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Biomedical subjects

B Bodaghi

Publications and source records attributed to B Bodaghi.

At least 19 recordsLinked to original sources
PubMed2000

Acyclovir-resistant bilateral keratitis associated with mutations in the HSV-1 thymidine kinase gene.

PURPOSE: To evaluate the contribution of molecular methods for the diagnosis of an acyclovir-resistant HSV-1 bilateral keratitis in an AIDS patient and to report a new point mutation in the nucleotide sequence of the thymidine kinase (tk) gene involved. METHODS: A 31 year old HIV-positive female presented with severe, active, bilateral and sight-threatening keratitis of 6 months duration, which was treated unsuccessfully with acyclovir. After corneal biopsy, samples were analysed by standard virological procedures, in situ hybridization, and PCR. The tk gene was cloned and subsequently sequenced. RESULTS: Conventional virological methods remained inconclusive. However, in situ hybridization and PCR rapidly confirmed the diagnosis of HSV-1 keratitis. The tk gene sequence revealed the presence of five variations previously described in two reference strains, but also a new point mutation at nucleotide position 431 which leads to an amino-acid change at position 144 that supported the hypothesis of a putatively altered functional form of the enzyme. Intravenous foscarnet treatment in an induction regimen was effective and cicatrization occurred within 3 weeks. CONCLUSIONS: PCR and in situ hybridization are effective and powerful techniques when other virological procedures are non-contributive, particularly in immunocompromised patients previously treated with antiviral drugs. The new point mutation identified in the tk gene may be associated with resistance to acyclovir.

AIDS-Related Opportunistic Infections↗
PubMed2000

Ocular and central nervous system lymphoma: clinical features and diagnosis.

PURPOSE: To evaluate the clinical, angiographic, and cytopathologic features of ocular and central nervous system (CNS) lymphoma. PATIENTS AND METHODS: Retrospective study of 44 patients over a 10-year period. RESULTS: A total of 36 women and six men, mean age 54 years (range: 36-90 years), were included. The mean time interval between onset of ocular symptoms and diagnosis was 40 months (range: 1-144 months). Ocular involvement was bilateral in 84% of the cases. Laser flare photometry readings averaged 9.6 photons/ms (2.9-78.3 photons/ms). Vitritis was constant. Funduscopy revealed RPE abnormalities in 60.49% of the cases and punctuate retinal infiltrates in 33.5%. The most common findings with fluorescein angiography were window defects and hypofluorescent round lesions. Patients had CNS involvement in 66% of the cases. Cytologic examination of the vitreous samples showed high-grade B lymphoma in 86% of the cases. Interleukin-10 dosage, when performed, showed elevated levels averaging 2352 pg/ml in all vitreous samples. Molecular biology based on PCR confirmed the diagnosis in 12 patients. Treatment included systemic chemotherapy alone or associated with radiotherapy in various regimens. Fourteen patients died during follow-up. Only 12 patients were in complete remission. CONCLUSION: The prognosis of the disease remains poor. However, the new diagnostic tools and therapeutic strategies may improve the diagnostic delay and the survival outcome.

Adult↗
PubMed2000

Efficacy of interferon alfa-2a in severe and refractory uveitis associated with Behçet's disease.

PURPOSE: To evaluate the efficacy of interferon alfa-2a (IFN alfa) in severe uveitis associated with Behçet's disease, that is refractory to steroids and conventional immunosuppressive agents. PATIENTS AND METHODS: Patients with Behçet's disease (according to the International Study Group criteria), who relapsed despite steroids and immunosuppressive agents, were included in this retrospective study. Ophthalmological examination, laser flare photometry, and fluorescein angiography associated with laboratory tests were performed at regular intervals. IFN alfa (3 millions units thrice a week) was injected subcutaneously. RESULTS: Eight patients (sex ratio: 1) were included between May 1995 and January 1999. The mean age was 29.1 years (14-54 years) and the disease was present between 11 and 167 months before the administration of IFN alfa. IFN alfa was efficient in all cases with a mean follow-up of 22 months (10-55 months). Steroids were tapered from a mean dosage of 47 mg/d to a mean dosage of 8.5 mg/d. Ocular inflammation was controlled and visual acuity improved in all cases. Treatment was generally well tolerated despite a constant but transient flu-like syndrome. IFN alfa was tapered in three patients and stopped in one case without any relapse after five months. CONCLUSIONS: Within the limitations of this retrospective study, low-dose IFN alfa seems to be well tolerated, promising in the management of refractory forms of uveitis due to Behçet's disease, and effective in allowing a reduction of steroid dosage. A prospective controlled study is necessary to confirm these preliminary results.

Adolescent↗
PubMed2000

Ocular tuberculosis.

Despite the use of highly sensitive molecular tools, such as polymerase chain reaction, for the detection of Mycobacterium tuberculosis, ocular tuberculosis remains a subject of controversy. The diagnosis is often presumptive in the absence of ocular biopsies. Choroiditis is the most common ocular manifestation in patients with pulmonary and systemic tuberculosis. Indocyanine green angiography seems to be an interesting method to determine choroidal involvement. PCR technology is proposed to evaluate the presence of the tubercule bacillus DNA in ocular fluids and tissues when conventional microbiologic methods fail to confirm a bacterial etiology. Most of the presumed cases of ocular tuberculosis should be treated with associations of antituberculous drug, especially when a systemic steroid regimen is required.

Antitubercular Agents↗
PubMed2000

[Total eclipse of the sun in August 11, 1999: a program of prevention and surveillance of ocular complications].

Watching directly at the sun without appropriate protection, particularly during a solar eclipse, can cause severe retinal injuries. On 11 August 1999, a total solar eclipse crossed France. The Direction Générale de la Santé implemented a prevention strategy. A formal agreement was developed with manufacturers and importers of protective glasses and more than 30 million glasses, conformed with safety standards, were distributed in France. Information campaign reach the whole population in France. In order to evaluate the impact of this campaign, The National Institute of Public Health in France implemented a nation-wide surveillance of ocular complications related to the eclipse. Information on patients was collected using a standardised questionnaire. The questionnaire was sent to the 5,600 private and public sector ophthalmologists practising in France and to five hundred hospital emergency units. A total of 147 patients were reported to have had a retinal injury associated with viewing the eclipse. Seventeen cases were severe (visual acuity < 2/10th) of whom 7 had bilateral injury. Forty-four per cent of patients were aged 15 to 29 years and 46% viewed the eclipse in three regions in the south of France which were sunny on 11th August. One hundred and six patients (67% aged 30 years and more) presented with keratitis. Thirty-six per cent occurred in 2 northern regions of France, which were overcast on the day. A hundred patients watched the whole eclipse without any protection, 74 reported to have removed their EC glasses, and 32 used non-appropriate devices. Only 4 patients presenting with retinal injury reported having used the EC glasses the whole time whilst viewing the eclipse. France is the only country in Europe to have implemented an exhaustive prospective surveillance of ocular injuries related to the solar eclipse. According to current data, the quality and availability of EC glasses did not contribute significantly to ocular injuries. Clinical and epidemiological studies are being conducted in order to further document the evolution of patients presenting with retinal injuries, the circumstances of observation, and their comprehension of preventive messages.

Adolescent↗
PubMed2000

[Current status of retinal detachment in AIDS patients].

Cytomegalovirus retinitis is the most common opportunistic ocular infection in patients with AIDS affecting 30 to 40% of the patients. It usually occurs in patients in the terminal stage of the disease presenting with low CD4+ count (<50/mm(3)). Retinal detachment (RD) is a frequent complication of this disease, with an incidence varying from 18% to 29%. Risk factors for development of rhegmatogenous RD in patients with CMV retinitis were peripheral involvement greater than 25%, the presence of active retinitis, greater patient age and lower CD4+ cell counts. Multiple or single holes, as well as micro holes, were observed in areas of retinal necrosis leading to complex retinal detachments. Strong vitreoretinal adherences in these young patients, associated with chronic inflammation, were important elements in the pathophysiology of retinal detachment in AIDS patients. For localized RD, demarcating laser photocoagulation may delayed or avoided vitreoretinal surgery. For RD with macula off, good anatomical results have been obtained by repairing CMV retinitis-related retinal detachments using primary vitrectomy and instillation of silicone oil. Despite good anatomical results, poor long term functional results are related to optic atrophy. Since the introduction of highly active antiretroviral therapy (HAART), retinal detachment incidence has nevertheless dramatically decreased. Under HAART, CMV retinitis remains quiescent for long periods of time with a reduction of retinal detachment incidence of approximately 77%. For some patients on HAART, retinal reattachment can be obtained using vitrectomy, posterior hyaloid removal, and intraocular tamponade with SF-6 gas.

AIDS-Related Opportunistic Infections↗
PubMed1999

Role of IFN-gamma-induced indoleamine 2,3 dioxygenase and inducible nitric oxide synthase in the replication of human cytomegalovirus in retinal pigment epithelial cells.

An in vitro model of human CMV infection of primary retinal pigment epithelial (RPE) cells was used to study the effects of cytokines on CMV replication in these cells, which are targets of CMV infection in vivo. IFN-gamma and IFN-beta were potent inhibitors of CMV replication in RPE cells, while TNF-alpha, IL-1beta, or TGF-beta2 did not affect viral replication. Inhibition by IFN-gamma, and to a lesser extent IFN-beta, was almost completely reversed by addition of L-tryptophan to the culture medium, strongly implicating the indoleamine 2,3 dioxygenase (IDO) pathway. Polyadenylated IDO mRNA accumulation was detected as early as 2 h after IFN stimulation. Furthermore, CMV blocked the production of nitric oxide by the inducible form of nitric oxide synthase. This inhibition depended on a functional viral genome. However, exogenous nitric oxide significantly inhibited viral protein expression in RPE cells. Thus, CMV infection blocks the inducible nitric oxide synthase pathway activated by IFN-gamma and IL-1beta, but cannot counteract the IFN-induced IDO pathway, which ultimately controls its replication in primary human RPE cells.

Antiviral Agents↗
PubMed1999

Cytomegalovirus: virological facts for clinicians.

Human cytomegalovirus (HCMV) is a complex DNA virus encoding more than 200 viral proteins. This highly adapted opportunist agent has developed several ways to evade the immune system. Among all clinical features due to HCMV, retinitis occurs especially in severely immunosuppressed patients, particularly during the end phase of HIV infection. Highly active antiretroviral therapy (HAART) has significantly reduced the incidence of this complication. However, in this HAART era, we observe the emergence of new clinical patterns in patients presenting with cicatricial HCMV retinitis. These patterns could be potentially related to immune mechanisms directed against viral antigens expressed at the surface of retinal cells that are still latently infected without any viral replication. We used a model of human retinal pigment epithelial (RPE) cells to evaluate virus-host interactions in the presence of different cytokines in the eye which play a major role in immunological or infectious conditions. Two different enzymatic pathways seem to be particularly involved during infection. Lack of tryptophan and production of nitric oxide seem to block HCMV replication in RPE cells. We propose a model to explain some of the mechanisms involved during severe immunosuppression and also after immune recovery.

Anti-HIV Agents↗
PubMed1999

CMV retinitis in the era of HAART.

Since 1996, major advances in the treatment of AIDS have markedly changed the incidence and the prognosis of CMV retinitis. Highly active antiretroviral therapy (HAART) is a combination of nucleoside reverse transcriptase inhibitors and protease inhibitors. This new therapeutic strategy is highly efficient in reducing the HIV viral load and increasing CD(4)+ T-lymphocyte count. These biological effects are associated with an improvement of immune functions. Clinically, the completely quiescent CMV retinitis and the unusual prolonged relapse-free interval suggest a certain restoration of immune functions, making possible the discontinuation of maintenance therapy. For most authors, the decision to stop anti-CMV maintenance therapy is based on a CD4+ cell count >100 cells/microl with a low HIV viral load for at least four months. The improvement of CMV retinitis on HAART may also be associated with an intraocular inflammation called immune recovery vitritis. For some patients, this vitritis may be associated cystoid macular edema and an epiretinal membrane responsible for visual loss.

AIDS-Related Opportunistic Infections↗
PubMed1999

Kinetics of transcription of human cytomegalovirus chemokine receptor US28 in different cell types.

In permissive cells, human cytomegalovirus encodes the protein US28, a functional CC chemokine receptor. US28 polyadenylated mRNA could be detected by RT-PCR as early as 2 h post-infection. US28 mRNA appeared after major IE1 transcripts (UL123), but before transcripts of the early genes pp65 (UL83) and gB (UL55), and the late gene pp150 (UL32). This temporal appearance indicates that US28 is transcribed earlier than previously reported. Furthermore, US28 mRNA could be detected in semi- and non-permissive cells.

Animals↗
PubMed1999

Cystoid macular oedema and cytomegalovirus retinitis in patients with HIV disease treated with highly active antiretroviral therapy.

BACKGROUND: Although cystoid macular oedema (CMO) is a rare cause of visual loss in AIDS related cytomegalovirus (CMV) retinitis, nine cases are reported of CMO occurring in HIV infected patients with a prior diagnosis of CMV who were receiving highly active antiretroviral therapy (HAART). METHODS: Medical and ophthalmological records of nine AIDS patients with inactive CMV retinitis were retrospectively analysed. Ophthalmic examination data, laboratory findings, and the systemic antiviral treatment were studied. Ophthalmic examination included visual acuity, anterior chamber flare measured with the laser flare cell meter (LCFM), vitreous haze quantification according to the Nussenblatt grading system, and fluorescein angiography. RESULTS: Nine HIV infected patients, eight men and one woman, mean age 39 years (range 29-53 years) presented with inactive CMV retinitis and CMO. On fluorescein angiography, CMO was present only in eyes (14 eyes) with signs of previous CMV retinitis. CMV retinitis was inactive in all of them. Visual acuity ranged from 20/200 to 20/30. In 10 eyes with CMV retinitis, anterior chamber flare measured with the LCFM ranged from 18.5 to 82 photons/ms (mean 35.42 ph/ms). A significant vitreous inflammation (1.5+) was observed in eight eyes. All patients had been treated with anti-CMV drugs for a mean period of 18 months (range 12-36 months). All nine patients received HAART with a combination of two nucleotide analogue reverse transcriptase inhibitors and one protease inhibitor for a mean period of 14 months (range 9-18 months). The HIV viral load was below detectable levels (< 200 copies/ml) in eight patients and low (3215 copies/ml) in one. At the time of CMO, the median CD4+ lymphocyte count was 232 cells x 10(6)/l (range 99-639). CONCLUSION: In AIDS patients, the usual absence of intraocular inflammation in eyes affected by CMV retinitis has been tentatively explained by the profound cellular immunodeficiency. In these patients, treated with HAART, CD4+ counts were increased for several months (mean 14 months). In their eyes, CMV retinitis was associated with significant ocular inflammation and CMO. These findings could be related to the restoration of immune competence after HAART as recently shown.

AIDS-Related Opportunistic Infections↗
PubMed1999

Entry of human cytomegalovirus into retinal pigment epithelial and endothelial cells by endocytosis.

PURPOSE: Human retinal pigment epithelial (RPE) cells and endothelial cells (HUVECs) are targets of human cytomegalovirus (HCMV) infection in vivo with significantly protracted replication in vitro compared with that in fibroblasts. This study analyzes the kinetics and mechanisms of HCMV entry into both cell types. METHODS: RPE cells were obtained from donor eyes. HUVECs were isolated from human umbilical cords. HCMV entrance was followed by electron microscopy and immunofluorescence in the presence of lysosomotropic agents and cytochalasin B. RESULTS: Human cytomegalovirus entered into RPE cells and HUVECs as early as 5 minutes after virus- cell contact. Entry was mediated by endocytosis, whereas HCMV enters fibroblasts through fusion. Most internalized viral particles and dense bodies appeared to be degraded within vacuoles. Viral entry, transport of viral proteins to the nucleus, and onset of viral transcription (immediate early [IE] protein expression) were significantly blocked by cytochalasin B. Lysosomotropic agents did not significantly reduce IE expression in RPE cells or HUVECs. CONCLUSIONS: This study shows that HCMV penetrates these highly specialized relevant cells via endocytosis. The low level of infection and the delay in the onset of HCMV expression seen in these cells compared with fibroblasts may be related to the sequestration and degradation of incoming viral particles in endocytic vacuoles.

Ammonium Chloride↗
PubMed1998

Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirus-infected cells.

Human cytomegalovirus (HCMV), a betaherpesvirus, has developed several ways to evade the immune system, notably downregulation of cell surface expression of major histocompatibility complex class I heavy chains. Here we report that HCMV has devised another means to compromise immune surveillance mechanisms. Extracellular accumulation of both constitutively produced monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor-superinduced RANTES (regulated on activation, normal T cell expressed and secreted) was downregulated in HCMV-infected fibroblasts in the absence of transcriptional repression or the expression of polyadenylated RNA for the cellular chemokine receptors CCR-1, CCR-3, and CCR-5. Competitive binding experiments demonstrated that HCMV-infected cells bind RANTES, MCP-1, macrophage inflammatory protein (MIP)-1beta, and MCP-3, but not MCP-2, to the same receptor as does MIP-1alpha, which is not expressed in uninfected cells. HCMV encodes three proteins with homology to CC chemokine receptors: US27, US28, and UL33. Cells infected with HCMV mutants deleted of US28, or both US27 and US28 genes, failed to downregulate extracellular accumulation of either RANTES or MCP-1. In contrast, cells infected with a mutant deleted of US27 continues to bind and downregulate those chemokines. Depletion of chemokines from the culture medium was at least partially due to continuous internalization of extracellular chemokine, since exogenously added, biotinylated RANTES accumulated in HCMV-infected cells. Thus, HCMV can modify the chemokine environment of infected cells through intense sequestering of CC chemokines, mediated principally by expression of the US28-encoded chemokine receptor.

Binding Sites↗
PubMed1998

Whipple's syndrome (uveitis, B27-negative spondylarthropathy, meningitis, and lymphadenopathy) associated with Arthrobacter sp. infection.

OBJECTIVE: To report an unusual case of Whipple's disease, including uveitis, seronegative spondylarthropathy, meningitis, and lymphadenopathy, associated with an Arthrobacter sp. infection. DESIGN: Interventional case report. PATIENT AND INTERVENTION: A 60-year-old white man presenting with severe chronic uveitis and systemic inflammatory manifestations was treated efficiently for Whipple's disease after histopathologic analysis of vitreous and inguinal adenopathy biopsy specimens. The authors performed a retrospective, laboratory-based evaluation of stored tissue specimens. MEASUREMENTS: Molecular analysis based on 16S ribosomal RNA gene amplification was applied to pretreatment biopsy specimens of inguinal lymph node to identify a causative bacterial agent. RESULTS: Tropheryma whippelii genome was not detected in these specimens. However, an amplification product was obtained after the first polymerase chain reaction run and subsequently was sequenced. It corresponded to an Arthrobacter sp., a gram-positive agent presenting diagnostic patterns and therapeutic management similar to those of Whipple's disease caused by T. whippelii. CONCLUSION: The absence of T. whippelii identification by molecular amplification during a clinically and histologically oriented Whipple's syndrome should not rule out the diagnosis. Arthrobacter infection may represent a new bacterial etiology of systemic inflammatory disorders involving the eye and associated with periodic acid-Schiff-positive inclusions.

Arthrobacter↗