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Biomedical subjects

P Chariot

Publications and source records attributed to P Chariot.

51 records · Page 3Linked to original sources

Cytochrome c oxidase reaction improves histopathological assessment of zidovudine myopathy.

Zidovudine can induce a mitochondrial myopathy with ragged-red fibers and partial cytochrome c oxidase deficiency. In an attempt to improve histological assessment of zidovudine myopathy, we evaluated cytochrome c oxidase histochemical reaction in the muscle of 10 patients with biopsy-proven zidovudine myopathy (Group 1), 10 myopathic zidovudine receivers without typical histopathological features of zidovudine myopathy (Group 2), and 10 human immunodeficiency virus (HIV)-infected patients not treated by zidovudine who had an immunohistological profile of HIV-associated myopathy or other neuromuscular disorders (Group 3). Among zidovudine receivers, cytochrome c oxidase deficiency was found in 10 of 10 patients from Group 1 and 7 of 10 from Group 2. No cytochrome c oxidase deficiency was observed in patients not treated by zidovudine. When present, cytochrome c oxidase-negative fibers accounted for 2 to 28% of fibers, and there was no difference for the number of cytochrome c oxidase-negative fibers between Group 1 and Group 2. Most patients with cytochrome c oxidase deficiency that could be evaluated clinically after muscle biopsy improved after withdrawal of zidovudine (5 of 7 in Group 1, 5 of 5 in Group 2). Patients who did not improve had an HIV-associated myopathy concurrently with zidovudine myopathy. We conclude that cytochrome c oxidase reaction may be used as a reliable marker of zidovudine mitochondrial toxicity in HIV-infected patients with muscular symptoms.

Acquired Immunodeficiency Syndrome↗

Tubular aggregates and partial cytochrome c oxidase deficiency in skeletal muscle of patients with AIDS treated with zidovudine.

We report on two patients, who had myalgias while receiving long-term zidovudine treatment for an HIV infection, in whom muscle biopsy findings included a partial cytochrome c oxidase (CCO) deficiency, a feature of zidovudine myopathy, and tubular aggregates, a finding hitherto unreported in HIV-infected patients. The CCO deficit was observed in 28% and 24% of muscle fibers, respectively. Tubular aggregates were the prominent histopathological feature in patient 1, and were detected by systematic electron microscopy in patient 2. Inflammation and myonecrosis were not detected. In patient 1, the typical mitochondrial and myofibrillar changes of zidovudine myopathy were present and 12% of fibers showed tubular aggregates. The aggregates were not stained at CCO reaction, and 96% of myofibers enclosing tubular aggregates showed a decreased CCO activity. This suggested more than a chance association between mitochondrial dysfunction and the formation of tubular aggregates. We conclude that tubular aggregates are detected in some patients treated by zidovudine, and that the finding could be related to the long-term administration of the drug.

Acquired Immunodeficiency Syndrome↗

Systemic mastocytosis following mediastinal germ cell tumor: an association confirmed.

A 24-year-old man had a mediastinal embryonal carcinoma containing yolk sac foci. Combination chemotherapy with cisplatin, bleomycin, etoposide, and vinblastine was given, and the residual mass was then resected. Histology showed only necrotic cells. No other treatment was given. Two years later the patient presented with episodes of flushing and syncopes related to a systemicmastocytosis. Bone marrow examination showed a diffuse infiltration with large, atypical mast cells often with multilobulated nuclei. The patient suffered several episodes of cardiovascular collapse and died during one of these episodes, 8 months after the diagnosis of systemic mastocytosis and 40 months after the diagnosis of mediastinal tumor. Autopsy findings included the absence of mediastinal tumor and a diffuse liver and spleen mast cell infiltration. This was the second case with the similar clinicopathologic picture of two rare diseases being associated. This fact supports the hypothesis of a distinct entity, part of the mediastinal germ cell tumor/hematologic malignancy syndrome. The hypothesis of a cytokine secretion induced by mediastinal germ cell tumor supporting mast cell proliferation may be considered.

Adult↗

Long-lasting postmortem viability of human immunodeficiency virus: a potential risk in forensic medicine practice.

To determine the time from death when an autopsy could be carried out without any risk of contamination by human immunodeficiency virus (HIV), we cultured HIV from serial samples of blood and liquid effusion, collected as long as possible alter death from refrigerated dead bodies of HIV-infected patients. Samples were cocultivated with stimulated normal human lymphocytes and viral replication was assessed by p24 HIV1 antigen ELISA determination and by reverse transcriptase HIV1 and HIV2 activity microassay. Viable HIV was isolated from blood obtained 16.5 days postmortem, from pleural liquid effusion obtained 13.8 days postmortem, and from pericardial liquid effusion obtained 15.5 days postmortem. Viral replication was in evidence in at least one sample from all nine patients of the study. The present study did not allow us to determine a time from death when an autopsy could be carried out without any risk of contamination by HIV. We conclude that postponement of autopsies does not eliminate occupational risk of contamination by HIV.

Adult↗

Miliary opacities diagnosed as lung metastases of a thyroid carcinoma after 13 years of stability.

A 29-year-old man was hospitalized for the diagnosis of clinically asymptomatic miliary opacities discovered 13 years earlier and unchanged since then. Transbronchial biopsy showed metastatic thyroid carcinoma. Thyroid surgery revealed massive local invasion by a papillary carcinoma. We conclude that thyroid carcinoma, whether clinically detectable or not, should be considered in the diagnostic investigation of stable miliary lesions.

Adult↗

Extensive small-cell lung cancer. A randomized comparison of two chemotherapy programs with early crossover in instances of failure. Association pour le Traitement des Tumeurs Intra-Thoraciques (ATTIT).

Two chemotherapy regimens for patients with extensive small-cell lung cancer were prospectively compared in a randomized multicentric trial with crossover. Every four weeks, 60 consecutive previously untreated patients received either DPE (doxorubicin, cisplatin and etoposide), or CIV (carboplatin, ifosfamide and vincristine) with crossover as soon as progression or end of response were observed. Pretreatment characteristics were similar in the two groups. Fifty-seven patients were evaluated for response. The response rate was higher with the DPE regimen both in first-line (for DPE: response rate 62% (18/29), including 17% (5/29) of complete response (CR), and for CIV: response rate 29% (8/28) with no CR, p < 0.02) and in second-line after crossover (for DPE: response rate 45% (9/20) including 5% (1/20) of CR, and for CIV response rate 0%, p < 0.02). Major toxicities were equally frequent in both groups. No significant difference was found between median survival times (9.7 months for the DPE group and 10.4 months for the CIV group). We conclude that: 1) DPE is a more active regimen than CIV, both in first- and second-line; 2) no alternating scheme may be considered with these two combinations. Of particular note is the similar median survival times in the two groups, contrasting with the different activities of the two regimens.

Adult↗

Nonfibrous mineral particles in bronchoalveolar lavage fluid and lung parenchyma from the general population.

It is recognized that bronchoalveolar lavage (BAL) gives access to particulate matter present at the surface of the peripheral airspace. The objective of the present study was to evaluate the ability of BAL fluid analysis to predict the lung parenchymal particulate content. A BAL fluid sample, the parenchyma sample having undergone BAL, and an adjacent parenchyma sample that had not undergone BAL were obtained at autopsy on 10 individuals without any known recent occupational exposure to mineral particles. The particles (larger than 0.1 micron) were analyzed using a transmission electron microscope equipped with a microanalysis system. Nineteen types of particles were distinguished. The distribution of particle types in the three samples was compared. No significant difference between the relative concentrations was found, except for two particle types: fly ash (excess in BAL fluid compared with lavaged lung) and kaolinite (excess in lavaged lung compared with adjacent area). Such differences may be due to limitations in methodology. Although no correlation could be found between the absolute concentrations of particles in BAL fluid and in lung tissue, analysis of particles in BAL fluid may provide information on the types of particles present in the lung parenchyma.

Adult↗

Partial cytochrome c oxidase deficiency and cytoplasmic bodies in patients with zidovudine myopathy.

A histochemical study of cytochrome c oxidase (CCO) was performed in the muscles from eight patients with full-blown zidovudine myopathy. All patients had ragged-red fibres (total cumulative count: 160) and myofilamentous changes, that predominated in type 1 fibres and included diffuse or punch-out myofibrillar loss (75 affected fibres) and constant cytoplasmic body formation (106 affected fibres). Inflammatory infiltrates were present in four out of eight patients. A partial CCO deficiency (22-47% of fibres; both types 1 and 2 affected) was detected in all cases, and contrasted with the normal or increased succinate dehydrogenase activity observed in most fibres. Among CCO-deficient fibres, 71% were normal on trichrome, but all ragged-red fibres were CCO-negative. Myofilamentous changes were restricted to CCO-deficient fibres. The present study strongly supports the idea that mitochondrial toxicity is the specific mechanism of zidovudine myopathy.

Acquired Immunodeficiency Syndrome↗

Systemic mast cell disease associated with primary mediastinal germ cell tumor.

The first known case of systemic mast cell disease associated with a germ cell tumor is reported. Six months after the complete remission of a primary mediastinal germ cell tumor treated by chemotherapy and resection, a young man had a series of episodes of hypotension and syncope and, a few months later, a gastric hemorrhage and coagulation disorder. The diagnosis of systemic mast cell disease was made in view of bone marrow and liver biopsies. A transient circulating heparin-like anticoagulant was noted. The occurrence in a short period of these two unusual conditions, given previous knowledge of hematologic disorders associated with germ cell tumors, suggests that the present association is not a coincidence. Systemic mast cell disease should be considered among the hematologic disorders associated with a germ cell tumor.

Adult↗

Organic arsenic-induced Guillain-Barré-like syndrome due to melarsoprol: a clinical, electrophysiological, and pathological study.

A young woman suffering from sleeping sickness was treated with melarsoprol. Thirty-eight days after the first administration of this organo-arsenic compound, myalgias, distal paresthesias and rapidly progressive weakness developed in all four limbs. Electrophysiological studies were misleading for Guillain-Barré syndrome. Neuropathological data included massive distal wallerian degeneration in peripheral nerves and abnormalities in dorsal ganglia and spinal cord where vacuolation of anterior horn cells and axonal neurofilamentous masses were observed. Very high concentrations of arsenic were found in the spinal cord, contrasting with undetectable levels in peripheral nerves. Our findings are consistent with an arsenic neuronopathy manifested by initial proximal demyelination and delayed distal axonal damage. Renal and hepatic dysfunctions, which were implicated in the toxic arsenic accumulation, should be systematically detected before administration of melarsoprol. The diagnosis of Guillain-Barré syndrome must be considered with caution in patients treated with this compound.

Adult↗

MRI of intralesional hemolysis in focal nodular hyperplasia of the liver.

A case of Kasabach-Merritt syndrome caused by focal nodular hyperplasia of the liver is presented with atypical magnetic resonance findings due to intratumoral hemosiderin deposition. The high sensitivity of magnetic resonance imaging for iron served to identify the site of hemolysis in this patient with Kasabach-Merritt syndrome.

Adult↗