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Biomedical subjects

M Renoux

Publications and source records attributed to M Renoux.

At least 19 recordsLinked to original sources

Distribution of the C282Y and H63D polymorphisms in hereditary hemochromatosis patients from the French Basque Country.

The distribution of HFE mutations was studied in patients from the French Basque Country with hereditary hemochromatosis (HH). The C282Y mutation was underrepresented but H63D seemed to demonstrate the highest prevalence when compared with other European countries. In addition, symptomatic HH was rarer in autochthonous Basques. This profile is interesting to consider in view of population genetics and should be associated with the search for non-HFE mutations.

Adult↗

Genetic hemochromatosis is a rare disease entity among French Basques: a center-based study from the general hospital of Basque County.

A center-based study from the general hospital of Basque country has been performed to evaluate the importance of genetic hemochromatosis among French Basques. A sample of 37 patients from 34 families fulfilling the diagnosis criteria of hemochromatosis was obtained. Only four of them were of Basque origin: two homozygotes for C282Y, one homozygote for H63D, and one heterozygote for C282Y. These results suggest a significant lower prevalence of genetic hemochromatosis in Basques than in people from other French regions (P=0.001). They underline further the biological specificity of this population.

Adult↗

Characteristics of deaths in a department of oncohaematology within a general hospital. A study of 81 cases.

We aimed to perform a prospective analysis of the main characteristics of deaths occurring in the oncohaematology department of a general hospital. From November 1995 to February 1997, a total of 81 patients died in our unit, 50 of whom (61.7%) were male. Their mean age was 67.8 (range 19-96) years. Underlying diseases were: multiple myeloma (9 cases), acute myeloid leukaemia (22), lymphoma (14), chronic lymphocytic leukaemia (6), acute lymphoblastic leukaemia (4), myelodysplastic syndromes (3), solid tumours (11), and other (12). The previous disease duration ranged from 5 days to 276 months (mean 31.9 months). The duration of the last hospital stay varied between 0 (death on arrival or on way to hospital) and 40 days (mean 9.3 days). Two patients died in the emergency unit just before entering our department (1 suicide). Only 15 patients had been admitted for the first time. In 70% of these cases death appeared predictable, as the consequence of refractory or end-stage disease. In these cases, all the "do not resuscitate" orders were in place at least 48 h before death. About half the patients died without any relative present. The frequencies of the clinical complaints evaluated were the following: pain necessitating opiates 27%; infection- or disease-related fever 40%; dyspnoea 44%; haemorrhage 20%; CNS disturbances 25%. The percentages of use of therapy tools chosen as indicators were: benzodiazepines 80%; chemotherapy 46%; anti-infectious agents 47%; transfusions 42%; major analgesics 27%; and steroids 40%. The circumstances and quality of patient deaths must be regularly evaluated so that palliative care in the final stages of life can be improved.

Adult↗

Reduced incidence and prevalence of atopy in rheumatoid arthritis. Results of a case-control study.

OBJECTIVE: To determine the cumulative incidence and the point prevalence of atopy in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A standardized questionnaire was sent to 300 RA patients. Questions concerned previous or present characteristics of atopy (hay fever, asthma and constitutive eczema) and RA. RA patients were matched with genetically unrelated controls (sister- or brother-in-law, neighbour or friend). The same questionnaire (except for questions about RA) was sent to the control subjects. In cases of atopy, patients, controls and the treating physicians were contacted by a physician to check the validity of the responses. RESULTS: Paired responses were obtained in 173 cases. Information about atopy was obtained for 69 other RA patients. The characteristics of RA were similar for patients who responded and those who did not respond. The frequency of atopy was significantly lower in RA patients than in controls, both for cumulative incidence (RA 7.5%, controls 18.8%; P: < 0.01) and point prevalence (RA 3.5%, controls 16.2%; P: < 0.0001). The clinical manifestations of atopy stopped before the onset of RA in eight of the 17 RA patients with an allergic condition, and there was no subsequent relapse. No effect of RA treatment could account for the remission of atopy. CONCLUSION: These data support the concept that atopy protects against the future development of RA and that the two diseases could counterbalance one another.

Arthritis, Rheumatoid↗

Descriptive epidemiology of non-Hodgkin lymphomas in a southwestern French hematology center: absence of significant relationship with hepatitis C virus infection.

From January 1995 to June 1998, 136 new cases of non-Hodgkin lymphomas (NHLs) were seen in our center which serves all the French Basque Country (300000 inhabitants). The crude and standardized incidence rates were respectively 13.2 and 7.6 cases/100000/year. The distribution of histologic subtypes according to the REAL classification showed a good correlation with the previous published data. Eleven patients (8%) were HIV-positive and two (1.4%) were HCV carriers. Hence, in our region, contrary to Italy, there is no evidence of relationship between HCV and NHLs.

Adolescent↗

Biochemical and molecular consequences of ethidium bromide treatment on Drosophila cells.

KC167 Drosophila cells were incubated with low concentrations of ethidium bromide (200 ng/ml), causing changes in mitochondrial DNA (mtDNA) content (2-184% of that of controls). SSCP (single strand conformational polymorphism) analysis of mtDNA indicated that the incubation with ethidium bromide also generated mutations. Compared with controls, there were marked reductions in the activities of respiratory complexes III and IV measured in these cells, and in respiration and ATP synthesis capacities measured in isolated mitochondria. These reductions matched that in mtDNA content. In contrast, no link could be demonstrated between mtDNA content and steady-state concentrations of the transcripts of genes COIII and Cyt b.

Adenosine Triphosphate↗

De novo and secondary acute myeloid leukemia in patients over the age of 65: a review of fifty-six successive and unselected cases from a general hospital.

Fifty-six patients older than 65 (median age: 77, range: 65-91) were treated in our general hospital, between January 1991 and November 1995 with the diagnosis of AML. Twenty-five were de novo AML (45%). The other cases which were considered as secondary AML (sAML) occurred after: myelodysplastic syndromes (19 cases: 34%), myeloproliferative disorders (7: 13%) or therapy of malignancies (5: 9%). Distribution of FAB subtypes was: M0: 4, M1: 8, M2: 14, M4: 10, M4eo: 1, M5: 10, M6: 1, unclassified: 8. Twenty-seven patients (48%) (de novo: 18, sAML: 9) received conventional "3 + 5" or "3 +7" induction chemotherapy +/- consolidation and maintenance (group 1). Low-dose Ara-C was given in eighteen cases (32%) (group 2), miscellaneous single agents were prescribed in seven cases and two patients received only supportive care. Sixteen early deaths (ED) (<1 month) occurred (29%). Distribution of age, WHO-PS, hyperleukocytosis, ED and median survival (MS) (3 months) was equivalent in de novo and sAML. Fifteen CR were achieved including twelve patients from group 1 (no difference between age <75 versus >75 years) and three from group 2. The MS of CR patients was 13 months. Eleven patients survived more than one year (de novo: 8). M5 subtype, fever >38 degrees C, high LDH level, WHO-PS>2, CR non achievement were predictive of reduced survival. Besides conventional induction, investigational therapies currently remain the best antileukemic modalities. Age per se should not be an exclusion criteria for treatment. Our data underline the high frequency of sAML in the community. Of note, this common type AML is largely excluded from many trials.

Aged↗

A leptomeningeal metastasis revealed by sciatica.

UNLABELLED: Meningeal metastatic disease usually occurs as a complication of a brain tumor and is exceptionally isolated in patients with solid tumors. We report the case of a 74-year-old woman admitted for mechanical S1 sciatica refractory to drug therapy. She had been treated for breast cancer three years earlier. Physical findings were pain upon hyperextension of the lumbar spine and absence of the ankle jerks. Analysis of cerebrospinal fluid sampled during an intrathecal glucocorticoid injection showed 1 g/L of protein and 11 normal cells per mm3. Grade 3 L5-S1 spondylolisthesis was seen on plain radiographs, computed tomography scans, and magnetic resonance imaging scans. At that point, the patient developed sphincter dysfunction and motor loss in the left lower limb in the distribution of several nerve roots. Findings were normal from a myelogram and a magnetic resonance imaging study of the brain. A repeat cerebrospinal fluid analysis showed 1.1 g/L of protein and 5 cells/mm3. Because of the discrepancy between the clinical and imaging study findings, the patient was transferred to a neurology department. A third cerebrospinal fluid study showed numerous adenocarcinoma cells, and a repeat magnetic resonance imaging demonstrated a mass in the dural sac opposite L2. A program of monthly intrathecal methotrexate injections was started. A fatal meningeal relapse occurred eight months later. CONCLUSION: This case shows that a leptomeningeal metastasis can cause isolated nerve root pain, and demonstrates the diagnostic value of magnetic resonance imaging and cerebrospinal fluid cytology in patients with atypical symptoms, particularly when there is a history of malignant disease.

Adenocarcinoma↗

Developmental changes in heteroplasmy level and mitochondrial gene expression in a Drosophila subobscura mitochondrial deletion mutant.

Eighty percent of DNA molecules are deleted in the mitochondrial population of an adult mutant strain of D. subobscura. Both intact and deleted genomes are autonomous monomers. The heteroplasmy level, which is lower in germ tissue, increases from the oocytes (60%) to the third larval instar (83%), and is then maintained throughout the life of the fly. The mtDNA/nuclear DNA ratio is on average two-times greater in the heteroplasmic strain than in the wild-type strain, irrespective of the stage, but the cellular content of mitochondria is elevated only in the embryos and pupae of the mutant strain. The steady state concentrations (SSCs) of the transcripts affected by the deletion are greatly reduced at the larval and adult stages, and less so at the pupal stage of the mutant strain compared with the wild-type. The SSCs of these transcripts are identical in the two strains at the embryonic stage. The fusion transcript, indicating that the deleted genome is expressed, was detected at all stages. The mechanisms involved in the changes in the heteroplasmy level during the course of development and in its maintenance from the third larval instar onwards are discussed.

Animals↗

Epidemiology of myelodysplastic syndromes in a French general hospital of the Basque country.

Epidemiologic studies concerning myelodysplastic syndromes (MDS) are rare. The estimated incidence varies between 1 and 12.6/100,000/year. The aim of this work was to compare our own experience with these data. Our general hospital represents a structure with 1197 beds which serves a population of 290,000 individuals (French Basques). Most of the inhabitants live in a rural environnement. Twenty percent of the population are aged over 65. During a 4-year period (1993-1996), 90 new cases of MDS were diagnosed on bone marrow studies in our laboratory. Among FAB subtypes refractory anemia (RA) represented 27 cases (31%), RA with ring sideroblasts (RARS): 21 (23%), RA with excess of blasts (RAEB) and in transformation (RAEB-t): 22 (24%), chronic myelomonocytic leukemia (CMML): 10 (11%). Ten cases were unclassifiable (11%). Therapy-related MDS were seen in 8 patients. The sex ratio was 1 and the mean age of the patients was 74.3 (range: 23-96), 37% of them being 80 years or older. The calculated incidence was 7.7/100,000/year for the entire cohort and 31.4/100,000/year for people over 65.

Adult↗

Cultured neonatal rat cardiomyocytes and 99mTc-sestamibi to assess the direct effects of cardioplegia.

The efficacy of cardioplegia in neonatal myocardial protection is still a matter of debate. 99mTc-sestamibi cellular accumulation reflects sarcolemmal and mitochondrial electrical gradients. It was used to monitor the direct effects of two cardioplegic solutions, modified St Thomas' Hospital and Bretschneider, on normoxic and metabolically-inhibited cultured cells. Cellular accumulation of 99mTc-sestamibi, expressed by the ratio between intra and extra cellular concentrations, was assessed in three different sets of neonatal rat cardiomyocytes. Cells were either treated with different concentrations of modified St Thomas' solution (50, 75, 100%), they were treated or recovering from a treatment with modified St Thomas and Bretschneider solutions at 50% concentrations, or were recovering from treatment with modified St Thomas' and Bretschneider solution at 50% concentrations mixed with metabolic inhibitors. Cardioplegia depressed the tracer accumulation in a concentration-dependent manner. This effect was independent of the type of cardioplegia (120-min uptake, as a percentage of control values, modified St Thomas' 68+/-12 and Bretschneider 59+/-7) and was rapidly reversible. Cardioplegia was unable to prevent the depression of tracer accumulation induced by metabolic inhibitors and even induced a deleterious effect (120-min uptake, as a percentage of control values, metabolic inhibitors 69+/-12, metabolic inhibitors + modified St Thomas 38+/-14, metabolic inhibitors + Bretschneider 43+/-6) during recovery after 30 min of metabolic inhibition. It was concluded that cardioplegia has an apparent detrimental effect on neonatal cardiomyocytes accumulation of 99mTc-sestamibi during recovery from an ischaemic-like insult.

Animals↗

Release of mast cell mediators and nitrites into knee joint fluid in osteoarthritis--comparison with articular chondrocalcinosis and rheumatoid arthritis.

In order to address the issue of the role of mast cells and nitric oxide (NO) in joint effusions occurring in the course of osteoarthritis (OA), synovial fluids collected from the knee of patients with OA, articular chondrocalcinosis and rheumatoid arthritis (RA) were studied for number of mast cells, and histamine, tryptase, phospholipase A2 and nitrite content. Mast cell counts are elevated in synovial fluid from OA patients when compared with RA. Histamine content in synovial fluid parallels the number of mast cells. Tryptase levels are elevated in OA in comparison with both other conditions, but do not reach the level of significance. Identical phospholipase A2 levels are recorded in three groups. Nitrite concentrations are also higher in synovial fluid from OA patients when compared with RA patients. These results suggest that mast cells in association with various inflammatory cells, may contribute to inflammation and cartilage breakdown in OA.

Aged↗

Occurrence of pulmonary complications during methotrexate therapy in rheumatoid arthritis.

Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The aim of this retrospective study was to evaluate, during a 6 yr period, the prevalence and severity of bronchopulmonary side-effects in RA patients treated with MTX. A cohort of 130 RA in-patients (106 women, 24 men) treated with MTX was studied for the occurrence of respiratory adverse events. Adverse bronchopulmonary side-effects were observed in 12 patients (two men, 10 women), with a mean disease duration of 15 yr. Only three patients had previously suffered from pulmonary disease. MTX treatment duration was between 1 month and 4.5 yr. The diagnosis was that of hypersensitivity pneumonitis (HSP) in four cases, non-HSP pneumonitis in five patients with one case of Pneumocystis carinii infection, and bronchitis in three cases. The initial respiratory symptoms were not discriminatory between the different conditions. Risk factors were not identified for the occurrence of HSP. HSP always occurred in the first 5 months of treatment. Two patients with HSP died, and another patient with opportunistic infection underwent tracheostomy. HSP represents a potentially lethal side-effect in RA patients treated with MTX. Improved education of patients and physicians should certainly lead to a reduction of both the prevalence and severity of pulmonary side-effects during MTX therapy in RA.

Adult↗

Monostotic Paget's disease involving the calcaneus. Diagnostic and therapeutic problems. Two case-reports.

The authors report the cases of two patients who had chronic incapacitating heel pain unresponsive to standard therapy. They were both found to have Paget's disease of the calcaneus. The diagnosis was difficult because the typical roentgenological changes required time to develop and because no other sites were involved. Local corticosteroid injections, elimination of weight-bearing, and standard analgesic therapy were ineffective. Bisphosphonate therapy (pamidronate) given as intravenous infusions ensured prompt lasting pain relief, making ambulation possible.

Calcaneus↗

Cellular activation products in osteoarthritis synovial fluid.

In order to address the issue of the role of mast cells (MC) and nitric oxide (NO) in rheumatic synovial-fluid diseases, synovial fluid (SF) collected from the knee of patients with osteoarthritis (OA), articular chondrocalcinosis (ACC) or rheumatoid arthritis (RA) was examined for the levels of mast cells (MC), histamine, tryptase, phospholipase A2 and nitrite. MC counts were found to be elevated in the SF of OA patients as compared with RA patients. Histamine content in SF parallelled the number of MC. Tryptase levels were elevated in OA in comparison to RA and ACC, but the difference was not statistically significant. Identical PLA2 levels were recorded among the 3 groups. Nitrite concentrations were also higher in SF from OA patients as compared to RA patients. These results suggest that mast cells (MC), in association with various inflammatory cells, may contribute to inflammation and cartilage breakdown in osteoarthritis (OA).

Aged↗

[Substance P and rheumatic diseases].

Substance pertains to a group of linear molecules of 10-30 amino-acid residues produced by nervous fibers and called neuropeptides. It is a mediator of pain transmission, and modulates or stimulates the activity of several cell types, i.e. lymphocytes and mast cells. The concept of neurogenic inflammation is based on the release of substance P and related peptides by an axon eflex mechanism. In rheumatic diseases, substance P may enhance inflammatory joint reactions. In rheumatoid arthritis, high SP levels were demonstrated in synovial fluid by our group and others. Results in fibromyalgia are contradictory. Algoneurodystrophia may be modulated by substance P release. Topical use or capsaicin and development of peripheral inhibitory drugs offer novel treatments based on this concept.

Animals↗