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C Pedersen

Publications and source records attributed to C Pedersen.

At least 37 records · Page 2Linked to original sources

Low body weight and type of protease inhibitor predict discontinuation and treatment-limiting adverse drug reactions among HIV-infected patients starting a protease inhibitor regimen: consistent results from a randomized trial and an observational cohort.

OBJECTIVES: To assess predictors for discontinuation and treatment-limiting adverse drug reactions (TLADR) among patients starting their first protease inhibitor (PI). METHODS: Data on patients starting a PI regimen (indinavir, ritonavir, ritonavir/saquinavir and saquinavir hard gel) in a randomized trial (RAS, n = 318) and an observational cohort (OBC, n = 505) were used to document reasons for discontinuation and TLADR. Risk factors for discontinuation of the initial PI/developing TLADR were assessed in Cox models. RESULTS: A total of 43 (RAS) and 48% (OBC) discontinued the initial PI therapy within less than 2 years. In both populations TLADR were the most common reason for discontinuation. The incidence of TLADR in RAS was: 8.5 (indinavir), 66.0 (ritonavir), 15.6 (saquinavir hard gel) per 100 person-years of follow-up (P < 0.001). Body weight and type of PI initiated were independent risk factors for treatment discontinuation and TLADR in both groups. In OBC, the risk of developing TLADR increased by 12% per 5 kg lower body weight when starting the PI regimen [the relative hazard (RH) was 1.12 (95% confidence interval: 1.05-1.19) per 5 kg lighter], and starting ritonavir was associated with a three- to sixfold higher risk of TLADR relative to other PI regimens. Very similar results were documented in RAS [RH for body weight was 1.18 (1.07-1.29)]. CONCLUSIONS: Nearly half of the patients stopped treatment with the initial PI, most commonly as a result of adverse drug reactions. Low body weight and initiation of ritonavir relative to other PIs were associated with an increased risk of TLADRs. Very consistent results were found in a randomized trial and an observational cohort.

Adult↗

Dependence of excitotoxic neurodegeneration on mitochondrial aconitase inactivation.

Using the inactivation of mitochondrial and cytosolic aconitases as markers of compartment-specific superoxide (O2(-)) production, we show that oxygen-glucose deprivation (OGD) or excitotoxin exposure produce a time-dependent inactivation of mitochondrial, but not cytosolic, aconitase in cortical cultures. To determine if mitochondrial O2(-) production was an important determinant in neuronal death resulting from OGD, metalloporphyrins with varying superoxide dismutase (SOD) activity were tested for their ability to protect against mitochondrial aconitase inactivation and cell death. OGD-induced mitochondrial aconitase inactivation and cell death was inhibited by manganese tetrakis (4-benzoic acid) porphyrin (MnTBAP), manganese tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) and NMDA receptor antagonists. By contrast, NMDA- or kainate (KA)-induced mitochondrial aconitase inactivation and cell death was inhibited by MnTBAP, but not MnTE-2-PyP. Moreover, both MnTBAP and MnTE-2-PyP penetrated mitochondrial fractions of cortical cells. These data suggest that mitochondrial aconitase inactivation closely correlates with subsequent neuronal death following excitotoxicity produced by OGD or NMDA/KA exposure. Assessment of biological rather biochemical antioxidant activities better predicted neuroprotection by metalloporphyrins. Moreover, antioxidants that protect oxidant-sensitive mitochondrial targets such as aconitase may be useful as therapies for disease states involving excitotoxicity.

Aconitate Hydratase↗

HIV-1 subtypes in Denmark.

The objective of this study was to investigate the presence of non-subtype B HIV-1 in Denmark. The C2-V3-C3 region of the env gene from proviral DNA obtained from patients suspected of being infected with non-subtype B virus was PCR-amplified and directly sequenced. The DNA sequences were aligned with full-length HIV-1 reference strains from each subtype and analysed using the phylogenetic package PHYLIP 3.1. The neighbour-joining method was used with 100 bootstraps. Of the 144 patients included in this study C2-V3-C3 sequences were obtained from 129 patients (90%). The phylogenetic analyses showed that virus from 49 patients (38%) was subtype A, 39 (30%) subtype C, 9 (7%) subtype D, 14 (11%) subtype CRF01_AE, 16 (12%) subtype B, 1 (1%) subtype F and 1 (1%) subtype J. This study demonstrates that almost all subtypes can be detected in Denmark; all non-subtype B infections could be traced to countries with a high prevalence of non-subtype B virus.

DNA, Viral↗

Changing demographics in an HIV-infected population: results from an observational cohort study in Western Denmark.

We present demographic data from an observational database of HIV and AIDS in the Western part of Denmark, a region with a population of 2,935,156 individuals (55.1% of the population of Denmark). Five centers in the region treat HIV-positive adults; all patients attached to these centers since 1995 are included in this study. In total, 749 adult HIV-infected individuals were enrolled as of 31 December, 1999. Estimates of prevalence and incidence of HIV infection in the area were 25.9/100,000 and 2.6/100,000, respectively, which are lower than average for the country. The number of newly diagnosed HIV-infected patients remained constant during the period 1995-99, with an average of 62 diagnoses per year. The number of HIV-related deaths declined from 43 in 1995 to 15 in 1999. Of the enrolled patients, 70.9% were of Danish origin, 75% were Caucasians, 69.7% were male and 47.2% had heterosexual contact as their primary risk behavior. There seems to have been a shift in the HIV epidemic in recent years, with a higher proportion of newly diagnosed HIV patients having contracted the infection through heterosexual contact, a higher proportion being immigrants from less developed countries and newly diagnosed individuals getting older.

Adult↗

Seroprevalence of human granulocytic ehrlichiosis in high-risk groups in Denmark.

The aim of this study was to evaluate the seroprevalence of human granulocytic ehrlichiosis (HGE) among 300 residents in the county of Funen, Denmark. All of these people had either suspected or confirmed borreliosis. Two hundred control sera were included in the study. Samples were submitted by general practitioners and by hospital departments. An indirect immunofluorescence assay was used to identify sera reactive to HGE and an enzyme-linked immunosorbent assay was used to analyse Borrelia burgdorferi antibodies. There were 63 (21%) HGE-positive sera, 53 of which came from Borrelia-seropositive patients. Among patients with negative Borrelia serology, but with clinical suspicion of borreliosis, 14.3% were HGE-positive (n = 70). Of the 200 control sera, 3.5% were HGE-positive and 10.5% were Borrelia-positive. No HGE-positive samples were found among subjects < 20 y of age, wheras 20.4% of Borrelia seropositive samples where from subjects < 20 y of age. No mortality was observed in the HGE-positive group and the percentage of serum samples positive for both Borrelia and HGE did not differ significantly between hospitalized and non-hospitalized patients. Our study indicates that HGE infection with or without concomitant or previous Borrelia burgdorferi infection is common in tick-exposed individuals > 20 y old in the county of Funen, Denmark.

Adolescent↗

[Ebola fever].

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Africa↗

[Amebiasis].

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Animals↗

[Lactic acidosis type B. A life-threatening adverse effect of antiretroviral therapy].

A thirty-year old HIV-positive woman, who had been receiving antiretroviral therapy (protease inhibitor, lamivudine and stavudine) for seven months, was diagnosed with severe lactic acidosis type B, most likely induced by nucleoside reverse transcriptase inhibitor treatment. The antiretroviral therapy was ceased, and she was treated with isotonic sodium bicarbonate intravenously. She made a full recovery apart from a perceptive hearing deficit.

Acidosis, Lactic↗

[HIV protease inhibitors and interactions].

The protease inhibitors are a new class of drugs for the treatment of HIV infection. Results of treatment have proved beneficial to HIV positive patients, resulting in slower disease progression to aids and death. However the potential of drug interactions is high because of the drug-transporting P-glycoprotein and cytochrome P450 3A4-mediated metabolism. Administration of protease inhibitors may result in increased or decreased concentrations of co-administered drugs, and the plasma concentration of protease inhibitors may be affected by other drugs. It is possible to take advantage of the interactions by combining two protease inhibitors. Attention is drawn to the protease inhibitors and their possible interactions because of the advantages and disadvantages this implies. It is possible to monitor interactions by measuring plasma concentrations of the protease inhibitors.

ATP Binding Cassette Transporter, Subfamily B↗

The danish protease inhibitor study: a randomized study comparing the virological efficacy of 3 protease inhibitor-containing regimens for the treatment of human immunodeficiency virus type 1 infection.

The Danish Protease Inhibitor (PI) Study has enrolled 318 human immunodeficiency virus (HIV)-infected, PI-naive patients for the purpose of comparing 3 PI-containing regimens for the treatment of HIV infection. The regimens include 2 nucleoside analogues in combination with indinavir (Idr), ritonavir (Rtv), or Rtv and saquinavir (Rtv/Sqv). Similar percentages of patients in the 3 study arms achieved reduced levels (</=20 copies/mL) of HIV RNA. In the area under the curve minus baseline analyses, a better response was found in the Rtv/Sqv arm than in the Rtv arm. No difference was found when comparing Rtv/Sqv with Idr and Rtv with Idr. Patients in the 3 arms had comparable increases in CD4 cell counts. At 72 weeks of follow-up, there was no statistical difference between arms for the primary study end point (</=20 HIV RNA copies/mL); however, some of the additional analyses indicated an advantage for the Rtv/Sqv arm, especially when compared with the Rtv arm.

Adolescent↗

[Cryptococcosis].

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Antifungal Agents↗