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Biomedical subjects

G Santoro

Publications and source records attributed to G Santoro.

At least 163 records · Page 9Linked to original sources

[The bidirectional cavo-pulmonary anastomosis: a clinico-functional assessment in a medium-term follow-up].

BACKGROUND: The bidirectional cavo-pulmonary anastomosis is a useful surgical procedure for patients with complex congenital heart disease characterized by univentricular physiology. This operation significantly increases effective pulmonary blood flow and rarely causes distortion of the main pulmonary arterial branches. The aim of this study was to evaluate the clinical and pathophysiologic consequences of bidirectional cavo-pulmonary anastomosis as well as the effectiveness of this surgical approach as a definitive palliation. METHODS: Clinical, hemodynamic and functional data of 12 patients who had undergone a bidirectional cavo-pulmonary anastomosis were reviewed. Each patient underwent clinical examination, chest x-ray, ambulatory EKG, bidimensional color-Doppler echocardiography, spirometric analysis, lung perfusion scintigraphy, cardiac catheterization and angiography, and stress test. Stress test data were compared to those obtained by a normal population of age-matched children. RESULTS: After a mean follow-up interval of 28 +/- 20 months all patients showed a good clinical condition. Improved oxygenation, exercise tolerance and growth velocity were noted in all patients. Only 34% of patients showed abnormalities of chest x-ray, 29% manifested significant arrhythmias during ambulatory EKG and 20% showed abnormal ventricular function echocardiographically. Spirometry was normal in all patients, while lung perfusion scintigraphy was constantly abnormal with right/left and upper/lower perfusion mismatch. At cardiac catheterization a reduction of end diastolic volume (from 106.9 +/- 50.6 to 67.3 +/- 41.6 ml, p < 0.05) and end systolic volume (from 58.0 +/- 27.9 to 32.5 +/- 33.5 ml, p < 0.05) was noted. The functional evaluation of these patients was highly abnormal due to an impaired response to effort as evidenced by work time (p < 0.0001 vs normal) and stress-induced cardiovascular modifications. CONCLUSIONS: On the basis of these findings, we suggest that: 1) bidirectional cavo-pulmonary anastomosis is useful as an intermediate step towards a Fontan procedure, as it improves the hemodynamic performance of the systemic ventricle; 2) conversely, bidirectional cavo-pulmonary anastomosis should not be considered a form of definitive palliation for complex congenital heart disease because in these patients the response to exercise remains unsatisfactory.

Adolescent↗

Blood-brain barrier dysfunctions following systemic injection of kainic acid in the rat.

Changes in blood-brain barrier (BBB) permeability and cerebral metabolic activity following intravenous injection of kainic acid (KA; 6, 12 mg/Kg) in rats were assessed by calculating respectively a blood-to-brain transfer constant (Ki) for [14C]alpha-aminoisobutyric acid and local cerebral glucose utilization (LCGU) values, at different times (1 h, or acute seizures phase, and 48 h, or chronic pathology phase) after the induction of seizures. A significant increase in the local permeability of the BBB was observed 1 h after the injection of KA 6 mg/Kg (eliciting no significant changes in cerebral metabolic activity, except within the frontal cortex and the hippocampus) and 12 mg/Kg (which induced a marked and widespread enhancement of LCGU). On the contrary, during the pathology phase, persistent regional increases in Ki values were evidenced in rats treated with the lowest dose of the convulsant, but not in rats injected with KA 12 mg/Kg (a dose able to cause extensive neuronal damage). Thus one can speculate that: 1) KA-induced regional changes in the permeability of the BBB are not correlated with changes in neuronal activity; 2) opening of the BBB is not reliably associated with neuronal injury.

Aminoisobutyric Acids↗

Effects of ischemia and reperfusion on cardiac tolerance to oxidative stress.

Oxidative stress may affect cardiac function and metabolism. Oxidants are normally inactivated by reacting with reduced glutathione (GSH), with resulting formation and release of oxidized glutathione (GSSG). However, ischemia might affect glutathione metabolism. This might render ischemic hearts less resistant against subsequent oxidant injury during reperfusion, and it might also affect the reliability of GSSG measurements as a means to investigate oxidative stress in reperfused hearts. We compared the metabolic and functional consequences of an oxidant load in control rabbit hearts and in hearts reperfused after 30 min of normothermic total ischemia. In controls, H2O2 infusion (H2O2; 5-30 microM) induced a dose-dependent stimulation of GSSG release and a progressive impairment of cardiac function. At these doses, H2O2 challenge of postischemic hearts resulted in biochemical and functional changes identical to those observed in controls. Release of lactate dehydrogenase (LDH) and of GSH was negligible, similar in both groups. In additional experiments, infusion of H2O2 at a much higher dose (200 microM) elicited a further increase in GSSG release from both groups, although GSSG concentrations were lower in postischemic hearts. The functional effects of the 200 microM H2O2 infusion were similar in both groups, all hearts showing rapid and irreversible deterioration of function. Occurrence of irreversible cell injury was also manifested by a large release of LDH and GSH to a similar extent in both groups. These data demonstrate that cardiac tolerance toward oxidants is largely unaffected by a relatively brief episode of severe ischemia and indicate that GSSG release can be reliably used to investigate oxidative stress in reperfused hearts.

Animals↗

Normal ultrasonic myocardial reflectivity in athletes with increased left ventricular mass. A tissue characterization study.

BACKGROUND: Ultrasonic integrated backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content. The integrated backscatter is also increased in hypertrophic cardiomyopathy, probably because of fiber disarray. The purpose of this study was to investigate myocardial tissue reflectivity in subjects with physiological hypertrophy caused by intense physical training and to assess the relation between the acoustic properties of myocardial tissue and left ventricular wall thickness assessed by conventional two-dimensional echocardiography. METHODS AND RESULTS: Twenty-four young male athletes (14 professional cyclists and 10 weight lifters, all in full agonistic activity) were studied together with 10 normal age-matched controls with sedentary life. By means of a commercially available two-dimensional echocardiograph, standard measurements were obtained according to the recommendations of the American Society of Echocardiography. With a prototype implemented in our Institute, an on-line radiofrequency analysis of ultrasound signals was also performed to obtain quantitative operator-independent measurements of the integrated backscatter of the myocardial walls. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent integrated backscatter (%IB). Compared with control subjects, athletes showed greater thickness values of septum (controls, 9 +/- 1; cyclists, 14 +/- 2; weight lifters, 15 +/- 1 mm, mean +/- SD; p less than 0.01) and posterior wall (9 +/- 1, 12 +/- 2, and 12 +/- 1 mm, respectively; p less than 0.01) but similar values of %IB for both septum (23 +/- 4%, 21 +/- 7%, and 23 +/- 8%, p = NS) and posterior wall (10 +/- 2%, 9 +/- 2%, and 11 +/- 2%, p = NS). In athletes, no correlation was found between septal and posterior wall thickness and the corresponding regional myocardial reflectivity (r = 0.23, p = NS and r = 0.01, p = NS, respectively). Furthermore, we compared the quantitative ultrasonic data between two subsets of 10 athletes and 10 patients with hypertrophic cardiomyopathy and similar degrees of septal thickness (16 +/- 1 versus 17 +/- 1 mm, respectively, p = NS). Septal and posterior wall %IB results were significantly higher in patients with hypertrophic cardiomyopathy (53 +/- 13% and 36 +/- 9%, respectively) than in athletes (21 +/- 7% and 10 +/- 3%, respectively; p less than 0.01 for both). CONCLUSIONS: We conclude that 1) endurance athletes show a normal pattern of quantitatively assessed ultrasonic backscatter despite of a marked left ventricular hypertrophy and 2) athletes and patients with hypertrophic cardiomyopathy and similar degrees of myocardial wall thickness can be differentiated on the basis of quantitative analysis of backscattered signal.

Adult↗

[HIV-1 proviral DNA sequences in the saliva of patients with HIV infection].

In order to understand the significance of presence of HIV-1 in saliva, we searched for by PCR HIV-1 proviral sequences in the saliva cells of 49 HIV-1 infected patients. Seven out 49 specimens resulted positive, 4 of which were from patients with PGL, 1 with ARC and 2 with AIDS. Four patients had a CD4+ lymphocyte counts < 200/cmm and in 3 patients the CD4+ lymphocyte count ranged from 200 to 400/cmm. Two patients were treated with AZT, 1 with DDI and 4 had no antiretroviral treatment. In conclusion, although HIV-1 proviral sequences have been found in saliva of HIV-1 infected patients, a larger group of patients should be investigated to define more precisely the role of HIV-1 in saliva.

Base Sequence↗

Bidirectional cavopulmonary anastomosis in congenital heart disease. Functional and clinical outcome.

The bidirectional cavopulmonary anastomosis is a surgical procedure suitable for patients with cyanotic congenital heart disease and univentricular physiology. This operation is able to increase the effective pulmonary blood flow without any additional load on the cardiac work and without any further distortion on the pulmonary artery branches. The cavopulmonary anastomosis can represent the first stage for patients destined for Fontan repair or a definitive palliative operation in high risk Fontan candidates. In order to test the hypothesis of a definitive palliation by cavopulmonary anastomosis in this kind of patients, we evaluated the hemodynamic data before and after this surgical approach and compared these data with their clinical and functional outcome. We evaluated 74 patients submitted to bidirectional cavopulmonary anastomosis by either hemodynamic or functional evaluation. End-diastolic and end-systolic ventricular volumes were significantly reduced by bidirectional cavopulmonary anastomosis (p less than 0.0005). Despite these data and a normal ambulatory ECG, spirometry and echocardiographic analysis, the stress test showed discouraging results. In fact, mean work time and peak heart rate were significantly different from normal values showing an impaired functional capacity of these children. In conclusion we think that bidirectional cavopulmonary anastomosis can not be considered an adequate definitive palliation but it represents a very good stage to preserve the pulmonary arteries and to prepare the systemic ventricle towards the Fontan repair.

Adolescent↗

[Changes in left ventricular filling after acute increase of afterload in essential arterial hypertension with or without left ventricular hypertrophy].

It is debatable whether a direct causal link exists between left ventricular hypertrophy (LVH) and abnormal left ventricular filling (LVF) in arterial hypertension (AH). To assess if LVH is responsible for peculiar patterns of LVF, we examined 30 selected subjects, similar in age and body surface area, by Doppler echocardiography: 10 hypertensives (SBP: 158 +/- 15; DBP: 105 +/- 7 mmHg) with LVH (IM: 154 +/- 19 mg/m2) (Group 1); 10 hypertensives (SBP: 157 +/- 9; DBP: 101 +/- 5 mmHg) without LVH (IM: 105 +/- 17 mg/m2; Group 2); 10 normotensives without familiar history of AH (Group 3). LVF was analyzed in baseline conditions and during transient afterload increase, obtained by isometric exercise (handgrip, HG, for 5 min at 30% of maximal effort). At rest: 1) A wave peak velocity resulted significantly higher (p less than 0.01) in Group 1 (61 +/- 3 cm/s) versus Group 3 (52 +/- 7 cm/s), and E wave peak velocity was significantly lower in Group 1 (58 +/- 13 cm/s) versus Group 3 (74 +/- 10 cm/s); 2) Group 2 values (E wave: 66 +/- 12; A wave: 58 +/- 15 cm/s) were intermediate between those of groups 1 and 3, and with no significant differences; 3) E/A ratio resulted significantly lower both in Group 1 (1.04 +/- 0.2) and Group 2 (1.21 +/- 0.2) versus Group 3 (1.6 +/- 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

[Chronic dissecting aortic aneurysm and Turner's syndrome. Apropos of a case].

Turner's syndrome is a genetic abnormality which is associated with cardiovascular anomaly in 20% of cases. Coarctation of the aorta and bicuspid aortic valve are the commonest malformations. Aortic dissection is the most serious complication affecting these patients. The authors report the case of chronic aortic dissection of the ascending and transverse aorta in a 27 year old patient with Turner's syndrome. The dissection was diagnosed on angiography. Transthoracic echocardiography showed aneurysmal dilatation of the aortic root. Surgical treatment consisted in replacement of ascending and transverse aorta with a Dacron tube. The anatomopathological analysis showed cystic medianecrosis of the aortic wall. The immediate postoperative evolution was satisfactory. The long-term outcome with a 4 year follow-up was excellent from the clinical and echocardiographic point of view. Turner's syndrome is probably associated with a congenital abnormality of the connective tissue especially of the elastic fibres of the aortic wall, explaining the development, though rare, of aneurysmal dilatation of the ascending and transverse aorta and dissection. These patients should be followed up regularly clinically and by transthoracic echocardiography. Other investigations such as transoesophageal echocardiography, magnetic resonance imaging and angiography are indicated when aortic dilatation, aortic regurgitation or chest pain suggesting aortic dissection are observed.

Adult↗

Effects of captopril on the development of rat doxorubicin nephropathy.

The effects of a daily administration of an anti-converting enzyme inhibitor. Captopril (CPT) (100 mg/kg/orally), on the development of functional and morphological alterations induced in rats by a single injection (7.5 mg/kg/iv) of Doxorubicin (DXR) (Adriamycin*), were investigated. Twenty-four-hour protein excretion, urine output, food intake, water intake, and body weight gain were measured weekly for 30 days. Transmission and scanning electron microscopy observations were performed on kidney samples after 30 days. Four groups were studied. Group 1 were control rats. Group 2 were rats injected with DXR. Group 3 were rats injected with DXR and treated with CPT for 30 days. Group 4 were rats injected with DXR and treated with CPT for 15 days (CPT treatment started 15 days after DXR injection). Group 1 did not show significant functional or morphological changes. Group 2 showed severe proteinuria, significant increase in urinary volume within 2 weeks, significant body weight reduction and diffuse morphological changes. These changes mainly consisted of podocyte swelling, severe foot process fusion, and presence of casts within tubular lumen. Group 3, with respect to group 2, showed a significant reduction of the 24 h protein excretion and urine output. This group displayed morphological changes similar to those observed in group 2, but with a focal distribution. Group 4 showed functional and morphological changes comparable with those of group 2. It is concluded that CPT partially inhibits the development of the functional and morphological damage induced by DXR in the rat kidney. However, CPT did not influence the natural development of nephropathy when treatment started 15 days after DXR injection.

Animals↗

Twenty-four-hour activity of felodipine extended release in chronic stable angina pectoris.

To investigate the antiischemic efficacy and duration of action of the dihydropyridine calcium antagonist felodipine, 15 patients with stable exertional angina were enrolled in a double-blind, crossover study comparing 2 doses (5 and 10 mg) of felodipine extended release (ER) and placebo given once daily for 1 week. Bicycle exercise tests were repeated at the end of each treatment period 4 and 24 hours after dosing. Four hours after dosing with both felodipine doses, only 5 patients discontinued the exercise test because of greater than 2 mm of ST-segment depression, whereas 10 continued until exhaustion (p less than 0.01 vs placebo). Compared with placebo, total exercise time was increased by 19% (p less than 0.001), with no difference between doses. After 24 hours, exercise duration was prolonged up to physical exhaustion in 6 patients taking felodipine 10 mg (p less than 0.05 vs both placebo and felodipine 5 mg); moreover, 11 patients taking 10 mg and 5 taking 5 mg increased time to 1 mm of ST depression greater than or equal to 15% compared with exercise time during the placebo test. Mean time to 1 mm of ST depression at 24 hours was increased by 8% with 5 mg and by 18% with 10 mg (p less than 0.001 vs placebo; p less than 0.01 between doses). Total exercise time at 24 hours was increased with both doses (p less than 0.001), with greater efficacy with the 10-mg dose (p less than 0.05 vs 5 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Neurochemical action of the general anaesthetic propofol on the chloride ion channel coupled with GABAA receptors.

The effect of propofol, a novel short acting anaesthetic, on the function of the GABAA/ionophore receptor complex was studied in vitro in cortical membrane preparations from rat cerebral cortex and was compared with the action of pentobarbital and alphaxalone, two general anaesthetics known to enhance GABAergic transmission. Propofol, mimicking the action of pentobarbital and alphaxalone, increased [3H]GABA binding, reduced [35S]TBPS binding and enhanced muscimol-stimulated 36Cl- uptake in a concentration-dependent manner. While the efficacy of the drugs in affecting these biochemical parameters was similar, they differed markedly in potency being alphaxalone greater than propofol greater than pentobarbital. However, separate sites of action or different mechanisms for these drugs can be suggested by the result that the concomitant addition of propofol either with alphaxalone or pentobarbital or diazepam produced a simple additive inhibition of [35S]TBPS binding as well as an additive enhancement of [3H]GABA binding and muscimol-stimulated 36Cl- uptake. The effect of propofol at the level of the GABA/ionophore receptor complex seems to be strictly dependent on the interaction of GABA with its recognition site. In fact, the specific GABAA receptor antagonist bicuculline antagonized the decrease of [35S]TBPS binding as well as the enhancement of [3H]GABA binding and muscimol-stimulated 36Cl- uptake induced by propofol. On the other hand, propofol was able to enhance [3H]GABA binding in membranes previously incubated with the specific chloride channel blocker picrotoxin. Finally, the finding that propofol fails to affect [3H]flunitrazepam binding together with the failure of Ro 15-1788 and PK 11195 to antagonize its effect on [35S]TBPS binding excludes a direct interaction at the level of benzodiazepine recognition sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗

The risk of breast cancer subsequent to histologic diagnosis of benign intraductal papilloma follow-up study of 339 cases.

The risk of developing breast cancer was investigated in 339 patients in whom histologically confirmed intraductal papilloma had been surgically removed. Follow-up ranged from 2 to 14 years, (average, 6.62 years). Ten breast cancers were observed, whereas 3 were expected on the basis of age-specific incidence rates drawn from local cancer registries (relative risk = 3.33, 95% confidence interval = 1.60-6.13). No significant difference in the relative risk was observed as far as papilloma type (single or multiple) was concerned. All breast cancers observed occurred in the same breast as the papilloma. Women in whom a benign intraductal papilloma has been excised should be carefully followed since they at are higher risk for ipsilateral breast cancer.

Adult↗

Platelet activating factor involvement in splanchnic artery occlusion shock in rats.

Splanchnic artery occlusion shock was induced in anesthetized rats by clamping the splanchnic arteries for 45 min. The survival rate, plasma levels of thromboxane B2 (TxB2) and 6-keto-PGF1 alpha, serum and peritoneal levels of macrophage tumor necrosis factor (TNF alpha), the phagocytotic and killing activity of peritoneal macrophages and white blood cells count were evaluated. Shocked rats died within 2 h, while all sham-shocked rats survived more than 6 h. Plasma TxB2 and 6-keto-PGF1 alpha levels were increased in rats subjected to splanchnic artery occlusion shock compared to the levels in sham-shocked animals. Serum and peritoneal macrophage TNF alpha levels were undetectable in sham-shocked rats, whereas shocked rats exhibited increased levels of TNF alpha. Moreover, splanchnic artery occlusion shock reduced peritoneal macrophage phagocytotic and killing activity, and also produced severe leukopenia. A specific receptor antagonist of platelet activating factor (PAF), L-652, 731 (an i.v. bolus of 3.2 mg/kg 2 min after removal of the clamps followed, 5 min thereafter, by a continuous infusion of 0.16 mg/kg per min for 30 min) significantly increased the survival rate, lowered plasma TxB2 levels and reduced both serum and macrophage TNF alpha levels in shocked rats. In addition, L-652,731 completely restored macrophage phagocytosis, partially improved macrophage killing and significantly inhibited leukopenia. Finally, the administration of L-652,731 had beneficial effects on the cardiovascular changes induced by splanchnic artery occlusion shock. These findings are consistent with the involvement of PAF in splanchnic artery occlusion shock and indicate that PAF produces shock through direct and indirect (TxB2-mediated and TNF alpha-mediated) actions.

6-Ketoprostaglandin F1 alpha↗