PubMed Health⌕ Search

Biomedical subjects

C M Farber

Publications and source records attributed to C M Farber.

At least 19 recordsLinked to original sources

Macular CMV retinitis: a case report.

PURPOSE: Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic infection associated with AIDS. It usually affects the peripheral retina, sparing the macula. We describe an atypical CMV retinitis exclusively confined to the macula. METHODS: A 43-year-old man with the diagnosis of AIDS developed a white retinal lesion confined to the macula of the right eye. Two weeks later, a more typical granular appearance was observed leading to presumption of CMV retinitis. RESULTS: The patient was treated with ganciclovir without success. With foscarnet, a good response was obtained, leading to total healing of the lesion. CONCLUSIONS: CMV retinitis has to be taken into consideration in all lesions confined to the macula in immunodepressed patients. An early diagnosis is crucial to avoid blindness.

AIDS-Related Opportunistic Infections↗

High-dose chemotherapy and autologous CD34-positive blood stem cell transplantation for multiple myeloma in an HIV carrier.

The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-positive patients is poorly documented. There are uncertainties concerning the optimal management of this rare disorder. We report on the use of myeloablative chemotherapy with autologous stem cell transplantation in an HIV-positive patient with multiple myeloma.

Acquired Immunodeficiency Syndrome↗

[The immunodeficiency treatment unit].

Physicians of the unit have first taken care of patients with acquired Immunodeficiency in 1981. We have become an independent "Reference Centre" in 1998. The multidisciplinary team follows more than 300 patients on a regular basis. AIDS has been amply publicized, but other immuno-deficiencies have not. Primary immunodeficiencies are "orphan" diseases; they can be as serious, or more severe even, than AIDS. About 60 patients with "PID" are followed by the team. We are involved in research, and have participated in the identification of a mutation of an HIV co receptor that protects against HIV infection. We also studied the pathogenesis of Kaposi's sarcoma, and the immunological basis of adverse reactions to intravenous gammaglobulins.

Allergy and Immunology↗

Immunologic and virologic response after tetanus toxoid booster among HIV-1- and HIV-2-infected Senegalese individuals.

Twelve HIV-1-infected, nine HIV-2-infected patients and eight HIV-negative subjects were given a 40IU booster dose of tetanus toxoid (TT). Blood was collected on days 0, 7 and 30 after immunization. Changes in HIV-1 or HIV-2 RNA load were evaluated by nested PCR. TT-IgG antibody levels were quantified by ELISA. CD4 cell counts as well as activation, memory and maturation markers of T lymphocyte subsets were determined by flow cytometry. The induction of apoptosis was investigated using 7-aminoactinomycin D (AAD) and propidium iodide (PI) staining. Proliferative responses to TT and pokeweed mitogen (PWM) were determined by the level of [(3)H] thymidine incorporation. Seven and 30 days after immunization, there was no detectable increase in HIV-1 or HIV-2 plasma load. There were also no changes in CD4 cell counts, CD69, HLA-DR and memory CD45RO or naive CD45RA antigens. Immunization did not increase the spontaneous apoptosis of peripheral blood mononuclear cells (PBMCs), CD4+ and CD8+ T cells subsets neither in controls nor in HIV-infected patients. Similarly, apoptosis induced in vitro by PWM or by the specific TT recall antigen did not vary during the study period. The proliferative response to PWM and to the TT recall antigen was decreased both in HIV-1- and HIV-2-infected patients compared to HIV-negative controls. Immunization significantly increased the TT-IgG levels in healthy controls and in HIV-infected patients. However, the anti-TT-IgG response, as measured by the fold-increase index between days 0 and 30, was significantly higher in healthy controls than in HIV-1- (P=0.036) and HIV-2-infected patients (P=0.003). In conclusion, we found no deleterious immunologic or virologic effect was detected in healthy HIV-1- and HIV-2-infected individuals after antigenic challenge with a TT booster. However, the response to TT vaccination was lower in HIV-1- and in HIV-2-infected individuals than in healthy HIV-negative controls.

Adult↗

[Immune deficiencies: diagnosis, management, some perspectives].

Severe primary immunodeficiencies (PID) are rare; their global incidence is comparable to that of childhood leukemia; they include more than 100 different entities. Clinical manifestations are: unusually severe or frequent infections or infections that do not respond to adequate treatment; an increased risk of certain malignancies; sometimes auto-immune manifestations. Delayed diagnosis and management of PID can lead to severe and irreversible complications or to death. PID can become manifest only in the adult; in common variable immune deficiency, the median age at diagnosis is between the 2nd and the 3rd decade of life. PID are often transmitted genetically; recent progresses in molecular biology have allowed more precise and earlier, including antenatal, diagnosis. Molecular treatment of 3 infants with a severe immunodeficiency has recently been achieved in April 2000. Those progresses were mostly based on the study of immunodeficiency databases. We present here the work of a Belgian group specialized in PID; meetings have started in June 1997. This group establishes guidelines for the diagnosis and treatment of PID, adapted to the local situation. The elaboration of a national register of PID is also underway; this has to provide all guaranties of anonymity to patients and families. Such a register already exists at the European level; it has provided the basis for new diagnostic and therapeutic possibilities. The inclusion of Belgian data in this register should allow essential progresses essential for our patients.

Adolescent↗

Spontaneous apoptosis and highly active antiretroviral therapy (HAART).

Increased programmed cell death (PCD) or apoptosis has been detected in the T cells of HIV-infected subjects; it is held partially responsible for the continuous loss of CD4+ T cells during the natural course of HIV infection. Highly active antiretroviral therapy (HAART) decreases the viral load and leads to an increase of CD4+ count in vivo. In this study we evaluated PCD in total peripheral blood mononuclear cells, CD8+ and CD4+ lymphocytes before and four weeks after initiation of HAART. Seven HIV-1-infected patients were investigated. Viral load was assessed by RT-polymerase chain reaction and PCD by flow cytometry using apoptosis by 7 amino actinomycin D (7AAD) and propidium iodide (PI). After four weeks of HAART, CD4+ T and CD8+ T cell levels were stable, and plasma HIV-RNA copies were significantly decreased. In four of the patients (4/7), HIV-RNA levels were reduced to undetectable levels (fewer than 400 copies per milliliter). A statistically significant reduction of apoptosis among CD4+ cells was observed (P < 0.03), though neither in the CD8+ T cell population nor in peripheral blood mononuclear cells (PBMCS). These results demonstrate the beneficial effect of HAART on apoptosis of CD4+ cells in the early treatment stage.

Adult↗

Iron as a potential co-factor in the pathogenesis of Kaposi's sarcoma?

The role of iron in the pathogenesis of several tumours is being increasingly investigated. In particular, its involvement in the pathogenesis of Kaposi's sarcoma (KS) is suggested by the distribution of the endemic form of KS corresponding to continental rifts and associated iron-oxide-rich volcanic clays. We investigated in vitro to what extent iron supplementation or withdrawal could affect the growth of KS-derived cells, by analysing the effects of adding iron salts (iron chloride and ferric nitrilotriacetate) and/or reducing iron by iron chelators (desferrioxamine) on KS-derived cell cultures. The addition of iron salts strongly stimulated the growth of KS cells, as reflected by increase in thymidine incorporation and cell number. Conversely, desferrioxamine and deferiprone inhibited cell growth. The inhibitory effect of iron chelation was more pronounced on rapidly dividing basic fibroblast-growth-factor-stimulated cells. These results may point to a novel therapeutic approach to KS.

Carcinogens↗

Constitutive release of metalloproteinase-9 (92-kd type IV collagenase) by Kaposi's sarcoma cells.

Kaposi's sarcoma (KS) is an angioproliferative disease characterized by proliferating spindle-shaped cells, angiogenesis, and inflammatory cell infiltration. Several lines of evidence suggest that KS is a multifocal cytokine-mediated disease of vascular origin. Because metalloproteinases (MMPs) are important enzymes involved in angiogenesis, we studied their activity in five different KS-derived cell lines and compared these data with those obtained with human umbilical vein endothelial cells (HUVEC). We focused on the activity of the 72- and 92-kd type IV collagenases because these enzymes are thought to play an important role in the process of tumoral invasion. Nonstimulated HUVEC released a weak 72-kd collagenase activity and no 92-kd collagenase activity, as determined by zymographic analysis. Stimulation of HUVEC with phorbol myristate acetate (PMA) or TNF-alpha increased the 72-kd collagenase activity and also induced a 92-kd collagenase activity. By contrast, KS-derived cells constitutively released significant 72- and 92-kd collagenase activities. The basal release of these enzymes by KS cells was further enhanced by TNF-alpha or PMA. Conversely after in vivo exposure to chemotherapy, KS-derived cells showed a downregulation of the production of MMPS that could be reversed by the addition of TNF or PMA. These results suggest that KS cells have constitutive features of activated cells that have an invasive and metastasizing potential.

Cells, Cultured↗

Efficient transport and accumulation of vitamin C in HL-60 cells depleted of glutathione.

Human myeloid leukemia cells (HL-60) transport only the oxidized form of vitamin C (dehydroascorbic acid) and accumulate the vitamin in the reduced form, ascorbic acid. We performed a detailed study of the role of glutathione in the intracellular trapping/accumulation of ascorbic acid in HL-60 cells. Uptake studies using HL-60 cells depleted of glutathione by treatment with L-buthionine-(S,R) sulfoximine and diethyl maleate, revealed no changes in the cells' ability to transport dehydroascorbic acid and accumulate ascorbic acid. Similar transport and accumulation rates were obtained using HL-60 cells containing intracellular glutathione concentrations from 6 mM to 1 microM. HL-60 cells, containing as little as 5 microM glutathione, were able to accumulate up to 150 mM ascorbic acid intracellularly when incubated with dehydroascorbic acid. Glutathione was capable of reducing dehydroascorbic acid by a direct chemical reaction, but only when present in a greater than 10-fold stoichiometric excess over dehydroascorbic acid. The accumulation of ascorbic acid by HL-60 cells was strongly temperature-dependent and was very inefficient at 16 degrees C. On the other hand, the direct chemical reduction of dehydroascorbic acid by excess glutathione proceeded efficiently at temperatures of 16 degrees C. Our data indicate that glutathione-dependent reductases in HL-60 cells are not responsible for the ability of these cells to accumulate millimolar concentrations of ascorbic acid. These findings indicate that alternative enzymatic mechanisms are involved in the cellular reduction of dehydroascorbic acid.

Antimetabolites↗

Pyogenic arthritis caused by streptococcus equisimilis (group-C streptococcus) in a patient with AIDS.

A patient with the Acquired ImmunoDeficiency Syndrome (AIDS) treated with a daily low dose of corticosteroids for chronic atopic dermatitis experienced a sudden episode of unilateral knee arthritis. Culture of the purulent synovial liquid yielded a pure culture of Streptococcus Equisimilis. A four week period of intravenous antibiotherapy combined with repeated drainages allowed a complete recovery of articular function.

AIDS-Related Opportunistic Infections↗

Importance of method in the determination of syncytium-inducing phenotype of human immunodeficiency virus type 1 clinical isolates.

The in vitro syncytium induction capacity of human immunodeficiency virus type 1 (HIV1) isolates is an important marker in the progression of the disease. Two methods have been widely used to determine the biological phenotype of HIV1. These two methods, the direct MT-2 assay and the supernatant assay, were compared for the detection of syncytium-inducing (SI) variants on 275 blood samples obtained from 87 HIV infected patients during a 13 month follow-up period. A SI virus was detected in 152 blood samples. In 44 blood samples, the HIV isolate was found to be SI by only one method, but was SI by both methods in another blood sample of the follow up. Among SI carriers discordant results between the methods were more frequent when the patient was on antiretroviral therapy, and a transient reversion to a non syncytium-inducing (NSI) strain confirmed by both assays was sometimes observed. The supernatant assay has a 93% sensitivity and the direct MT-2 assay has a 78% sensitivity for detection of the SI phenotype. The supernatant assay is as rapid as and less tedious than the MT-2 assay. Antiretroviral therapy could have some effects in decreasing or even suppressing the SI part of the virus population of patients with SI phenotype.

Cell Line, Transformed↗

Autologous stem cell infusion for acute myeloblastic leukemia in an HIV-1 carrier.

We present the case of an asymptomatic HIV carrier, who presented with acute myeloblastic leukemia in third relapse and successfully underwent autologous stem cell transplantation as a rescue treatment. This observation supports the conclusion that tolerance of autologous bone marrow or stem cell transplant in patients with HIV may correlate with a low viral burden and relatively good immune function.

Acute Disease↗