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Biomedical subjects

P Grossi

Publications and source records attributed to P Grossi.

At least 55 records · Page 3Linked to original sources

Diagnosis of cytomegalovirus infections by shell vial assay and conventional cell culture during antiviral prophylaxis.

A total of 3,552 specimens for conventional cytomegalovirus (CMV) culture and shell vial assay for CMV immediate-early antigen were obtained during a prospective randomized trial for prophylaxis of CMV disease after liver transplantation. Prophylaxis with ganciclovir for 2 weeks and then high-dose acyclovir for 2.5 months was compared with high-dose acyclovir alone for 3 months. During the first 12 weeks after transplantation, when the patients were on prophylaxis, there were significantly more clinical samples positive by the shell vial assay and negative by standard culture in comparison with the number of samples obtained from weeks 13 to 24, after prophylaxis was discontinued, that were positive by the shell vial assay and negative by standard culture. In contrast, significantly fewer samples were positive by both the shell vial assay and standard culture during the first 12 weeks compared with the number obtained 13 to 24 weeks after transplantation that were positive by both methods. Samples positive by the shell vial assay only were obtained significantly more frequently from patients with asymptomatic than symptomatic CMV infections, while samples positive by both methods were obtained significantly more often from patients with symptomatic CMV infection. It was concluded that antiviral prophylaxis with high-dose acyclovir or ganciclovir and then high-dose acyclovir and asymptomatic CMV infection are associated with a decrease in the level of CMV isolation by standard cell culture in comparison with that by the shell vial assay.

Acyclovir↗

[AIDS: biological aspects].

In June 1981 a new clinical syndrome, now called acquired immunodeficiency syndrome (AIDS) was first reported by the CDC. This entity has grown to be a pandemic disease with major socioeconomics, political and medical consequences. HIV-induced immunodeficiency infection typically occurs gradually over several years and leads to secondary opportunistic infections and malignancies. Similar features are observed in transplant recipients; the same clinical and diagnostic management is mandatory, but only in transplant complications an effective cure is possible.

Acquired Immunodeficiency Syndrome↗

Lacidipine metabolism in rat and dog: identification and synthesis of main metabolites.

1. The main metabolites of lacidipine were isolated from bile and plasma of rats and dogs following an oral dose of the 14C-labelled drug (10 mg/kg for rats: 2 and 1 mg/kg for dogs). They were identified by comparison of chromatographic and spectral data with authentic reference compounds synthesized ad hoc. 2. Five metabolites (I-V) were isolated and identified in dog bile by gradient h.p.l.c. with u.v. detection and h.p.l.c.-thermospray mass spectrometry. In all metabolites the heterocyclic ring has been oxidized to pyridine. Further biotransformation reactions involved hydroxylation of the methyl substituents and hydrolysis of the ethyl and t-butyl ester groups to produce carboxylic acids and a lactone. Some of these metabolites also occurred as glucuronide conjugates. 3. A metabolite retaining the intact dihydropyridine ring, the des-ethyl analogue of lacidipine (VI), was isolated from rat plasma where it accounted for 60% of the total circulating radioactivity up to 24 h after administration. To characterize this metabolite, h.p.l.c. with photodiode array u.v. detection also was employed. This compound was detected in dog plasma, but there was no evidence of its presence in dog bile samples. 4. Profiles of circulating metabolites were qualitatively similar in rats and dogs. Identified metabolites accounted for the large majority of total radioactivity in all the analysed samples.

Animals↗

Histopathologic and molecular profile of human cytomegalovirus infections in patients with heart transplants.

From November 1985 to December 1990, 2,552 endomyocardial biopsy specimens from 209 heart transplant patients were studied. Forty-four (21%) patients developed 45 episodes of major human cytomegalovirus infection (HCMV). Human cytomegalovirus infection was primary in 13 of 44 patients. Thirty-one patients developed episodes of recurrent major infection. One patient had both primary and recurrent infections. Conventional histopathologic and immunohistochemical study, in situ hybridization, and polymerase chain reaction were used to diagnose HCMV myocardial involvement on corresponding endomyocardial biopsy specimens performed during infection. Conventional morphologic study showed typical viral inclusion bodies in four biopsy specimens. Two cases had myocyte HCMV localization with necrotizing myocarditis, whereas two had endothelial cell involvement without any inflammatory reaction. In these four biopsy specimens, immunohistochemistry showed a higher number of infected cells than that recognized by conventional histopathologic study. In situ hybridization detected infected cells with no evidence of cytopathic effect. Polymerase chain reaction gave HCMV amplification products in two additional biopsy specimens otherwise interpreted as moderate and mild rejection, respectively. Therefore, 6 biopsies showed HCMV myocardial involvement (6 of 45; 13.3%): all were from patients with primary HCMV infection (6 of 13; 46%). None of 32 major recurrent infections showed any myocardial involvement. In conclusion, our study is the first to demonstrate that myocardial HCMV involvement preferentially occurs in primary infection and HCMV endothelial localization can be free from inflammatory reaction, whereas HCMV myocyte localization leads to necrotizing myocarditis. Polymerase chain reaction has a higher diagnostic sensitivity than in situ hybridization. However, polymerase chain reaction findings of HCMV DNA on otherwise negative endomyocardial biopsy specimens remains of questionable significance because polymerase chain reaction-positive biopsy samples do not necessarily indicate tissue infection. It is impossible to determine whether amplified sequences derive from circulating leukocytes or from tissue cells.

Antigens, Viral↗

[The general practitioner and clinical records: a survey of the knowledge of users of a software package].

The FATMA project--subproject 6, Line of Research 2--aims at implementing a new computerized information network for general practitioners using the same kind of software and homogeneously located throughout Italy. Thus, patients' case form data can be collected for public health purposes. After a study of literature in order to check whether other countries had implemented similar projects and what they consisted of, a survey based on a computerized questionnaire was carried out on a group of g.p.s. who had already received a software for the management of their clinical and professional activities from Janssen Informedica. This survey aimed at judging some aspects of users in order to select potential monitors of the information network who would test a new software. The analysis regards both g.p.s' social and professional data and the use of a computer package with reference to the quality and quantity of the clinical data they input. 2,010 questionnaires were filled in all their parts and mailed back to Informedica. It came out that g.p.s. believe more and more they can improve the organization and management of their work by using a software equipped with routines and easy access procedures so that clinical data, diagnostic reports and treatment can be collected, placed on files and updated. Thus, a new software should be developed. While meeting g.p.s' needs, it must overcome the limits of packages now available concerning the possibility of carrying out epidemiological studies. The software can become a tool to collect clinical data of patients, diseases and diagnostic procedures through standard protocols directly from g.p.s records.

Adult↗

Monitoring of human cytomegalovirus infections and ganciclovir treatment in heart transplant recipients by determination of viremia, antigenemia, and DNAemia.

Fourteen heart transplant recipients were monitored for human cytomegalovirus (HCMV) infection based on determination of antigenemia, viremia, and DNAemia (by polymerase chain reaction [PCR]) in peripheral blood polymorphonuclear leukocytes (PMNL). Three patients had symptomatic primary, 10 had recurrent (3 asymptomatic), and 1 (seronegative) had no HCMV infection. Severe clinical symptoms appeared when levels of viremia/antigenemia were greater than 50 infected PMNL/2 x 10(5) cells examined. Of 200 blood samples examined, 93 (46.5%) were positive for viremia/antigenemia and DNAemia, whereas 48 (24.0%) were positive for DNAemia only; 59 (29.5%) were negative in all assays. Follow-up of HCMV infections in heart transplant recipients showed that PCR can detect viral appearance in blood 7-10 days earlier than assays for antigenemia/viremia. On the other hand, viral disappearance from blood, as assessed by PCR, occurred weeks or months later than revealed by other assays. Detection of virus by PCR only was never associated with overt HCMV-related clinical symptoms. Of the 8 symptomatic patients treated with ganiclovir, 2 became PCR-negative at the end of treatment and 1 cleared virus from blood in the following weeks, whereas 5 showed persistent or recurrent infection.

Antigens, Viral↗

[Endomyocardial biopsy in the heart transplant patient: the state of the art].

Data regarding 2176 endomyocardial biopsies (EMB) (Nov. '85-Dec. '89) performed in 164 transplanted hearts (4 etherotopic) from 158 patients (6 retransplants) are herein reported. This study was aimed to evaluate: 1) Incidence and characteristics of early ischemic myocardial damage. 2) The influence of different immunosurveillance protocols on incidence, degree and aggressiveness of acute rejection and the inflammatory infiltrate composition. 3) The immunophenotype of infiltrating cells in moderate acute rejection episodes. 4) HLA-DR antigen expression on myocyte sarcolemma. 5) Characterization of cells expressing immune response mediators. 6) Myocardial localization of opportunistic infections. 7) Useful information on chronic rejection. Our results demonstrate that: a) Mild rejection seldom progresses to moderate degree. b) Different immunosuppressive protocols can influence the incidence of acute rejection: in fact, in OKT3 protocol, the incidence of rejection episodes is higher than in other protocols as well as aggressiveness toward myocytes. c) Infiltrating cells maintain T lymphocyte prevalence with minor amounts of B lymphocytes and macrophages in the 3 different protocols. T cell subset characterization showed a slight prevalence of CD8 bearing cells over CD4 positive cells whereas CD57 cells were few and scattered. d) Class II Major Histocompatibility Complex (HLA-DR) expression never occurs on myocyte sarcolemma. e) TNF alpha is expressed in acute cardiac rejection by immunologically activated T lymphocytes and macrophages and the number of immunoreactive cells increases with progression of the rejection. f) Human cytomegalovirus infections can be primary or recurrent. Myocardial involvement has been observed in primary forms. Virus can affect endothelial cells (with no inflammatory reaction) or myocytes (myocarditis) and its diagnosis requires a combination of immunohistochemical and molecular biology techniques. Diagnosis of Toxoplasma gondii infection can be usually accomplished by routine histopathological study. g) Chronic rejection diagnosis is rarely based on biopsy derived information.

Biopsy↗

Absorption, distribution and excretion of lacidipine, a dihydropyridine calcium antagonist, in rat and dog.

1. The absorption, distribution and excretion of lacidipine have been studied in rat and dog after i.v. (0.05 mg/kg for rat; 0.5 mg/kg for dog) and oral dosage (2.5 mg/kg for rat; 2.0 mg/kg for dog). 2. Lacidipine was rapidly and extensively absorbed after oral dosing, in both species. Oral bioavailability was up to 26% in rat and up to 32% in dog, due to extensive first-pass metabolism. 3. After oral administration, peak levels of radioactivity were reached at 4-8 h in rat and 1-2 h in dog. Unchanged lacidipine peaked at 1-2 h in both species. Plasma levels of radioactivity were higher in female rats than in males but there was no difference in levels of unchanged drug. 4. After i.v. dosing the terminal half-life of unchanged drug was 2.9 h in rat and 8.2 h in dog. The half-life of radioactivity in plasma was longer in both species. 5. After both routes of administration, radioactivity was rapidly distributed in rat tissues with the highest concentration in liver, fat and gastrointestinal tract. Only traces of radioactivity were detected in the CNS and in rat foetuses. 6. Extensive biliary elimination occurred, and most of the radioactivity (73-95%) was excreted in the faeces after i.v. or oral administration. 7. The compound was extensively metabolized, no significant amount of unchanged drug was excreted in bile or urine.

Absorption↗

Cytomegalovirus prophylaxis by intravenous immunoglobulins in five heart transplanted patients.

The present study was set up to evaluate the efficacy of hyperimmune anti-CMV immunoglobulins (IVIG) in the prophylaxis of CMV infection in five patients suffering from dilatative myocardiopathy and submitted to hearth transplant. Different commercial IVIG were tested for anti-CMV neutralizing antibodies before administrated them to patients; the lots immunochemically prepared by PEG resulted to have the highest anti-CMV titer. IVIG treatment, when administered at high doses and at closes intervals of time, proved able to prevent and control CMV infections; when treatment was stopped, a primary infection occurred, easily controlled by short courses of DHPG. Even if our survey was limited to only five cases, it should be emphasized that after the suspension of the therapy, clinical symptoms were restricted to simple mononucleosis syndrome without organ disease. Furthermore it should be noted that during IVIG therapy no immediate or delayed adverse effects were observed.

Antibodies, Viral↗

Detection of human cytomegalovirus immediate early antigen in leukocytes as a marker of viremia in immunocompromised patients.

Peripheral blood polymorphonuclear (PMN) cells from 35 immunocompromised patients (22 heart transplant recipients and 13 AIDS patients) and four normal subjects were tested for the presence of human cytomegalovirus (HCMV) immediate early antigen (IEA) (antigenemia) by indirect immunofluorescence (IFA) and IEA-specific monoclonal antibodies (MAb). PMN samples were tested in parallel for HCMV isolation (viremia) by using MAb to viral early antigens (EA) and the IFA technique 24-48 hr after inoculation onto human fibroblast monolayers. HCMV was isolated from 26 of 83 PMN samples examined: of these, 25 were also positive for HCMV IEA (96% sensitivity). Seven additional PMN samples negative for viral isolation resulted IEA-positive (87.7% specificity). Six of the seven discordant samples were taken from four patients during ganciclovir treatment. The transitory dissociation between positive HCMV antigenemia and negative viremia during antiviral treatment was followed, at the end of the therapy, either by virus clearance and disappearance of IEA-positive PMNs (one patient) or by reappearance of viremia (three patients). Among concordant positive samples, a significant correlation was observed between the number of IEA-positive PMN leukocytes and EA-positive nuclei of infected fibroblasts, when the same number of PMNs were used for both tests.

Acquired Immunodeficiency Syndrome↗

Clinical safety and efficacy of ofloxacin.

In this study we report about the efficacy and tolerability of ofloxacin in the treatment of 15 patients with severe and moderately severe infections including osteomyelitis (5), soft tissue infections (5), salmonellosis in AIDS patients (2), acute or chronic pulmonary infections (2) and mediastinitis (1). The following organisms were isolated in culture specimens: Staphylococcus aureus (4), Pseudomonas aeruginosa (4), Staphylococcus epidermidis (3), Serratia marcescens (1), Escherichia coli (1), Aeromonas hydrophila (1), Klebsiella oxytoca (1), Klebsiella pneumoniae (1), Salmonella cholerae-suis (1), Salmonella sp. (1), Enterobacter cloacae (1). All isolates were sensitive to the drug. Of 5 cases with osteomyelitis, 2 were cured and 3 improved clinically (with bacteriological eradication of the pathogens). The best results were obtained in patients with soft tissue infections: 4 patients were cured and 1 improved. Two patients with salmonella bacteremia and AIDS experienced a recurrence 1 month and 2 months respectively after stopping therapy. The patient with mediastinitis was successfully treated. Improvement was recorded for 2 patients with bronchiectasis and exacerbation of chronic bronchitis. The drug was well tolerated, only one episode of mild nausea and vomiting was reported and did not require discontinuation of the therapy. The study indicates that ofloxacin is a safe and effective agent in the treatment of various infections.

Adult↗