B-type natriuretic peptide in athletes performing an Olympic triathlon.

AIM: Brain natriuretic peptide (BNP) is a cardioactive molecule produced in the myocardium. BNP is a sensitive marker of cardiac failure and its measurement in blood could be useful to the diagnosis and the treatment of this disease. Sporting activities, especially endurance ones, can induce cardiac problems, owing to the high workload for the myocardium during long and ultralong heavy effort. There are 2 papers describing the behavior of BNP in endurance events. BNP was elevated in marathoners, immediately after the race and also after 4 h. We studied the behavior of BNP in the triathlon, which is a complex sport characterized by 3 different activities (swimming, cycling, running). METHODS: We recruited 49 athletes, all males, except for 4 females; 2 athletes did not finish the race and were not included in the statistical analysis in 2 different competitions. In these subjects we measured BNP using an immunological method before and after a triathlon. RESULTS: No statistical significance between BNP values, before and after the triathlon, was found. CONCLUSIONS: We found no significant differences between pre- and postcompetition BNP values. Moreover, the range of values in both the blood drawings are similar of those of the general population, representing the biological variability of the analyte. The values in regularly trained athletes,, are not different from the general population and BNP is not modified by a triathlon, a typical endurance sport performance. We can underline that BNP increases in plasma are induced by heavy pathologies and are not influenced by physical activities, even strenuous ones.

Serum proteins by capillary zone electrophoresis: approaches to the definition of reference values.

The Paragon CZE 2000 (Beckman Analytical, Milan, Italy) is an automatic dedicated capillary zone electrophoresis (CZE) system, producing a five-zone serum protein pattern with quantitative estimation of the zones. With the view of substituting this instrument for two previously used serum protein electrophoresis techniques, we planned to produce reference values for the "new" systems leading to compatible interpretation of the results. High resolution cellulose acetate electrophoresis with visual inspection and descriptive reporting (HR-CAE) and five-zone cellulose acetate electrophoresis with densitometry (CAE-D) were the previously used techniques. Serum samples (n = 167) giving "normal pattern" with HR-CAE were assayed with the CZE system, and the results were statistically assessed to yield 0.95 reference intervals. One thousand normal and pathological serum samples were then assayed with the CAE-D and the CZE techniques, and the regression equations of the CAE-D values over the CZE values for the five zones were used to transform the CAE-D reference limits into the CZE reference limits. The two sets of reference values thereby produced were in good agreement with each other and also with reference values previously reported for the CZE system. Thus, reference values for the CZE techniques permit interpretation of results coherent with the previously used techniques and reporting modes.

Inter-method differences in the measurement of some specific plasma proteins: commutability of control materials.

We compared the inter-method differences shown by control materials and by patients' sera for the measurement of some plasma proteins in the same pair of analytical systems. Sets of 100 to 110 samples of patients' sera and of 18-19 control materials, including the recently available CRM 470, were assayed with up to five automatic analytical systems, in two different experiments. About 5500 values were produced and assessed statistically. Materials (either patients' sera or control materials) were considered non-commutable (i.e. exhibiting significantly different inter-method behaviour) when their distance from the regression line in a stated pair of methods exceeded 3 standard deviations. According to this criterion, less than 1.5% of the patients' sera, and an even lower proportion of control materials were non-commutable. However, the inter-method behaviour of control materials was usually slightly different from that of patients' sera. Some systematic inter-method difference in the measurements on patients' sera may therefore exist, even though inter-method equivalence has been demonstrated with control materials.

In vitro anti-HIV-1 antibody production in subjects in different stages of HIV-1 infection.

We evaluated the in vitro antibody production from peripheral blood mononuclear cells (PBMC) against HIV-1 proteins in infected adults. Fifty-four HIV-1 infected patients (four recent seroconverters, 15 asymptomatics with a CD4 count higher than 500/microliters, 27 asymptomatics with a CD4 count between 200 and 500/microliters and eight symptomatic patients) were tested. PBMC were incubated in the presence or absence of 1% pokeweed mitogen (PWM) at 37 degrees C for 8 days. Western blot assay, p24 antigen ELISA and anti-p24 antibody ELISA were performed on serum and culture supernatants. Spontaneous production of anti-env antibody in culture supernatants was evidenced in all subjects. All the positive supernatants for anti-core antibodies (18/54) were derived from asymptomatic patients. PBMC from recent seroconverters and from symptomatic patients did not produce any anti-core antibody. Antibody production decreased after stimulation with PWM. The concentration of p24 antigen did not significantly increase in p24 positive supernatants following acidification (P = 0.1), suggesting that the inability to detect p24 antibody was not due to the anti-p24 antibody complexed to p24 antigen in culture supernatants. In vitro production of anti-p24 antibodies was significantly more frequent in asymptomatic subjects with high CD4+ cell counts (P = 0.02) and was absent in recent seroconverters. This last finding suggests that during the initial phases of the infection, anti-p24 antibody production may be restricted to cells residing in lymphoid organs. In addition, the lower percentage of anti-core antibody in people with low CD4+ cell counts is not merely a consequence of the binding of the antibody to an increased amount of antigen, but probably reflects an impaired production or a sequestration of producing cells in lymphoid tissue during the late stages of the infection.

Persistent albuminuria in normotensive non-insulin-dependent (type II) diabetic patients: comparative effects of angiotensin-converting enzyme inhibitors and beta-adrenoceptor blockers.

1. Some non-insulin-dependent (type II) diabetic patients show albuminuria without arterial hypertension. In these patients, angiotensin-converting enzyme inhibitors reduce urinary albumin excretion without producing any changes in systemic blood pressure and renal haemodynamics. However, up to now it has not been clear whether these favourable renal effects are specifically related to angiotensin-converting enzyme inhibition or not. 2. Twelve type II diabetic outpatients with persistent macroalbuminuria (greater than 300 mg/daily on at least three consecutive occasions), without any other signs of renal disease and whose blood pressure was persistently below 140/90 mmHg, were studied. 3. In a randomized sequence and in a double-blind fashion, after a 2-month run-in period, patients were allocated to receive 5 mg of enalapril or 50 mg of atenolol daily for the next 6 months. At the end of this first period and after 6 months on placebo in a cross-over fashion, active treatment was replicated. Blood pressure and urinary albumin excretion were measured every 2 months, whereas the other variables studied were determined at the end of each period. 4. Kidney function and blood pressure did not change significantly, whereas albuminuria decreased significantly, after both of the drugs. 5. These data suggest that the inhibition of tissue angiotensin formation and the consequent reduction in glomerular permeability, rather than changes in renal and systemic haemodynamics, are the common mechanisms by which both enalapril and atenolol decreased albuminuria in our patients.

Comparative effects of enalapril, atenolol and chlorthalidone on blood pressure and kidney function of diabetic patients affected by arterial hypertension and persistent proteinuria.

Arterial hypertension and proteinuric nephropathy are common features in diabetic patients. In streptozotocin-diabetic rats, it has been possible to reduce the blood pressure and proteinuria by converting enzyme inhibitors, and so slowing the decline of kidney function. These results have been confirmed in diabetic patients affected by arterial hypertension and persistent proteinuria. However, up to now it has not been clear if these favorable renal effects are related specifically to converting enzyme inhibition. In the attempt to clarify this last point, from a practical as well as from a speculative point of view, 12 type 2 diabetic outpatients affected by mild to moderate arterial hypertension and persistent macroalbuminuria (greater than 250 mg/daily, at least on three consecutive occasions) without any other signs of renal diseases were studied. In a randomized sequence and in a double blind fashion, after a washout period of 3 weeks, the patients underwent pharmacological treatment which consisted of enalapril 20 mg o.d., chlorthalidone 12.5 mg o.d., atenolol 50 mg o.d. and placebo o.d. Each treatment lasted 45 days. Kidney function, blood pressure and heart rate were checked at the beginning and at the end of each treatment, while urinary albumin excretion was measured at the end of the 4th, 5th, and 6th week of each treatment. Blood pressure significantly decreased in a similar fashion after each active treatment, while kidney function did not change significantly. Urinary albumin excretion rate significantly decreased after enalapril and atenolol, but did not change after chlorthalidone. According to these results we can hypothesize that the inhibition of tissue angiotensin formation and its related change on the glomerular permeability, rather than renal and systemic hemodynamic features, seem to be the common mechanisms by which both enalapril as well as atenolol decrease the albuminuria in our patients.

Long-term effects of indapamide: final results of a two-year Italian multicenter study in systemic hypertension.

To evaluate the antihypertensive efficacy and tolerability of a low-dose diuretic, indapamide, 2.5 mg once daily, was given to 248 patients with uncomplicated, mild to moderate hypertension for a period of 24 months. Blood pressure during sitting was 165 +/- 1/105 +/- 1 mmHg (mean +/- standard error of the mean) at the end of the placebo run-in period and 143 +/- 1/88 +/- 1 and 140 +/- 1/85 +/- 1 mmHg after 2 and 24 months, respectively; heart rate was clinically unmodified (from 77 +/- 1 to 75 +/- 1 beats/min). Total cholesterol, high-density cholesterol and serum triglycerides were unchanged, and uric acid increased significantly (from 292.0 +/- 6.5 to 377.7 +/- 56.5 mumols/liter). A mild reduction in serum potassium (-0.36 +/- 0.03 mmol/liter) was observed after 2 and 6 months of therapy; however, the degree of reduction appeared to be lower than that from reported studies with other thiazide diuretics. The incidence of hypokalemia (serum potassium less than 3.5 mmol/liter) was highest in northern Italy (17%), intermediate in the central region (14%) and lowest in southern Italy (2%), although the absolute reduction in serum potassium was similar in all the geographic areas. Blood glucose tolerance was unchanged despite the changes in serum potassium. The tolerability was good on the whole, with a tendency toward an improvement in the well-being of patients, most of whom were already asymptomatic before starting the study.

Angiotensin converting enzyme inhibition in normotensive type II diabetics with persistent mild proteinuria.

To evaluate the effect of enalapril on proteinuria, 16 normotensive type II diabetics with persistent proteinuria were studied. At random, the patients were allocated to enalapril (5 mg once a day) or placebo, in a double-blind fashion, for 12 months. Blood pressure, heart rate, urinary albumin excretion, plasma renin activity and aldosterone, blood glucose, serum fructosamine, urine urea and body weight were checked monthly during the run-in period and every 2 months during the treatment period. The kidney function was studied at the beginning of the study and during the sixth and 12th months. Enalapril decreased urinary albumin excretion in our patients in the absence of any effect on blood pressure and kidney function. Our data may be interpreted on the basis of a direct vascular effect of enalapril that is probably related to a tissue mechanism consisting of reduced angiotensin formation, increased kinins, or both, or of other unknown factors.

Hemodynamic, renal, and humoral effects of the calcium entry blocker nicardipine and converting enzyme inhibitor captopril in hypertensive type II diabetic patients with nephropathy.

We compared the effect of nicardipine, a dihydropiridine derivative calcium entry blocker (CEB), with that of captopril (CAP), a converting-enzyme inhibitor (CEI), and that of the two drugs combined, on blood pressure (BP), heart rate (HR), and renal function in 12 hypertensive type II diabetic outpatients with nephropathy (persistent proteinuria greater than 500 mg/24 h) according to a 2 x 2 factorial design. For 4-week treatments, the patients received nicardipine (NIC) 20 mg t.i.d., CAP 50 mg b.i.d., NIC plus CAP, and matched placebo. Each active treatment significantly reduced BP, with an additive effect of NIC and CAP combined versus either drug alone. HR did not change. Effective renal plasma flow (RPF) and glomerular filtration rate (GRF) were unmodified, but renal vascular resistances (RVRs) were significantly reduced by the three active treatments. Filtration fraction (FF) did not change with NIC or with NIC plus CAP and was significantly reduced with CAP. Urinary albumin excretion (UAE) was significantly reduced by each active treatment to a similar extent. Plasma renin activity (PRA) increased significantly with NIC plus CAP only and did not change when the drugs were administered singly. Plasma aldosterone, glucose, potassium, fructosamine, and urinary sodium and volume did not change during the trial. We conclude that the two drugs singly and combined are useful for treatment of hypertensive non-insulin-dependent diabetes (NIDD) patients with persistent proteinuria.

Systemic and renal effects of chronic angiotensin converting enzyme inhibition with captopril in hypertensive diabetic patients.

Nine outpatients with mild to moderate arterial hypertension, type 2 diabetes mellitus and persistent macroalbuminuria were studied. After 1 month of placebo, the patients were treated with 50 mg captopril twice a day for the following 6 months. Blood pressure and urinary albumin excretion were significantly reduced but no relationship was found between these two variables. No changes were detected in the renal plasma flow, glomerular filtration rate, filtration fraction, renal vascular resistance or metabolic pattern. Captopril significantly reduced blood pressure and albuminuria without any change in the renal function. The decrease in albuminuria may be related to the reduction in blood pressure as well as to a direct effect of captopril on glomerular haemodynamics.

Automated amidolytic method for evaluating the activated partial thromboplastin time compared with a conventional coagulation method.

We report studies of the validity and clinical application of a new amidolytic method for evaluating the activated partial thromboplastin time (APTT) compared with a conventional clotting method. The results with the two methods were well correlated for normal plasma and plasma from hemophilia patients. Congenital deficiencies of of the intrinsic coagulation pathway other than hypo- and dysfibrinogenemia detected by the amidolytic method agreed with those detected by the clotting APTT. The results with the two methods for plasma from patients under heparin treatment were statistically different, suggesting a lesser sensitivity of the amidolytic method to heparinization. The use of the amidolytic APTT reagent in combination with factor VIII and IX deficient plasma allowed the measurement of both factors. The results obtained with normal and hemophilic plasma were in agreement with those obtained with the one-stage clotting method in all except two occasions. Even though the amidolytic method demonstrated the presence of the lupus anticoagulant in the majority of tested samples of known lupus subjects, it was less sensitive to the abnormality than the clotting method.

Angiotensin converting enzyme inhibition with a low dose of enalapril in normotensive diabetics with persistent proteinuria.

Angiotensin II is the main regulator of both glomerular haemodynamics and glomerular capillary permeability. An alteration in the function of intrarenal angiotensin II seems to be the cause of diabetic glomerulopathy in animals and humans. In order to investigate the renal effects of the angiotensin converting enzyme (ACE) inhibitor enalapril (5 mg once a day), 24 normotensive diabetic patients with persistent proteinuria, after a 3-month run-in period, were randomly allocated to receive the active drug (12 patients) or the corresponding placebo, for the 6 months. Effective renal plasma flow, glomerular filtration rate, renal vascular resistance and filtration fraction were measured at the end of the run-in and the treatment periods. Blood pressure, heart rate, urinary albumin excretion, plasma renin activity and aldosterone, blood glucose, serum fructosamine and body weight were checked monthly during the run-in and every 2 months during the treatment period. Enalapril decreased urinary albumin excretion in the normotensive diabetic patients without any changes in systemic blood pressure or glomerular haemodynamics. These results indicate that ACE inhibition interferes with the glomerular capillary permeability induced by angiotensin II.

Tolerability and well-being with indapamide in the treatment of mild-moderate hypertension. An Italian multicenter study.

Since hypertension is an important risk factor of cardiovascular morbidity and mortality that can be at least in part decreased by pharmacologic reduction in elevated blood pressure, it is necessary that an antihypertensive agent be effective, but at the same time well tolerated and, according to some recent hypotheses, have no deleterious effect on serum electrolyte levels, as well as lipoprotein and glucose tolerance. However, due to different cultural and social backgrounds, lifestyles, and so on, the tolerability may differ from one population to another and the conclusions drawn from a population cannot be extrapolated to people of other countries. For these reasons, the well-being of patients, as well as the tolerability of indapamide, a non-thiazide diuretic, have been investigated in patients with hypertension of mild and moderate degree from different parts of Italy with a satisfactory blood-pressure response to this drug (-22.8 +/- 0.6/-17.1 +/- 0.5 mm Hg). Simultaneous to the significant blood-pressure reduction, the only significant change among the metabolic effects was a slight reduction in plasma potassium levels (-0.37 +/- 0.03 meq/liter). The tolerability was, on the whole, very good with a tendency toward an improvement of well-being in patients, the majority of whom were already asymptomatic before starting the treatment.

Monoclonal antibody-defined T lymphocyte subpopulations in monoclonal gammapathy of undetermined significance.

We used monoclonal antibodies of the OK series to study T lymphocyte subpopulations in 55 patients with monoclonal gammapathy of undetermined significance (MGUS) and in 40 healthy control subjects, with the aim to investigate if alterations in T lymphocyte subpopulations occur also in MGUS. Mean OKT3+ and OKT8+ cell counts were higher (p less than 0.01 and p less than 0.001, respectively) and the mean OKT4/OKT8 ratio was lower (p less than 0.02) in MGUS patients than in the control subjects. MGUS with the IgM-type monoclonal immunoglobulin (IgM-MGUS) showed the most evident derangement of T lymphocyte subpopulations, i.e., a significant increase of OKT8+ cells and a significant reduction of the OKT4/OKT8 ratio. OKT4+ and OKT8+ cells were significantly increased in patients with high paraprotein concentration (above 16 g/l). Our data suggest that alterations of T lymphocytes are present in MGUS, and that they are similar to those observed in malignant lymphoproliferative disorders.

Humoral and hemodynamic effects of nitrendipine versus clonidine in patients with essential hypertension.

A single-blind, randomized controlled study was conducted to assess and compare the antihypertensive effectiveness and the effects on glucose tolerance and renin-angiotensin-aldosterone balance of nitrendipine (Bay e 5009), a new dihydropyridine calcium antagonist, and clonidine. Twenty-six outpatients with uncomplicated mild to moderate essential hypertension were randomly allocated to receive 20 mg of nitrendipine or 0.25 mg of clonidine (slow-release formulation) daily for five weeks. One patient in the clonidine group dropped out. Both treatments significantly reduced systolic and diastolic blood pressures with negligible modifications in heart rate. However, diastolic blood pressure was reduced significantly more (P less than 0.001) with nitrendipine. Accordingly, 12 of 13 patients given nitrendipine attained the goal of diastolic pressure less than or equal to 90 mmHg, according to criteria of the Hypertension Detection and Follow-up Program, while only three of 12 patients in the clonidine group achieved this goal. Side effects were mild and transient in both treatment groups. No definite trends in plasma renin activity or plasma aldosterone concentration, or in blood glucose or immunoreactive insulin (measured both in fasting conditions and after an oral glucose tolerance test), were evident when baseline and posttreatment values were compared. The results of this study suggest that nitrendipine is an effective and safe antihypertensive agent and is devoid of adverse effects on glucose tolerance and renin-aldosterone homeostasis.

Humoral and haemodynamic interactions between clonidine and nifedipine in human essential hypertension.

Acute administration of nifedipine (NIF), a calcium entry blocker (CEB), in animals reduces the hypotensive effect of clonidine (CLN), an alpha-adrenergic agonist. In order to evaluate possible negative interactions between NIF and CLN in man during chronic treatment with these drugs, 12 patients with mild to moderate uncomplicated essential hypertension received either NIF (20 mg twice daily), CLN (0.25 mg once daily), the two drugs together at the same doses, or their matched placebos for a 2-week period each. NIF (-13.5% versus placebo) and CLN (-10.2% versus placebo) decreased blood pressure significantly and when combined, blood pressure was further decreased (-17.1% versus placebo). Heart rate was increased by NIF and NIF + CLN but unchanged by CLN alone. Plasma renin activity (PRA) tended to increase with NIF, decreased with CLN (P < 0.05) and was unchanged with NIF + CLN. Plasma aldosterone did not vary during any of the phases of the trial. These results indicate that NIF and CLN do not interact negatively on blood pressure control in essential hypertensive subjects.

The role of endogenous opioids in the baroreflex dysfunction of dialysis patients.

We studied the effect of the opiate antagonist naloxone on the response to Valsalva manoeuvre in nine dialysis patients, in six diabetics with normal renal function whose response to Valsalva manoeuvre was similar to that of dialysis patients and in eight healthy subjects. Naloxone caused a progressive increase in the subnormal Valsalva ratio in dialysis patients but it did not cause any change in diabetics nor in healthy subjects. The increase in Valsalva ratio observed in dialysis patients was due to restoration of the parasympathetically mediated reflex bradycardia of the release phase of the manoeuvre. Endogenous opioids may be responsible for the baroreflex dysfunction of dialysis patients.