Biomedical subjects
Publications and source records attributed to C Michon.
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The synthesis of a series of chiral cyclomanganated 2-[(eta 6-phenyl)-Cr(CO)3]pyridine complexes derived from (-)-beta-pinene enables, by a "spirogenic transformation", the preparation of four different chiral helical heterobimetallic syn-facial complexes or Cr0/Mn1-spiralenes, among which two possess a right-handed P molecular helicity and two other a left-handed M one. These organometallic helical molecules are synthesised by applying two different methods to the chiral cyclomanganated (eta 6-arene)tricarbonylchromium substrates. The first method is the so-called "Fischer route" which involves a sequential addition of PhLi and MeOTf. The second method based on reaction of the cyclomanganated complex with diphenyldiazomethane which has been tested on achiral bimetallic substrates is a reasonable neutral alternative to the "Fischer methodology" for the synthesis of Cr0/Mn1-spiralenes. The crystal structure of one of these heterobimetallic chiral helical compounds serves as a starting point in the configurational and structural assessment of the synthesised chiral (eta 6-arene)tricarbonylchromium complexes. Application of the "Fischer route" to a cyclomanganated chiral 2-phenylpyridine generates a single chiral eta 3-benzylic complex--or Mn1-spiralene--bearing a left-handed M helicity which has been characterized by X-ray diffraction analysis. Circular dichroic spectroscopic measurements underline the predominant contribution of the chiral and chirally induced aromatic chromophores to the sign of the Cotton effects and confirm the helical configurations of the considered heterobimetallic species.
BACKGROUND: The regularity of medical followup of HIVinfected patients greatly influences the effectiveness of antiretroviral treatments and of prophylaxis of opportunistic infections. METHODS: To identify potential barriers to a regular followup, a retrospective study was conducted among the adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts (Gironde and HautsdeSeine). Medical followup was described based on the frequency of CD4 counts in the medical file and on a confidential interview among patients whose HIV infection had been diagnosed at least 6 months before AIDS. Irregular followup (less than one CD4 count per year when CD4> 500/ mm(3), and per 6months when CD4< 500/ mm(3)) within the two years preceding AIDS diagnosis was analysed according to socioeconomic status and to social and behavioral factors. RESULTS: Among 290 patients, followup was irregular in 51% of the patients (injecting drug users: 66%, homo/bisexual men: 41%, patients infected through heterosexual contact: 49%, p<0.01). Factors independently associated with irregular followup were low income level (adjusted odds ratio (aOR)= 2.4; 95% confidence interval (CI), 1.44.1); absence of regular practitioner at HIV diagnosis (aOR= 1.9; 95% CI 1.13.3); imprisonment between HIV diagnosis and AIDS (aOR= 3.8; 95% CI 1.310. 9), and being non homo/bisexual male (aOR= 2.4; 95% CI 1.15.1) versus homo/bisexual male (aOR= 1.3; 95% CI 0.72.7) and female (reference). CONCLUSIONS: Results of this study show that several socioeconomic, psychological and cultural barriers to a regular preAIDS medical followup still exist. Impact of new antiretroviral therapy may only be optimal if these barriers are overcome.
OBJECTIVE: To describe the circumstances of the first HIV-positive test and to study the determinants of a delayed diagnosis of HIV infection. METHODS: In a retrospective study among adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts, data on socioeconomic characteristics, circumstances of first HIV-positive test and attitudes and behaviours regarding medical care were collected in a confidential interview and analysed for potential association with a late test, defined as a first HIV-positive test within 6 months of AIDS diagnosis. RESULTS: Of the 359 AIDS patients studied, 69 (19.2%) had a late test. Late testers were more likely than other patients to have had an HIV-positive test because of clinical symptoms (89.7 versus 38.9%, P < 0.001) and not to perceive themselves as being at risk of infection with HIV (53.6 versus 39.3%, P < 0.05). The proportion of late testers was 34.6% among heterosexually infected patients, 12.7% among homo-/ bisexual men and 9.6% among injecting drug users. Factors independently associated with a late test were male gender [adjusted odds ratio (aOR), 5.6; 95% confidence interval (CI), 1.7-18.9] and absence of earned income (aOR, 5.2; 95% CI, 1.4-19) among heterosexually infected patients; high education (aOR, 3.1; 95% CI, 1.0-9.6) and having consulted a person practising alternative medicine (aOR, 3.4; 95% CI, 1.2-10) in homo-/bisexual men. CONCLUSIONS: Despite incentives to be tested for HIV, many individuals in France are still tested too late, even if they are in known high-risk groups. Efforts to test HIV-infected people as early as possible should be made by increasing the perception of HIV risk and decreasing the level of missed opportunities for testing. Current case management approaches make this recommendation critically important from both public health and an individual perspective.
Gelatin gel properties have been studied using three techniques. Optical rotation measurements have shown that the lower the ageing temperature, the faster the helix content increases but the lower the helix stability. Rheological measurements show that a small increase in temperature leads to a melting of some junction zones followed by a build up of new ones. By ageing the gel at two successive temperatures one can show the existence of two populations of junction zones with different thermal stabilities. The same result is shown on melting thermograms obtained by differential scanning calorimetry. All these results are consistent with the hypothesis of the presence of junction zones of various lengths, the thermostability of which being proportional to their lengths.
We present a literature review about extrapulmonary and disseminated pneumocystosis in AIDS. The prevalence of such infections seems low but is probably under-estimated. Disseminated pneumocystosis occurs in patients with profound immunosuppression, who do not receive prophylaxis against Pneumocystis carinii pneumonia or are treated with aerolized pentamidine. The lack of specificity of symptoms may delay the diagnosis. Most organs may be involved. Three different presentations may be individualized: disseminated pneumocystosis, intra-thoracic only disseminated pneumocystosis, in an intra-thoracic localization alone, and localized extrapulmonary pneumocystosis. The mortality from disseminated disease is high, especially in the presence of low serum albumin level.
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The present article describes the clinical and pathological findings in 5 human immunodeficiency virus (HIV)-infected patients with muscle toxoplasmosis. The patients had marked lymphopenia (5/5), with less than five CD4+ cells/mm3 (3/3), when they developed fever (5/5), and multiorgan failure (5/5), including diffuse encephalitis, pneumonia, pancytopenia, and myopathy. Muscle involvement included weakness and wasting (4/5), myalgias (3/5), and high serum creatine kinase levels (3/3). Serology for toxoplasmosis showed high IgG titers in 3 patients (3/4). Anti-Toxoplasma therapy resulted in complete recovery in 2 patients. Muscle toxoplasmosis was detected by biopsy (3/5) or postmortem evaluation (2/5), and was identified using immunocytochemistry and electron microscopy. Toxoplasma cysts were detected in 0.5 to 4% of muscle fibers close to or remote from necrotic fibers and inflammatory infiltrates. Muscle fibers strongly expressed the major histocompatibility complex class I antigen (2/2) as in polymyositis. We suggest that Toxoplasma gondii should be sought by muscle biopsy in patients who have acquired immunodeficiency syndrome with fever, encephalitis, multiorgan dysfunction, and elevated serum creatine kinase levels of obscure origin.
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The clinical and bacteriological features of 51 infections due to Streptococcus milleri observed in 43 patients over a 2-year period were reviewed. Clinical syndromes included bacteremia in 6 cases, endocarditis in 4 cases, cellulitis and subcutaneous abscesses in 8 cases, pleural empyema in 8 cases, brain abscesses in 5 cases, abdominal infections in 5 cases, and other miscellaneous infections in 15 cases. An underlying condition was associated with infection in 33/43 patients (77%). S. milleri was the only pathogen isolated in 19 patients (44%). All strains of S. milleri were susceptible to penicillin. Surgery was combined with antimicrobial therapy in 27 (63%) patients. Nine patients died during hospitalization, and death was directly related to S. milleri infection in 4 patients (9%). These results confirm that S. milleri frequently causes serious suppurative infections and that species identification is a clinically useful procedure.
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The histopathologic changes of bone marrow during infection with the human immunodeficiency virus type 1 (HIV-1) are described. Bone marrow biopsies from 73 patients at different stages of HIV-1 infection were studied. Indications for biopsy included peripheral blood abnormalities, suspicion of lymphoma, or search for specific pathogens. Common histopathological features, suggestive of HIV-1 infection but nonpathognomonic were hypercellularity (67%), myelodysplasia (86.1%), plasmacytosis (98.6%), lymphocytic infiltration (31.1%) and histiocytic infiltration with or without granulomata (13.7%). Increases in reticulin fibers (54.7%), and stainable iron deposits, vascular congestion and serous atrophy of fat were frequent features. Opportunistic infections and neoplastic complications were detected in 7 cases: pathogens were demonstrated in 4 cases (Mycobacterium avium intracellulare (MAI), Cryptococcus neoformans, Toxoplasma gondii and Leishmania) and lymphoma in 3 cases (1 Burkitt lymphoma and 2 Hodgkin's disease). Bone marrow hypoplasia is usually a terminal event in AIDS and may be iatrogenic.
In order to determine the extent of liver abnormalities occurring during acquired immunodeficiency syndrome, the available histological analyses of liver samples (32 biopsies, 52 autopsies) from 71 AIDS patients, for the period 1982-1986, were studied retrospectively. Hepatomegaly was the most common clinical symptom (23 patients, 32.4%), while jaundice was rare, being seen in only 5 cases (7%). Progressive anicteric cholestasis was the most frequently observed biological anomaly (29/52, 55.7%). Ten patients had liver infections: 2 Mycobacterium tuberculosis, 8 Mycobacterium avium intracellulare. Cytomegalovirus was present in 3 patients and 1 individual was infected with Cryptococcus neoformans. Granulomatous hepatitis was associated with these infectious agents in 11 patients, but remained unexplained in 11 others. Three patients had cholangitis (2 with CMV inclusions, 1 unexplained). Among the 32 biopsies, 5 elucidated the origin of unexplained fever. Kaposi's sarcoma of the liver was found in 10/52 autopsy samples (19%) and hepatic lymphoma in 2 cases. Non-specific histological lesions were common: inflammation of the portal spaces (48 cases, 67.6%), steatosis (32 patients, 45%), peliosis hepatis (9 cases, 12.6%) and sinusoidal dilations (39 cases, 54.9%).