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Biomedical subjects

J Favier

Publications and source records attributed to J Favier.

At least 19 recordsLinked to original sources
PubMed2005

Succinate dehydrogenase deficiency in human.

Mitochondrial succinate dehydrogenase (SDH) consists merely of four nuclearly encoded subunits. It participates in the electron transfer in the respiratory chain and in succinate catabolism in the Krebs cycle. Mutations in the four genes, SDHA, B, C and D, have been reported, resulting in strikingly diverse clinical presentations. So far, SDHA mutations have been reported to cause an encephalomyopathy in childhood, while mutations in the genes encoding the other three subunits have been associated only with tumour formation. Following a brief description of SDH genes and subunits, we examine the properties and roles of SDH in the mitochondria. This allows further discussion of the several hypotheses proposed to account for the different clinical presentations resulting from impaired activity of the enzyme. Finally we stress the importance of SDH as a target and/or marker in a number of diseases and the need to better delineate the consequences of SDH deficiency in humans.

Humans↗
PubMed2001

The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway.

Hereditary paragangliomas are usually benign tumors of the autonomic nervous system that are composed of cells derived from the primitive neural crest. Even though three genes (SDHD, SDHC, and SDHB), which encode three protein subunits of cytochrome b of complex II in the mitochondrial respiratory chain, have been identified, the molecular mechanisms leading to tumorigenesis are unknown. We studied a family in which the father and his eldest son had bilateral neck paragangliomas, whereas the second son had a left carotid-body paraganglioma and an ectopic mediastinal pheochromocytoma. A nonsense mutation (R22X) in the SDHD gene was found in these three affected subjects. Loss of heterozygosity was observed for the maternal chromosome 11q21-q25 within the tumor but not in peripheral leukocytes. Assessment of the activity of respiratory-chain enzymes showed a complete and selective loss of complex II enzymatic activity in the inherited pheochromocytoma, that was not detected in six sporadic pheochromocytomas. In situ hybridization and immunohistochemistry experiments showed a high level of expression of markers of the angiogenic pathway. Real-time quantitative reverse transcriptase (RT)-PCR measurements confirmed that vascular endothelial growth factor and endothelial PAS domain protein 1 mRNA levels were significantly higher (three- and sixfold, respectively) than those observed in three sporadic benign pheochromocytomas. Thus, inactivation of the SDHD gene in hereditary paraganglioma is associated with a complete loss of mitochondrial complex II activity and with a high expression of angiogenic factors.

Adult↗
PubMed2001

Coexpression of endothelial PAS protein 1 with essential angiogenic factors suggests its involvement in human vascular development.

Endothelial PAS protein 1 (EPAS1) is a bHLH-PAS transcription factor involved in cellular response to hypoxia. Its precise role in angiogenesis is unclear, but several genes essential to vascular development, including those encoding vascular endothelial growth factor (VEGF), its receptor VEGFR-2 and Tie2, are thought to be targets of EPAS1. To investigate whether this transcription factor and its putative targets were expressed concomitantly, we performed in situ hybridization on serial adjacent sections of human embryos at gestational ages of 3 to 6 weeks. We studied expression of the genes encoding EPAS1, VEGF, VEGFR-1, and -2, Tie2, and its ligands, angiopoietin (Ang) 1 and 2. We also compared these expression profiles with that of hypoxia-inducible factor 1alpha (HIF1alpha). EPAS1 transcripts were detected in several types of endothelial cell: in blood vessels walls, the endocardium, the glomeruli of the mesonephros, and the sinusoids of the liver. In these endothelial cells, expression of EPAS1 systematically or partly coincided with Tie2 and the VEGF receptors expression. There was also some overlap between the sites of synthesis of EPAS1 and VEGF mRNAs, principally in hepatocytes and sympathetic ganglion cells. In addition, we found that EPAS1 and HIF1alpha transcripts were often colocalized, suggesting a functional redundancy of these two transcription factors during development. These observations are consistent with transactivation by EPAS1 of the expression of its putative target genes during embryogenesis, suggesting that this transcription factor is involved in human angiogenesis. They provide evidence that EPAS1 is involved in the regulation of vascular maturation, remodeling, or stabilization rather than in the early steps of embryonic angiogenesis.

Angiogenesis Inducing Agents↗
PubMed2001

The interpretation of train-of-four monitoring in intensive care: what about the muscle site and the current intensity?

OBJECTIVES: To investigate the effect of current intensity and choice of the stimulated muscle group on train-of-four (TOF) interpretation in the intensive care unit (ICU). DESIGN AND SETTING: Intervention study in a surgical intensive care unit. PATIENTS: 13 ventilated patients requiring prolonged muscle relaxation. MEASUREMENTS AND RESULTS: Prior to blockade TOF responses of left and right orbicularis oculi, adductor pollicis, and plantar flexors were recorded by setting the current intensity at 20, 40, 60, and 80 mA. The minimal current intensity (MCI) providing a supramaximal response was then identified for each muscle. Cisatracurium was then infused aiming to continuously observe a TOF at 2/4 on the left orbicularis oculi at 40 mA. The responses to TOF on all the muscle sites were further recorded at 40, 60, and 80 mA when the endpoint was reached for the first time, and after a 48-h infusion. After cessation of infusion the delay to observe 4/4 responses at TOF was recorded at each site at 40 mA or at MCI if MCI was above 40 mA. MCI did not differ between muscle groups. When the fixed endpoint was reached for the first time on left orbicularis oculi, the TOF response at 40 mA on right orbicularis oculi differed significantly. In contrast, no difference was observed between left and right sides at 40 mA at the other sites, nor at any sites at 60 and 80 mA. The TOF response on orbicularis oculi (left and right sides together) was different at 40 mA, compared to 60 and 80 mA. TOF responses at orbicularis oculi at 60 or 80 mA significantly differed from responses on adductor pollicis or plantar flexor, orbicularis oculi being less sensitive to cisatracurium than adductor pollicis or plantar flexor. After a 48-h infusion the same differences in sensitivities were observed between the muscle groups. At any current intensity the recovery was slower at adductor pollicis than at orbicularis oculi or plantar flexor. CONCLUSIONS: For a good TOF interpretation in the ICU the current intensity should be tested before onset of blockade. The orbicularis oculi is less sensitive to cisatracurium than adductor pollicis and plantar flexor both at onset and after a prolonged infusion. The recovery from relaxation is faster on orbicularis oculi and plantar flexor than on adductor pollicis.

APACHE↗
PubMed2000

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.

OBJECTIVE: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. METHODS: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses. RESULTS: Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy. CONCLUSIONS: Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Cloning and expression pattern of EPAS1 in the chicken embryo. Colocalization with tyrosine hydroxylase.

EPAS1 is a hypoxia-inducible transcription factor, highly expressed in vasculature and recently shown to be necessary for catecholamine production during embryogenesis. We report here the cloning and detailed expression pattern of this factor in the chicken embryo. We show that chicken EPAS1 presents an overall identity of 76% with the human sequence and that it is strongly expressed in the blood vessel wall, mostly in endothelial cells, but also in vascular smooth muscle cells. Moreover, we report non-vascular expression sites: liver, kidney, and, quite interestingly, cells of the sympathetic nervous system where EPAS1 is coexpressed with one of its putative target genes, the tyrosine hydroxylase. EPAS1 could therefore represent the link between the vascular system and the sympathetic nervous system, both sensitive to hypoxia.

Amino Acid Sequence↗
PubMed1995

Head injuries in children: a chronicle of a quarter of a century.

Children aged 0-15 years hospitalized in Geneva for head trauma during the last quarter of a century are reviewed. More than half of the severely injured children were not from Geneva area. New methods of management have been introduced progressively. The cases are divided in four successive time periods and classified according to their pathology. A continuous improvement in mortality is obvious, decreasing from 29.4% to 2.2%, but climbing again to 15.2% in the last period, probably due to more severe pathologies. For the Geneva area the mortality decreased progressively from 10.4/100,000 to 3.5/100,000 annually, due to better organization and management, but also to a drop in the incidence of severe cases from 35.5-13.5/100,000 per year. A decrease in the number of traffic accidents is responsible for this. However, the number of handicapped children has not changed.

Accidents, Traffic↗
PubMed1994

Paediatric head trauma: influence of age and sex. I. Epidemiology.

A consecutive unselected series of 1812 children (up to 15 years old) admitted for head injuries over a period of 8.5 years was studied. The cases were divided up according to five categories of pathology: benign injury, extradural haematoma, subdural haematoma, open brain laceration and brain contusion in a broad sense. All cases of benign injury were from the Geneva area (57000 children) and 52% of the cases of severe injury were referred from other places. To these 1812 cases were added those of 23 children who died before admission recorded by the police. In the Geneva area the mortality was 6.8/100,000 per year. Patients were divided into three age groups: I (0-3 years), II (3-9 years), and III (9-15 years); group I was further subdivided into subgroups I a (0-1 year) and I b (1-3 years). The incidence of each type of accident was calculated for each age group, separately for girls and boys. Each type of pathology was correlated, sex by sex and for different ages, with the type of accident. Overall, two boys were injured for each girl. Road accidents were responsible for 15% of head injuries in group I girls, 17% in group I boys, 43% in group II girls, 45% in group II boys, 50% in group III boys and 61% in group III girls. They were responsible for 94% of all deaths and 85% of deaths of hospitalized patients. Falling was the most frequent cause of injury. Benign injuries were more frequent in group I. Only 1 of 25 patients with extradural haematomas died, and there were only 8 patients with subdural haematomas, 4 in subgroup I a (babies aged less than 1 year).

Accidental Falls↗
PubMed1994

Paediatric head trauma: influence of age and sex. II. Biomechanical and anatomo-clinical correlations.

A consecutive, unselected series of 1812 cases of head trauma in children less than 15 years of age and admitted hospital over a period of 8.5 years was studied. Data concerning the grade of energy involved, the ages of the victims, the types of pathologies caused and the clinical features noted were collected and statistically analysed. Babies and toddlers (0-3 years) were shown to sustain rather low-energy trauma and suffer more skull fractures, more subdural haematomas and more benign injuries. They lost consciousness less frequently and were less frequently in coma than the other children. By contrast, they had more frequent signs of lateralization, and early seizures were much more frequent in babies than in other children. Young children (3-9 years) had rather higher-energy accidents, frequently lost consciousness, were more frequently in coma and have more frequently had a free interval associated with the development of brain swelling. They did not suffer subdural effusion or contrecoup lesions. Schoolchildren (9-15 years) were statistically more or less like young adults: the clinical sequences of trauma were more severe than in the other children, mortality was a little bit higher, the risk of extradural haematoma was higher, and they rarely suffered subdural haematomas or contrecoup lesions. Traffic accidents, with higher energy involved, were more severe.

Accidents, Traffic↗
PubMed1994

[Prevention of infections of cerebrospinal fluid shunts for hydrocephalus].

Two consecutive series of patients operated for insertion or revision of a shunt for hydrocephalus have been followed for at least 18 months. The series are comparable. The first series (84 cases) did not receive antibiotic prophylaxis, whereas the second series (59 cases) received a unique dose of intravenous Vancomycin immediately before the operation. In the first series (168 operations), there were 18 infections, 8 in the group of 34 children and 10 in the group of 50 adults. In the second series, only one infection happened in the group of 27 adults (41 operations) and none among the 22 children (44 operations). The difference was significative. Bacteriological samples were taken during these operations. The positive cultures, mostly for sta. epidermidis, were as frequent among the cases of the first series than among those of the second series. The antibiotics are considered effective in protecting the shunting device against contamination during the surgical procedure by germs from the skin of the patient.

Adolescent↗
PubMed1985

Oligodendroglial tumors in childhood.

A series of 20 hemispheric tumors in children less than 16 years of age, over a period of 20 years, is presented. Among them, 8 were oligodendroglial tumors, a proportion well above the level reported in the literature. The World Health Organization (WHO) classification, which includes mixed oligoastrocytomas, in the oligodendrogliomas was used. This addition does not explain this unusually high proportion. Selection of cases and the correct histological diagnosis are probably important.

Adolescent↗
PubMed1985

Brain specific gravity and CT scan density measurements after human head injury.

White matter specific gravity was measured using the microgravimetric method in 20 comatose patients with diffuse head injury who were undergoing intracranial pressure (ICP) monitoring, and in 19 patients with focal injuries who were undergoing evacuation of contusions or intracerebral hematomas. Computerized tomography (CT) density readings were obtained for each site of white matter sampling by locating the sampling site on the preoperative CT scan. A significant correlation was found between the specific gravity values and the CT density numbers (r = 0.775; p less than 0.001). Patients with focal injuries demonstrated reduced perifocal specific gravity, suggesting brain edema. The mean specific gravity in patients with diffuse injury was within the normal range. In 10 of 12 patients in whom the specific gravity was above the normal range, the CT density was also above the normal range. These data suggest that cerebral vascular engorgement is the cause of the high specific gravity. Six (60%) of this small subgroup of 10 patients also demonstrated a high ICP.

Adult↗