Search

Supplemental Digital Content is Available in the Text.

Research on immune modulation in HIV infection suggests antiviral drugs that prevent immunosuppression may be more effective than immunopotentiators that act to stimulate the immune system. Successful immune modulation requires both a thorough understanding of normal immune function and of the immunodeficiencies occurring in HIV infection. While over 50 possible immune modulating agents have been studied, only colony-stimulating factors (CSF) have proved useful in treating HIV patients. CSFs are a type of cytokine that seem to lessen neutropenia in patients with AIDS or AIDS-related complex. Another immunostimulant, Tacrine, is being studied for its ability to increase levels of CD4 T cells, which are depleted in HIV infection. Ironically, Trental, a drug that suppresses some aspects of the immune system, may enhance the quality of life and promote survival in HIV patients.

An outbreak of a 'rash' syndrome in patients attending methadone clinics in New South Wales is described. The rash is pruritic, exanthematous or purpuric involving the trunk, limbs, palms and soles, which develops over a week and proceeds in most patients to desquamation persisting for 3-4 weeks.

Context: Anterior cruciate ligament (ACL) injuries greatly impact patients in terms of future performance, reduced physical activity and athletic participation, and overall economic burden. Decades of research have investigated how to improve ACL reconstruction (ACLR) outcomes. Recently, there has been growing interest to understand the effects of psychosocial factors on patient outcomes.Study Design: Clinical review.Evidence Acquisition: A search of the PubMed database was performed in March 2023. Articles were reviewed by at least 2 authors to determine relevance. We highlighted publications of the past 5 years while incorporating previous pertinent studies.Level of Evidence: Level 5.Results: There is no standardization of psychosocial factors regarding ACLR. As such, there is a lack of consensus regarding which psychosocial measures to use and when. There is a need for clarification of the complex relationship between psychosocial factors and physical function. Despite this, psychosocial factors have the potential to help predict patients who are more likely to return to sport: (1) desire/motivation to return; (2) lower levels of kinesiophobia; (3) higher levels of self-efficacy, confidence, and subjective knee function; (4) risk acceptance; and (5) social support. However, there are no standardized interventions to improve psychosocial factors after ACLR.Conclusion: Psychosocial factors affect outcomes after ACLR. However, the interplay between psychosocial factors and physical function is complex. There is emerging evidence that testing and interventions may improve ACLR outcomes. There is a lack of standardized interventions to determine or improve psychosocial factors after ACLR. Further research is needed to identify psychosocial factors and to develop standardized interventions for clinicians to implement to improve clinical outcomes.

Interleukin 12 (IL-12) production is believed to be impaired in individuals with HIV infection and this impairment manifests early in disease, when the CD4+ cell counts are within normal values. The reduced antigen-specific and mitogen-stimulated T cell-proliferative responses that occur in HIV infection can be corrected by the addition of recombinant human interleukin 12 (rhIL-12). As the IL-12 receptor (IL-12R) is central to the IL-12 signaling pathway, we examined whether the augmentation of antigen-specific proliferation of HIV+ peripheral blood mononuclear cells (PBMCs) related to altered IL-12R expression. rhIL-12 augmented antigen-specific proliferation of HIV+ PBMCs but not of HIV- PBMCs. Examination of resting PBMCs from HIV+ and HIV- donors showed that neither of these populations expressed IL-12Rβ1 or IL-12Rβ2 chains on their cell surface as detected by flow cytometry. However, examination of mRNA showed that both IL-12Rβ1 and IL-12Rβ2 mRNAs were markedly reduced in HIV+ PBMCs when compared with HIV- PBMCs. After mitogen activation there was an increase in IL-12Rβ1 expression on the cell surface of HIV+ and HIV- PBMCs and this level was not altered by coculture with rhIL-12 or interferon γ (IFN-γ). However, coculture of phytohemagglutinin (PHA)-activated HIV+ or HIV- PBMCs with rhIL-12 (but not IFN-γ) increased IL-12Rβ2 expression on the cell surface of both populations. Examination at the message level showed a correction of IL-12Rβ1 to normal levels with activation that was further enhanced by rhIL-12 coculture for both the HIV+ and HIV- PBMCs. However, although the level of IL-12Rβ2 for the HIV+ PBMCs was normalized by PHA, rhIL-12 caused a further augmentation. This information provides a strong link between IL-12R upregulation, and the significant improvement in antigen-specific HIV-proliferative responses seen with the addition of rhIL-12. It also reveals that the dysfunction in IL-12R expression seen in cells from HIV+ patients occurs at the transcriptional level. In addition, we provide further evidence that IL-12Rβ1 and IL-12Rβ2 regulation in human PBMCs is independent of IFN-γ.

IL-12 production is reduced in HIV infection, and recombinant human IL-12 (rhIL-12) augments in vitro HIV-specific proliferative responses in PBMC from HIV-seropositive individuals. To determine whether rhIL12 could also augment HIV-specific CTL responses we studied 41 HIV-seropositive individuals. Recombinant hIL-12 increased the detectable in vitro HIV-specific CD8 CTL activity of PBMC taken from HIV-seropositive individuals with CD4 counts >500 cells/μl and from some individuals with lower CD4 counts. IL-12 increased cell recovery in cultures of PBMC from HIV-seropositive individuals with CD4 counts >500 cells/μl and also increased the precursor CTL frequency. However, the increase in HIV-specific CTL activity was not due to IL-2 or IFN-γ production or an increase in the number of cells with surface markers characteristic of CTL effector cells. This study demonstrates that rhIL-12 augments in vitro HIV-specific CTL activity and provides evidence to justify further investigation within clinical trials of this cytokine in HIV infection.

• Ophthalmic and neurologic involvement in chronic lymphocytic leukemia is uncommon, and if it does occur, it is usually only late in the course of the disease. We report three cases in which progressive visual loss from optic nerve infiltration was an early clinical manifestation of chronic lymphocytic leukemia. Progressive optic atrophy with loss of acuity and visual field occurred in all cases, preceded in one patient by transient visual obscurations and disc edema. Surface marker studies of cerebrospinal fluid lymphocytes were useful in differentiating leukemic optic nerve infiltration from other causes of optic nerve damage. Optic nerve irradiation gave considerable clinical improvement in all three cases.

This study aimed to determine the prognostic significance of DNA ploidy and S-phase fraction (SPF) measurements in our laboratory for patients with node-negative breast cancer. Frozen tumors from axillary node-negative breast cancer patients (n=50) treated at Westmead Hospital, NSW, between 1988 and 1991 were analysed by flow cytometry. The median duration of follow-up for all patients was 8.4 years. Forty-six specimens provided evaluable DNA histograms with 43% (n=20) diploid and 56% (n=26) aneuploid tumors identified. Comparisons of DNA ploidy status and SPF were made with traditional prognostic variables, which included age, menopausal status, tumor size, histologic grade and hormone receptor status. Our results showed that there was no significant difference in disease-free or overall survival between patients with diploid and aneuploid tumors. Histologic grade 3 tumors were more likely to be aneuploid and had higher SPF than grade 1 or 2 tumors. Patients with grade 3 tumors and a high SPF were four times more likely to relapse than the rest of the population. These results indicate that DNA flow cytometric analysis in our laboratory provides additional prognostic data that could be utilised alongside traditional clinical and histopathologic indicators for predicting outcome for patients.

Immune‐based therapy is in its infancy and to date no therapies are licensed in Australia. A number of the reagents are reaching phase III clinical trials and may be available within two years. Patient and physician interest is high because antiretroviral agents have not as yet had a significant impact on survival.

Polymerase chain reaction (PCR) was used to amplify the DNA fragments of the framework 3 region (FR3) of the immunoglobulin heavy (IgH) chain genes, from the tissue of 66 patients with Blymphoproliferative diseases and 74 patients with other malignant diseases, reactive or normal tissue. The assay performed with 77% sensitivity,100% specificity and 89% efficacy. In addition, the PCR assay cost less than 250 of the cost of performing Southern blot analysis of tumor DNA, which has been the test performed to date, and had a turn around time of 24 hrs rather than the 7-14 days required to obtain a result from Southern blot analysis. These results suggest that PCR analysis of B-cell lymphoproliferative disease is superior to Southern blot analysis, in the setting of a diagnostic laboratory.

This study evaluates the impact of therapeutic vaccination with p24-VLP and zidovudine on the induction or maintenance of HIV-specific cytotoxic lymphocyte activity in a cohort of asymptomatic patients with CD4 counts greater than 400 cells/mu l. In a dummy, randomized, phase II clinical trial of the therapeutic vaccine, participants were randomized to one of three arms for 6 months: p24-VLP (500 mu g) in alum monthly plus zidovudine 200 mg tds, alum adjuvant plus zidovudine, or p24-VLP plus placebo. Subjects were studied for a total of 52 weeks from baseline. Monitoring included viral load, CD4 and CD8 counts, markers of immune activation, delayed-type hypersensitivity (DTH) skin testing, and cytotoxic T lymphocyte (CTL) measurement. The nine subjects who received p24-VLP and zidovudine had an augmentation and/or broadening of their CTL response compared with baseline (p = 0.004). The eight subjects receiving p24-VLP and seven subjects receiving zidovudine did not have a statistically significant increase or broadening of CTL activity. The augmentation of the CTL response in the subjects who received p24-VLP and zidovudine was not associated with a decline in viral load or an increase in CD8 counts. This study suggests that HIV-specific CTL activity can be augmented in HIV-infected individuals receiving p24-VLP and zidovudine, supporting the hypothesis of therapeutic vaccination in the presence of antiretroviral therapy.

PBLs from 10 normal seropositive donors, 15 precardiac transplant patients, and 17 postcardiac transplant patients have been assayed for their ability to mount a cytotoxic T cell response to both A- and B-type EBV. Compared with the results obtained with healthy seropositive donors, pre- and posttransplant patients had significantly weaker T cell responses against both A-type and B-type EBV. Analysis of individual patients showed a preferential T cell response to B-type EBV in 4/15 pre- and 6/17 posttransplant patients and a preferential T cell response to A-type EBV in 1/15 pretransplant and 2/17 posttransplant recipients. PBMCs were obtained from patients and analyzed for the presence of A- and B-type EBV using polymerase chain reaction. EBV types detected in the PBMCs of each individual were correlated with their EBV-specific CTL response. The results obtained indicated that the EBV-specific cytotoxic T cell response of these patients matched the EBV types with which they were infected.

The decision to order an HIV antibody test is easier for the practitioner who has a clear plan for coping with a positive result: how to handle the initial support and counselling, how to answer questions on assessment of immune function and available treatments and how to seek specialist partnership with a local HIV physician.

Science and logic are again being applied to AIDS research