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Biomedical subjects

R Villani

Publications and source records attributed to R Villani.

At least 19 recordsLinked to original sources
PubMed2006

Is there a possibility for a glutaraldehyde-free porcine heart valve to grow?

OBJECTIVE: A challenging issue is to create a heart valve with growth and remodeling potential, which would be of great interest for congenital heart valve surgery. This study was performed to evaluate the growth and remodeling potentials of a decellularized heart valve. METHODS: In 4 juvenile sheep (age 12 +/- 1 weeks) with a weight of 24.3 +/- 4.4 kg, a 17-mm diameter decellularized porcine valve was implanted as pulmonary valve replacement. Valve growth was evaluated by transthoracic echocardiography. At explantation, valves were evaluated by gross examination, light microscopy (hematoxylin and eosin, von Kossa, Sirius red, Weigert and Gomori staining), electron microscopy and immunohistochemistry. Atomic absorption spectrometry was performed to evaluate calcium content. RESULTS: All animals showed fast recovery. The mean follow-up was 9.0 +/- 1.8 months. All sheep at least doubled their weight (54.3 +/- 9.2 kg). Echocardiography showed no regurgitation and a flow velocity of 0.7 +/- 0.1 m/s at the latest follow-up. The valve diameter increased from 17.6 +/- 0.5 to 27.5 +/- 2.1 mm (p < 0.018). Gross examination showed a similar wall thickness of the implanted valve and native pulmonary wall, with smooth and pliable leaflets. Histology showed a monolayer of endothelial cells, fibroblast ingrowth and production of new collagen. No calcification was seen at von Kossa staining, confirmed by low calcium content levels of the valve wall and leaflets at atomic absorption spectrometry. CONCLUSIONS: This glutaraldehyde-free heart valve showed not only the absence of calcification, but also remodeling and growth potential.

Animals↗
PubMed2005

One-step nested PCR for detection of 2 LTR circles in PBMCs of HIV-1 infected patients with no detectable plasma HIV RNA.

A highly sensitive nested PCR was carried out in order to detect 2 LTR circles as a marker of recent and ongoing viral replication in HIV-1 infected patients with HIV plasma RNA undetectable. This "in house" two-step nested PCR is very sensitive, but it is not feasible for routine tests and presents a high risk of contamination. In order to reduce the time of reactions and crossover contamination, the possibility was explored to carry out a single step nested PCR, in which the two successive amplification rounds are carried out in the same tube. This single step nested PCR has the same sensitivity of the two-step nested, is easy to conduct and requires a short time of reaction. The two different PCR methods were compared and the clinical use of monitoring 2 LTR DNA circles in HIV-1 infected patients with undetectable plasma viral load is discussed.

Biomarkers↗
PubMed2003

Long-term inhibition of glioma growth by systemic administration of human PEX.

AIM: The growth of gliomas depends on the balance of factors stimulating or inhibiting angiogenesis, tumor cell invasion and proliferation. The administration of endogenous inhibitors to experimental human gliomas in animal models resulted in a significant inhibition of tumor growth. It is becoming apparent that resistance can develop over time to many types of endogenous inhibitors and seems to be influenced by the tumor type and system of delivery. METHODS: We recently isolated a potent endogenous inhibitor, called human PEX, from human glioma cells in culture. Human PEX is a potent inhibitor of angiogenesis, tumor and endothelial cell proliferation and migration. In this paper, we investigated the ability of human PEX to sustain inhibition of glioma growth for a prolonged period of time. We initially developed a recombinant form of the inhibitor and showed that this form had similar in vitro and in vivo activities to the natural one. Human PEX was then administered to nude mice intracranial human glioma model, in combination with metronomic chemotherapy, for a period of 185 days, starting 15 days after tumor cells implantation. RESULTS: Our data showed that the systemic administration of human PEX mantained a very prolonged inhibition of glioma growth (50% survival of animals treated with 2 mg/kg/days was 160 days vs 24 days of the control) and had a synergistic effect with low dose chemotherapy. Histological analysis of tumors, showed that treatment with PEX was associated with a decrease of vascularity, cell proliferation, and increase in apoptosis. CONCLUSION: These data indicate that human PEX controls tumor growth by separate mechanisms. In addition, treatment with PEX produced well delineated tumors, indicating the persistence of a direct anti-invasive effect of the molecule even after a prolonged period of treatment.

Angiogenesis Inhibitors↗
PubMed2001

Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo.

This study evaluates the efficacy of the combination of an antiangiogenic drug and conventional chemotherapeutics for the treatment of experimental human gliomas. As an antiangiogenic, we used recombinant human PEX, a fragment of matrix metalloproteinase-2 that we have previously shown to have a significant antimitotic, anti-invasive, and antiangiogenic properties against human glioblastoma in vitro and in vivo. We used carboplatin and etoposide as the two chemotherapeutic drugs routinely used in our institution (Ospedale Maggiore de Milano) for the treatment of malignant gliomas. Conventional chemotherapeutic drugs were administered at high dose or at a low and semicontinuous regimen. Combined treatment of high-dose chemotherapy and PEX did not produce an improvement of survival in comparison with chemotherapy alone, but it was associated with a decrease in tumor volume, vascularity, and proliferative index and an increased apoptosis. All of these animals experienced severe side effects. The longest survival was documented in animals submitted to low and semicontinuous chemotherapy and antiangiogenic treatment. This regimen was associated with no side effects, marked decrease in tumor volume, vascularity, and proliferative index, and an increased apoptosis. Our data suggest that low-dose chemotherapy in combination with PEX can be successfully used against human malignant glioma in vivo.

Angiogenesis Inhibitors↗
PubMed2001

Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery.

OBJECTIVE: This study analyzed the expression of integrins alpha(v)beta3 and alpha(v)beta5 in glioma tissue and focused on the periphery of high-grade gliomas. METHODS: The analysis was performed with Western blot, immunohistochemistry, and immunofluorescence, by use of two monoclonal antibodies able to recognize the functional integrin heterodimer. The expression of integrin-related ligands and growth factors also was studied. Sections from the tumor periphery were classified as either tumor periphery (light tumor infiltrate or scant visible cells) or peritumor (heavy tumor infiltration). RESULTS: Our data on glioma tissues demonstrated that both integrins were expressed in glioma cells and vasculature and their expression correlated with the histological grade. Alpha(v)beta3 expression was prominent in astrocytic tumors. Both integrins were markers of tumor vasculature, particularly of endothelial proliferation. A high-grade glioma periphery demonstrated a prominent expression of integrin alpha(v)beta3. Cells demonstrating alpha(v)beta3 positivity were identified as tumor astrocytes and endothelial cells by double imaging. The same cells were surrounded by some alpha(v)beta3 ligands and co-localized fibroblast growth factor 2. Matrix metalloproteinase 2 also was found to be co-localized with alpha(v)beta3 in the same cells. Alpha(v)beta3 expression was more relevant in tumor astrocytes. Alpha(v)beta3 integrin and vascular endothelial growth factor expression increased from the periphery to the tumor center. CONCLUSION: Our data support the role of integrins alpha(v)beta3 and alpha(v)beta5 in glioma-associated angiogenesis. In addition, they suggest a role for integrin alpha(v)beta3 in neoangiogenesis and cell migration in high-grade glioma periphery.

Adult↗
PubMed1998

Neuroendocrine, immunohistochemical, and ultrastructural study of pineal region tumors.

Thirteen patients with tumors in the pineal region were submitted to pre- and post-operative blood sampling (08:00, 14:00, 20:00, and 02:00 hr) for three or four consecutive days. A single cerebrospinal fluid (CSF) sample was collected at surgery, and melatonin levels determined. In all patients, serum and CSF beta subunit of human chorionic gonadotrophin (betaHCG), carcino embryonic antigen (CEA), and alpha-fetoprotein (AFP) levels were measured. Histology revealed four pineocytomas, one pineoblastoma, four germinomas, one immature teratoma, one pilocytic astrocytoma, one lymphoma, and one meningioma. Serum and CSF levels of serological biomarkers were normal, except for one of the germinoma cases. In most patients, alteration either in the circadian rhythm or in the melatonin concentration was observed before surgery. In benign neoplasms the circadian rhythm was conserved. In pineoblastoma, lymphoma, and three out of four germinomas, melatonin concentrations were undetectable. In one case of germinoma, melatonin levels were high, with the circadian rhythm being abolished. According to conventional histology, all germinomas were similar. Therefore, in a rare case of pineal germinoma with high melatonin levels, the tissue was subjected to an in depth investigation (immunohistochemical and ultrastructural) in order to determine the pathology and the possible differences from the other typical germinomas. Results were compared to those provided from other pineal neoplasms. Electron microscopy examination detected the presence of clusters of intermediate filaments and numerous electrondense granules only in the case of a germinoma producing melatonin.

Adult↗
PubMed1997

Prognostic factors in oligodendroglioma.

BACKGROUND: A reliable marker for tumor oligodendroglial cells is not yet available, so that the histological recognition of the tumor still encounters uncertainties. There is no general agreement also on prognostic factors in oligodendroglioma. The inconsistency concerns mainly the histopathological factors. The aim of the study was recognition of prognostic factors in oligodendroglioma. METHODS: In a series of ninety-eight oligodendrogliomas, including twenty mixed oligoastrocytomas, clinical [sex, age at surgery, tumor location, symptoms at presentation], therapeutic [extent of resection, year of surgery, post-operative Karnofsky score, post-operative radiotherapy, post-operative chemotherapy], histological [cell density, nuclear pleomorphism, vascular endothelial proliferation, necrosis, microcysts, mitoses, mitotic index (MI), apoptosis, apoptotic index (AI)] and immunohistochemical parameters [MIB-1 and PCNA Labeling Indexes (LIs), staining for GFAP, positivity for p53] were correlated with survival in uni- and multivariate analysis in order to identify their prognostic significance. RESULTS: Age at surgery, extent of surgical resection, year of surgery, post-operative Karnofsky score and MIB-1 LI were associated with survival in both uni- and multivariate analysis. Location, symptoms at presentation, mitoses, MI, AI, and PCNA LI showed a significant correlation with survival in uni- but not in multivariate analysis. The twenty cases of oligoastrocytomas did not show any difference in survival from pure oligodendrogliomas. CONCLUSIONS: Some clinical and therapeutic factors together with MIB-1 LI play a prognostic role. MIB-1 LI is prognostic with a cutoff of 8%. Histology gives a limited contribution to the prognosis. Oligoastrocytomas had the same outcome and prognostic factors as pure oligodendrogliomas.

Adolescent↗
PubMed1997

Transcallosal approach to tumors of the third ventricle. Surgical results and neuropsychological evaluation.

A series of 34 patients with tumours of the third ventricle were operated on by a transcallosal route. Basal extrinsic lesions compressing or invading the ventricle as well as tumours located in the pineal area were excluded from this review. Tumours were approached by a transforaminal entry in 16 cases (47%), by an interforniceal route in 11 (32%), by a subchoroidal entry in 4 (14%) and by a combined transforaminal and subchoroidal entry in 3 (9%). Four out of 34 patients were submitted to a second operation, through the same approach corridor: 2 for an incomplete removal of an intrinsic tumour and 2 for a late regrowth. Postoperative mortality rate accounted for 5.8% (2 patients). Major post operative complications were hemiparesis (4 patients) and diabetes insipidus (4 patients), that were transient in 3. Akinetic mutism like status was observed in only 1 patient. Postoperative psychic disturbances were noticed in 5 cases. Nine out of 21 patients (62%) with preoperative hydrocephalus required a permanent CSF shunt. Histology revealed that 21 tumours (62%) were intraaxial (4 pilocitic astrocytoma, 10 low grade glioma, 1 giant cell astrocytoma, 1 subependymoma, 4 ependymoma/ependymoblastoma, 1 neurocitoma) and 13 (38%) were extraaxial (8 colloid cyst, 2 craniopharingioma, 1 ectopic pituitary adenoma, 1 lymphocytic hypophysitis and 1 metastasis). Total excision of third ventricle tumours was achieved in all patients with extraaxial tumours and in 62% and 71% of intraaxial tumours with the first and second surgical procedure respectively. Ten out of 34 patients of this series were submitted to a complete neuropsychological evaluation at an interval of 2-9 years after surgery. Memory tests were pathological in 2. Disconnection signs were constantly absent. Control function were preserved. Transcallosal approach remains the best microsurgical method of third ventricle tumours treatment. This route provides the capability for a superior visualization of the entire cavity of the third ventricle through different corridors. Permanent neurological and neuropsychological deficits are not frequent. Epilepsy, that accounted for 28% in patients submitted to transcortical transventricular approach to third ventricle tumours, was never noticed in this series operated on through a transcallosal route.

Adolescent↗
PubMed1997

[Hypokinetic arrhythmia, paradoxical chronotropic reaction and hypotension during dobutamine stress test].

AIM: The aim of this study was to evaluate the incidence of hypokinetic arrhythmias, bradycardiac (BR) and hypotensive reactions in a population of 775 patients during dobutamine stress test (DST): 281 patients (36.2%, group I) were symptomatic for thoracic pain without any history of coronary artery disease (CAD); 494 patients (63.8%, group II) were evaluated 3-4 weeks after an acute myocardial infarction (AMI) to stratify ischemic risk. None of these patients was receiving coronarodilating therapy. MATERIALS AND METHODS: DST was performed using an infusion of 5, 10, 20, 40 micrograms/kg/min for 5 minutes during the first two stages and for 3 minutes during subsequent stages, and was accompanied by EKG and echocardiographic monitoring. BR was defined as severe when heart rate diminished more than 40 b/min, moderate when the decrease ranged between 20 and 39 b/min, and mild when the decrease was less than 20 b/min. RESULTS: A total of 34 (4.38%) BR were observed, 19 (55%) in group I and 15 (45%) in group II. BR were severe in 12 patients (35.9%), 3 with recent AMI (2 inferior and 1 anterior) and 9 without a history of CAD. Fifteen (45%) presented moderate BR, 8 with recent AMI (6 inferior and 2 anterior); 7 cases were in group I. Mild BR was observed in 7 patients (20%), 2 with recent AMI (1 inferior, 1 anterior), of which 5 were in group I. Episodes of junctional rhythm were also observed in 10 patients (29.4%) and 1 patient (2.9%) presented 2nd degree AV block during DST positive for ischemia. The mean duration of bradycardic episodes was 89.6 seconds (+/- 29.8) and only 3 patients (8.8%) presented significant hypotension. In 13 patients (38.2%) arrhythmia was observed during dobutamine-induced ischemia. In spite of the often severely diminished heart rate, no significant hypotension was evident during the bradycardiac episode in 19 patients (55%). Only one patient (2.9%) showed a decrease of more than 40 mmHg. CONCLUSIONS: In conclusion, we found that the incidence of BR during DST (4.38%) is higher than that reported in the literature; moreover, patients with recent inferior AMI showed a higher incidence of BR compared to patients with AMI in other sites (9 vs 4, p = n.s.). We feel that ischemia alone may not be responsible for hypokinetic arrhythmia during DST, but that dobutamine-induced neurovegetative reflexes may also contribute to the pathophysiological mechanisms underlying the phenomenon.

Adult↗
PubMed1995

Long-term outcome in aqueductal stenosis.

In this study, 78 patients with aqueductal stenosis were submitted to detailed neurodevelopmental assessment with a follow-up of 5-25 years. Sixty-eight percent of patients were categorized as normal; they either attended normal school courses or had regular jobs. Among these, 34% had some motor abnormalities (ataxia, mild hemiparesis, visual disturbances). Twenty-four percent (19 cases) were moderately disabled (trainable retardation) and 8% (6 cases) were severely handicapped. Epilepsy was observed in 13% of the cases. Incidence of recurrent and generalized seizures paralleled neurodevelopmental outcome (5% in normal, 16% in moderately disabled and 50% in severely disabled patients). Endocrine dysfunctions were evident in 28% of the cases and were characterized by precocious or delayed puberty, amenorrhea and somatic underdevelopment. No patient with ventricular enlargement and a cortical mantle width below 20 mm showed a good outcome. Large ventricles were compatible with normal mental development when compensated with a corresponding cranial vault enlargement. In patients with normal mental status and motor abnormalities, long-term CT scan findings revealed the presence of focal brain abnormalities (poroencephaly, brain atrophy, calcifications, extracerebral collections).

Adolescent↗
PubMed1994

[Primary antiphospholipid syndrome and cardiac involvement. Description of a clinical case of right atrial thrombosis].

Antiphospholipid syndrome is a well-defined clinical and serological entity characterized by venous and arterial thrombosis, recurrent abortion and thrombocytopenia. The immunological feature shows the presence of anticardiolipin antibodies and lupus anticoagulant. Cardiac involvement includes pericardial effusion, myocardial dysfunction, valvular disease, coronary artery occlusion. The literature reports only a few cases of intracardiac thrombosis associated with primary antiphospholipid syndrome. Here we describe a case of a 54 year-old woman with thrombocytopenia and history of recurrent abortions. When she was 51 she presented a left deep iliac venous thrombosis, followed by recurrent pulmonary embolism; a caval filter was placed in the inferior vena cava. Transthoracic and transoesophageal echocardiogram showed 3 masses in the right atrium: the first one was connected with the atrial wall, hyperechogenic and extending to the right ventricle in diastole: th second was connected with the interatrial septum and less echogenic; the third was in connection with septum-tricuspid valve junction and it was floating in the atrium. The immunological feature showed the presence of lupus anticoagulant and antiphospholipid antibodies; the histological examination of the masses, surgically removed, proved they were thrombi coated by endothelial cells. The case reported is very uncommon and offers the opportunity to emphasize the difficulty of diagnostic differentiation of intracardiac masses using echocardiographic imaging: thrombotic masses may present similar characteristics of seat, morphology and echogenicity of other cardiac masses. For these reasons it can be useful to look for antiphospholipid antibodies and lupus anticoagulant in such clinical conditions.

Antiphospholipid Syndrome↗
PubMed1994

[Infectious endocarditis following artificial insemination. A clinical case report and review of the literature].

We describe a case of infective endocarditis in a 33 year old patient, with mitral valve prolapse (MVP), who underwent nine attempts of artificial insemination with semen by donor. Several blood cultures demonstrated the presence of Enterococcus faecalis; the same agent was identified in some vaginal cultures. Despite antibiotic therapy, infective endocarditis was complicated by severe mitral regurgitation, followed by the rupture of a chorda tendinea. The patient underwent cardiac surgery: valvuloplasty of posterior mitral cusp, chordae tendineae in Goretex and anulus reinforcement with autologous pericardium. MVP is the most common heart disease associated with infective endocarditis in non-drug addict patients (32-54%). The review of the literature did not show any other case of infective endocarditis after artificial insemination procedures. Because of the large spread of these procedures, we think antibiotic prophylaxis of infective endocarditis should be considered in patients with MVP.

Adult↗
PubMed1992

Serum cortisol concentration and testosterone to cortisol ratio in elite prepubescent male gymnasts during training.

Serum cortisol concentrations and testosterone:cortisol concentration ratios of eight prepubescent elite male gymnasts (mean age 10 years 11 months) and 11 controls (mean age 11 years 1 month) were examined during 5 consecutive training days. During this period, the gymnasts trained 3 h each day with moderate intensity mobility, strength and skill exercises while the controls were relatively sedentary. Blood samples were taken from all the boys in both groups before (1630 hours) and 30 min after (2000 hours) training on 4 days. Serum cortisol concentrations of the gymnasts were not significantly different from those of the controls throughout the experiment. Serum cortisol concentrations of both groups were significantly larger (P < 0.05) at 1630 hours than at 2000 hours, indicating that cortisol secretion followed the typical adult circadian change, seemingly unaltered by training. However, there was a significant decrease (P < 0.05) in the testosterone:cortisol ratio of the gymnasts when compared with controls from day 1 to day 3. After a rest on day 4 the testosterone: cortisol ratio of the gymnasts significantly increased (P < 0.05) but the ratio of the control group also increased indicating that there may have been some day-to-day change by factor(s) other than training. The most obvious factor which may have accounted for the unresponsiveness of serum cortisol concentration to the gymnastics training was that the exercise intensity was too low. However, several days of the training seemed to reduce the anabolic to catabolic balance but further experiments are needed to confirm this finding.

Child↗
PubMed1992

[A comparison between amiodarone and disopyramide in a delayed-release formulation in the prevention of recurrences of symptomatic atrial fibrillation].

In order to compare the efficacy in preventing recurrencies of symptomatic atrial fibrillation of amiodarone (A.) and slow release disopyramide (D.RET.), 76 consecutive patients with recent onset atrial fibrillation (1 to 24 hrs.) were enrolled. In 20 (26%) conversion to sinus rhythm was obtained by electrical cardioversion, and in 56 (74%) by oral quinidine loading. Forty-one patients (group A) were assigned at random to treatment with D.RET. (250 mg twice daily) and 35 patients (group B) to amiodarone treatment (1200 mg daily for 10 days, and subsequently 200 mg daily). The two groups were similar as to age, sex and cardiac pathology. Patients were followed as to clinical condition, standard and dynamic ECG after one and three months and every three months subsequently for an average of 13.2 months (group A) and 14.1 months (group B). Six group A patients (14%) were excluded from follow-up on account of side effects which arose during the first week of treatment. Crises of symptomatic atrial fibrillation occurred in 20 patients of group A (57%) and in 11 (32%) group patients; this difference is statistically significant (p less than 0.05). Four (10%) group A patients stopped taking the drug due to side effects of an anticholinergic type, and three (8.5%) patients developed hyperthyroidism during follow-up. The authors therefore come to the conclusion that amiodarone is more effective than slow-release disopyramide in preventing recurrencies of atrial fibrillation; besides untoward side effects are less frequent with amiodarone.

Amiodarone↗
PubMed1992

[Neurosurgical aspects of urologic metastases].

Metastases in the central nervous system (C.N.S.) from urological tumors can be spinal or craniocerebral. The experience of 30 patients with spinal and craniocerebral metastases from urological tumors admitted to Neurosurgical Clinic of the University of Milan, is reported. They were 7.5% of the all number of metastases admitted at the Neurosurgical Department, during the same period. The brain metastases constitute 10% of brain metastases diagnosed in this period. Only patients with solitary (to CT scan and NMR) metastasis, and with a general prognosis that allow to an adequate and useful period of survival, are submitted to surgical treatment. 23 patients (76.6%) are surgical treated. The mean survival from the discovery of the C.N.S. metastases was 9 months (9.4 months among surgically treated patients and 7.8 months among those were not operated). Surgical mortality was 13%. Out of patients with survival until 5 months, patients submitted to surgical treatment showed a better quality of life. Our results allow us to affirm that in selected patients surgical removal of solitary metastases, could improve the quality of survival, but is not able to prolong substantially the period of survival.

Adult↗