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Biomedical subjects

P Grossi

Publications and source records attributed to P Grossi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Rising levels of human cytomegalovirus (HCMV) antigenemia during initial antiviral treatment of solid-organ transplant recipients with primary HCMV infection.

In 7 of 18 solid-organ transplant recipients with primary human cytomegalovirus (HCMV) infection, HCMV antigenemia levels were unexpectedly found to rise significantly (P = 0.018) during a mean time of 7.3 +/- 3.2 days after initiation of specific antiviral treatment, whereas corresponding levels of viremia dropped significantly (P = 0.043). Thus, shifting to an alternative antiviral drug based solely on increasing antigenemia levels is not justified in this group of patients.

Adolescent↗
PubMed1997

Sanfetrinem and sanfetrinem-cilexetil: disposition in rat and dog.

1. The absorption, distribution, metabolism and excretion of sanfetrinem have been investigated in the rat and dog after intravenous (i.v.) administration of the radiolabelled parent compound, and oral dosing of the hexetil ester prodrug, 14C-sanfetrinem-cilexetil. 2. Sanfetrinem-cilexetil was rapidly absorbed and hydrolysed pre-systemically to sanfetrinem. The oral bioavailability was 32% in rat and 15% in dog. 3. Drug-related radioactivity was distributed in all tissues with high levels present in bladder, kidney and liver. The volume of distribution was approximately that of extracellular fluid. There was no indication of any significant binding or retention to any tissues, including those containing melanin. 4. Protein binding of sanfetrinem determined in rat and dog plasma was constant over a wide range of concentrations equivalent to 14-18% in dog and about 67% in rat plasma. 5. Two metabolites were identified in urine after i.v. administration: the open beta-lactam ring derivative (GV173923) and the dimeric compound (GV196359). 6. After i.v. dosing the terminal half-life of the unchanged drug was 12 min in rat and 35 min in dog. The half-life of the total radioactivity was longer due to low levels of metabolites. Of the dose, > 90% was excreted in the urine both in rat and dog, and 69% of the dose was excreted as unchanged sanfetrinem in rat urine. The radioactivity excreted in the bile accounted for 3-7% of the dose.

Absorption↗
PubMed1997

Factors increasing the risk of allograft vascular disease in heart transplant recipients.

Allograft vascular disease is the major cause of late cardiac graft failure. A multifactorial etiopathogenesis is supposed. Our study investigated factors associated with allograft vascular disease occurrence. After stratifying our series on the basis of potential risk factors, we calculated allograft vascular disease incidence rate in 267 grafts from 258 patients who underwent transplant between November 1985 and August 1996. Chi-square test was used for the identification of univariate risk factors to be included in a multivariate model. Multivariate analysis was based on a Poisson model. Seventy of the 267 grafts (26.2%) were diagnosed with allograft vascular disease. Heart disease other than idiopathic dilated cardiomyopathy, donor's age, number of mismatches for HLA-B = 2, presence of systo-diastolic hypertension, number of acute rejection positive endomyocardial biopsies > or = 7 and the association of human Cytomegalovirus and hepatitis C virus infections proved to be univariate risk factors, and were included in the Poisson multivariate model. The association of Cytomegalovirus and hepatitis C infections multiplied allograft vascular disease incidence rate by 3.9, systo-diastolic hypertension by 2.2, occurrence of 2 HLA-B mismatches by 2, a high number (> or = 7) of acute rejection positive-endomyocardial biopsies by 1.8, and heart disease other than idiopathic dilated cardiomyopathy by 1.8. The association of human Cytomegalovirus and hepatitis C virus infections, of HLA-B mismatches, of acute rejection-positive endomyocardial biopsies, as well as post-transplantation hypertension and native heart disease other than idiopathic dilated cardiomyopathy, proved to be positively associated with an increased risk of allograft vascular disease. Given the concordance of our data with those of numerous prior series, we are going to adopt a special surveillance angiographic protocol for patients with these factors.

Adolescent↗
PubMed1997

FK506 effectiveness in reducing acute rejection after heart transplantation: a prospective randomized study.

BACKGROUND: Tacrolimus (FK506) has recently become available clinically as an alternative to cyclosporine-based immunosuppression. This study reports the middle-term results of a prospective, randomized trial that compared FK506 with cyclosporine-based immunosuppression in heart transplant recipients. METHODS: Twenty-five consecutive patients were randomized at a 2:1 ratio into two groups, one of which received FK506 (15 patients), the other cyclosporine (10 patients). Both groups received similar concomitant immunosuppression. The patients were followed up for 12 months. The following outcome parameters were analyzed: survival, rejection and infection rate, lymphocyte subsets, new-onset diabetes, renal and hepatic function, hypertension, right-sided heart catheterization data, graft coronary artery disease, and neurologic side effects. RESULTS: The mortality rate (two patients) in the FK506 group was 13% versus 0% in the cyclosporine group (p = NS). The two deaths were the consequences of early infections and higher doses of FK506. From the outset, the FK506 group presented a lower prevalence of acute rejection, a lower requirement for rejection treatments and a higher incidence of infections. Accordingly, we reduced overall immunosuppression for the last seven patients in the FK506 group; the decrease in FK506 and prednisone dosage led to a decrease in the early infection rate without an increase in the rejection rate. There was no difference between the two groups in diabetes incidence, renal and hepatic function, right-sided heart catheterization data, or coronary angiograms. Hypertension was less frequent and milder in the FK506 group. CONCLUSIONS: This experience suggests that FK506 can be safely used in heart transplantation. It can decrease the frequency of rejection episodes. Low-dose administration allows a lower infection rate without an increase in rejection. With a protocol of delayed starting and low dosing, side effects such as renal toxicity, hypertension, and neurologic toxicity seem to be unlikely. Further studies are needed to establish the exact dosage and therapeutic levels of the drug.

Acute Disease↗
PubMed1996

Human cytomegalovirus early infection, acute rejection, and major histocompatibility class II expression in transplanted lung. Molecular, immunocytochemical, and histopathologic investigations.

The present study aimed to investigate the relationship between acute rejection and human cytomegalovirus (HCMV) infection, as well as the coexpression of HLA-DR and immediate-early (IE) viral antigens, in 143 transbronchial biopsies and bronchoalveolar lavage fluids of 32 lung transplant recipients. We investigated the occurrence of morphologically overt viral infection with conventional histopathology, the expression of IE antigens with single labeling immunohistochemistry, the coexpression of IE antigens and HLA-DR molecules with double labeling techniques, and the presence of viral IE genes with polymerase chain reaction. Histopathologic study showed overt viral infections (12.6%) in 18 of the 143 biopsies; 8 were in a context of pneumonia and 10 were localizations without surrounding inflammatory cells; immunohistochemistry showed IE viral antigen expression in 31 (21.67%); PCR detected viral IE genes in 73/143 lavage fluids and biopsies (51%). The double labeling immunohistochemical technique showed that most IE antigen-expressing, noncytopathic cells were either HLA-DR negative in areas without infiltrates, or HLA-DR positive in those areas where inflammatory infiltrates were consistent, in the absence of viral cytopathy, with acute rejection. The results indicate that, in transplanted lung, the frequency of morphologically occult HCMV infection (as detected by immunohistochemically and/or PCR) is much higher than that of morphologically overt viral infection. The occurrence of inflammatory infiltrates (consistent with acute rejection) around morphologically occult infected cells and the possible lack of inflammation around both early- and late-infected cells suggest that in biopsies with occult infection the infiltrates should be attributed to allograft reaction. This conclusion would be in keeping with the coexpression of HLA-DR and HCMV IE in infiltrate-rich biopsies that are consistent with acute rejection, as well as with the absence of HLA-DR expression in IE antigen-positive cells in infiltrate-free-areas.

Acute Disease↗
PubMed1996

Time to detection of cytomegalovirus (CMV) DNA in blood leukocytes is a predictor for the development of CMV disease in CMV-seronegative recipients of allografts from CMV-seropositive donors following liver transplantation.

In 35 cytomegalovirus (CMV)-seronegative recipients of livers from CMV-seropositive donors, 32 (91%) developed CMV infection and 24 of them (75%) experienced disease. Polymerase chain reaction for CMV DNA in leukocytes had the best positive and negative predictive values for the development of disease within 2 months from transplantation, and shell-vial or tube culture viremia was the best predictor thereafter. In patients who developed CMV disease, CMV DNA was first detected at 46 days (median; range, 13-128) after transplantation, significantly earlier than the 77 days (range, 46-174) for those who did not develop CMV disease (P = .02). By a semiquantitative method, the CMV DNA level in the first positive sample did not predict disease development. However, the maximum CMV DNA level during infection was significantly higher in patients who developed CMV disease. In CMV-seronegative recipients of livers from CMV-seropositive donors, the time to DNA positivity following transplantation may predict disease progression and be useful as a guide for the initiation of preemptive therapy.

Antibodies, Viral↗
PubMed1996

Digital pressure during interscalene block is clinically ineffective in preventing anesthetic spread to the cervical plexus.

The application of digital pressure above the injection site during interscalene block has been advocated to prevent cephalad spread of local anesthetic. In prior studies, radiographs taken immediately after interscalene injection of radiographic contrast have supported this concept. However, the clinical efficacy of digital pressure has not been previously tested. If digital pressure were effective in inhibiting cephalad spread of local anesthetic, attenuation of both hemidiaphragmatic paresis and the resulting compromise in pulmonary function would be expected. Sensory, motor, and pulmonary effects were prospectively evaluated in 20 patients presenting for elective shoulder surgery. Patients were randomly assigned to receive interscalene block with or without digital pressure. No clinical differences were seen between groups. All 20 patients had ipsilateral hemidiaphragmatic paresis by ultrasonographic evaluation and large mean decreases in forced vital capacity, 31.2% +/- 7.8% (with digital pressure), 33.7% +/- 12.8% (without digital pressure), and forced expiratory volume at one second, 27.9% +/- 9.3% (with digital pressure), 33.7 +/- 12.8% (without digital pressure). Peak sensory level of anesthesia to pinprick was not significantly different between groups, each group having mean levels of C-2 to C-3. Digital pressure was ineffective in limiting the flow of local anesthetic into the cervical plexus. Digital pressure influenced neither the incidence of diaphragmatic paresis nor the resulting large decreases in pulmonary function that result from interscalene block.

Adolescent↗
PubMed1996

Prognostic determinants of six-month morbidity and mortality in heart transplant recipients. The Italian Study Group on Infection in Heart Transplantation.

BACKGROUND: Knowledge of time course and risk factors for morbidity and mortality may allow better cardiac graft allocation, surveillance timing, and planning of immunosuppressive strategies. METHODS: Six-month morbidity and mortality were retrospectively analyzed in a multiinstitutional series of 645 heart transplant recipients. RESULTS: During a 3432 patient-months follow-up, 87 patients died of infection (n = 11), rejection (n = 11), multiorgan failure (n = 9) and other transplant-related causes (n = 56); six-month survival rate was 86%. Three hundred thirty-seven recipients had 967 treated rejection episodes (2.87 episodes/patient with rejection, lethality 3.2%); 223 major infectious episodes occurred in 162 patients (1.38 episodes/infected patient, lethality 7%). Six-month rejection and infection-free survival rates were 44% and 73%. Total mortality and cause-specific morbidity sharply declined after the first month; 160 patients (25%) had no events during follow-up. At multivariable analysis, significant risk factors for mortality were postoperative acute kidney failure, prolonged cardiopulmonary bypass time, and previous cardiac surgery. Rejection was associated with steroid-free and globulin-free immunosuppression and infection was associated with steroid immunosuppression, cytolytic treatment, venous lines placement greater than 7 days, and mechanical ventilation time. No single or combination of variables was able to discriminate patients with an event-free course. CONCLUSIONS: Morbidity and mortality have the highest incidence during the early posttransplantation phase. Preoperative variables are of limited value with respect to immunosuppressive treatment in predicting outcome. Infection is far less frequent than rejection but, in view of the higher lethality rate, deserves a vigorous effort for prevention, which is best addressed by appropriate modulation of immunosuppressive strategies.

Adult↗
PubMed1995

Clinical and virological monitoring of human cytomegalovirus infection in 294 heart transplant recipients.

Two hundred and ninety-four heart transplant recipients (HTR) were followed prospectively for a mean of 44.9 +/- 28.4 (range 1.0-100.8 months) after transplantation (tx). Immunosuppression was based on cyclosporine, azathioprine, and steroids, supplemented by a 7-day course of antithymocyte globulins. All patients were virologically monitored by inoculating aliquots of 2 x 10(5) peripheral blood polymorphonuclear leukocytes (PMNs) onto human embryonic lung fibroblasts monolayers grown in shell vials for early cytomegalovirus (CMV) identification and quantification (viremia). The same number of PMNs was cytocentrifuged onto glass slides for direct CMV pp65 antigen detection and quantification (antigenemia). Heparinized blood samples were collected weekly during the first 3 months following tx and at least twice a week if antigenemia and viremia levels were increasing. After 3 months, samples were collected if antigenemia and viremia persisted or when clinically indicated. The overall incidence of CMV infection was 53.4% (157/294). Only 32.4% (51/157) of the viremic patients required antiviral treatment because of symptomatic infection. Of the remaining 106 untreated CMV viremic HTR, 104 were asymptomatic while 2 had only mild clinical symptoms. The overall incidence of CMV infection in pre-tx CMV seropositive (CMV+) HTR was 50.9% (136/267); 75.7% (103/136) were asymptomatic and 24.3% (33/267); 75.7% (103/136) were asymptomatic and 24.3% (33/136) were symptomatic. The overall incidence of CMV infection in pre-tx CMV-seronegative (CMV-) HTR was 77.8% (21/27; P = 0.007 vs. seropositive HTR). Among 22 CMV- HTR with CMV+ donor, 20 (90.9%) had a CMV infection and all of them were symptomatic (versus 1 of 5 (20%) CMV- HTR with CMV- donor; P = 0.002, Fisher's exact test). The median numbers of circulating CMV-infected PMNs detected at the onset of clinical symptoms by the antigenemia and viremia assays were 385/2 x 10(5) and 100/2 x 10(5), respectively.

Adolescent↗
PubMed1995

Qualitative analysis of potential metabolites and degradation products of a new antiinfective drug in rat urine, using HPLC with radiochemical detection and HPLC-mass spectrometry.

High-performance liquid chromatography (HPLC) was used in combination with radioactivity detection and mass spectrometry (MS) to elucidate the metabolic fate of GV104326, a novel tricyclic beta-lactam antibacterial agent. Metabolic profiles were obtained by analysis of rat urine samples collected after intravenous administration of the 14C-labelled drug at the dose of 50 mg kg-1 (12.95 MBq kg-1). Methods for solid-phase extraction from urine samples and for reversed-phase chromatographic separation of drug related material were developed. HPLC-MS was used to confirm that the parent compound corresponded to the principal peak in the chromatograms, and two minor peaks were identified as potential metabolites of GV104326. They were shown to be an open beta-lactam ring derivative (GV173923) and a dimeric compound (GV196359).

Animals↗
PubMed1995

Frequency of provirus-bearing CD4+ cells in HIV type 1 infection correlates with extent of in vitro apoptosis of CD8+ but not of CD4+ cells.

Lymphocytes from HIV-1-infected subjects undergo massive apoptosis when cultured in vitro, and this phenomenon might reflect pathogenetic mechanisms leading to immune dysfunction in vivo. However, (1) lymphocyte death is not restricted to CD4+ cells but seems to involve predominantly CD8+ cells, and (2) the same phenomenon occurs in other viral infections. Furthermore, it is not known whether a relationship exists between the HIV-1 burden and this type of cell death. In this work we sought to determine whether the HIV-1 provirus load correlates with the propensity to apoptosis of CD4+ and CD8+ cells. We studied 10 HIV-1-infected patients with CD4+ cell counts above 500/mm3 and free of concomitant infections. We correlated the frequency of HIV-1-infected CD4+ cells with the extent of culture-induced apoptosis as well as with the phenotype of the apoptotic lymphocytes. We found that the magnitude of apoptosis correlated with the frequency of HIV-1-infected CD4+ cells (p = 0.0007), and that increasing viral load and apoptosis were associated with a shift to the selective death of CD8+ cells. Our data support the view that, in addition to CD4+ cell killing, another immunopathogenic effect of HIV might be that of priming CD8+ cells to apoptosis. In vivo, this could eventually lead to the exhaustion of the cytotoxic T cell compartment.

Adult↗
PubMed1995

Use of AIDS surveillance data to describe subepidemic dynamics.

BACKGROUND: Official reports on AIDS surveillance mainly consist of absolute numbers of AIDS cases or cumulative incidence rates. More detailed analyses focusing on the clusters of subepidemics within Italy seemed necessary for a better understanding and more accurate description of the epidemic. METHODS: Age-specific AIDS incidence rates were calculated with reference to resident population by sex, calendar time and geographical area. Age-standardized incidence rates, with the Italian resident population in 1990 as standard, were used to present time trends and geographical distributions. All analyses were repeated for injecting drug users, homosexual/bisexual men, heterosexual contacts and individuals with other or undetermined risk factors. RESULTS: Annual incidence rates for AIDS in Italy increased over the study period. The highest rates were observed in the North and in Sardinia, while Southern regions showed generally lower rates. This heterogeneity was more evident when examining small geographical areas (i.e. provinces). Epidemics in some of the smaller provinces, such as Imperia and Livorno (Northwestern port towns), were shown to be important in that they greatly affect AIDS incidence rates in the regions in which they are located. CONCLUSIONS: According to our analysis, the crude presentation of data from the Italian AIDS Registry is not adequate for understanding the national spread of the AIDS epidemic in terms of several local subepidemics, which may differ by size, temporal trend, and risk group composition. Classifying cases according to their place of residence, which we considered as a good proxy of the place of life, was fundamental for correctly locating these subepidemics. Furthermore, the use of age-standardized rates allowed for unbiased comparisons between regions whose population may have a different age structure and dynamics.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Relationship between eating patterns meeting recommendations and subsequent mortality in 20 years.

OBJECTIVE: Study of the relationships of conformity to dietary recommendations and subsequent rates of total mortality and mortality from specific causes. DESIGN: Prospective investigation of risk factors related to cardiovascular disease. SETTING: Two Italian rural cohorts of the Seven Countries Study. SUBJECTS: The study populations are defined samples from two villages, Crevalcore in Northern Italy and Montegiorgio in Central Italy. The examination in 1965, which included an individual dietary survey, involved 1538 men aged 45-64 years. The 20-year follow-up system was able to track every participant. RESULTS: Conformity to recommended levels of intake of carbohydrates (55-75% of calories) is associated to the relative risks: 0.84 (0.68-1.03) for total mortality, 0.73 (0.50-1.07) for cancer mortality, 1.34 (0.90-1.99) for coronary heart disease mortality. Relative risks for other nutrients are reported. CONCLUSIONS: Overall, recommended levels of intake of macronutrients are associated with lower total mortality, but are not equally appropriate for specific causes of death, cancer and coronary heart disease. Diet-associated differences in mortality persisted after adjustment for confounding by age, smoking habit and physical activity. In this population, intakes meeting the principal recommendations (total carbohydrate and total fat) seem to involve automatically meeting the other recommendations. SPONSORSHIP: Research partly supported by the project 'ACRO-clinical uses of Oncological Research' (contract 93.02289.PF39) and by the project 'FATMA-Risk Factors and Disease Control' (contract 93.00773.PF41) of the Italian National Research Council, CNR.

Adult↗