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C Benvenuti

Publications and source records attributed to C Benvenuti.

At least 55 records · Page 3Linked to original sources

Granzyme B and perforin can be used as predictive markers of acute rejection in heart transplantation.

We have investigated perforin and granzyme B expression in graft-infiltrating lymphocytes of patients who underwent heart transplantation. Those proteins are commonly present in the cytoplasmic granules of cytotoxic T lymphocytes and are released upon effector-target cell interaction. From 28 patients 103 endomyocardial biopsies were obtained and examined by histology and immunocytochemical analysis using relevant monoclonal antibodies. We found that "high" biopsy histological grades were associated with perforin and granzyme B expression in graft-infiltrating lymphocytes of patients with acute severe rejection crisis. In contrast, these markers were not detected in patients without rejection or during graft stabilization. Interestingly, in patients with mild rejection and "low" histological grades, two groups could be distinguished with a differential expression of the two intracytoplasmic proteins. The presence of perforin and granzyme B-expressing cells was found to be predictive of rapid progression to severe rejection, so that this situation required additional treatment; in contrast, their absence seemed to correlate with a good graft outcome without additional treatment. Moreover, perforin and granzyme B expression seemed to be down-regulated by immunosuppressive drugs, which coincided with graft stabilization. In conclusion, our data suggest that detection of granzyme B and perforin in graft-infiltrating lymphocytes might be helpful for routinely monitoring heart transplant patients.

Acute Disease↗

Results of transurethral resection and intravesical doxorubicin prophylaxis in patients with T1G3 bladder cancer.

OBJECTIVES: This retrospective study evaluates the outcome of patients with T1G3 bladder cancer treated by transurethral resection (TUR) and intravesical doxorubicin prophylaxis and identifies clinically useful prognostic factors. METHODS: One hundred twenty-eight consecutive patients with primary T1G3 bladder cancer were treated by TUR followed by 1-year intravesical prophylaxis with doxorubicin. Sex, age, number, size, and morphology of the tumors, exfoliative cytology, presence of dysplasia at first observation, pathologic findings of the first recurrence, and number of recurrences were the parameters considered in a multivariate analysis whose object was to identify specific risk factors for recurrence and progression. RESULTS: The recurrence rate was 56.3% and progression of disease was seen in 23.4% of cases with a disease-specific mortality rate of 7.8%. The disease-free survival in patients who had cystectomy was 37.7 months and the disease-specific mortality rate for this group was 35.7%. The recurrence rate was found to be significantly higher for multiple tumors, solid morphology, size greater than 3 cm, positive exfoliative cytology, and concurrent dysplasia. The reappearance of Stage 1, grade 3 tumor on first recurrence was the only factor found to be correlated with progression. CONCLUSIONS: Up front therapy consisting of TUR and intravesical doxorubicin prophylaxis is appropriate for T1G3 bladder cancer. Patients with unfavorable prognostic factors should be kept under strict control; and if a T1G3 tumor is identified on first recurrence, immediate cystectomy should be considered.

Administration, Intravesical↗

Additive haemodynamic effects of piroximone and prostacyclin in severe chronic heart failure.

This study was undertaken to assess the haemodynamic effects of the combined infusion of prostacyclin and piroximone, a phosphodiesterase inhibitor, in 18 patients with severe congestive heart failure. Right heart catheterization was performed with a Swan-Ganz thermodilution catheter and arterial blood pressure was monitored using a radial line. After baseline haemodynamic measurements, prostacyclin was administered in all patients at the incremental infusion rate of 2, 4, 6 and 8 and 10 ng.kg-1.min-1 during 15 min each. After recovery of baseline haemodynamics, patients were randomly assigned to the piroximone infusion rate of 5 or 10 micrograms.kg-1.min-1 or placebo. After 24 h piroximone or placebo infusion, the same prostacyclin protocol was applied. Prostacyclin infusion added to piroximone resulted in a significant improvement in haemodynamics, as compared to the group receiving prostacyclin added to placebo. As compared to the curve observed with the placebo infusion, 10 ng.kg-1.min-1 prostacyclin infusion resulted in a further increase in cardiac index, by 41 and 38% (P < 0.01) at the piroximone-infusion rates of 5 and 10 micrograms.kg-1.min-1, respectively, whereas systemic vascular resistance decreased by 25 and 21%, respectively (P < 0.01). Additionally, a further decrease in pulmonary capillary wedge pressure by 13 and 11% (P < 0.05) and in pulmonary vascular resistance by 21 and 19% (P < 0.05) was observed at the piroximone-infusion rates of 5 and 10 micrograms.kg-1.min-1, respectively. Consequently, stroke work index increased significantly, as compared to the group receiving prostacyclin added to placebo. This haemodynamic improvement occurred without significant changes in heart rate and mean arterial pressure. Thus, this study shows that in patients with severe congestive heart failure, short-term infusion of prostacyclin is safe and has additive haemodynamic effects on phosphodiesterase inhibitors.

Adult↗

Pharmacological bridge to cardiac transplantation: current limitations.

Addition of intravenous enoximone to sympathomimetic agents permits a rapid and drastic improvement in the clinical and hemodynamical condition of patients in cardiogenic shock referred for a mechanical bridge to transplantation. The present experience, based on the management of 52 patients, permits us to point out the current limitations of this pharmacological bridge: the rate of sudden death, the incompleteness of the physical rehabilitation of the patients, and the vanishing effect of intravenous enoximone.

Adult↗

Acetylcholine-induced constriction of angiographically normal coronary arteries is not time dependent in transplant recipients. Effects of stepwise infusion at 1, 6, 12 and more than 24 months after transplantation.

OBJECTIVES: The aim of this study was to evaluate whether acetylcholine may be a useful tool for detection of early angiographically undetectable coronary atherosclerosis in heart transplant recipients. BACKGROUND: Coronary artery disease is the main determinant of long-term prognosis in transplant recipients. Acetylcholine-induced constriction of angiographically normal coronary arteries in heart transplant recipients could be due to early atherosclerosis, and acetylcholine has been proposed for early detection of coronary artery disease. METHODS: The responses of large coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) mol/liter) were compared in five control subjects and in four groups of transplant recipients 1, 6, 12 and > 24 months postoperatively (group 1, n = 6; group 2, n = 7; group 3, n = 6; group 4, n = 6, respectively). All patients had normal coronary arteriographic findings. Vessel dimensions were measured in four segments in each patient. RESULTS: In control subjects, acetylcholine increased diameters significantly at 10(-8), 10(-7) and 10(-6) mol/liter (all p < 0.001 vs. basal value). No significant variation was observed at 10(-5) mol/liter. Intracoronary isosorbide dinitrate increased diameters of all segments (p < 0.001). In transplant recipients, vessel diameters did not vary significantly from baseline at 10(-8) and 10(-7) mol/liter concentrations in groups 1 and 3 and at 10(-8) mol/liter in group 4. Vessels constricted significantly in all the other cases. Comparisons of each group with control subjects showed that responses were significantly different for all concentrations but 10(-8) mol/liter in groups 3 and 4. Intracoronary isosorbide dinitrate elicited coronary vasodilation similar to that of control subjects in all groups of transplant recipients. CONCLUSIONS: This study indicates that the acetylcholine response is persistently abnormal in transplant recipients compared with that in normal control subjects and that this abnormality may not be related simply to the presence of atherosclerosis. Thus, acetylcholine may not be a useful tool for early detection of coronary atherosclerosis in heart transplant recipients.

Acetylcholine↗

Intranasal versus intravenous neostigmine in myasthenia gravis: assessment by computer analysis of saccadic eye movements.

Intranasal (i.n.) neostigmine has been developed to obtain a quicker onset of action and a more adaptable dosage regimen than oral neostigmine. The effect of this neostigmine formulation in myasthenia gravis (MG) was studied by means of computer analysis of saccadic eye movements (SEMs). Six MG patients were selected on the basis of a positive effect of Tensilon on hypometria of the first saccade. The effect of the i.v. formulation (0.5 mg) was compared to 1, 2, 3, and 4 puffs of i.n. neostigmine (one puff = 4.6 mg). The drug effect on SEMs was monitored at intervals up to 2 h. Administration of i.v. neostigmine produced a marked effect immediately after the injection and the benefit lasted over 1 h. Following administration of i.n. neostigmine a marked effect was found for two, three, and four puffs. The drug effect was evident within 3 min, peaked at 18-33 min, and lasted over 2 h. Our data indicate the efficacy of the new formulation of neostigmine in MG as measured by means of quantitative analysis of SEMs.

Administration, Intranasal↗

[Doppler echocardiographic evaluation of mitral flow velocity and prognosis of cardiac insufficiency].

The aim of this study was to determine the role of Doppler echocardiography in establishing the prognosis of Stages to 4 cardiac failure. The echocardiographic indices of left ventricular filling were correlated with catheter data and the 2 year out come of patients. The study population included 54 patients examined prospectively in the context of an evaluation of their cardiac failure. Two years after the initial examination, 19 patients were dead or transplanted. Of the remaining 35 patients, 18 were reevaluated at 6 months. Of the echocardiographic parameters, "hyper normal" mitral flow with a high E/A ration indicated poor prognosis; when E/A > 2, the one year survival was 50% and the 2 year survival 42%. There was overlap between the groups of dead or transplanted and surviving patients only when the E/A ratio was between 2 and 3. The patients with E/A < 2 were all alive without any major events at 2 years. All patients with E/A > 3 had a poor prognosis. The E/A ratio was closely correlated with pulmonary capillary pressure levels (p < 0.001, r = 0.55) and lees closely with cardiac index (p < 0.05, r = 0.4) and radionuclide ejection fraction (p < 0.05, r = 0.28). After 6 months' vasodilator treatment with an angiotensin converting enzyme inhibitor (captopril) the E/A ratio decreased significantly from 1.85 +/- 0.78 to 1.0 0.55 (p < 0.02). A "hyper-normal" mitral flow is related to many factors, including high left ventricular filling pressures, mitral regurgitation and reduced left ventricular compliance. This appearance of mitral flow is a poor prognosis factor in severe cardiac failure.

Actuarial Analysis↗

[Simultaneous heart and kidney transplantation using the same donor].

From 1988 to 1991, five cases of combined heart and kidney transplantation using the same donor have been achieved at our institution. All patients were males, 58 +/- 6 (46 to 64). The cardiac condition leading to the cardiac replacement was a dilated cardiomyopathy in one case, end-stage ischemic disease in 3, and failure of a previous cardiac transplantation in one. The renal condition claiming for a graft was a Glomerular nephritis in one, a polycystic disease in 3, and renal failure due to CyA toxicity in one; chronic hemodialysis was mandatory in all patients but one. There were no hospital deaths. The five patients are current survivors, the mean follow-up being 22 +/- 10 months (2-50 months). Five rejection episodes occurred in three patients; two patients have never demonstrated any cardiac rejection. All but one recovered a normal renal function as soon as the 7 th post operative day; only one episode of renal rejection has been detected, easily reversed by corticoids. No simultaneity was ever observed between cardiac and renal rejection episodes. Thus, the detection of rejection must be carried out separately for each graft organ. In four patients, cineangiograms of the coronary vessels were done respectively 12, 30 and 50 months post operatively and revealed a normal coronary bed. Thus, combined heart and kidney transplantation seems to be a realistic approach in properly selected patients in whom cardiac and renal failures cannot be treated by more conventional procedures.

Heart Transplantation↗

Effects of time and previous acute rejection episodes on coronary vascular reserve in human heart transplant recipients.

OBJECTIVES: This study examined whether previous rejection episodes may have deleterious effects on coronary vascular reserve of heart transplant recipients months after transplantation. BACKGROUND: Coronary reserve has been demonstrated to be within the normal range in long-term transplant patients without previous episodes of rejection. Conversely, acute rejection is associated with a dramatic reduction of coronary reserve, which is rapidly restored after therapy. METHODS: Coronary flow velocity was measured by intracoronary Doppler catheter before and after a maximally vasodilating dose of intracoronary papaverine in 16 control subjects and in 59 transplant patients classified into three groups with respect to time after transplantation: 1 to 6 months (group 1, n = 17), 7 to 18 months (group 2, n = 22) and > 18 months (group 3, n = 20). Coronary vascular reserve was evaluated through peak/rest coronary flow velocity ratio and minimal coronary vascular resistance index. All patients had normal findings on left ventricular angiography and coronary arteriography and a normal left ventricular mass. RESULTS: Arterial pressure was normal in all groups. Heart rate in the three groups of transplant patients, mean aortic pressure in groups 1 and 2, left ventricular systolic pressure in group 2 and rate-pressure product in groups 1 and 2 were higher than in control subjects. Average number of rejection episodes per patient was similar in the three groups of patients (group 1, 2.4 +/- 1.4; group 2, 2.5 +/- 1.9, and group 3, 2.1 +/- 1.3). Results showed no difference between each group of transplant patients and control subjects for peak/rest coronary flow velocity ratio (control subjects, 5.2 +/- 0.8; group 1, 5.3 +/- 1.5; group 2, 4.9 +/- 1.2, and group 3, 4.4 +/- 1.6) and for minimal coronary vascular resistance index (control subjects, 0.18 +/- 0.03; group 1, 0.18 +/- 0.04; group 2, 0.20 +/- 0.06, group 3, 0.23 +/- 0.11). In addition, patients with zero or one rejection episode had similar values of peak/rest coronary flow velocity ratio and minimal coronary vascular resistance index (4.3 +/- 1.3 and 0.23 +/- 0.10, respectively, n = 22) as did those with one or two rejection episodes (5.1 +/- 1.5 and 0.19 +/- 0.07, respectively, n = 24), and those with four or more episodes (5.2 +/- 1.4 and 0.19 +/- 0.05, respectively, n = 13). CONCLUSIONS: This study showed that coronary vascular reserve remains within normal range and is independent from the number of previous episodes of rejection until late after transplantation in human heart transplant patients with angiographically normal coronary arteries.

Analysis of Variance↗

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function.

BACKGROUND: Bronchial hyperresponsiveness to cholinergic stimuli such as the inhalation of methacholine is common in patients with impaired left ventricular function. Such hyperresponsiveness is best explained by cholinergic vasodilation of blood vessels in the small airways, with extravasation of plasma due to high left ventricular filling pressure. Because this vasodilation may be prevented by the inhalation of the vasoconstrictor agent methoxamine, we studied the effect of methoxamine on exercise performance in patients with chronic left ventricular dysfunction. METHODS: We studied 19 patients with a mean left ventricular ejection fraction of 22 +/- 4 percent and moderate exertional dyspnea. In the first part of the study, we performed treadmill exercise tests in 10 patients (group 1) at a constant maximal workload to assess the effects of 10 mg of inhaled methoxamine on the duration of exercise (a measure of endurance). In the second part of the study, we used a graded exercise protocol in nine additional patients (group 2) to assess the effects of inhaled methoxamine on maximal exercise capacity and oxygen consumption. Both studies were carried out after the patients inhaled methoxamine or placebo given according to a randomized, double-blind, crossover design. RESULTS: In group 1, the mean (+/- SD) duration of exercise increased from 293 +/- 136 seconds after the inhalation of placebo to 612 +/- 257 seconds after the inhalation of methoxamine (P = 0.001). In group 2, exercise time (a measure of maximal exercise capacity) increased from 526 +/- 236 seconds after placebo administration to 578 +/- 255 seconds after methoxamine (P = 0.006), and peak oxygen consumption increased from 18.5 +/- 6.0 to 20.0 +/- 6.0 ml per minute per kilogram of body weight (P = 0.03). CONCLUSIONS: The inhalation of methoxamine enhanced exercise performance in patients with chronic left ventricular dysfunction. However, the improvement in the duration of exercise at a constant workload (endurance) was much more than the improvement in maximal exercise capacity assessed with a progressive workload. These data suggest that exercise-induced vasodilation of airway vessels may contribute to exertional dyspnea in such patients. Whether or not inhaled methoxamine can provide long-term benefit in patients with heart failure will require further study.

Administration, Inhalation↗

Pharmacokinetics of oxatomide given percutaneously to healthy volunteers.

The percutaneous absorption of oxatomide gel at 5 per cent concentration was studied after single and repeated administration (85 mg b.i.d.) in six male and six female healthy volunteers, aged 25.7 +/- 0.8 years (mean +/- SEM) weighing 64.4 +/- 4.5 kg and the results compared with those obtained following a single oral dose (30 mg). The measurement of oxatomide was by means of a new sensitive and specific HPLC assay with limits of detection of 0.2 ng ml-1 in plasma and 1.0 ng ml-1 in urine. Poor percutaneous absorption was confirmed by the peak plasma concentrations which were 5.03 +/- 0.79 ng ml-1 following application of the gel for 7 days and 10.08 +/- 1.29 ng ml-1 following oral administration; the corresponding amounts of unchanged oxatomide recovered from 24 h urine collections were 1.42 +/- 0.39 micrograms and 3.93 +/- 0.92 micrograms.

Administration, Cutaneous↗

Efficacy of intranasal administration of neostigmine in myasthenic patients.

The efficacy of intranasally administered neostigmine was tested in 22 patients with generalized myasthenia gravis (MG). Topical therapy to the highly vascularized oropharynx proved to be quickly effective in 5-15 min both clinically and electrophysiologically. Twenty-eight MG patients were then recruited from different centres and their morning doses of oral pyridostigmine were substituted with intranasal neostigmine over a period of 2 or 3 weeks. Intranasal neostigmine proved to be equally efficacious in this regimen. No side-effect was noted even in 4 patients treated in this way for 1 year. Intranasal administration of anti-acetylcholinesterase may be very beneficial: (1) for patients with irregular absorption of oral doses; (2) early in the morning and every time a fast and temporary effect is needed; (3) in bulbar impairment and emergencies, in which a handy atomizer may be life-saving.

Administration, Intranasal↗

Beta-adrenergic contractile reserve as a predictor of clinical outcome in patients with idiopathic dilated cardiomyopathy.

To examine the ability of beta-adrenergic contractile reserve assessment to predict the outcome of patients with heart failure, a prospective study was undertaken in 35 patients with idiopathic dilated cardiomyopathy and radionuclide ejection fraction below 40%. During right- and left-sided catheterization, right atrial and left ventricular (LV) pressures, peak positive LV dp/dt, cardiac index, and plasma norepinephrine and epinephrine concentrations were measured at baseline. After a left main intracoronary infusion of dobutamine (25 to 200 micrograms.min-1), beta-adrenergic contractile responsiveness was assessed as the net increase in peak positive LV dp/dt (delta LV dp/dt). After the initial examination, patients were treated with diuretics, digitalis, and angiotensin converting enzyme inhibitors and then followed-up. After a mean follow-up period of 13 +/- 7 months, two groups of patients were distinguished: those who responded to medical therapy (group A, n = 26) and those with clinical deterioration (group B, n = 9) leading to death (n = 4) or heart transplantation (n = 5). Initial peak positive LV dp/dt, LV end-diastolic pressure, cardiac index, and LV ejection fraction were better in group A than in group B (p less than 0.001). Initial plasma norepinephrine and epinephrine concentrations were significantly higher and delta LV dp/dt was lower in group B than in group A (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship among neuropeptide Y, catecholamines and haemodynamics in congestive heart failure.

The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was assessed both at baseline and during inotropic intervention in patients with congestive heart failure. Eighteen patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction (LVEF) = 26 +/- 10%) underwent both right and left catheterization. Haemodynamic parameters were recorded at baseline and during dobutamine infusion. To measure norepinephrine (NE), epinephrine (E) (nmol.l-1: radioenzymatic assay) and NPY (pmol.l-1: immunoradiometric assay) plasma concentrations, blood samples were drawn from the femoral artery and from the coronary sinus, both at baseline and during dobutamine infusion. At baseline, NPY concentration were 2.15 +/- 0.97 pmol.l-1 in the femoral artery and 1.97 +/- 0.63 pmol.l-1 in the coronary sinus. Peripheral concentrations of NPY were, however, no different from those of patients without congestive heart failure: 2.4 +/- 2.7 pmol.l-1. Peripheral NE concentration was correlated to haemodynamic parameters: LVEF (r = -0.65; P less than 0.01), cardiac index (r = -0.54; P less than 0.05), LV end-diastolic pressure (r = +0.59; P less than 0.05), while peripheral NPY and E concentrations were not. Dobutamine improved haemodynamics, since cardiac index increased by 30% and LV end-diastolic pressure decreased by 40% (P less than 0.01). Peripheral NE concentration decreased from 6.48 +/- 4.5 to 4.82 +/- 2.69 nmol.l-1 (P less than 0.05) but there was no change in E (0.99 +/- 0.61 vs 1.04 +/- 0.74 nmol.l-1) or NPY concentrations (2.41 +/- 0.99 pmol.l-1). In the coronary sinus, neither NE nor NPY concentrations changed during dobutamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myocardial beta-adrenergic desensitization and neuronal norepinephrine uptake function in idiopathic dilated cardiomyopathy.

Desensitization of myocardial beta-adrenergic receptors may result both from an impairment of the norepinephrine (NE) neuronal uptake function and from an increase in circulating NE concentrations. The respective role of these two mechanisms of desensitization was examined in 18 patients with congestive heart failure related to an idiopathic dilated cardiomyopathy. The neuronal NE uptake system was evaluated by [123I]metaiodobenzylguanidine (MIBG) scintigraphy. The desensitization level of beta-adrenoceptors was assessed as the net increase in peak positive left ventricular (LV) dP/dt during intracoronary dobutamine infusion. Arterial NE concentrations were determined at baseline. To obtain control values, we performed MIBG scintigraphy and determined baseline NE concentration in 12 normal subjects. Cardiac MIBG uptake was significantly decreased in patients as compared with controls. This decrease was related to the severity of the disease based on hemodynamic indexes. The inotropic response to intracoronary dobutamine infusion of heart failure patients correlated with both increased baseline NE concentration and diminished cardiac MIBG uptake (r = -0.63, p less than 0.01 and r = 0.73, p less than 0.001, respectively). These findings indicate that the desensitization process is related both to impaired neuronal NE uptake function and increased circulating NE concentrations. Moreover, a subset of 11 patients with moderate heart failure was identified who had diminished cardiac MIBG uptake but normal circulating NE concentrations. This suggests that impairment of the NE uptake function is an early mechanism of desensitization in idiopathic cardiomyopathy. Cardiac MIBG imaging may be a noninvasive means to assess severity of heart failure patients and may also be used to evaluate therapy effects on myocardial alterations of the adrenergic pathway.

3-Iodobenzylguanidine↗

[Artificial hearts. The experience of Henri Mondor University Hospital].

Results obtained with 52 patients referred for urgent heart transplantation or when transplantation was impossible because no graft, mechanical assistance or circulatory support were available, are reported. These suggest that the protocol used to select the indications of assistance and transplantation, based on the response to the introduction of enoximone into the medical treatment, allows reconciling the patients' interest-their survival-with the community's interest-i.e. the control of the costs of implemented treatments.

Adult↗