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Biomedical subjects

P Roux

Publications and source records attributed to P Roux.

At least 73 records · Page 4Linked to original sources

Treatment of non-meningeal cryptococcosis in patients with AIDS. Centre d'Informations et de Soins de l'Immunodéficience Humaine de l'Est Parisien.

Amphotericin B, alone or combined with flucytosine, is the reference curative treatment for neuromeningeal cryptococcosis associated with the acquired immune deficiency syndrome (AIDS). Treatment of non-meningeal forms is less well standardized. Out of 75 human immunodeficiency virus (HIV)-infected patients with cryptococcosis, 16 had no meningeal involvement. One died before receiving any treatment, another received amphotericine B and recovered, and the remaining 14 received curative therapy with fluconazole (200-400 mg/day); 11 of the latter entered complete remission, while three deteriorated during the first week of treatment but recovered on amphotericin B combined, in two cases, with fluconazole. Only one relapse occurred during maintenance treatment with low-dose fluconazole (100 mg/day). No adverse effects of fluconazole treatment were observed. One of the patients on amphotericin B developed acute renal impairment requiring drug withdrawal. These results suggest that first-line fluconazole therapy is effective and well tolerated in patients with AIDS-associated non meningeal cryptococcosis.

AIDS-Related Opportunistic Infections↗

Isolation and characterization of c-fos-expressing murine bone marrow stromal cell lines supporting myeloid differentiation.

We have previously reported that constitutive expression of c-fos oncogene allows long-term proliferation of primary mouse bone marrow stromal cells favoring the granulocytic differentiation of myeloid precursors in an in vitro assay. Retrovirus-mediated gene transfer of the human c-fos gene was used here for immortalizing nine mouse bone marrow cell lines which were studied in detail. However, due to low expression of the ectopic c-fos gene, none of them showed characteristics of transformation as assayed by dependence upon serum for growth, the inability to form colonies in agar and contact inhibition. All of them displayed a fibroblastoid phenotype, as deduced from morphological observation and analysis of several differentiation markers. They mostly supported the granulocytic differentiation of bone marrow myeloid precursors in a GM-assay, as did c-fos-expressing primary stromal cells. Their potential for supporting myeloid progenitor proliferation was however significantly lower than that of the whole adherent layer of the Dexter-type long-term bone marrow culture they derived from (STNT cells). They showed significant variations with respect to their cytokine gene expression analyzed at the RNA level in keeping with the notion of stromal cell heterogeneity in the bone marrow. Interestingly, none of them secreted GM-CSF, SCF or IL-3, which are cytokines reputed for their ability to stimulate hematopoietic progenitors, and strikingly, only two of them were able to produce detectable levels of G-CSF in culture supernatants despite the propensity of all of them to favor granulocyte differentiation. Finally, in coculture assay, bone marrow cells were able to diminish the expression of several cytokine genes albeit at a much lower degree than in the original STNT cells.

Animals↗

Outbreak of Pneumocystis carinii pneumonia in a renal transplant unit.

The charts for seven renal transplant recipients who developed Pneumocystis carinii pneumonia were reviewed. They included six men and one woman transplanted a mean of 150 days before the diagnosis of this infection. Six presented at least one episode of acute graft rejection. Cytomegalovirus pneumonia was diagnosed in six of the patients. All patients were treated with cotrimoxazole. Global mortality was 43%. In additional to the classic hypothesis of latent Pneumocystis carinii reactivation in immunocompromised hosts, this and previous reports of outbreaks strongly suggest either a person-to-person transmission or acquisition from the environment. Molecular typing of isolates could be of value in identifying the source of such outbreaks. Chemoprophylaxis should be more systematically administered to renal transplant patients, co-trimoxazole being the drug of choice.

AIDS-Related Opportunistic Infections↗

[Histoplasmosis, caused by Histoplasma capsulatum, and AIDS].

Histoplasma capsulatum histoplasmosis occurs frequently in endemic areas and with the AIDS outbreak, it appears as an opportunistic fungus involved in disseminated disease. We report the clinical, biological and treatment features of seven cases diagnosed in the CISIH of the Eastern part of Paris. Clinically, four patients were suffering from pulmonary symptoms, in three cases digestive disorders and in three cutaneous lesions. In all cases, the mycologic diagnosis was necessary. Amphotericin B and itraconazole were used as treatment for five patients (two died before the diagnosis was completed). Among these five subjects, four died (death was attributed to histoplasmosis in only one case). These observations emphasize the importance of this infection in HIV-infected patients coming from endemic areas.

AIDS-Related Opportunistic Infections↗

Ophthalmoscopic visualization of the inferior ophthalmic vein through a chorioretinal coloboma.

PURPOSE/METHODS: In a patient with a coloboma of the optic nerve, inferior retina and choroid, and deep portions of the sclera, a retrobulbar vessel moved irregularly relative to the retinal vessels, which moved contiguously with the posterior globe. RESULTS/CONCLUSION: Fluorescein angiography showed the retrobulbar vessel filling slightly later than overlying retinal vessels. We conclude that the retrobulbar vessel was a vein situated inferiorly to the optic nerve.

Adult↗

Preliminary report of sutureless phacotrabeculectomy through a modified self-sealing scleral tunnel incision.

A method of combined cataract extraction and trabeculectomy using phacoemulsification through a modified 5 mm sutureless scleral tunnel incision is described. In eight patients who were followed for a minimum of five months in an initial series, the intraocular pressure (IOP) decreased to less than 19 mm Hg; six achieved this result at six months on no medication. The IOP decreased from a mean of 30.88 mm Hg preoperatively to 13.75 mm Hg at two months and 14.00 mm Hg at six months. The preoperative mean of 3.63 antiglaucoma medications per patient decreased to 0.25 postoperatively. Although all patients had advanced glaucomatous optic neuropathy with a preoperative mean cup/disc ratio of 0.79, visual acuity improved in six patients; four patients had an acuity of 20/40 or better at both one week and two months. Surgically induced astigmatism averaged 0.57 diopter (D) at two months, with a mean astigmatic shift of 0.08 D with the rule at two months and 0.41 D with the rule at three months. No hypotonous or flat anterior chambers were encountered; there were visible blebs in seven patients at six months. The sutureless phacotrabeculectomy preserves all the advantages of small incision phacoemulsification and appears to be a safe and effective combined procedure for IOP control in glaucoma patients with cataracts.

Aged↗

Use of the polymerase chain reaction technique on induced-sputum samples for the diagnosis of Pneumocystis carinii pneumonia in HIV-infected patients. A clinical and cost-analysis study.

The purpose of this study was to assess the sensitivity and specificity of the polymerase chain reaction (PCR) on induced sputum (IS) for the diagnosis of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients, as well as its diagnostic value and cost as a routine clinical tool. Forty-nine patients with suspected PCP who had IS were studied and if negative, followed by bronchoalveolar lavage (BAL). Pneumocystis carinii was detected in these samples using standard staining techniques. Polymerase chain reaction was used with IS samples in a blinded fashion. The patients with negative BAL samples were closely monitored for 1 month. In the absence of any clinical or radiologic features of PCP during this period, they were considered as being free of PCP. The cost analysis considered only the direct costs of the various tests in three diagnostic strategies: routine BAL (BAL); IS with standard staining, if negative, followed by BAL (IS); and IS with standard staining followed, if negative, by PCR on IS samples (PCR-IS). Using standard staining P carinii was found in 13 cases (6 IS and 7 BAL). None of the 36 patients with negative BAL developed further signs of PCP. Thus, the prevalence of PCP was 26.5% and the sensitivity and specificity of BAL were 100%. Standard staining of IS had a specificity of 100% and a sensitivity of 46.5%. The sensitivity and specificity of PCR-IS were each 100%. The costs of strategies BAL, IS, and PCR-IS were $14,010, $18,300, and $18,040, respectively. The costs of the BAL strategy depended only on the cost of the relevant tests, whereas the costs of strategies IS and PCR-IS depended on the costs of the tests, the sensitivity of IS with standard staining, and the prevalence of PCP in the test population. The routine clinical use of PCR-IS is currently limited by the time required to obtain the results.

AIDS-Related Opportunistic Infections↗

Pulmonary cryptococcosis: localized and disseminated infections in 27 patients with AIDS.

We reviewed the records of 85 patients infected with both human immunodeficiency virus and Cryptococcus neoformans. Twenty-seven patients (32%) had pulmonary cryptococcosis. C. neoformans was cultured from bronchoalveolar lavage (BAL) or pleural fluid in 25 cases; the remaining two patients had cryptococcal antigen (CA) detected in BAL fluid and C. neoformans cultured from other sites. All but one of the 27 patients had detectable CA in serum. The CD4+ lymphocyte count was low in all cases (median, 24/mm3). Clinical manifestations of pulmonary cryptococcosis included fever (94%), cough (71%), dyspnea (7%), expectoration (4%), chest pain (2%), and hemoptysis (1%). Diffuse interstitial opacities (70.5%), focal interstitial abnormalities, alveolar opacities, adenopathies, cavitary lesions, and pleural effusions were evident. Outcome was poor (mean survival time, 23 weeks) despite treatment. Patients with localized pulmonary cryptococcosis appeared to have a higher CD4+ lymphocyte count, an earlier diagnosis, lower serum CA titers, fewer previous or concomitant infections, and a better prognosis than patients with disseminated cryptococcosis.

AIDS-Related Opportunistic Infections↗

Pulmonary toxoplasmosis in HIV-infected patients: usefulness of polymerase chain reaction and cell culture.

Toxoplasmosis is a serious opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). The lung is a major site of infection after the central nervous system. The aim of the study was to assess the polymerase chain reaction (PCR) and cell culture for the detection of Toxoplasma gondii. One hundred and thirty two human immunodeficiency virus (HIV)-infected patients with respiratory manifestations, who underwent fibreoptic bronchoalveolar lavage, were investigated. Detection of Toxoplasma gondii was compared using three techniques: Giemsa staining; polymerase chain reaction with specific primers derived from the P30 gene; and culture on the MRC5 cell line. Toxoplasma gondii was detected in the same four samples by all three techniques. We conclude that PCR adds little to conventional (and cheaper) tools already used to diagnose pulmonary toxoplasmosis.

AIDS-Related Opportunistic Infections↗

[Disseminated histoplasmosis in an HIV seropositive patient].

The authors report a case of disseminated pulmonary histoplasmosis in an HIV positive patient who had travelled in countries where the disease was endemic. The principle clinical characteristics of the disease are reviewed including the radiology and the methods of treatment particularly in the forms occurring in this context. Finally the authors underline the difficulty in the differential diagnosis with tuberculosis.

Adult↗

Affinity modification of human immunodeficiency virus reverse transcriptase and DNA template by photoreactive dCTP analogs.

New base-substituted analogs of dCTP containing an azido group have been synthesized and applied to a selective photoaffinity modification of HIV-RT (p66/p51 heterodimer). The labeling of only the 66 kDa subunit of HIV-RT was detected when the enzyme was first irradiated with the analogs and then template (5'-(d)GGTTAAATAAAATAGTAAGAATGTATAGCCCCTACCA-3') and 5' 32P end-labeled 3'-(d)TTACATATCGGGGATGGT-5' primer were added. The 5' 32P end-labeled primer elongated by dCTP analogs in the presence of both HIV-RT and DNA template is able to modify both subunits of HIV-RT and DNA template. This way of specific cross-linking to both DNA (RNA) template and HIV-RT opens up new possibilities to study the HIV-RT active site.

Affinity Labels↗

HIV-1 reverse transcription. A termination step at the center of the genome.

During HIV-1 reverse transcription, the plus-strand of viral DNA is synthesized as two discrete segments. We show here that synthesis of the upstream segment terminates at the center of the genome after an 88 or 98 nucleotide strand displacement of the downstream segment, initiated at the central polypurine tract. Thus, the final structure of unintegrated linear HIV-1 DNA includes a central plus-strand overlap. In vitro reconstitution using only purified reverse transcriptase with appropriate DNA hybrids gave rise to efficient and accurate termination, which was dramatically amplified in the context of strand displacement. Mutation of the sequence immediately upstream of the termination sites almost completely abolished termination both in infected cells and in vitro. This mutation profoundly impaired replication of HIV-1. We conclude that proper central plus-strand termination, mediated by a novel cis-active termination sequence, is a key step in HIV-1 replication.

Base Sequence↗

Preliminary results of Pneumocystis carinii strain differentiation by using molecular biology.

The mode of Pneumocystis carinii transmission is controversial. Recent studies point to exogenous inoculation rather than reactivation, and person-to-person transmission has also been suggested. Comparison of nucleotide sequences of the large-subunit mitochondrial rRNA gene of P. carinii from human immunodeficiency virus-seropositive patients showed strain differences.

AIDS-Related Opportunistic Infections↗

Usefulness of PCR for detection of Pneumocystis carinii DNA.

Diagnosis of Pneumocystis carinii pneumonia is based on the identification of the various stages of the parasite in lung samples by standard staining techniques. We therefore assessed the value of the PCR for detection of P. carinii in bronchoalveolar lavage, induced sputum, and blood samples relative to that of standard staining techniques.

AIDS-Related Opportunistic Infections↗