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Biomedical subjects

G A Hardy

Publications and source records attributed to G A Hardy.

4 recordsLinked to original sources

Self-poisoning with Colchicum autumnale L. flowers.

UNLABELLED: A 44-year-old man ingested about 40 flowers of Colchicum autumnale L. The patient presented with nausea, vomiting, and abdominal pain 2 hours after ingestion and had diarrhea 14 hours after ingestion. Hematological values remained within normal range. Treatment was mainly supportive. The outcome was favorable. The intoxication was confirmed by high-performance liquid chromatography-mass spectrometry. Maximal colchicine levels were 4.34 ng/mL at 13 hours in plasma and 5.43 ng/mL at 16 hours in erythrocytes. CONCLUSION: We report one of the few symptomatic cases of Colchicum autumnale L. poisoning confirmed by toxicological analysis.

Adult↗

Assessment of type 1 and type 2 cytokines in HIV type 1-infected individuals: impact of highly active antiretroviral therapy.

Although the effect of highly active antiretroviral therapy (HAART) on HIV-1 replication has been established, the mechanisms involved in restoration of immune responses and reconstitution remain unknown. This study provides evidence of changes in expression of type 1 and type 2 cytokine-specific mRNA occurring during HIV-1 infection, before and after initiation of HAART. Unstimulated PBMCs from nine HIV-1-infected individuals obtained at different time intervals before and after the initiation of HAART were assessed for specific IFN-gamma, IL-2, IL-4, and IL-10 mRNA expression, using RT-PCR. Correlation with CD4+ T cell counts and viral load was also carried out. Before initiation of HAART, in all patients, little expression of specific IFN-gamma and IL-2 (type 1 cytokine) mRNA was noted. In contrast, expression of specific IL-4 and/or IL-10 (type 2) mRNA was readily detectable in the majority of patients. After initiation of HAART there was a continuous increase in IFN-gamma and IL-2 mRNA expression, although the latter occurred in lower amounts. This paralleled a dramatic reduction in viral load and increase in CD4+ T cell counts. Type 2 cytokine-specific mRNA expression fell to undetectable levels and in some cases reappeared later in the course of HAART. Predominant expression of type 2 cytokine mRNA, before initiation of HAART, concurs with previous findings of a dominant antiproliferative, type 2 cytokine profile during HIV-1 infection. Reversion of the cytokine profile, after HAART, to a strong type 1 profile suggests that in addition to suppressing virus replication directly the immune system may be given a chance to recover.

Anti-HIV Agents↗

Induction of HIV-1-specific T cell responses by administration of cytokines in late-stage patients receiving highly active anti-retroviral therapy.

Highly active anti-retroviral therapy (HAART) is associated with reduction in the morbidity and mortality of patients with advanced HIV-1 disease. The ability of such treatment to improve immune responses against HIV-1 and opportunistic pathogens is variable and limited. Addition of cytokine immunotherapy to this treatment may improve immune responses. IL-2 with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to HIV-1+ individuals receiving HAART with undetectable viral loads, and CD4 counts < 100 cells/microl. In one patient presenting with Mycobacterium avium complex (MAC) infection, we evaluated the effect of cytokine immunotherapy on lymphocyte phenotype; plasma viral load; proliferative responses to mitogens, recall and HIV-1 antigens; cytokine production and message in response to non-specific and specific stimuli; and natural killer (NK) cell activity. Proliferation assays were performed in two similar patients. Before cytokine immunotherapy the predominant CD8+ population was mainly CD28-. No proliferation or IL-2 production was seen in response to mitogens, recall or HIV-1 antigens; and no HIV-1 peptide-specific interferon-gamma (IFN-gamma)-secreting cells were present. Low levels of IL-4 were detected in response to antigens to which patients had been exposed, associated with up-regulated expression of costimulatory molecules influenced by IL-4. Following IL-2 administration, loss of IL-4 was associated with increased NK cell activity and HIV-1 peptide-specific and non-specific IFN-gamma-producing cells. Proliferative responses associated with IL-2 production and responsiveness were only seen after subsequent concomitant administration of GM-CSF with IL-2. These changes mirrored clinical improvement. An imbalance of lymphocyte subsets may account for immune unresponsiveness when receiving HAART. Restoration of responses following immunotherapy suggests a shift towards a lymphocyte profile with anti-pathogen activity.

Acquired Immunodeficiency Syndrome↗