| 1. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Cerebral palsy in preterm infants: a population-based case-control study of antenatal and intrapartal risk factors.
- 2002
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - 0803-5253. ; 91:8, s. 946-51
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have indicated that foetomaternal infection increases the risk of spastic cerebral palsy (CP) in term infants, whereas this association appears to be less evident in preterm infants. The aim of this study was to analyse infection-related risk factors for spastic CP in preterm infants. A population-based series of preterm infants with spastic CP, 91 very preterm (<32 wk) and 57 moderately preterm (32-36 wk), born in 1983-90, were included and matched with a control group (n = 296). In total, 154 maternal, antenatal and intrapartal variables were retrieved from obstetric records. In the entire group, histological chorioamnionitis/pyelonephritis, long interval between rupture of membranes and birth, admission-delivery interval <4 h and Apgar scores of <7 at 1 min just significantly increased the risk of CP, and Apgar scores of <7 at 5 and 10 min were strongly associated with an increased risk. Abruptio placentae, Apgar scores <7 at 1 min and pathological non-stress test (reason for delivery) were significant risk factors of CP only in the moderately preterm and hemiplegic groups, whereas fever before delivery was a significant risk factor in the very preterm and spastic diplegic groups. Antibiotics during pregnancy was associated with CP only in the spastic diplegic CP group. Conclusion: Antenatal infections marginally increased the risk of CP. Low Apgar score and abruptio placentae were associated with CP, especially in moderately preterm infants with hemiplegic CP.
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| 2. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Higher HIV-1 RNA cutoff level required in cerebrospinal fluid than in blood to predict positive HIV-1 isolation
- 2000
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Ingår i: J Med Virol. ; 62:1, s. 9-13
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 can be isolated from the vast majority of blood samples taken from HIV-1-seropositive patients not treated with antiretroviral drugs. Isolation rates from cerebrospinal fluid (CSF) samples are considerably lower, ranging between 20-70%. The objective of this study was to determine the cutoff levels for HIV-1 RNA that would yield a positive predictive value > or =90% for positive virus isolation from CSF and blood. Quantitative HIV-1 RNA PCR (Amplicor HIV monitor, version 1.0, Roche Diagnostic Systems) and virus isolation were used to examine 303 CSF samples and 278 paired blood samples from 157 HIV-1-seropositive patients. Patients on antiretroviral treatment provided 140 of the CSF samples and 131 of the blood samples. CSF samples that were positive by culture numbered 137 of 303 (45%), as compared with 216 of 278 (78%) blood samples. In the case of samples taken from patients with antiretroviral treatment, 28% were positive by culture from CSF and 63% from blood. As expected, mean HIV-1 RNA levels were higher in CSF and blood samples positive by culture than in samples negative by culture. A cutoff level of >5,000 HIV-1 RNA copies/ml was required to yield a positive predictive value for positive virus isolation from CSF samples of > or =90%, whereas the cutoff level for blood samples was just above the detection limit of the assay (>200 HIV-1 copies/ml).
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| 3. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Increased blood-brain barrier permeability in neuro-asymptomatic HIV-1-infected individuals--correlation with cerebrospinal fluid HIV-1 RNA and neopterin levels
- 2001
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Ingår i: J Neurovirol. ; 7:6, s. 542-7
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to assess the frequency of blood-brain barrier (BBB) impairment, as measured by the albumin ratio, in neuro-asymptomatic HIV-1-infected individuals without antiretroviral treatment and the correlation between BBB disruption and intrathecal immune activation and HIV-1 RNA levels. Serum and cerebrospinal fluid (CSF) albumin, neopterin, and HIV-1 RNA levels were analysed in 110 neuro-asymptomatic HIV-1-infected individuals at different stages of disease; 63 classified as CDC A, 25 as CDC B, and 22 as CDC C. Increased BBB permeability was found in 17 of 110 (15%) of HIV-1-infected individuals. This proportion was sustained throughout the CDC stages. The albumin ratio was correlated with the CSF neopterin levels (r(s) = 0.36, P < 0.001), the serum neopterin levels (r(s) = 0.37, P < 0.001), and the CSF HIV-1 RNA levels (r(s) = 0.26, P < 0.01), but not with the plasma HIV-1 RNA levels. The correlations between the albumin ratio and the CSF and serum neopterin concentrations and the CSF HIV-1 RNA levels indicate that immune activation and, possibly, intrathecal HIV-1 virus replication are important factors associated with increased BBB permeability in HIV-1 infection.
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| 4. |
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| 5. |
- Hagberg, Lars, 1951, et al.
(författare)
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Intrathecal immune activation is associated with cerebrospinal fluid markers of neuronal destruction in AIDS patients
- 2000
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Ingår i: J Neuroimmunol. ; 102:1, s. 51-5
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Tidskriftsartikel (refereegranskat)abstract
- We analysed the relationship between cerebrospinal fluid (CSF) concentrations of the light subunit of the neurofilament protein (NFL, a marker of neurons, mainly axons), neopterin (a marker of immune activation), and quantitative HIV RNA levels in 47 patients with HIV-1 infection, 25 of whom had AIDS. In the AIDS patients, the mean levels of CSF NFL were high indicating neuronal destruction. The CSF NFL and the CSF neopterin concentrations were correlated in the subgroup of patients without CNS opportunistic infection (p < 0.05). There was no significant correlation between NFL and HIV RNA levels in CSF. In HIV seropositive patients without AIDS, only 3/22 had CSF NFL concentrations above the upper normal reference value. The results suggest that CNS neuronal destruction occurs frequently in patients with AIDS but rarely in those without AIDS, and that immune activation rather than the HIV viral load is associated with neurochemical signs of axonal destruction.
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| 6. |
- Yilmaz, Aylin, 1974, et al.
(författare)
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Cerebrospinal fluid and plasma HIV-1 RNA levels and lopinavir concentrations following lopinavir/ritonavir regimen.
- 2004
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 36:11-12, s. 823-8
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to study the effect of lopinavir/ritonavir on cerebrospinal fluid (CSF) viral load as part of an antiretroviral combination treatment for HIV-1 infected individuals, and to determine the steady-state concentrations of lopinavir in CSF in relationship to plasma concentrations. Paired CSF and plasma samples from 12 antiretroviral-naïve HIV-1 infected patients starting combination therapy containing lopinavir/ritonavir were collected at baseline, and during treatment at a first follow-up at median 3.0 months (range 2.6-6.0 months), and at a second follow-up at median 12.1 months (range 6.0-16.5 months). Levels of HIV-1 RNA, CD4+ T-cell count, beta2-microglobulin, neopterin, and lopinavir concentration were analysed. In addition, CSF and plasma lopinavir concentrations in 4 patients already on combination therapy including lopinavir/ritonavir were analysed. Nine of 11 patients had undetectable viral load in CSF and 5/11 in plasma at the first follow-up. At the second follow-up 7/7 had undetectable viral load in CSF and 9/9 in plasma. Intrathecal immunoactivation, measured by neopterin and beta2-microglobulin, decreased significantly both in CSF and serum. The total CSF concentrations of lopinavir were of the same order of magnitude as the unbound concentrations in plasma. Lopinavir mean (+/-SD) concentrations were 42.1 (+/-31.5) nM in CSF and 52.7 (+/-25.2) nM unbound in plasma. We found that antiretroviral combination therapy including lopinavir/ritonavir substantially decreases the viral load, both in CSF and plasma, as well as the intrathecal immunoactivation, measured by beta2-microglobulin and neopterin. CSF concentrations of lopinavir were low, but probably sufficient to have a virological effect.
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| 7. |
- Abdulle, Sahra, 1970, et al.
(författare)
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Continuing intrathecal immunoactivation despite two years of effective antiretroviral therapy against HIV-1 infection
- 2002
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Ingår i: Aids. ; 16:16, s. 2145-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the effect of antiretroviral combination treatment on intrathecal immunoactivation in HIV-1 infection. METHOD: Lumbar punctures were performed at baseline, and after 4 months, 1 and 2 years on 30 neurologically asymptomatic, treatment-naive HIV-1-infected patients started on antiretroviral treatment with three or more drugs. Levels of neopterin, beta2-microglobulin and HIV-1 RNA were measured in cerebrospinal fluid (CSF) and blood. RESULTS: All patients continued the study until the 4-month follow-up, although seven discontinued before the 1-year control, and an additional five discontinued before the control after 2 years. Neopterin, beta2-microglobulin and HIV-1 RNA decreased significantly both in CSF and blood, but although 100% of the patients decreased their CSF concentrations of beta2-microglobulin and HIV-1 RNA to normal levels, only 55% had normal CSF neopterin concentrations after 2 years treatment. CONCLUSIONS: In addition to CSF viral load, antiretroviral combination therapy substantially decreases the intrathecal immunoactivation as reflected by CSF neopterin and beta2-microglobulin in neuroasymptomatic HIV-1-infected patients. However, almost half of the patients still have slightly increased CSF neopterin concentrations after 2 years of effective treatment, which might reflect an ongoing low-grade viral replication in brain tissue.
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| 8. |
- Arvidson, Nicklas, 1967, et al.
(författare)
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Cerebrospinal fluid viral load, virus isolation, and intrathecal immunoactivation in HIV type 2 infection.
- 2004
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Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 0889-2229 .- 1931-8405. ; 20:7, s. 711-5
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Tidskriftsartikel (refereegranskat)abstract
- Four patients with HIV-2 infection were followed longitudinally with cerebrospinal fluid (CSF) analyses. Two patients had positive CSF HIV-2 isolations. These two patients had CD4 cell count below 200 x 10(6)/liter and maximum CSF HIV-2 RNA viral loads above 4000 copies/ml. Intrathecal immune activation was demonstrated by elevated CSF neopterin concentrations (14-18 nmol/liter). No opportunistic infections were diagnosed. After antiretroviral treatment CSF viral counts decreased to below 125 copies/ml and CSF neopterin concentrations decreased. In two other patients who had CD4 counts within the normal range CSF virus isolations were repeatedly negative and viral CSF loads were below 125 copies/ml. However, a slightly elevated CSF neopterin concentration in one sample and pleocytosis in another might also be caused by HIV-2 in these patients. Before antiretroviral treatment HIV-2 isolations from blood were positive in all four patients. Maximum HIV-2 RNA viral loads were higher in blood than in CSF. Treatment failure in one patient with increasing viral loads in blood did not result in viral rebound in CSF.
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| 9. |
- Brandin, Eleonor, et al.
(författare)
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pol gene sequence variation in Swedish HIV-2 patients failing antiretroviral therapy
- 2003
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Ingår i: AIDS Res Hum Retroviruses. ; 19:7, s. 543-50
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Tidskriftsartikel (refereegranskat)abstract
- There is limited knowledge about how to treat and interpret results from genotypic resistance assays in HIV-2 infection. Here, genetic variation in HIV-2 pol gene was studied in 20 of 23 known HIV-2 cases in Sweden. Five patients with signs of virological treatment failure were longitudinally studied. Clinical, virological and immunological data were collected and the protease (PR) and first half of the reverse transcriptase (RT) was amplified and directly sequenced from plasma samples. Moderate to extensive genetic evolution was observed in four of the five patients who failed treatment. Some mutations occurred at positions known to confer resistance in HIV-1, but many occurred at other positions in PR and RT. All patients had been treated with zidovudine alone or in combination with other antiretroviral drugs, but none displayed a mutation at position 215, which is the primary zidovudine resistance site in HIV-1. Instead, a E219D mutation evolved in virus from two patients and a Q151M mutation evolved in two other patients. A M184V mutation indicative of lamivudine resistance was detected in three patients. The virus of one patient who had been treated with ritonavir, nelfinavir, and lopinavir successively acquired nine unusual mutations in the protease gene, most of which are not considered primary or secondary resistance mutations in HIV-1. Our data indicate that the evolutionary pathways that lead to antiretroviral resistance in HIV-2 and HIV-1 exhibit both similarities and differences. Genotypic HIV-2 resistance assays cannot be interpreted using algorithms developed for HIV-1, instead new algorithms specific for HIV-2 have to be developed.
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| 10. |
- Cinque, Paola, et al.
(författare)
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The urokinase receptor is overexpressed in the AIDS dementia complex and other neurological manifestations.
- 2004
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Ingår i: Annals of neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 55:5, s. 687-94
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Tidskriftsartikel (refereegranskat)abstract
- The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in extracellular matrix degradation and cell migration in the central nervous system (CNS). To investigate the role of the uPA/uPAR system in the pathophysiology of acquired immunodeficiency syndrome dementia complex (ADC), we measured soluble uPAR (suPAR) levels in cerebrospinal fluid (CSF) and plasma from human immunodeficiency virus (HIV)-1-infected patients and controls. CSF suPAR levels were significantly higher in HIV-1-infected patients than in controls and in patients with ADC or opportunistic CNS infections (CNS-OIs) than in neurologically asymptomatic patients, irrespective of HIV-1 disease stage. The highest levels of suPAR were found in patients with ADC, and among those with CNS-OIs in patients with cytomegalovirus encephalitis or cryptococcosis. Plasma suPAR levels were higher in HIV-1-infected patients than in controls and increased with HIV-1 disease stage regardless of the presence of CNS disease. In patients with ADC or CNS-OIs, CSF suPAR levels correlated with CSF HIV-1 RNA, but not with plasma suPAR concentrations. Highly active antiretroviral therapy was associated with a significant and parallel decrease of both CSF suPAR and HIV-1 RNA. In brain tissue from patients with HIV-1 encephalitis, uPAR was highly expressed by microglial and multinucleated giant cells staining positively for HIV-1. The overexpression of uPAR in the CNS of patients with ADC suggests that the uPA/uPAR system may contribute to the tissue injury and neuronal damage in this disease.
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