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Biomedical subjects

P Cinque

Publications and source records attributed to P Cinque.

At least 55 records · Page 3Linked to original sources
PubMed1996

JCV-DNA and BKV-DNA in the CNS tissue and CSF of AIDS patients and normal subjects. Study of 41 cases and review of the literature.

SUMMARY: We studied the distribution and localization of the human papova-viruses JCV and BKV in the central nervous system (CNS) and cerebrospinal fluid (CSF) of HIV-positive patients with and without progressive multifocal leukoencephalopathy (PML) as compared with HIV-seronegative patients. The presence of JCV-DNA and BKV-DNA was evaluated by nested polymerase chain reaction (PCR) and in situ hybridization (ISH) on CNS autopsy tissues of AIDS patients with (group A, n = 13) and without (group B, n = 16) PML and of HIV-negative patients (group C, n = 12). PCR for JCV-DNA and BKV-DNA was also performed on CSF samples collected 7-420 days before death in all the 29 AIDS patients. Tissue PCR for JCV-DNA was positive in all the cases in group A, in 44 percent of the patients in group B, and in 33 percent of the patients in group C. ISH was positive in all the cases with PML and in three AIDS cases without PML (12 percent), but negative in all the HIV-negative cases. BKV-DNA was detected in two cases from group A and in one case from group B. CSF was PCR-positive for JCV-DNA in 8 of 13 (62 percent) AIDS patients with PML, but in none of the HIV patients without PML, irrespective of the presence of JCV-DNA in CNS tissues. No CSF sample was positive for BKV-DNA. Our data demonstrates that JCV-DNA and, rarely, BKV-DNA can be detected in the CNS of immunocompromised patients with and without PML and also in the CNS of HIV-negative subjects. However, only HIV-positive patients with clinically evident PML and JCV-DNA in the brain have PCR-detectable JCV-DNA in their CSF.

AIDS-Related Opportunistic Infections↗
PubMed1996

Coinfection of the central nervous system by cytomegalovirus and herpes simplex virus type 1 or 2 in AIDS patients: autopsy study on 82 cases by immunohistochemistry and polymerase chain reaction.

We evaluated the frequency and histopathological features of concomitant infections of the central nervous system (CNS) with cytomegalovirus (CMV) and herpes simplex viruses type 1 or 2 (HSV1/2) in a large series of patients who had died from AIDS. Eighty-two autopsy cases with a histological diagnosis of CMV necrotizing encephalitis were examined retrospectively. CMV and HSV1/2 were detected by immunohistochemistry (IHC) with poly- and monoclonal antibodies and by nested polymerase chain reaction (PCR) for HSV 1 and 2 on DNA extracted from paraffin blocks. PCR for a beta-globin genomic sequence was performed in all IHC-positive cases to verify the integrity of extracted DNA. Concomitant CMV/HSV infections were demonstrated by IHC in 13 cases (16%); using monoclonal antibodies, HSV1 was found in 9 cases and HSV2 in 4 cases. In half of the cases, HSV1- or HSV2-positive cells represented more than 25% of immunopositive CMV cells. In all 13 cases, double immunochemical staining showed cells containing both CMV and HSV antigens. PCR for HSV1 and 2 was positive in only 7 of 13 cases (5 HSV1 and 2 HSV2). In the remaining 6 negative cases PCR for beta-globin was also repeatedly negative. HSV1 or 2 infection can be demonstrated by IHC in a significant proportion of AIDS cases with necrotizing CMV encephalitis. Nested PCR for HSV1 and 2 on DNA extracted from formalin-fixed and paraffin-embedded autopsy tissues was positive in only slighty above 50% of IHC-positive cases.

AIDS-Related Opportunistic Infections↗
PubMed1996

Selective elevation of monocyte chemotactic protein-1 in the cerebrospinal fluid of AIDS patients with cytomegalovirus encephalitis.

The CC chemokine monocyte chemotactic protein-1 (MCP-1) was markedly elevated in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-infected patients with cytomegalovirus (CMV) encephalitis. The MCP-1 CSF levels in CMV encephalitis were markedly higher than those in the CSF of HIV-infected patients with or without unrelated neurologic diseases, including progressive multifocal leukoencephalopathy, cryptococcal meningitis, toxoplasmic encephalitis, and primary lymphoma. Interleukin-8, RANTES, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta were not substantially increased in the CSF of CMV encephalitis patients. High levels of MCP-1 may underlie monocyte recruitment and tissue damage in CMV encephalitis and may represent a rapid and useful tool in the diagnostic armamentarium for neurologic disorders associated with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic diseases of the central nervous system in HIV-infected patients.

OBJECTIVE: To assess the diagnostic reliability of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for virus-associated opportunistic diseases of the central nervous system (CNS) in HIV-infected patients. DESIGN: CSF samples from 500 patients with HIV infection and CNS symptoms were examined by PCR. In 219 patients the PCR results were compared with CNS histological findings. METHODS: Nested PCR for detection of herpes simplex virus (HSV) type 1 or 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and JC virus (JCV) DNA. Histopathological examination of CNS tissue obtained at autopsy or on brain biopsy. RESULTS: DNA of one or more viruses was found in CSF in 181 out of 500 patients (36%; HSV-1 2%, HSV-2 1%, VZV 3%, CMV 16%, EBV 12%, HHV-6 2%, and JCV 9%). Among the 219 patients with histological CNS examination, HSV-1 or 2 was detected in CSF in all six patients (100%) with HSV infection of the CNS, CMV in 37 out of 45 (82%) with CMV infection of the CNS, EBV in 35 out of 36 (97%) with primary CNS lymphoma, JCV in 28 out of 39 (72%) with progressive multifocal leukoencephalopathy. Furthermore, HSV-1 was found in one, VZV in four, CMV in three, EBV in three, HHV-6 in seven, and JCV in one patient without histological evidence of the corresponding CNS disease. CONCLUSIONS: CSF PCR has great relevance for diagnosis of virus-related opportunistic CNS diseases in HIV-infected patients as demonstrated by its high sensitivity, specificity, and the frequency of positive findings.

AIDS-Related Opportunistic Infections↗
PubMed1996

The role of laboratory investigation in the diagnosis and management of patients with suspected herpes simplex encephalitis: a consensus report. The EU Concerted Action on Virus Meningitis and Encephalitis.

As effective therapies for the treatment of herpes simplex encephalitis (HSE) have become available, the virology laboratory has acquired a role of primary importance in the early diagnosis and clinical management of this condition. Several studies have shown that the polymerase chain reaction (PCR) of CSF for the detection of herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) DNA provides a reliable method for determining an aetiological diagnosis of HSE. The use of PCR in combination with the detection of a specific intrathecal antibody response to HSV currently represents the most reliable strategy for the diagnosis and monitoring of the treatment of adult patients with HSE. The use of these techniques has also led to the identification of atypical presentations of HSV infections of the nervous system and permits the investigation of patients who develop a relapse of encephalitic illness after an initial episode of HSE. A strategy for the optimal use of the investigative laboratory in the diagnosis of HSE and subsequent management decisions is described.

Acyclovir↗
PubMed1996

Serum polymerase chain reaction for cytomegalovirus DNA for monitoring ganciclovir treatment in AIDS patients.

The virological response to antiviral treatment of cytomegalovirus (CMV) infection in patients with AIDS can be monitored by the identification and quantification of CMV pp65 antigen in blood polymorphonuclear leukocyte cells (PMNL). To assess the value of nested polymerase chain reaction (PCR) in serum for therapy follow-up, we compared PCR and pp65 antigenemia results in 21 acquired immune deficiency syndrome (AIDS) patients with CMV infection, before and after 3 weeks of intravenous ganciclovir at standard doses. pp65 antigenemia was positive in 18/21 (86%) patients at the start of the therapy and in 2/15 (13%) at the end of therapy. CMV DNA was found in serum from 18/21 (86%) patients at the beginning of therapy and in 3/21 (14%) patients after 3 weeks of therapy. A clinical improvement was seen in 16/21 (76%) patients: 11/16 (69%) were negative by both PCR and antigenemia at the end of ganciclovir treatment. The sensitivity and specificity of serum PCR versus the antigenemia assay were 85% and 81%, respectively. Nested PCR on serum can be useful for treatment follow-up of CMV infection in patients with AIDS. It can be used where antigenemia cannot be performed and in retrospective studies.

AIDS-Related Opportunistic Infections↗
PubMed1995

Ganciclovir therapy for cytomegalovirus (CMV) infection of the central nervous system in AIDS patients: monitoring by CMV DNA detection in cerebrospinal fluid.

Seven AIDS patients with central nervous system (CNS) disease and cytomegalovirus (CMV) DNA in cerebrospinal fluid (CSF) were evaluated before and 3 weeks after standard ganciclovir treatment by nested polymerase chain reaction (PCR) on limiting dilutions and by quantitative PCR. After therapy, PCR CSF was negative for CMV in 3 patients with low baseline levels of CMV DNA and positive with decreased DNA titers in 4 patients with higher baseline levels. CMV pp65 antigen in polymorphonuclear leukocytes was found in 6 of 7 patients before therapy and in none of 5 after therapy. At autopsy, CMV was found in the CNS of the 4 cases examined, including 3 whose CSF was continuously positive by PCR. Quantitative PCR of CSF is useful for monitoring ganciclovir treatment in CMV infection of the CNS. In AIDS patients, standard ganciclovir treatment seems effective in reducing but not suppressing viral replication in severe cases of CMV infection of the CNS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Nested polymerase chain reaction for diagnosis and monitoring treatment response in AIDS patients with tuberculous meningitis.

OBJECTIVE: To investigate the usefulness of polymerase chain reaction (PCR) from cerebrospinal fluid (CSF) for rapid diagnosis and assessing treatment response of tuberculous meningitis (TBM) in AIDS patients. PATIENTS: Forty-four CSF samples from 10 patients with TBM confirmed by autopsy or by a culture of CSF (41 samples) and from two patients with highly probable TBM (three samples) were analysed. CSF specimens were collected before and during standard antituberculous treatment. CSF samples from 24 AIDS patients with autopsy evidence of other neurologic diseases were studied as controls. METHODS: A nested PCR amplifying a 123 base-pair fragment of the IS6110 sequence was developed. Heating to 95 degrees C for 15 min was used for pre-PCR treatment of samples. RESULTS: Detection limit was 10(2) colony-forming units per ml or 10 fg purified Mycobacterium tuberculosis DNA. M.tuberculosis DNA was detected in CSF from all the 12 confirmed or highly probable TBM cases. CSF was positive by nested PCR in 17 of 17 (100%) and 18 of 27 (67%) samples collected before and during therapy, respectively. Clinical and microbiological follow-up > or = 2 weeks was available for seven patients. PCR-positive CSF converted to M. tuberculosis DNA negative in four patients that showed improvement during treatment, but it remained positive in three patients who died of disseminated tuberculosis. All the CSF samples from the non-TBM controls were negative by nested PCR. CONCLUSIONS: Nested PCR for detection of M. tuberculosis DNA is specific for diagnosis of TBM and more sensitive than conventional bacteriology. Moreover, nested PCR could be a useful method for assessing treatment response in AIDS patients with TBM.

AIDS-Related Opportunistic Infections↗
PubMed1995

Diagnosis of cytomegalovirus infection of the nervous system in AIDS by polymerase chain reaction analysis of cerebrospinal fluid.

To evaluate the diagnostic relevance and the clinical impact of the cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for cytomegalovirus (CMV) DNA in the diagnosis of CMV infection of the central nervous system (CNS), 220 acquired immune deficiency syndrome (AIDS) patients with neurological disease were examined. CSF was drawn 1-180 days before death, concomitantly with clinical neurological disease, and autopsy was performed in all the cases. CMV DNA was detected in the CSF from 36 of 45 patients (82%) with CMV infection of the CNS, and in 2 of 175 without CMV infection of the CNS at autopsy. The sensitivity of the method was 82%, the specificity 99%, the positive predictive value 95%, and the negative predictive value 96%. An extensive CMV ventriculitis or encephalitis was shown by histopathology in the majority of the CSF PCR-positive patients with overt clinical encephalitis. Minor CMV lesions only, not likely to cause relevant clinical symptoms, were observed in some CSF PCR-positive patients, concomitant with other opportunistic CNS diseases. CSF PCR is a reliable means for diagnosis of CMV infection of the CNS in patients with AIDS. A positive PCR result, however, requires careful interpretation in the individual clinical context.

AIDS Dementia Complex↗
PubMed1994

Pharmacokinetics of zidovudine in HIV-positive patients with liver disease.

The pharmacokinetics of zidovudine (ZDV) have been studied in eight AIDS patients with normal liver function, and in four AIDS patients with liver disease. Patients who were previously untreated with ZDV were given 250 mg ZDV, and plasma levels of ZDV and its glucuronic metabolite, GZDV, were determined at 0.5, 1, 1.5, 2, 3, and 4 hours after the dose. In patients with liver disease, Cmax and AUC of ZDV were higher, the oral clearance was only one-eighth that of patients without liver disease, and the elimination half-life was longer. There was a trend for concentrations of the principal metabolite, GZDV, to be lower in patients, and, therefore, the ratio of the AUC for GZDV to that for ZDV was much lower in patients with liver disease. Therefore, HIV-seropositive patients with liver disease had the same markedly altered disposition of ZDV as seronegative patients with liver disease. Although this therapy was not clearly associated with a higher incidence of toxicity, some patients with liver disease had to discontinue therapy because of intolerance; therefore, plasma levels of these patients should be monitored when such therapy is undertaken.

Adult↗
PubMed1994

Nested PCR for detection of BK virus and JC virus DNA.

BACKGROUND: A nested polymerase chain reaction (PCR) was developed to detect BK virus (BKV) and JC virus (JCV) DNA sequences. The unique clevage site for BamHI restriction enzyme was located in the JCV amplimer and cleavage was used to differentiate between BKV and JCV. STUDY DESIGN: Twenty-three urine specimens from 17 bone marrow recipients with haemorrhagic cystitis and one liver transplant patient were tested for the presence of BKV and JCV DNA. Four brain tissue specimens (paraffin embedded brain tissues and a fresh frozen brain biopsy) and 5 cerebrospinal fluids from 3 AIDS patients and one liver transplant patient, all with progressive multifocal leukoencephalopathy (PML), were also examined by PCR. RESULTS: The sensitivity of the PCR was 10 genomes for each virus. BKV DNA was detected in 15 urine specimens from 12 bone marrow transplant patients. JCV DNA was detected in 4 cerebrospinal fluids and 4 brain tissues from patients with PML. CONCLUSION: Our results show that the nested PCR is a sensitive and rapid assay that can be used for diagnosis of BKV and JCV infections. The cerebrospinal fluid appears to be a suitable material for diagnosis of JC virus reactivation in the brain.

Journal Article↗
PubMed1994

Nested PCR for detection of BK virus and JC virus DNA.

BACKGROUND: A nested polymerase chain reaction (PCR) was developed to detect BK virus (BKV) and JC virus (JCV) DNA sequences. The unique clevage site for BamHI restriction enzyme was located in teh JCV amplimer and cleavage was used to differentiate between BKV and JCV. STUDY DESIGN: Twenty-three urine specimens from 17 bone marrow recipients with haemorrhagic cystitis and one liver transplant patient were tested for the presence of BKV and JCV DNA. Four brain tissue specimens (paraffin embedded brain tissues and a fresh frozen brain biopsy) and 5 cerebrospinal fluids from 3 AIDS patients and one liver transplant patient, all with progressive multifocal leukoencephalopathy (PML), were also examined by PCR. RESULTS: The sensitivity of the PCR was 10 genomes for each virus. BKV DNA was detected in 15 urine specimens from 12 bone marrow transplant patients. JCV DNA was detected in 4 cerebrospinal fluids and 4 brain tissues from patients with PML. CONCLUSION: Our results show that the nested PCR is a sensitive and rapid assay that can be used for diagnosis of BKV and JCV infections.

Journal Article↗
PubMed1993

Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system.

Epstein-Barr virus (EBV) is constantly associated with AIDS-related primary lymphomas of the central nervous system (CNS). To assess whether EBV DNA in cerebrospinal fluid (CSF) could be used as a tumour marker, CSF samples that had been taken within 180 days before death from 85 patients with HIV infection and neurological disorders at necropsy were examined retrospectively by nested polymerase chain reaction (PCR) for EBV. Histologically evident primary CNS lymphomas were found in 17 patients, and EBV was shown in tissue by in-situ hybridisation in 16 of the 16 cases examined. All 17 patients with primary CNS lymphoma had EBV DNA in CSF. EBV DNA was found in CSF from 1 of 68 HIV-infected patients without histologically detectable lymphoma at necropsy. PCR for EBV DNA in CSF was 100% sensitive and 98.5% specific for AIDS-associated primary CNS lymphoma, and may be useful as a diagnostic tumour marker.

Base Sequence↗
PubMed1993

Multiple viral infections in HIV-infected children with chronically-evolving hepatitis.

Hepatic involvement was investigated in 31 children with perinatal HIV-1 infection, who were followed for 2-82 months (mean 30.5). Liver disease, as revealed by increased aminotransferase levels, liver biopsy or necroscopy, was diagnosed in 18 children (58%), of which 7 (22.5%) had acute hepatitis and 11 (35.5%) showed chronic liver disease. Overall, 40 persistently active or recurrent viral infections, as demonstrated by positive culture and/or detection of serum DNA, specific IgM, IgA and high levels of IgG, were revealed in the children with liver disease, while 12 similar infections were detected in 13 children without liver disease (p < 0.001). In particular, the children with liver disease showed a significantly (p < 0.002) higher incidence of cytomegalovirus (CMV) infections than children without liver disease (13 versus 3). Moreover, hepatitis C and B virus infections were revealed only in children with liver disease (5 and 1 patients, respectively). Clinical outcome showed a significantly (p < 0.001) higher mean survival in the children without liver disease than those with liver disease (47.5 versus 18.2 months). In fact, nine of the children with liver disease (50%) died, as opposed to only one of the children without liver disease (7.7%; p = 0.01). Based on these findings, liver disease is indicative of a poor prognosis in children with HIV infection, being related to the presence of multiple active viral infections.

AIDS-Related Opportunistic Infections↗
PubMed1993

Comparison of two dose regimens of zidovudine in an open, randomized, multicentre study for severe HIV-related thrombocytopenia.

OBJECTIVE: To compare the effect of two dose regimens of zidovudine in the treatment of severe HIV-related thrombocytopenia (TP). DESIGN: Eighty-four patients with severe HIV-related TP and platelet counts < 50 x 10(9)/l were enrolled in an open study at six centres. Patients were randomized into two groups to receive zidovudine (group A, 500 mg per day; group B, 1000 mg per day) for 6 months. METHODS: Platelet counts were determined monthly and patients categorized as complete responders (CR; platelets > 100 x 10(9)/l), partial responders (PR; platelets > 50 to < 100 x 10(9)/l), or failures (F; platelets to < 50 x 10(9)/l). CD4+ and CD8+ lymphocytes, HIV antigenaemia, beta 2-microglobulin, white blood cells, mean cell volume and haemoglobin were also determined. RESULTS: Seventy-one patients (35 and 36 in groups A and B, respectively) completed the study; 11.4% of group A patients were CR and 45.7% PR; 38.9% of group B were CR and 33.3% PR. Increase in mean platelet counts was dose-related, more rapid in the higher dose group and remained significantly higher after 6 months of treatment (56.4 x 10(9)/l in group A versus 98.2 x 10(9)/l in group B; P < 0.01). CONCLUSIONS: The results confirm the efficacy of zidovudine in the treatment of severe HIV-related TP. The average for CR and PR in the two groups was 64.8%; the higher dose of zidovudine was more effective at increasing platelet counts.

Adult↗
PubMed1993

Long-term treatment with zidovudine in patients with human immunodeficiency virus (HIV)-associated thrombocytopenia: modes of response and correlation with markers of HIV replication.

The effects of zidovudine on the platelet count were studied in 152 patients with HIV-related thrombocytopenia of severe grade (platelet count < 50 x 10(9)/l) and moderate grade (platelet count < 100 and > 50 x 10(9)/l). In both groups of patients there was a significant increase in the mean platelet count from the baseline value, after 2 weeks (from 21 x 10(9)/l to 48 x 10(9)/l and from 75 x 10(9)/l to 97 x 10(9)/l) and 3 months of therapy (to 59 x 10(9)/l and to 144 x 10(9)/l). Sixty-five and 39 patients were followed up for 12 and 18 months, respectively, and the mean platelet values after 12 and 18 months of therapy were still significantly increased, compared to the respective mean baseline values, in both groups of patients. Clinical progression of the disease was observed in 23 treated patients, none of them showing concomitant reductions of the platelet number. An increase in the mean CD4+ cell count after 3 months of therapy was followed by a progressive decline in the 65 patients with a 12-month follow-up, while no significant changes of the p24 antigenemia rates were observed after 1 year of therapy in 53 patients evaluated. The long-term effects of zidovudine on the platelet count, but not on other parameters of clinical outcome, might be explained by the involvement of specific mechanisms in the pathogenesis of this kind of thrombocytopenia and of its response to zidovudine.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Reduced frequency of HIV-induced brain lesions in AIDS patients treated with zidovudine.

We evaluated the effect of zidovudine on HIV-induced lesions of the brain by comparing the neuropathological findings in 82 treated and 120 untreated patients who died from AIDS. We observed a statistically significant reduction of the number of cases with multinucleated giant cells (MGCs) in the brain and MGC-associated neuropathological damage in patients treated with zidovudine. The effects of zidovudine were time and dose related in the first 12 months of treatment, while longer periods of therapy produced no further results. The antiretroviral treatment particularly affected the frequency of diffuse demyelinating lesions of the cerebral white matter. In the patients who died with HIV-induced brain lesions but no other opportunistic brain diseases, the percentage of cases with clinical history of severe dementia was significantly lower in the group treated with zidovudine.

AIDS Dementia Complex↗