequence at 2 week-intervals: V alone, or ANF 4, 8 and 16 ng.kg-1.min-1, induced over 90 min. Plasma irANF was increased 2.5- to 11-fold during the ANF infusion as compared to the test with the vehicle. Plasma insulin did not change during V administration (baseline vs V: 22 vs 21 microU.ml-1) and was unchanged during ANF at 4, 8 and 16 ng.kg-1.min-1 (19, 19, 21 microU.ml-1, respectively). Blood pressure, ERPF and GFR were not affected, and diuresis, FENa and urinary Na excretion were increased significantly and dose-dependently during ANF, but not V infusion. Compared to baseline, ANF 4, 8 and 16 ng.kg-1.min-1 increased urinary Na excretion by 147,241 and 446 mumol.min-1, respectively. The findings indicate that, in normal humans, an acute increase in irANF within or slightly above the physiological range, which modified natriuresis and diuresis, did not alter circulating plasma insulin.
Atrial Natriuretic Factor↗
Effect of prolonged bicarbonate administration on plasma potassium in terminal renal failure.
In hemodialysis patients with hyperkalemia, i.v. sodium bicarbonate has recently been found to be ineffective in lowering plasma potassium within one hour. In the present study the effect of a prolonged bicarbonate infusion on plasma potassium was investigated. Twelve patients with terminal renal failure who were on hemodialysis were infused i.v. with 8.4% sodium bicarbonate (4 mmol/min) for one hour and with 1.4% (0.5 mmol/min) for five hours (total amount 390 mmol). Plasma bicarbonate rose from 17.5 at baseline to 28.4 and 29.6 mmol/liter, and blood pH from 7.32 to 7.46 and 7.48 at one and six hours, respectively. Plasma potassium did not change significantly after one and two hours (6.04 at baseline, 5.91 and 5.77 mmol/liter, respectively). Only at four and six hours did a moderate decline to 5.44 (P less than 0.05) and to 5.30 (P less than 0.01) occur, of which approximately half was calculated to be due to ECF volume expansion. However, no change or a very moderate decrease was observed in three patients even after six hours (+0.19, -0.32, -0.33 mmol/liter). Five patients with higher baseline plasma potassium (6.15 to 8.15 mmol/liter) behaved like seven with lower levels (5.25 to 5.87 mmol/liter). Tented T-waves in the ECG of seven patients disappeared after one hour only in one patient. Plasma aldosterone, norepinephrine and epinephrine were normal to elevated before and tended to fall during i.v. bicarbonate. Plasma dopamine and insulin were in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of diuretics on the plasma lipid profile.
Hypertension, dyslipidaemia, glucose intolerance (associated with insulin resistance and compensatory hyperinsulinaemia) and other abnormalities are complementary coronary risk factors which often occur in association. A familial trait for essential hypertension seems to coexist commonly with defects in carbohydrate and lipoprotein metabolism which can be detected before the appearance of hypertension. Diabetes mellitus as well as obesity promotes the development of hypertension and dyslipidaemia. Moreover, certain drugs used for antihypertensive therapy can further modify lipoprotein and glucose metabolism. Thiazides in high dosage and loop-diuretics can increase serum low-density-lipoprotein cholesterol (LDL-C) and/or very-LDL-C and the total C/high-density lipoprotein cholesterol (HDL-C) ratio, while HDL-C is largely unchanged; triglycerides (Tg) are also often elevated. Premenopausal women may be protected from this side effect. Whether diuretic-induced dyslipidaemia is dose-dependent and low thiazide doses (i.e. hydrochlorothiazide < or = 12.5 mg daily) are less active, awaits clarification. The diuretic-antihypertensive agent, indapamide, given at a dose of 2.5 mg.day-1, seems to exert no relevant effect on serum lipoprotein or glucose metabolism. The potassium-sparing diuretic, spironolactone, also may be largely neutral with regard to lipids. Moreover, potassium sparing diuretics may possibly counteract, at least in part, a dyslipidaemic influence of potassium-loosing diuretics in medium dose. Drug-induced dyslipidaemia, as well as glucose intolerance, represent potentially adverse influences. In the hypertensive population, effective blood pressure control with traditional drug therapy based on thiazide-type diuretics in high dosage led to a distinct decrease in cerebrovascular morbidity and mortality, but a lesser decrease in coronary events.(ABSTRACT TRUNCATED AT 250 WORDS)
Diuretics↗
Chemoimmunotherapy for prophylaxis of recurrence in superficial bladder cancer: interferon-alpha 2b versus interferon-alpha 2b with epirubicin.
Eighty-five patients who had undergone transurethral resection (TUR) of superficial bladder cancer were randomized to one of two treatments. Patients in Group 1 received a 10-month course of intravesical therapy with interferon (IFN)-alpha 2b (50 MU dose), commencing 21 days after TUR once a week for 8 weeks, then once every 15 days for 4 months and then finally once a month for 4 months. Patients in Group 2 received epirubicin (80 mg) intravesically 0, 24 and 48 h after TUR, and then 21 days after TUR received IFN-alpha 2b as for Group 1. The results confirmed the efficacy of immunoprophylaxis with IFN-alpha 2b, and early treatment with epirubicin tended to further reduce the percentage of relapses and extended the disease-free interval.
Antineoplastic Combined Chemotherapy Protocols↗
Left ventricular structure and determinants in normotensive offspring of essential hypertensive parents.
OBJECTIVE: To assess whether currently normotensive offspring of essential hypertensive parents may have alterations in left ventricular mass (LVM) and function, and how these relate to some potential determinants. DESIGN AND METHODS: Echocardiographical indices of LVM (assessed by two-dimensional guided M-mode echocardiogram), 'clinic' blood pressure and daytime ambulatory blood pressure profiles, blood pressure responses to dynamic and isometric exercise testing, haematocrit, plasma and 24-h urinary electrolytes and catecholamines, and plasma angiotensin II were assessed on a defined Na+ intake in 31 normotensive lean sons of essential hypertensive parents (OHYP group) and 30 body mass index- and age-matched sons of normotensive parents (ONORM group). RESULTS: Clinic supine systolic blood pressure was higher in the OHYP than the ONORM group, but clinic diastolic and daytime ambulatory mean blood pressures, blood pressure loads and blood pressure during dynamic or isometric exercise did not differ significantly. LVM index (LVMI), interventricular septum thickness (IVST), posterior wall thickness (PWT), the IVST:PWT ratio, ejection fraction, fractional shortening, cardiac index and measured biochemical variables also did not differ significantly between groups. In the whole study population the LVMI correlated positively with the body mass index and negatively with plasma noradrenaline. CONCLUSIONS: In young lean men with one essential hypertensive parent and blood pressure still in the normal range, left ventricular structure and systolic function, as assessed by echocardiography, seem to be often unaltered and appropriate relative to the existing body habitus and blood pressure. Moreover, an early tendency for increasing resting blood pressure in genetically hypertension-prone humans may be more apparent under clinic than usual ambulatory conditions, whereas the blood pressure reactivity to physical stress seems to be largely normal at this stage.
Adult↗
Teicoplanin metabolism in humans.
Teicoplanin, a lipoglycopeptide antibiotic, consists of five major components (A2-1 through A2-5), one hydrolysis component (A3-1), and four minor components (RS-1 through RS-4). All the major components contain an N-acyl-beta-D-glucosamine, but they differ in the lengths and branchings of their acyl-aliphatic chains. Previous studies with radiolabeled teicoplanin in rats and humans have shown that the drug is eliminated by the renal route and that metabolic transformation is very minor, about 5%. A possible metabolic transformation of teicoplanin into A3-1 was also suggested. In the present study in humans, two metabolites (metabolites 1 and 2; 2 to 3% of total teicoplanin) were isolated after intravenous administration of radiolabeled teicoplanin. After purification, their structures were determined by fast atom bombardment mass spectroscopy and 1H nuclear magnetic resonance spectroscopy on the basis of the well-known correlations established in this field, and they were found to be new teicoplaninlike molecules, bearing 8-hydroxydecanoic and 9-hydroxydecanoic acyl moieties. This metabolic transformation is likely due to hydroxylation in the omega-2 and omega-1 positions for metabolites 1 and 2, respectively, of the C-10 linear side chain of component A2-3. This might explain the low extent of metabolism of teicoplanin if we consider that only component A2-3 has a linear chain that is susceptible to such oxidation.
Anti-Bacterial Agents↗
Ouabainlike factor in Milan hypertensive rats.
Ouabainlike factor (OLF) has been extracted from the hypothalamus and adrenals of the ox and rats of the Milan hypertensive strain (MHS) and their normotensive controls (MNS). OLF was identified by its ability to 1) inhibit ouabain-sensitive 86Rb uptake into human erythrocytes, 2) displace [3H]ouabain binding, and 3) inhibit purified dog kidney Na-K-adenosinetriphosphatase (ATPase). Rat and bovine OLF have similar characteristics. Those that are close to ouabain are 1) ligand conditions for maximal inhibitory activity, 2) high-performance liquid chromatography retention time, 3) reversibility of inhibitory activity on Na-K-ATPase, 4) reduced Na-K pump inhibitory activity by K, 5) high affinity for Na-K-ATPase, and 6) no activity on calcium ATPase. OLF does not resemble ouabain in the following characteristics: 1) the capacity of OLF to inhibit ouabain low-affinity Na-K-ATPase isoform is greater than that of ouabain and 2) the capacity of OLF to inhibit renal Na-K-ATPase isoforms is greater when the enzyme is obtained from adult rather than young rats. The yield of OLF is greater from MHS than MNS. These findings represent the first direct evidence that a higher amount of OLF is present in tissues from genetically hypertensive rats than from their inbred normotensive controls, maintained under the same dietary and environmental conditions. This further supports previous observations on the role of OLF in the pathogenesis of MHS hypertension.
Adrenal Glands↗
Swiss hypertension treatment programme with verapamil and/or enalapril in diabetic patients.
The purpose of the present study was to assess the efficacy and tolerability of diuretic-free antihypertensive therapy with a calcium antagonist and/or an angiotensin converting enzyme (ACE) inhibitor in patients with diabetes mellitus. 54 hypertensive [blood pressure (BP) above 140/90mm Hg] patients with diabetes mellitus type 1 (n = 7) or 2 (n = 47) and normal serum creatinine levels (mean 82 +/- 6 mumol/L) received either verapamil or enalapril after a 2-week washout and a 4-week placebo phase. If BP remained elevated, both agents were combined. Verapamil or enalapril alone normalised diastolic BP (to less than 90mm Hg) in 36 patients; verapamil decreased BP from 159/98 to 147/87mm Hg (n = 19, p < 0.001) and enalapril decreased BP from 166/99 to 146/88mm Hg (n = 17, p < 0.001). In 18 patients who remained hypertensive after 10 weeks of monotherapy, a combination of both drugs decreased BP from 169/104 to 151/90mm Hg (p < 0.001). Overall, 87% of patients achieved a target BP response at 30 weeks. Urinary albumin as related to creatinine excretion (UAE; micrograms albumin:mg creatinine) was on average not significantly changed after verapamil or enalapril treatment, alone or combined. Nevertheless, in patients with initial microalbuminuria, UAE decreased (p < 0.05) during enalapril treatment. Serum potassium, total lipids, high density lipoprotein cholesterol, low density lipoprotein cholesterol, glycosylated haemoglobin, serum C peptide and fructosamine levels were not significantly modified by treatment. Subjective tolerability of the drugs was also generally good. Thus, in hypertensive patients with diabetes, a diuretic-free therapy based on the calcium antagonist verapamil or the ACE inhibitor enalapril, alone or combined, can effectively decrease BP without adversely affecting carbohydrate and lipid metabolism.
Adolescent↗