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Biomedical subjects

M Pecorari

Publications and source records attributed to M Pecorari.

At least 19 recordsLinked to original sources

Pharmacokinetic interaction between Amprenavir/Ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation.

The pharmacokinetic interaction between highly active antiretroviral therapy (HAART) and immunosuppressive drugs is a critical element in the management of patients with human immunodeficiency virus infection who undergo orthotopic liver transplantation (OLT). We describe the effect of the coadministration of Amprenavir/Ritonavir (APV/r) and FosAmprenavir (FosAPV) on cyclosporine (CsA) concentrations in two patients receiving OLT for end-stage liver disease due to hepatitis C Virus. Patient 1, who was maintained on 300 mg CsA twice a day with a trough concentration (C(trough)) around 250 ng/mL, restarted HAART 12 days after transplantation with 300 mg APV/r twice a day with corresponding APV C(trough) of 5293 ng/mL and RTV C(trough) of 186 ng/mL. Forty-eight hours after initiation of HAART, C(trough) of CsA was 1200 mg/mL, so it was necessary to reduce the CsA dosage 12-fold (50 mg every day) to achieve a therapeutic effect. In Patient 2, who was maintained on 300 mg CsA twice a day and a corresponding C(trough) of 400 ng/mL, HAART was restarted 12 days post-OLT with FosAPV 1400 mg twice a day. After 48 hours C(trough) of CsA was around 600 ng/mL and C(trough) of FosAPV, 1221 ng/mL. In this case it was necessary to reduce the CsA administration 3.5-fold (175 mg every day). In conclusion, therapeutic drug monitoring was necessary to monitor HAART and CsA post-OLT to prevent toxicity due to both therapies. The use of FosAPV without ritonavir boostering is sufficient to maintain adequate CsA blood concentrations, avoiding any event of toxicity.

Adult↗

A simultaneous outbreak of Serratia marcescens and Klebsiella pneumoniae in a neonatal intensive care unit.

We describe two concurrent outbreaks of Serratia marcescens and Klebsiella pneumoniae in a neonatal intensive care unit (NICU). Over a 16-month period, a total of 27 infants were either colonized (N=14) or infected (N=13). There were 15 cases of S. marcescens and 11 cases of K. pneumoniae. Both micro-organisms were involved in one fatal case. Seven preterm babies developed septicaemia, two had bacteraemia, three had respiratory infections and one had purulent conjunctivitis. The S. marcescens and K. pneumoniae isolates were investigated by three molecular methods: enterobacterial repetitive intergenic consensus polymerase chain reaction (PCR), arbitrary primed PCR with M13 primer, and random amplification of polymorphic DNA. Different patterns were found in the 16 S. marcescens epidemic isolates from 16 newborn infants. The major epidemic-involved genotype was linked to the first nine cases and this was subsequently replaced by different patterns. Eight different typing profiles were also determined for the 13 K. pneumoniae isolates from 12 newborn infants. Four K. pneumoniae bacteraemic strains proved to be identical. In conclusion, the typing results revealed that two different micro-organisms (S. marcescens and K. pneumoniae) were simultaneously involved in invasive nosocomial infections in preterm newborns. Two simultaneous clusters of cases were documented. Heterogeneous genotypes among both species were also demonstrated to be present in the NICU at the same time. A focal source for both micro-organisms was not identified but cross-transmission through handling was probably an important route in this outbreak. Strict adherence to handwashing policies, cohorting, isolation of colonized and infected patients, and rigorous environmental hygiene were crucial measures in the containment of the epidemic.

Bacteremia↗

Fatal cytomegalovirus necrotising enteritis in a small bowel transplantation adult recipient with low pp65 antigenaemia levels.

Although advances in immunosuppressive therapy have led to increased survival of solid organ transplantation recipients, it is well established that current protocols have been associated with an increased risk of developing tissue-invasive infections. In particular, cytomegalovirus still represents an important cause of morbidity. We report a case of cytomegalovirus infection involving the graft ileum with documented necrotising enteritis that developed after small bowel transplantation. The patient, a 56-year-old Caucasian female with a postsurgery short bowel syndrome, underwent a small bowel transplantation. Immunosuppression was maintained by combination of tacrolimus, steroids and daclizumab. Both the donor and the recipient were serologically negative for cytomegalovirus IgG. Nevertheless, ganciclovir prophylaxis was given for 21 days after surgery, as standard procedure. On hospital day 174, routine pp65 antigenaemia resulted positive (14/200,000 peripheral blood leukocytes). The patient was asymptomatic and preemptive ganciclovir therapy was instituted. In the following 3 days, due to a cytomegalovirus antigenaemia increase, ganciclovir was changed to foscarnet with subsequent virological response (7/200,000 peripheral blood leukocytes, on day 181). Two days later, the patient complained of acute abdominal pain and she underwent surgery for the diagnosis. Since the intraoperative findings consisted of a diffuse acute purulent peritonitis, the intestinal graft, together with native rectum, was removed. Biopsy specimens showed evidence of tissue-invasive cytomegalovirus infection. Postsurgery, the patient developed septic shock and died on day 198 as a consequence of multiple organ failure.

Aged↗

Outcome, incidence, and timing of infections in small bowel/multivisceral transplantation.

The objective of this study was to assess the timing, incidence, and outcome of infections in patients with small bowel/multivisceral transplants (SB/MV Tx). A 180-day follow-up was obtained on 13 SB/MV patients transplanted from January 2001 to June 2002. Fifty-six documented infections were observed. By Kaplan-Meier analysis for time to infection, most of which were of bacterial origin (more than 86%), revealed most events to have occurred within the first month post-Tx. Viral infections were equally distributed after the 30th postoperative day.

Adult↗

Search for viruses in the CSF of patients with acute neurological disorders: possible involvement of beta-and gamma-herpesviruses.

In the years 1999-2001, 868 samples of cerebrospinal fluid (CSF) from as many patients with acute neurological manifestations of suspected viral origin were analysed for the presence of viruses at the Centre for the Diagnosis of Viral Diseases of the University of Modena and Reggio Emilia. Neurological patients included 788 immunocompetent subjects and 80 patients with impaired immunity due to human immunodeficiency virus (HIV) seropositivity. Of the CSF samples, 125 (15.8%) were positive for one or more viruses among the immunocompetent patients, whereas 33 (41.1%) were positive among the HIV cohort. DNA and RNA viruses were detected in the first group of CSF samples whereas only DNA viruses were found in the second group. In immunocompetent patients the frequency of enteroviruses prevailed over that of other RNA virus families (p = 0.001) and that of herpesviruses over the frequency of other DNA virus families (p = 0.001). Among herpesvirus members, the Epstein-Barr gamma-herpesvirus prevailed on alpha-herpesviruses in each of the two groups of patients (p = 0.05 in the immunocompetent group and p = 0.006 in HIV-positive patients). The clinical relevance both of this virus and of beta-herpesviruses as a cause of neurological disorders is discussed.

Alphaherpesvirinae↗

Severe encephalopathy associated with reactivated human herpesvirus 6 in a six year-old immunocompetent child.

When a six year-old immunocompetent child affected by encephalitis was subjected to virological studies, human herpesvirus 6 variant B2 resulted to be the cause of illness. Laboratory diagnosis based on the finding of human herpesvirus 6 genome in the cerebrospinal fluid of the patient both at the beginning of the disease and on the occasion of a relapse which occurred forty days after the patient's hospital discharge. The presence of high-avidity IgG to human herpesvirus 6 detected in the patient's serum at the time of the first hospital admission proved that he had suffered from a past infection by human herpesvirus 6. In the consequence of this, the human herpesvirus 6 DNA finding in the patient's cerebrospinal fluid was to ascribed to virus reactivation. In the light of virological and serological results, the clinical case described underlines the ability of human herpesvirus 6 to cause neurological disorders not only during primary infections but also during infections supported by rescued virus.

Child↗

Symptomatic infections by toscana virus in the Modena province in the triennium 1999-2001.

We report nine cases of clinical manifestations by Toscana virus (TOSV) diagnosed at the Centre for the Diagnosis of Viral Diseases of the University of Modena and Reggio Emilia, in the inhabitants of Modena province (Emilia Romagna region), in the triennium 1999-2001. TOSV was involved in six cases of meningitis, two of meningoencephalitis and one case of febrile erythema without meningeal manifestations. Six TOSV-infected patients had stayed for a few days in a different area of the Tuscany region before the onset of clinical manifestations so, only three cases of infections by TOSV had an autochthonous origin.

Humans↗

Effects of the CSN1A(G) allele on the clotting time of cow milk and on the rheological properties of rennet-curd.

The aim of this research was to study the effects of the CSN1A(G) allele on the main rennet coagulation properties of milk. The study was carried out on individual milk samples with low alphas1-casein obtained from 19 Italian Brown cows heterozygous for the CSN1A(G) allele (seventeen CSN1A BG and two CSN1A CG) from four herds in the province of Parma (Italy). Control cows (sixteen CSN1A BB and three CSN1A BC) giving milk with normal alphas1-casein levels were chosen from within the same herds in order to establish pairs of cows with identical environment and management conditions, and comparable lactation stages and numbers. Individual milk samples from single pairs of cows with somatic cell counts and lactose and chloride levels within the normal ranges were collected and analysed in parallel. Rennet coagulation properties of milk were analysed using Formagraph and Gel Tester. Milk from low alphas1-casein cows was characterized by lower casein content, lower titratable acidity and a higher proportion of kappa-casein in total casein. The clotting time of this milk was approximately 23% lower than that obtained with milk from normal alphas1-casein cows. Rennet curd from low alphas1-casein milk was obtained more rapidly and had a higher final firmness: curd-firming time was approximately 35% lower and curd firmness measured 30 min after rennet addition was approximately 27% higher compared with that for normal alphas1-casein milk. In addition, curd from low alphas1-casein milk had a higher resistance to compression. These results suggest that, although a role for the CSN2 locus cannot be definitely excluded, the CSN1A(G) allele can considerably affect the main rennet coagulation properties of milk.

Alleles↗

Outbreak of aseptic meningitis by echo 4: prevalence of clinical cases among adults.

Twenty five cases of meningitis occurred in urban areas surrounding a city (Modena) in Northern Italy, in the period May-July 1999. When the patients were admitted to the Infectious Diseases Division of the University of Modena and Reggio Emilia Hospital and studied by virological and serological methods, the meningitis proved to have an enteroviral origin and enterovirus ECHO 4 type was responsible for all cases of illness. An epidemiological characteristic of the enteroviral meninigitis outbreak was the adult age in 23 out of the 25 patients (mean age 24.50 +/- 7.84 years). The monthly distribution of the aseptic meningitis cases was the following: five cases occurred in May, 13 in June and seven in July. The origin of the spread of the virus infection and the reason for its sudden end remained unknown. The unusual drop in temperature which occurred in the geographic area involved in the aseptic meningitis outbreak at the beginning of August could have interfered with the slowdown in virus circulation.

Adolescent↗

Case of fatal encephalitis by HHV-6 variant A.

A fatal case is reported of encephalitis in an 85-year-old man caused by the human herpesvirus 6 variant A. The virological diagnosis was based on the findings of the virus variant genomic sequences both in the cerebrospinal fluid and serum of the patient. Moreover, virus replication in nervous tissue was suggested by a viral load higher in the cerebrospinal fluid than in the peripheral blood. The association of a central nervous system infection with the A variant of human herpesvirus 6 is interesting because of the difficulty in establishing a pathological role for this virus strain. Epstein-Barr virus DNA was detected in the patient's cerebrospinal fluid in association with human herpesvirus 6 DNA. The presence of the Epstein-Barr virus genomic sequences in the cerebro-spinal fluid was considered to be unimportant clinically.

Aged↗

Detection of Epstein-Barr virus DNA in cerebrospinal fluid from immunocompetent individuals with brain disorders.

Fifty four cerebrospinal fluid samples obtained from as many immunocomponent patients with disorders of the central nervous system were investigated for the presence of herpesvirus DNA by nested polymerase chain reaction in order to determine an etiological diagnosis. Four of these samples proved positive for the presence of Epstein-Barr virus DNA (7.4%). The result of this diagnostic study is reported to draw insiders' attention to the possible presence of EBV in cerebrospinal fluid from patients with central nervous system diseases.

Adult↗

Relevance of clinical and laboratory findings in the diagnosis of cytomegalovirus encephalitis in patients with AIDS.

A retrospective evaluation was conducted in patients with AIDS and an autopsy diagnosis of cytomegalovirus (CMV) encephalitis to determine the relevance of clinical and laboratory findings in establishing a diagnosis. On autopsy of 100 patients, CMV encephalitis was diagnosed in 13 patients; eight had periventricular CMV encephalitis, four micronodular CMV encephalitis, and one both conditions. Seven patients had had a CMV infection previously (6 cases of retinitis, 1 case of colitis), and at the onset of encephalitis all of them were receiving a maintenance dose of ganciclovir. Examination of the CSF showed specific changes in patients with periventricular encephalitis. CT revealed no characteristic findings, while MRI showed an increased signal intensity on T2 weighted images. CMV DNA amplification by nested PCR was performed in nine patients with CMV encephalitis; PCR was positive in eight patients whose CSF was collected during CMV encephalitis, and negative in one patient whose CSF was collected six months before death. In conclusion, some clinical findings suggest a presumptive diagnosis, especially of periventricular encephalitis, and nested PCR appears to be a reliable and rapid technique for making an antemortem diagnosis.

AIDS-Related Opportunistic Infections↗

Phenotypic characteristics and tendency to apoptosis of peripheral blood mononuclear cells from HIV+ long term non progressors.

The aim of this study was to analyze (i) phenotype, (ii) in vitro spontaneous and induced apoptosis, (iii) glutathione (GSH) intracellular content and (iv) inhibitors of apoptosis of potential therapeutical use in peripheral blood mononuclear cells (PBMC) from HIV+ long term non progressors (LTNP), in comparison with progressors (HIV+P) and seronegative controls (HIV-). Three groups of subjects were studied: 15 HIV+P (patients losing >150 CD4+/year), 9 LTNP (subjects infected by HIV for at least 7 years without clinical and immunological signs of progression, with a mean of 898 CD4+/microL) and 18 HIV-. All subjects were living in a large community for former drug addicts, and were matched for age and sex. We used flow cytometry for analyzing PBMC phenotype and apoptosis; high performance liquid chromatography for measuring intracellular GSH content. PBMC phenotype of LTNP shared characteristics with those of both HIV- and HIV+P. Indeed, LTNP showed a normal number CD4+ cells (an inclusion criteria), but significantly increased numbers of CD8+ lymphocytes, activated T cells, CD19+, CD5+ B lymphocytes and CD57+ cells, as well as a decrease in CD19+, CD5- B lymphocytes and CD16+ cells. In LTNP, spontaneous apoptosis was similar to that of HIV- and significantly lower than that of HIV+P. Adding interleukin-2 (IL-2) or nicotinamide (NAM) significantly decreased spontaneous apoptosis in LTNP and HIV+P. Pokeweed mitogen-induced apoptosis was also similar in LTNP and HIV-, but significantly lower than that of HIV+P. In HIV+P, but also in LTNP, spontaneous apoptosis was inversely correlated to the absolute number and percentage of CD4+ cells and directly correlated to the number and percentage of activated T cells present in peripheral blood. GSH intracellular content was greatly decreased in PBMC from HIV+P and slightly, but significantly, reduced in LTNP. Adding 2-deoxy-D-ribose, an agent provoking apoptosis through GSH depletion, to quiescent PBMC resulted in similar levels of massive cell death in the three groups. This phenomenon was equally prevented in the three groups by N-acetyl-cysteine but not by IL-2. A complex immunological situation seems to occur in LTNP. Indeed, PBMC from LTNP are characterized by a normal in vitro tendency to undergo apoptosis despite the presence of a strong activation of their immune system, unexpectedly similar to that of HIV+P. Our data suggest that NAM and IL-2 are possible candidates for reducing spontaneous apoptosis in HIV infection.

Journal Article↗

Search for herpesvirus DNA in cerebrospinal fluid of HIV patients with brain disorders: prevalence of cytomegalovirus DNA findings.

A study was carried out to search for the presence of the seven human herpesvirus DNAs in cerebrospinal fluid from 52 human immunodeficiency virus-infected patients with brain disorders. Cytomegalovirus DNA was the most prevalent with 12 positive samples; Epstein-Barr virus and varicellazoster DNAs were detected in three and two samples, respectively, while no sample was positive for the DNA of the other herpesviruses.

AIDS Dementia Complex↗

SupT-1: a cell system suitable for an efficient propagation of both HHV-7 and HHV-6 variants A and B.

HHV-7 growth on Sup-T1, an immature T-cell line, was studied using different HHV-7 isolates obtained in our laboratory. Titration of viral yields showed that all the virus isolates propagate on this cell line more efficiently than in cord blood lymphocytes, the cells usually recommended for HHV-7 growth. The permissivity of Sup-T1 to HHV-6, whose ability to replicate in these cells was still unknown, was also investigated using two virus isolates representative of variants A and B respectively. Both isolates were able to propagate on Sup-T1 and viral titres were similar to those obtained in cord blood lymphocytes. As the efficient propagation of both HHV-7 and HHV-6 isolates in Sup-T1 cultures, these cells may replace more time consuming and expensive cord blood lymphocyte preparations for the propagation of both the viruses.

Cell Line↗

Search for human herpesvirus 6 and human cytomegalovirus in bronchoalveolar lavage from patients with human immunodeficiency virus-1 and respiratory disorders.

Virus isolation and viral DNA detection by the polymerase chain reaction were used to investigate the presence of human herpesvirus 6 (HHV-6) and human cytomegalovirus (HCMV) in bronchoalveolar lavage from 34 human immunodeficiency virus-1 (HIV-1)-infected patients with respiratory disorders. The aim was to assess the presence of reactivated HHV-6 in lung tissues for a subsequent evaluation of the frequency of virus involvement in respiratory clinical manifestations in the course of HIV-1 infection. Bronchoalveolar lavage samples were tested for the presence of HCMV, as a routine investigation within a protocol monitoring opportunistic infections in symptomatic HIV-1 patients. Whereas HCMV DNA was detected by the polymerase chain reaction in 12 bronchoalveolar lavage specimens, 10 of which were also positive for virus isolation, all samples were negative for HHV-6 by both virological procedures. The HHV-6 DNA finding in bronchoalveolar lavage from an HIV-1-seronegative patient with renal carcinoma, investigated accidentally together with the bronchoalveolar lavage specimens from HIV-1 seropositive patients, stressed the HHV-6 polymerase chain reaction-negative results in the bronchoalveolar lavage samples under study. It is concluded that the lung may be a target organ for HCMV infection in HIV-1-seropositive patients affected by respiratory symptoms but that this does not seem to be the case for HHV-6.

Bronchoalveolar Lavage Fluid↗

Growth of human herpesvirus 6 in HEPG2 cells.

HepG2 cells, a well differentiated liver cell line, were shown to be permissive for both human herpesvirus 6 (HHV-6) A and B strains by three independent methods of analysis: detection of viral antigens, viral DNA sequences and infectious virus. HepG2 cell infection with HHV-6 resulted in functional damage as shown by the increased release in the culture medium of some hepatocyte markers. Cells surviving the acute infection were serially passaged without showing cytopathic effect, but, some months later, HHV-6 DNA was still present in the cells and virus induction with a phorbol ester was successful. A possible pathogenetic role of HHV-6 in liver diseases is discussed. Experiments of HepG2 infection with human herpesvirus 7 (HHV-7) were also carried out. The lack of an efficient virus replication suggested a difficulty for HHV-7 to infect hepatic cells.

Cells, Cultured↗