Search PubMed⌕ Search

Biomedical subjects

A Perin

Publications and source records attributed to A Perin.

At least 19 recordsLinked to original sources

Endoscopic treatment of brain abscesses.

BACKGROUND: Stereotactic aspiration with external drainage has become widely accepted as the standard treatment for intracerebral abscesses. Although neuroendoscopic technique has only been occasionally adopted for this pathology, it introduces some advantages because it presents visual awareness that the pus has been removed. METHODS: Four patients with cerebral abscess and one with a subdural empyema were operated using a neuroendoscopic technique in our Department between 1996 and 2003. A 4-mm flexible endoscope was introduced into the purulent collection through a burr hole, the pus was meticulously aspirated, and the cavity washed with isovolumetric antibiotic lavages using the working channel for both irrigation and suction. CONCLUSION: Neuroendoscopic treatment of brain abscesses presents some additional advantages as a possible alternative to stereotactic aspiration, which still constitutes the gold standard for this pathology. The adoption of stereotactic or frameless guidance systems can probably be recommended particularly for deep, complex lesions.

Adult↗

Cooperative study by the Italian neuroendoscopy group on the treatment of 61 colloid cysts.

OBJECTS: Microsurgical resection, stereotactic aspiration and VP shunt have for years been the choice options for the treatment of colloid cysts of the third ventricle. Recently, endoscopic approaches have aroused increasing interest and gained acceptance. Although safer, this minimally invasive approach is considered less efficacious than microsurgery. Relatively long-term results are now available and some conclusions might be inferred on the usefulness of this procedure. MATERIALS AND METHODS: Between 1994 and 2005, 61 patients harbouring a colloid cyst of the third ventricle were treated with neuroendoscopic technique in 11 Italian neurosurgical centres. Cyst diameters ranged from 6 to 32 mm. A flexible endoscope was used in 34 cases, a rigid one in 21, both instruments in six. The technique consisted in cyst fenestrations, colloid aspiration, coagulation of the internal cyst wall and, occasionally, capsule excision. Mean postoperative hospital stay was 6.7 days. Early postoperative neuroimaging revealed a cyst residue in 36 cases (mean diameter 4.3 mm). There were two complications (3.2%). Follow-up varied between 1 and 132 months (mean 32 months, more than 5 years in 17 patients). There were seven asymptomatic recurrences, three of them evolving from a previous residue. CONCLUSION: The endoscopic approach to the treatment of colloid cysts is safe, effective and well accepted by patients. Although asymptomatic, recurrences (11.4%) cast a persisting shadow on the long-term results, and, therefore, the controversy with the traditional microsurgical treatment remains open.

Adolescent↗

Efficacy of cyclosporin-A in the long-term management of thrombocytopenia associated with systemic lupus erythematosus.

Thrombocytopenia frequently complicates systemic lupus erythematosus (SLE), and its long-term management may be problematic. Intravenous immunoglobulins and high doses of steroids are often effective as induction therapy, but thrombocytopenia frequently relapses during steroid tapering. Several immunosuppressive agents have been evaluated as induction or maintenance therapy in small series or in case reports. We describe six consecutive unselected SLE patients where cyclosporin-A (CyA) was effective and safe in the long-term management of thrombocytopenia and allowed steroid tapering. One relapse occurred during CyA reduction and responded to CyA dose adjustment. Steroids could be stopped in three out of six patients, and were maintained at very low doses in the remaining patients. CyA was stopped in one patient after one year of treatment, without relapse at month 11+ from discontinuation. No severe side effects were documented. Overall, these data suggest that CyA may prove to be an effective and safe therapeutic option for SLE-related thrombocytopenia.

Adrenal Cortex Hormones↗

Phase II study of pegylated liposomal doxorubicin and oxaliplatin in relapsed advanced ovarian cancer.

OBJECTIVE: This phase II study evaluated the efficacy and safety of pegylated liposomal doxorubicin (PLD) 30 to 35 mg/m(2) plus oxaliplatin 70 mg/m(2) every 28 days in women with advanced ovarian cancer that recurred or progressed after a platinum-based regimen. METHODS: 43 women received a median of 6 courses of treatment. RESULTS: Objective response was 54% in the evaluable population and was higher in women with platinum-sensitive (67%) compared with platinum-resistant disease (29%). At a median duration of follow-up of 15.5 months, median overall survival was 15.8 months and time to tumor progression 7.3 months. Most toxicity was no greater than grade 1 or 2. There was no grade 3 or 4 palmar-plantar erythrodysesthesia. After 264 cycles administered, neutropenia was the most common cause of severe toxicity and required one patient to withdraw from the study. No cardiotoxicity was reported. CONCLUSION: PLD plus oxaliplatin is active and well tolerated in women with relapsed advanced ovarian cancer, regardless of platinum sensitivity.

Adult↗

Endoscopic selective sampling of human ventricular CSF: a new perspective.

Neuroendoscopy has achieved extensive acceptance among neurosurgeons as a minimally invasive technique for the treatment of patients affected by blocked hydrocephalus. During endoscopic procedures minimal CSF amounts from selected anatomic sites of the ventricles can be withdrawn. Steerable endoscopes are used and their flexibility facilitates the aspiration of CSF during the preliminary inspection through the ventricular cavities, without any interference with the surgical actions or additional risks for the patients. In this preliminary study the concentrations of melatonin and other related metabolites in the lateral ventricles, third ventricle, pineal recess and infundibular recess were examined. The data obtained from a patient affected by blocked hydrocephalus confirmed a constant and significant difference of concentration of these substances, for instance, melatonin levels were found to be much higher in the third ventricle (542 pg/mL in its centre) than in the lateral ventricle (172 pg/mL in the right ventricle). Nevertheless, instead of what we would expect, the highest melatonin concentrations were not found in the pineal recess (438 pg/mL). In the future, neuroendoscopy, beside its evident therapeutic efficacy, could open new perspectives in the study of both CSF biochemistry and physiology, allowing a highly selective approach to the various substances which are released and float in it.

Aged↗

Surveillance of screening for hepatitis C through the laboratory network RENA-VHC, France, 2000-2001.

Over the period 2000-2001, 189 private or hospital laboratories scattered throughout France participated to the laboratory network RENA-VHC. A total of 759 591 serologies (screening tests and validation of screening tests) were performed, revealing an increase of 10% between 2000 and 2001. The rate of the amount of tests to validate screening found positive over the overall amount of tests performed was 1.2% in 2000 and 1.0% in 2001. This suggests that screening covered more people with little risk of acquiring HCV infection. The per-sons confirmed HCV positive were predominantly men (sex ratio 1.5) of which 31% were 30 to 39 years of age.

Age Distribution↗

B7 costimulatory molecules from malignant cells in patients with b-cell chronic lymphoproliferative disorders trigger t-cell proliferation.

BACKGROUND: B7 family molecules are involved in T-B-cell communications after interaction with their ligands CD28 and CD152. They play a key role in costimulatory mechanisms and during antigen presentation by efficient antigen presenting cells. B7 molecules are usually absent or expressed at low intensity on B lymphocytes from healthy subjects. In this study, the authors addressed the questions of whether B7 molecules are expressed and modulated in vitro on malignant B lymphocytes from patients with chronic lymphoproliferative diseases of B-cell type and whether they are able to trigger allogenic T-cell reactions. METHODS: Malignant B cells from the peripheral blood of 32 patients with B-cell chronic lymphocytic leukemia, mantle cell lymphoma, hairy cell leukemia, and its variant form were investigated for the expression of B7 molecules on the cell surface and for the ability to trigger allogenic T lymphocytes in different experimental conditions. RESULTS: Flow cytometry analysis demonstrated that freshly isolated malignant B cells express B7 molecules and that their expression may be up-regulated by the in vitro triggering of the CD40 molecule. Furthermore, freshly isolated malignant B cells induce allogenic T-cell proliferation. The in vitro triggering of malignant B lymphocytes by CD40, alone and in combination with interleukin-4, elicits a strong allogenic T-cell proliferation. This T-cell proliferation is related mainly to the presence of B7 molecules on malignant and normal B lymphocytes. CONCLUSIONS: These findings indicate that malignant B cells are efficient antigen presenting cells. It might be suggested that vaccination with pulsed malignant B cells themselves or dendritic cells with in vitro preactivated tumor B cells may represent an alternative therapeutic approach in these patients to generate an antilymphoma T-cell response in vivo.

Adult↗

Analysis of TNF-receptor and ligand superfamily molecules in patients with lymphoproliferative disease of granular lymphocytes.

In 21 patients with lymphoproliferative disease of granular lymphocytes (LDGL), we investigated the expression and the function of molecules belonging to TNF-receptor and TNF-ligand superfamilies (CD30/CD30L; CD40/CD40L; CD27/CD70; Fas [CD95]/FasL[CD95L]). Fourteen patients were characterized by a proliferation of granular lymphocytes (GLs) expressing the CD3(+)CD16(+) phenotype, whereas 7 cases showed the CD3(-)CD16(+) CD56 +/- phenotype. Our data show that both CD3(+) and CD3-GLs are preferentially equipped with CD30, CD40, CD40L, CD70, and CD95 antigens; this pattern is usually associated with the lack of CD27 and CD30L antigens expression. CD95L was demonstrated in the cytoplasm in 14 of 21 cases by flow cytometry, but a definite signal was demonstrated in all cases studied using polymerase chain reaction analysis. On functional grounds, a stimulatory activity on rIL-2 mediated redirected-cytotoxicity against Fcgamma+ P815 targets was demonstrated with anti-CD30, CD40, CD40L, CD70, CD95, and CD95L mAbs, although resting cells were unable to exhibit significant redirected-cell lysis. The addition of anti-CD30, CD30L, CD40, CD40L, CD95, and CD95L mAbs did not show any significant effect on cell proliferation at resting conditions or after rIL-2 stimulation, whereas anti-CD70 mAb mediated cell proliferation in 6 of 10 cases tested. This figure was not related to an increase in apoptotic cells, as investigated by Annexin-V expression. Our data indicate that both CD3(+) and CD3(-) GLs are equipped with different costimulatory antigens, supporting the concept that these cells are in vivo activated and suggesting that these molecules might play a role in the cytotoxic mechanisms of GLs. (Blood. 2000;96:647-654)

Adult↗

Polyamine oxidase and tissue transglutaminase activation in rat small intestine by polyamines.

Polyamine degradation was studied in the small intestine from rats fed on a polyamine-supplemented diet. Lactalbumin diet was given to Hooded-Lister rats, with or without 5 mg rat(-1) day(-1) of putrescine or spermidine for 5 days. Polyamine oxidase activity increased with putrescine and spermidine in the diet, whereas spermidine/spermine N(1)-acetyltransferase and diamine oxidase activities were unchanged. We also studied the calcium-dependent and -independent tissue transglutaminase activities, since they can modulate intestinal polyamine levels. Both types of enzymes increased in the cytosolic fraction after putrescine (about 65%) or spermidine (80-100%). Our results indicate that exogenous polyamines stimulate intestinal polyamine oxidase and tissue transglutaminase activities, probably to prevent polyamine accumulation, when other pathways of polyamine catabolism (acetylation and terminal catabolism) are not activated.

Acetyltransferases↗

Distribution and activity of transglutaminase in rat brain carcinogenesis and in gliomas.

Tissue transglutaminase is a calcium-dependent enzyme which may influence cell morphology, cytoskeletal processes and membrane functions. During rat brain carcinogenesis induced by transplacental administration of N-ethyl-N-nitrosourea to BD IX rats, cytosolic tissue transglutaminase activity was increased by about 140% at 30 days of extrauterine life and returned towards the control values at 3-5 months. In the particulate fraction, enzyme activity progressively increased, reaching values similar to those present in the developed gliomas. Tissue transglutaminase activity in gliomas had a behavior inverse to that observed in controls, with a decrease (about 50%) in the cytosol and a marked increase (380%) in the particulate fraction, indicating a redistribution of enzyme activity.

Animals↗

CD8 T-cell infiltration in extravascular tissues of patients with human immunodeficiency virus infection. Interleukin-15 upmodulates costimulatory pathways involved in the antigen-presenting cells-T-cell interaction.

Interleukin (IL)-15 regulates the proliferative activity of the CD8(+) T-cell pool in human immunodeficiency virus (HIV)-infected patients, thereby contributing to the maintenance of the CD8(+) T-cell-mediated immune response against HIV in extravascular tissues, including the lung. However, the effects of IL-15 on antigen-presenting cells (APC) during HIV infection are still unclear. In this study, we evaluated whether IL-15 regulates the macrophage stimulatory pathways governing inflammatory events that take place in the lung of patients with HIV infection. As a first step we evaluated the in vitro effects of IL-15 on lung macrophages retrieved from the respiratory tract of eight normal subjects. Although macrophages from uninfected individuals expressed the IL-15 binding proteins (IL-15Ralpha and the common gammac) at resting conditions, they did not express IL-15 messenger RNA (mRNA). However, a 24-hour stimulation with IL-15 induced the expression of interferon-gamma (IFN-gamma) and IL-15 itself, suggesting a role for this cytokine in the activation of the pulmonary macrophage pool during inflammation. As a confirmation of the role of IL-15 in this setting, at resting conditions, alveolar macrophages of patients with HIV infection and T-cell alveolitis expressed IL-15, IFN-gamma, and IL-15 binding proteins; showed an upmodulation of costimulatory molecules, B7 and CD72, which are involved in the APC of macrophages; and behaved as effective accessory cells because they elicited a strong proliferation of T cells. The accessory effect was inhibited by pretreatment with anti-CD72, anti-B7 (CD80 and CD86), and anti-IL-15 monoclonal antibodies (MoAb). We then investigated the relationship between IL-15 and the expression of costimulatory molecules by macrophages. A 24-hour stimulation of IL-15Ralpha+/gammac+ macrophages with IL-15 upregulated the expression of CD80 and CD86. The evidence that IL-15 upregulates the expression of coligands that favor the contact between T cells and APC, per se, triggers T-cell activation and proliferation and acts as a chemoattractant for T cells, suggests that IL-15 plays a key role in Tc1-mediated defense mechanisms taking place in extravascular tissues of patients with HIV disease.

Adult↗

Telomerase activity in chronic lymphoproliferative disorders of B-cell lineage.

The progressive shortening of telomeres at each cell division is a key mechanism in controlling cell proliferative capacity. The activation of telomerase, a reverse transcriptase that extends telomere length, potentially leads to unlimited cell proliferation, and is believed to play a critical role in the neoplastic process. High levels of telomerase activity have been demonstrated in almost all solid tumours; however, little data is available concerning its expression in chronic B-cell neoplasms. By using a quantitative polymerase chain reaction-based method we quantified telomerase activity in normal B lymphocytes, and in various B-cell malignancies, including chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL) and hairy cell leukaemia (HCL). Compared to normal B cells, which expressed very low levels of telomerase activity, malignant cells from most of the patients showed a significant increase in telomerase activity, with highest values observed in HCL samples. Moreover, among the CLL and HCL cases, significantly higher levels of telomerase activity were found in patients with progressive disease at 1 year follow-up versus patients with stable disease. These data suggest that telomerase activity might correlate with disease progression.

Aged↗

Lipoprotein(a) and apolipoprotein(a) isoforms and proteinuria in patients with moderate renal failure.

BACKGROUND: Atherosclerotic diseases are a major cause of death in patients with renal failure. Increased serum concentrations of lipoprotein(a) [Lp(a)] have been established as a genetically controlled risk factor for these diseases and have been demonstrated in patients with moderate renal failure, suggesting that this lipoprotein contributes to the increased cardiovascular risk seen in these patients. Variable alleles at the apolipoprotein(a) [apo(a)] gene locus are the main determinants of the serum Lp(a) level in the general population. The purpose of this study was to investigate apo(a) isoforms in patients with moderate renal failure and mild proteinuria (less than 1.0 g/day). METHODS: In 250 consecutive subjects recruited at a hypertension clinic, we assessed the renal function by 24-hour creatinine clearance, proteinuria, and microalbuminuria, as well as the prevalence of atherosclerotic disease, and we also measured apo(a) isoforms, serum albumin, and Lp(a) concentrations. RESULTS: Moderate impairment of renal function (creatinine clearance, 30 to 89 ml/min per 1.73 m2 of body surface area) was found in 97 patients. Lp(a) levels were significantly greater in patients with moderate renal failure (21.7+/-23.9 mg/dl) as compared with patients with normal renal function (15.6+/-16.4 mg/dl, P<0.001), and an inverse correlation was observed between log Lp(a) and creatinine clearance (r = -0.181, P <0.01). However, no difference was found in the frequency of low molecular weight apo(a) isoforms between patients with normal (25.5%) and impaired (27.8%) renal function. Only patients with the smallest size apo(a) isoforms exhibited significantly elevated levels of Lp(a), whereas the large-size isoforms had similar concentrations in patients with normal and impaired renal function. No significant relationship was found between serum Lp(a) and proteinuria. Clinical and laboratory evidence of one or more events attributed to atherosclerosis was found in 9.8% of patients with normal renal function and 25.8% of patients with moderate renal failure (P<0.001). CONCLUSIONS: These results indicate that renal failure per se or other genes beside the apo(a) gene locus are responsible for the elevation of serum Lp(a) levels in patients with moderate impairment of renal function. The elevation of Lp(a) levels occurs independently of the level of proteinuria and may contribute to the risk for atherosclerotic disease in these patients.

Adult↗

Regulation of alveolar macrophage-T cell interactions during Th1-type sarcoid inflammatory process.

The accessory function of antigen-presenting cells depends on the presence of a number of costimulatory molecules, including members of the B7 family (CD80 and CD86) and the CD5 coligand CD72. The aim of this study was to evaluate the regulation of T cell-antigen-presenting cell costimulatory pathways in the lung of patients with a typical Th1-type reaction, i.e., sarcoidosis. Although normal alveolar macrophages (AMs) did not bear or bore low levels of costimulatory molecules, AMs from sarcoid patients with CD4 T-cell alveolitis upmodulated CD80, CD86, and CD72 and expressed high levels of interleukin (IL)-15; lymphocytes accounting for T-cell alveolitis expressed Th1-type cytokines [interferon (IFN)-gamma and/or IL-2] and bore high levels of CD5 and CD28 but not of CD152 molecules. In vitro stimulation of AMs with Th1-related cytokines (IL-15 and IFN-gamma) upregulated the expression of CD80 and CD86 molecules. However, stimulation with IL-15 induced the expression of Th1-type cytokines (IFN-gamma) and CD28 on sarcoid T cells, suggesting a role for this macrophage-derived cytokine in the activation of the sarcoid T-cell pool. The hypothesis that CD80 and CD86 molecules regulate the sarcoid T-cell response was confirmed by the evidence that AMs induced a strong proliferation of T cells that was inhibited by pretreatment with CD80 and CD86 monoclonal antibodies. To account for these data, it is proposed that locally released cytokines provide AMs with accessory properties that contribute to the development of sarcoid T-cell alveolitis.

Adult↗

The chemokine receptor CXCR3 is expressed on malignant B cells and mediates chemotaxis.

B- and T-cell recirculation is crucial for the function of the immune system, with the control of cell migration being mainly mediated by several chemokines and their receptors. In this study, we investigated the expression and function of CXCR3 on normal and malignant B cells from 65 patients with chronic lymphoproliferative disorders (CLDs). Although CXCR3 is lacking on CD5(+) and CD5(-) B cells from healthy subjects, it is expressed on leukemic B lymphocytes from all (31/31) patients with chronic lymphocytic leukemia (CLL). The presence of CXCR3 was heterogeneous in other B-cell disorders, being expressed in 2 of 7 patients with mantle cell lymphoma (MCL), 4 of 12 patients with hairy cell leukemia (HCL), and 11 of 15 patients with other subtypes of non-Hodgkin's lymphomas (NHLs). Chemotaxis assay shows that normal B cells from healthy subjects do not migrate in response to IFN-inducible protein 10 (IP-10) and IFN-gamma-induced monokine (Mig). In contrast, a definite migration in response to IP-10 and Mig has been observed in all malignant B cells from patients with CLL, but not in patients with HCL or MCL (1/7 cases tested). Neoplastic B cells from other NHLs showed a heterogenous pattern. The migration elicited by IP-10 and Mig was inhibited by blocking CXCR3. No effect of IP-10 and Mig chemokines was observed on the cytosolic calcium concentration in malignant B cells. The data reported here demonstrate that CXCR3 is expressed on malignant B cells from CLDs, particularly in patients with CLL, and represents a fully functional receptor involved in chemotaxis of malignant B lymphocytes.

Adult↗

In vivo modulation of 73 kDa heat shock cognate and 78 kDa glucose-regulating protein gene expression in rat liver and brain by ethanol.

BACKGROUND: In cultured cells of various origin, ethanol induces the synthesis of 70 kDa family heat shock proteins (hsp70 family), which play a role in the protection of protein traffic and secretion, as well as in cytoskeleton organization. To assess whether ethanol also can induce such genes in vivo, we studied the behavior of hsp70, hsc73, and grp78 messenger ribonucleic acids (mRNAs) and related proteins in the liver and brain of rats acutely treated with ethanol. METHODS: Overnight fasted Sprague-Dawley rats (220-250 g) were acutely treated with a low (2 g/kg body weight) or a high (5 g/kg body weight) dose of ethanol as a 30% solution in saline or an equal volume of saline (controls) by gastric intubation. Animals were killed at various times after treatments (3-72 hr). Messenger RNA levels for different members of hsp70 family (hsp70; 73 kDa heat shock cognate, or hsc73; and 78 kDa glucose-regulating protein, or grp78) were determined by Northern blot analysis and hybridization with specific complementary deoxyribonucleic acid (cDNA) probes. The amounts of related proteins were assayed by Western blot analysis with specific antibodies. Autoradiograms and fluorograms were subjected to densitometric scanning. RESULTS: Ethanol (2 g/kg) caused a slight increase in hsc73 and grp78 mRNA levels only in the liver, without enhancing the amount of proteins. Ethanol (5 g/kg) increased the level of hsc73 and grp78 mRNAs and related proteins in the liver. In the brain, the amount of hsc73 mRNA was enhanced, but this did not change hsc73 protein. In addition, we observed an increase in cerebral grp78 transcript and related protein. Hsp70 gene was not induced in the examined tissues by either dose of ethanol. CONCLUSIONS: Hepatic and cerebral hsc73 and grp78 genes are responsive to ethanol in vivo, and their activation may signal the cell's effort to counteract the harmful action of ethanol.

Animals↗

Involvement of the IP-10 chemokine in sarcoid granulomatous reactions.

The accumulation of T cells and monocytes at sites of ongoing inflammation represents the earliest step in the series of events that lead to granuloma formation in sarcoidosis. In this study, we evaluated the pulmonary production of IFN-inducible protein 10 (IP-10), a CXC chemokine that stimulates the directional migration of activated T cells. Striking levels of IP-10 were demonstrated in the bronchoalveolar lavage (BAL) fluid of 24 patients with pulmonary sarcoidosis and lymphocytic alveolitis, as compared with patients with inactive disease or control subjects. A positive correlation was demonstrated between IP-10 levels and the number of sarcoid CD45R0+/CD4+ cells in the BAL. Immunochemistry, performed with an anti-human IP-10 polyclonal Ab in lymph nodes displaying prominent sarcoid granulomas, showed that cells bearing IP-10 were mainly epithelioid cells and CD68+ macrophages located inside granulomatous areas. Macrophages recovered from the BAL of sarcoid patients stained positive for IP-10 protein. Furthermore, alveolar macrophages isolated from sarcoid patients with T cell alveolitis and cultured for 24 h in presence of IFN-gamma secreted definite levels of IP-10 capable of inducing T cell chemiotaxis. Interestingly, alveolar lymphocytes recovered from patients with active sarcoidosis were CD4+ T cells expressing Th1 cytokines (IL-2 and IFN-gamma) and high levels of CXCR3. Taken together, these data suggest the potential role of IP-10 in regulating the migration and activation of T cells toward sites of sarcoid inflammatory process and the consequent granuloma formation.

Adult↗