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Biomedical subjects

P Leone

Publications and source records attributed to P Leone.

At least 19 recordsLinked to original sources
PubMed2002

Adsorption of imidazolinone herbicides on smectite-humic acid and smectite-ferrihydrite associations.

Adsorption of imazapyr (IMZ), imazethapyr (IMZT), and imazaquin (IMZQ) was studied on two smectite-humic acid and two smectite-ferrihydrite binary systems prepared by treating a Wyoming smectite with a humic acid extracted from soil (4 and 8% w/w of the smectite) and with just-precipitated synthetic ferrihydrite (8 and 16% w/w of the smectite). Adsorption of the three herbicides on the smectite was not measurable at pH >4.5, presumably because of negative charges on the surface of the smectite. Adsorption on the smectite-humic acid systems was also not measurable, presumably because of negative charges on the surface, despite the high affinity of the three herbicides for humic acid, the adsorption order of which was IMZ < IMZT << IMZQ. Adsorption decreased in the order IMZ < IMZT < IMZQ on the smectite-ferrihydrite systems and IMZQ < IMZT < IMZ on ferrihydrite, although here the differences were small. These results show that even though pure smectite cannot adsorb herbicides, it modifies the adsorption capacity of ferrihydrite. The mutual interaction of active phases such as humic acid, ferrihydrite, and smectite alters the characteristics of the resulting surface and hence the adsorption process. Investigations of herbicide adsorption have been seen to produce more reliable results if conducted on polyphasic systems rather than on single soil components.

Adsorption↗
PubMed2002

[Stenosis of the new bladder neck, a complication of radical prostatectomy: personal experience].

BACKGROUND: To describe personal experience on stenosis of the new bladder neck, a complication of radical prostatectomy. After a review of the literature, guidelines are proposed to avoid this complication, both from a prophylactic and treatment point of view. METHODS: Between 1992 and 2000, 54 patients were submitted to radical prostatectomy, 18 of whom later presented stenosis in the new bladder neck. Mean age of patients was 65.6 years (range 55-76). According to TNM classification, 46 patients (85%) were stage pT2N0M0 and eight patients (15%) stage pT3N0M0, no significant correlation being found with PSA values. All patients were submitted to pre- and postmicturition retrograde cystourethrography, four weeks after surgery; patients presenting dysuric symptoms also underwent further retrograde cystourethrography and flowmeter examinations. RESULTS: Of the 54 patients, 18 (33%) presented stenosis of the new bladder neck as a complication of radical prostatectomy. Of these 18 patients, 12 (22%) presented acute dysuria symptoms. In 14 cases, one-two cycles of urethral dilation were sufficient to improve flowmeter values. In the four remaining cases showing no improvement following urethral dilations, endoscopic resection was necessary in two and urethrotomy according to Sachse in the other two. CONCLUSIONS: Stenosis of the anastomosis of the new bladder neck is a complication of radical prostatectomy occurring within six months of surgery, no correlation being found with tumour stage, recurrence, or duration of catheter in situ. Of the 18 patients presenting stenosis in the series described, in 78%, cycles of urethral dilation were sufficient to successfully resolve the complication thus avoiding further surgery, which, on the other hand, was necessary in four patients, two submitted to endoscopic resection of the stenosis and the other two to incision according to Sachse.

Aged↗
PubMed2002

[Immunotherapy in the management of metastatic renal carcinoma].

BACKGROUND: Renal cell carcinoma (RCC) is a relatively rare tumor representing 2-3% of all neoplasias. Approximately 30% of patients diagnosed as having RCC present metastases: mean survival ranges between 6 and 10 months, whilst 10-20% present a 2-year survival rate. Treatment of patients with metastatic RCC is a difficult challenge. Hormones and chemotherapy, either alone or associated with surgical resection of the primary lesion have been used. In our experience, IL-2 + IFN-a has been shown to be an encouraging form of treatment. METHODS: During the period between October 1997 and December 1999, 5 patients (3 males, 2 females), mean age 52.5 years, with metastatic RCC, came to our attention. TC revealed a circumscribed area the margins of which were not well defined, in a mid-renal localization, positive inter aorta caval and obturator lymph nodes, but no lung, brain or hepatic involvement. Patients were submitted to nephrectomy and lymphadenectomy followed later by immunotherapy with IFN-alpha (3 Mil twice a week) + low dose IL-2 (1 Mil/m2/12 h): treatment was given for 4 consecutive weeks and then repeated every 3 weeks for 1 year. RESULTS: At 30 months' follow-up all patients showed regression of the disease (100% of cases) and in none of the cases there was evidence of metastases. Only one patient (20%) presented side-effects (nausea, vomiting, slight rise in temperature) all of which disappeared at the end of the first week of treatment. CONCLUSIONS: These results, even if on a limited number of patients and for a limited follow-up period, show that in some patients with metastatic renal cell carcinoma, treatment with IL-2 and IFN-a following nephrectomy and lymphadenectomy should be considered the therapy of choice.

Carcinoma, Renal Cell↗
PubMed2001

Clearance of human herpesvirus 8 from blood and regression of leukopenia-associated aggressive classic Kaposi's sarcoma during interferon-alpha therapy: a case report.

A human immunodeficiency virus-negative woman with severe classic Kaposi's sarcoma, idiopathic leukopenia, and massive spread of human herpesvirus 8 (HHV-8) in circulating cells showed stable disease remission in response to systemic interferon-alpha treatment that was accompanied by increased CD3(+) and CD4(+) T cell numbers and complete clearance of HHV-8 from the circulation. These results suggest a direct relationship between HHV-8 clearance from blood and regression of Kaposi's sarcoma and are consistent with the in vitro inhibitory effects of interferon-alpha on HHV-8 infection.

Antiviral Agents↗
PubMed2001

Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P).

Recent evidence suggests that a CD8-mediated cytotoxic T cell response against the Tat protein of human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) controls primary infection after pathogenic virus challenge, and correlates with the status of long-term nonprogressor in humans. Due to the presence of unmethylated CpG sequences, DNA vaccination can boost the innate immunity driving more potent T cell-mediated immune responses. Therefore, cynomolgus monkeys were vaccinated with a tat-expressing vector containing defined unmethylated CpG sequences (pCV-tat). Here it is shown that the intramuscular inoculation of the pCV-tat contained primary infection with the highly pathogenic SHIV89.6P virus preventing the CD4(+) T cell decline in all the vaccinated monkeys. Undetectable virus replication and negative virus isolation correlated in all cases with the presence of anti-Tat CTLs. However, a CD8-mediated non cytolytic antiviral activity was also present in all protected animals. Of note, this activity was absent in the controls but was present in the monkey inoculated with the CpG-rich vector alone that was partially protected against viral challenge (i.e. no virus replication but positive virus isolation). These results suggest that a CTL response against Tat protects against primary infection by blocking virus replication at its early stage, in the absence of sterilizing immunity. Nevertheless, the boost of the innate immunity by CpG sequences can contribute to this protection both by driving more potent CTL responses and by inducing other CD8-mediated antiviral activities. Thus, the CpG-rich tat DNA vaccine may represent a promising candidate for preventive and therapeutic vaccination against AIDS.

AIDS Vaccines↗
PubMed2001

Viral-based gene transfer to the mammalian CNS for functional genomic studies.

A fundamental problem in neuroscience has been the creation of suitable in vivo model systems to study basic neurological phenomena and pathology of the central nervous system (CNS). Somatic cell genetic engineering with viral vectors provides a versatile tool to model normal brain physiology and a variety of neurological diseases.

Animals↗
PubMed2001

Role of ferrihydrite in adsorption of three imidazolinone herbicides.

Adsorption of the imidazolinone herbicides imazapyr, imazethapyr, and imazaquin on synthetic ferrihydrites, either freeze-dried or not-freeze-dried, has been studied. The synthetic ferrihydrites were characterized by X-ray diffraction, scanning electron micrographs, and specific area determination. On each ferrihydrite, adsorption was found to be strongly dependent on pH. The highest extent of adsorption took place at pH values close to the pK(a) of the carboxylic group of the herbicides. No adsorption was observed at pH > 8. The freeze-drying process reduced the adsorptive capacity of the ferrihydrite by formation of larger aggregates provoking a decrease of the surface area. The chemical differences between the herbicides did not strongly affect the adsorption process of the herbicides. However, imazaquin was more adsorbed than the other two herbicides, in particular at pH close to its pK(a).

Adsorption↗
PubMed2001

Quantitative comparison of expression with adeno-associated virus (AAV-2) brain-specific gene cassettes.

This study compared a range of mammalian CNS expression cassettes in recombinant adeno-associated virus (AAV-2) vectors using strong endogenous promoter sequences, with or without a strong post-regulatory element and polyadenylation signal. Changes in these elements led to transgene expression varying by over three orders of magnitude. In experiments conducted in primary cell culture and in >100 stereotactically injected rats, we observed highly efficient and stable (>15 months) gene expression in neurons and limited expression in glia; the highest expression occurred with endogenous, nonviral promoters such as neuron-specific enolase and beta-actin. The packaging size of AAV-2 was maximized at 5.7 kb without impairing gene expression, as judged by direct comparison with a number of smaller AAV-2 constructs. The genomic insert size and titer were confirmed by Southern blot and quantitative PCR, and infectivity was tested by particle titer using ELISA with a conformation-dependent epitope that requires the full intact capsid. A packaging and purification protocol we describe allows for high-titer, high-capacity AAV-2 vectors that can transduce over 2 x 10(5) neurons in vivo per microliter of vector, using the strongest expression cassette.

Animals↗
PubMed2001

Prevalence, incidence and correlates of HHV-8/KSHV infection and Kaposi's sarcoma in renal and liver transplant recipients.

BACKGROUND: To determine whether the incidence of HHV-8/KSHV infection and the risk of developing KS among organ transplant recipients differ by type of organ transplanted, we calculated the rate of HHV-8/KSHV seroconversion and the risk of developing KS among renal and liver transplant recipients. METHODS: The study population consisted of renal and liver transplant recipients recruited in two transplant centres in Rome, Italy. Both pre-transplant and post-transplant serum samples were available for all participants. The prevalence of HHV-8/KSHV infection before transplantation was calculated. To determine risk factors for infection, we calculated ORs and 95% CI. Seroconversion rates (i.e. attack rates) after transplantation were also calculated. Differences in attack rates were calculated using a binomial test for proportions. RESULTS: Of the 130 participants, 21 (16.1%) were HHV-8/KSHV-positive before transplantation. Women were more likely to be infected than men, whereas no difference was observed by type of organ transplanted. Of the 109 initially negative individuals, 13 (11.9%) developed anti-HHV-8/KSHV antibodies after transplantation. The incidence of HHV-8/KSHV infection tended to be higher among liver transplant recipients. Four renal transplant recipients and none of the liver transplant recipients developed KS after transplantation. The risk of KS was higher among recipients who were already HHV-8/KSHV-positive before transplantation. CONCLUSIONS: HHV-8/KSHV seroconversion rates appear to be higher among liver transplant recipients, compared to renal transplant recipients. However, renal transplant recipients tend to have a higher risk of KS. HHV-8/KSHV reactivation appears to play a greater role on the risk of KS than incident infections.

Adolescent↗
PubMed2001

Orthodontic finalization strategies in dysfunctional adult patients.

Although orthodontic treatment for the finalization of temporomandibular dysfunction (TMD) patients is often advocated, it represents a risk of failure. Furthermore, in the literature there are few articles that illustrate appropriate orthodontic strategies for the finalization of these patients. In this article the authors suggest a step-by-step clinical procedure in order to: 1. verify the rationale for orthodontic finalization in TMD patients; 2. illustrate the guidelines for correct orthodontic treatment; and 3. suggest a strategy to stabilize the mandible during orthodontic treatment and to retain that stabilization after treatment. If splint therapy is successful in relieving the TMD symptoms, a fixed posterior bilateral stop is used for occlusal stability. After one or two months during which the bilateral stop is shown to be adequate in maintaining TMJ health without a splint, orthodontic finalization can be performed with minimal risk of failure. The essential sequences of Class I, Class II, and Class III treatment for the finalization of TMD patients are also presented. The difficult goal of a long term stability in cases that have been orthodontically finalized is reached by the conversion of the posterior bilateral stops (crown build-ups) into permanent vertical stops.

Adolescent↗
PubMed2001

Adsorption of imidazolinone herbicides on ferrihydrite-humic acid associations.

Adsorption of the imidazolinone herbicides imazapyr, imazethapyr and imazaquin was studied on two binary systems (ferrihydrite-humic acid) prepared by treating ferrihydrite (Fh) immediately after its precipitation with a soil humic acid (HA) at different loadings (4% and 8% HA content), and on a blank ferrihydrite sample prepared in the same way, but without HA addition. Imidazolinone adsorption on pure Fh and on the 4% Fh-HA decreased with increasing of the herbicide hydrophobicity (imazaquin<imazethapyr<imazapyr), whereas on the 8% Fh-HA system the order of adsorption was nearly the same, indicating that higher amounts of HA on Fh increase the hydrophobicity of the surface and thus increases its affinity for the herbicides, specially for imazaquin. Adsorption was also enhanced by low pH values and slight changes in pH enhanced the contribution of each component in adsorption. Both the nature of the surface exposed and its ability to interact with herbicides are greatly altered by the mutual interaction of Fh and HA. The results show that albeit artificial polyphasic associations are more representative of the real situation than single model components and are thus better indicators of the behaviour of a given herbicide in the soil.

Adsorption↗
PubMed2001

Activation of matrix-metalloproteinase-2 and membrane-type-1-matrix-metalloproteinase in endothelial cells and induction of vascular permeability in vivo by human immunodeficiency virus-1 Tat protein and basic fibroblast growth factor.

Previous studies indicated that the Tat protein of human immunodeficiency virus type-1 (HIV-1) is a progression factor for Kaposi's sarcoma (KS). Specifically, extracellular Tat cooperates with basic fibroblast growth factor (bFGF) in promoting KS and endothelial cell growth and locomotion and in inducing KS-like lesions in vivo. Here we show that Tat and bFGF combined increase matrix-metalloproteinase-2 (MMP-2) secretion and activation in endothelial cells in an additive/synergistic manner. These effects are due to the activation of the membrane-type-1-matrix-metalloproteinase and to the induction of the membrane-bound tissue inhibitor of metalloproteinase-2 (TIMP-2) by Tat and bFGF combined, but also to Tat-mediated inhibition of both basal or bFGF-induced TIMP-1 and -2 secretion. Consistent with this, Tat and bFGF promote vascular permeability and edema in vivo that are blocked by a synthetic MMP inhibitor. Finally, high MMP-2 expression is detected in acquired immunodeficiency virus syndrome (AIDS)-KS lesions, and increased levels of MMP-2 are found in plasma from patients with AIDS-KS compared with HIV-uninfected individuals with classic KS, indicating that these mechanisms are operative in AIDS-KS. This suggests a novel pathway by which Tat can increase KS aggressiveness or induce vasculopathy in the setting of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Single-dose gatifloxacin compared with ofloxacin for the treatment of uncomplicated gonorrhea: a randomized, double-blind, multicenter trial.

BACKGROUND: Treatment of gonorrhea is complicated by widespread resistance of Neisseria gonorrhoeae to antimicrobial agents of choice, including decreased susceptibility to ciprofloxacin. GOAL: To demonstrate the efficacy and safety of gatifloxacin, a novel 8-methoxy fluoroquinolone antibiotic, compared with ofloxacin in treating patients with uncomplicated gonococcal infection. STUDY DESIGN: In a double-blind, randomized (2:2:1), controlled trial, 340 men and 388 women with uncomplicated gonorrhea who were 16 years or older received a single oral dose of gatifloxacin (400 mg or 600 mg) or ofloxacin (400 mg). Primary analysis of efficacy was based on bacteriologic eradication from sites of infection. Secondary analyses examined clinical response and adverse event profiles. RESULTS: Bacteriologic eradication rates for gatifloxacin in evaluable men with urethral gonorrhea were 99% (400 mg) and 100% (600 mg) versus 100% for ofloxacin (n = 117, 122, and 55, respectively; P = ns). Eradication rates in evaluable women with endocervical gonorrhea were 99% for both 400 mg and 600 mg gatifloxacin versus 100% for ofloxacin (n = 101, 104, and 55, respectively; P = ns). Eradication rates were 100% for both rectal (n = 43) and pharyngeal (n = 31) infection across all treatment groups. All three drug regimens were well tolerated and exhibited similar clinical response profiles. CONCLUSION: Gatifloxacin is safe and effective as a single 400-mg or 600-mg dose for the treatment of uncomplicated gonorrhea. Similar efficacy rates were observed with the 400-mg and 600-mg doses. A single 400-mg dose can be recommended for treatment of uncomplicated gonorrhea.

Administration, Oral↗
PubMed2001

[Postprostatectomy erectile dysfunction].

BACKGROUND: To evaluate the frequency of erectile dysfunction in patients submitted to radical prostatectomy due to prostate carcinoma and to the possibility, with appropriate treatment, of restoring adequate erections for a satisfactory sexual activity. METHODS: Between 1996 and 2000, thirty-eight patients with prostate carcinoma have been submitted to radical prostatectomy. According to TNM classification upon diagnosis, thirty-three patients (87%) were stage pT2N0M0 and five patients (13%) stage pT3N0M0. Mean age of patients was 62.4 years (range 55-76). Mean follow-up was two years and seven months. Diagnosis of erectile dysfunction was made from personal history as well as that of the patient plus partner, and from nocturnal penile tumescence evaluation with Rigiscan. RESULTS: Eighteen patients (47%) presented erectile dysfunction as a complication 16 (89%) of whom showed no nocturnal reaction at the Rigiscan test, while in the remaining two (1%), one-two nocturnal erections of less than five minutes were obtained. Of the eighteen patients, 14 (78%) showed a positive response to treatment with intracavernous drug infusion (papaverine+Phentolamine+Alprostadil), whilst only one patient benefited from treatment with oral Sildenafil. CONCLUSIONS: This study showed the high frequency (47%) of erectile dysfunction in patients submitted to radical prostatectomy as well as the need to perform radical nerve-sparing surgery (particularly in the neoplastic forms not involving the prostate capsule) which is useful not only for preserving erectile function but also on account of better response to oral Sildenafil treatment following the use of this technique.

Aged↗
PubMed2000

Multi-site partitioned delivery of human tyrosine hydroxylase gene with phenotypic recovery in Parkinsonian rats.

Parkinson's disease (PD) is a leading candidate for neurological gene therapy, given our increasing knowledge of the functional anatomy of the striatonigral system and the localized nature of the affected cell populations. Here we report that stereotactic introduction of a human tyrosine hydroxylase (TH-2) gene using multi-site partitioned doses resulted in behavioral recovery in 6-OHDA-lesioned rats, with transient 100% recovery observed in some animals. We also show correlation between numbers of TH-immunoreactive cells and loss of apomorphine induced rotation, with a near-linear relationship between TH expression and phenotypic recovery. Furthermore, the data suggest that only a fraction of striatal cells need to be transduced in order to exert phenotypic effects, and therefore TH partitioned gene transfer may have clinical potential in PD.

Adenoviridae↗
PubMed2000

An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy.

The brain is generally considered immunoprivileged, although increasing examples of immunological responses to brain antigens, neuronal expression of major histocompatibility class I genes, and neurological autoimmunity have been recognized. An adeno-associated virus (AAV) vaccine generated autoantibodies that targeted a specific brain protein, the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor. After peroral administration of the AAV vaccine, transgene expression persisted for at least 5 months and was associated with a robust humoral response in the absence of a significant cell-mediated response. This single-dose vaccine was associated with strong anti-epileptic and neuroprotective activity in rats for both a kainate-induced seizure model and also a middle cerebral artery occlusion stroke model at 1 to 5 months following vaccination. Thus, a vaccination strategy targeting brain proteins is feasible and may have therapeutic potential for neurological disorders.

Administration, Oral↗
PubMed2000

Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease.

With the ultimate goal of developing safe and effective in vivo gene therapy for the treatment of Canavan disease and other neurological disorders, we developed a non-viral lipid-entrapped, polycation-condensed delivery system (LPD) for central nervous system gene transfer, in conjunction with adeno-associated virus (AAV)-based plasmids containing recombinant aspartoacylase (ASPA). The gene delivery system was tested in healthy rodents and primates, before proceeding to preliminary studies in 2 children with Canavan disease. Toxicity and expression testing was first carried out in human 293 cells, which demonstrated effective transduction of cells and high levels of functional ASPA activity. We performed in vivo toxicity and expression testing of LPD/pAAVaspa and LPD/pAAVlac in rodents, which demonstrated widespread gene expression for more than 10 months after intraventricular delivery, and local expression in deep brain nuclei and white matter tracts for more than 6 months after intraparenchymal injections, with no significant adverse effects. We also performed intraventricular delivery of LPD/pAAVaspa to 2 cynomologous monkeys, with 2 additional monkeys receiving LPD and saline controls. None of the monkeys demonstrated significant adverse effects, and at 1 month the 2 LPD/pAAVaspa monkeys were positive for human ASPA transcript by reverse transcriptase polymerase chain reaction of brain tissue punches. Finally, we performed the first in vivo gene transfer study for a human neurodegenerative disease in 2 children with Canavan disease to assess the in vivo toxicity and efficacy of ASPA gene delivery. Our results suggest that LPD/pAAVaspa is well tolerated in human subjects and is associated with biochemical, radiological, and clinical changes.

Amidohydrolases↗