Effect of lithium carbonate in hiv-infected patients with immune dysfunction

Ten homosexual men received oral lithium carbonate at doses that maintained their serum lithium concentrations between 0.5 and 1.5 mEq/L. Prior to treatment all patients had HIV isolated from PHA-activated peripheral blood lymphocytes (PBLs) using a quantitative antigen-capture enzyme-linked immunosorbent assay (ELISA) assay for detection, and had an absolute number of CD4 (helper) lymphocytes of \u3c300/mm3. Eight of 10 patients developed symptoms of drug toxicity requiring discontinuation of the drug in 7 patients. Two patients completed only 4-5 weeks of lithium therapy, and 5 patients received 7-8 weeks. All patients remained culture positive for HIV during the trial, and viral titers as measured by the antigen capture assay were unchanged or increased. There were no significant changes in the absolute number of CD4 lymphocytes, CD4/CD8 ratio, or phytohemagglutinin (PHA) or tetanus toxoid induced proliferative responses. There was a significant decrease in mixed lymphocyte reaction (MLR). Lithium carbonate demonstrated no immunorestorative or antiviral activity when given in therapeutic doses. Drug toxicity limited therapy in the majority of patients. © 1988 Raven Press, Ltd., New York

In vitro effects of thymosin and lithium on lymphoproliferative responses of normal donors and HIV seropositive male homosexuals with AIDS-related complex

The in vitro effects of thymosin fraction 5 (TF5) and lithium chloride (LiCl) on the ability of peripheral blood mononuclear cells (PBMC) obtained from 37 normal male donors and 33 male patients with AIDS-related complex (ARC) to respond to alloantigenic stimulation (mixed leukocyte reaction, MLR) and to produce interleukin 2 (IL-2) in response to mitogens were studied. TF5 significantly increased MLR responses in normal donors (P \u3c 0.01) and in a group of 33 ARC patients with depressed cellular immunity (P \u3c 0.05). Similar effects were observed when LiCl was added to the MLR assays in both the normal and the ARC patient groups. Furthermore, TF5 and LiCl exhibited additive immunoenhancing properties. In 10 normal donors TF5 enhanced phytohemaggutinin (PHA)-induced IL-2 production as well as IL-2 production in response to pokeweed mitogen (PWM) (P \u3c 0.02). TF5-mediated enhancement of IL-2 production by PBMC obtained from ARC patients was observed in response to both mitogens, i.e., PHA and PWM. Additionally, LiCl increased PHA-induced IL-2 production in both normal subjects and ARC patients. LiCl and TF5 together had an additive effect in the enhancement of IL-2 production in both groups of subjects. Our data extend previous observations regarding the immunoregulatory activities of TF5 and LiCl and provide evidence that PBMC obtained from ARC patients have the potential to respond in vitro to these agents. The significance of these findings is discussed. © 1987

Cancer burden in individuals with single versus double pathogenic variants in cancer susceptibility genes

Purpose: As panel testing expands, more individuals with double pathogenic variants (DPVs) in cancer susceptibility genes are likely to be identified. Little is known about the effects of DPVs on cancer phenotype, although this information is crucial for genetic counseling and risk management. We sought to describe the cancer phenotype among individuals with DPVs in cancer susceptibility genes. Methods: A retrospective study of individuals with DPVs identified through a single testing laboratory from 2012 to 2017 was conducted. DPV combinations were enumerated. For DPV gene combinations that occurred >10 times, cancer histories of individuals with DPVs were compared with cancer histories of controls with a single PV matched by gene. Results: Among 644 individuals with DPVs, combinations that included the ATM, BRCA1, BRCA2, CHEK2, and PALB2 genes occurred >10 times. There were 8883 matched controls for a single PV in these genes. The median age of first cancer diagnosis was younger with ATM+CHEK2 (43), compared with ATM (47, P = .016) or CHEK2 (47, P = .015) alone. Similar findings were observed when comparing age at first breast cancer (BC) for the ATM+CHEK2 with single-gene controls. Individuals with 2 CHEK2 PVs also were younger at first cancer diagnosis (40) compared with single CHEK2 PV controls (47, P = .0038). This difference was not driven by age at first BC diagnosis among females. Conclusion: Individuals with ATM+CHEK2 or 2 CHEK2 PVs have a greater cancer burden than single gene controls. These findings can be used to counsel individuals with DPVs and their families and inform cancer screening recommendations

CLINICAL, IMMUNOLOGICAL, AND VIROLOGICAL EFFECTS OF AMPLIGEN, A MISMATCHED DOUBLE-STRANDED RNA, IN PATIENTS WITH AIDS OR AIDS-RELATED COMPLEX

10 patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), or lymphadenopathy syndrome (LAS) were given 200-250 mg ampligen, a mismatched double-stranded (ds) RNA with in-vitro antiviral activity against human immunodeficiency virus (HIV), twice a week for up to 18 weeks, without side-effects or toxicity. In all 9 patients who were positive for HIV RNA in peripheral blood mononuclear cells before therapy, levels became undetectable between days 10 and 40 of the start of therapy. 6 of the 7 patients with ARC or LAS also showed a progressive reduction in HIV load as measured by co-culture assays. All 10 patients had augmentation of delayed-type hypersensitivity skin reactions. Other changes noted during ampligen therapy included an increase in or maintenance of numbers of helper-inducer T lymphocytes, improvements in HIV-related symptoms, rises in titre of neutralising antibodies against HIV, and restoration of proper functioning of the natural lymphocyte antiviral dsRNA-dependent (2\u27-5\u27 oligoadenylate/RNA-ase L) pathway. Thus, in the short term, ampligen seems to have the dual ability to restore immunological function and to control HIV replication. © 1987