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Biomedical subjects

P Hubert

Publications and source records attributed to P Hubert.

At least 145 records · Page 8Linked to original sources
PubMed1994

Clinical outcome of long-term management of patients with vitamin B12-unresponsive methylmalonic acidemia.

We performed a retrospective study of all patients with methylmalonic acidemia diagnosed during the past 20 years. Only those patients who were nonresponsive to vitamin B12 in vivo and in vitro were included. The final study group consisted of 26 patients, of whom 16 had a neonatal (early) onset; in 10 patients the diagnosis was made after 2 months to 2.2 years (late onset). Of the early-onset patients, 14 (87%) died, with a mean survival time of 1.5 years (range, 10 days to 2.5 years), whereas four of the late-onset patients (40%) died (range, 1.2 to 15 years). At present, eight patients are alive; their mean age is 4.6 years (range, 1 to 10 years). In the early 1970s, treatment was based on the principles of treating patients with phenylketonuria: restricting natural protein intake and supplementing essential amino acids, vitamins, and trace elements. After about 1980, nasogastric tube feeding became a mainstay of the therapy, natural protein restriction became stricter, and the use of essential amino acid mixtures diminished. Carnitine was added to the therapy and, in later years, metronidazole. Since these changes were implemented, the number of episodes of metabolic decompensation and hospitalizations has decreased. Mean survival time of the patients, in particular those with early onset, has only slightly improved, partly because of psychosocial problems in many of these families. Almost all the patients, especially those with early onset, had some degree of neurologic impairment and mental retardation, and many patients were at less than 2 SD for weight or height or both. In contrast, the neurologic and mental status of the late-onset patients was frequently normal, and their weight and height were more often within normal limits. Our results show that the treatment of methylmalonic acidemia still poses considerable problems; despite intense medical efforts and familial stress, the prognosis for the early-onset patients is disappointing. The patients with late-onset disease, however, appear to have a fairly good prognosis with the present therapeutic approach. Liver transplantation or possibly genetic therapy might improve our results in the future.

Age Factors↗
PubMed1994

[Acute subdural hematoma of the convexity caused by rupture of an aneurysm in the anterior communicating artery. Apropos of a case in a pregnant woman].

We present a case of a pure acute subdural haematoma of the convexity from a ruptured communicating anterior aneurysm, in a full-term pregnant woman. She was managed in emergency as follows: cranial computed tomography, general anaesthesia, caesarean section, cerebral angiography, evacuation of the subdural haematoma and clipping of the aneurysm. The outcome was excellent. Pure subdural haematoma from ruptured aneurysm, with little or no subarachnoid, intraventricular or intracerebral haemorrhage is very rare. We discuss the treatment of such a haematoma and discuss the other causes for spontaneous subdural haematomas. Our observation stresses the need for a high-performance technical plate in the management of ruptured aneurysms, but also for the importance of a correct clinical diagnosis of minor leaks by the general practitioners who decide on the hospitalization.

Acute Disease↗
PubMed1994

Dietary fish oil and olive oil improve the liver insulin receptor tyrosine kinase activity in high sucrose fed rats.

In order to shed light on the possible beneficial effect of dietary unsaturated fatty acids on insulin binding, the effect of fish oil and olive oil administration on insulin binding, autophosphorylation and tyrosine kinase activity of partially purified liver insulin receptors were investigated. These data were confronted with the parameters of sugar and lipid metabolism (blood glucose, insulin and triglycerides), with liver plasma membrane fluidity and fatty acid composition. High sucrose feeding resulted in the elevation of blood glucose and triglyceride level, while the supplementation of animals with fish oil reduced that of triglycerides and olive oil that of insulin. Any significant changes between experimental groups were not detected either in insulin binding to partially purified liver insulin receptor nor in receptor autophosphorylation. However, the insulin stimulated tyrosine kinase activity towards an exogenous substrate (poly(Glu,Tyr)) was decreased by about 50% in the receptors solubilized from liver membranes of sucrose fed rats. Increased dietary intake of fish oil or olive oil restored the activity of insulin tyrosine kinase towards control values, half maximal effect being obtained at similar insulin concentration in all groups. Such improvement might be due to the induced increase of membrane fluidity by unsaturated fatty acids, and/or to the decrease of insulinemia.

Animals↗
PubMed1994

[Mid-term outcome of 2 cases with maple syrup urine disease: role of liver transplantation in the treatment].

BACKGROUND: Dietary treatment of maple syrup urine disease remains difficult; chronic nutritional support in the child does not always avoid acute crises so that liver transplantation may represent an alternate choice in some cases. CASE REPORTS: Two gypsy cousins were born by an interval of 4 days; both had maple syrup urine disease and were similarly treated from the first days of life. They were given exchange transfusions followed by diet restricted in the branched chain amino acids, maintaining normal growth and plasma leucine concentrations under 7 mg/100 ml. Laura, at 10 years, was retarded at school. Compliance to school attendance was limited by her diet problems. Helen suffered at 7 yr 3 mo from liver failure due to hepatitis A virus infection which required liver transplantation. Protein intake was normal 1 week later. At 10 years, she presented with the same degree of school retardation as her cousin, and was placed in the same class. CONCLUSION: Liver transplantation may be effective for treating metabolic problems in MSVD without significative difference between outcome post classic treatment or post liver transplantation.

Child↗
PubMed1993

Fully automated determination of sulfamethazine in ovine plasma using solid-phase extraction on disposable cartridges and liquid chromatography.

An automatic sample preparation procedure followed by on-line injection of the sample extract into a HPLC system has been developed for the quantitative analysis of sulfamethazine and its N4-acetyl metabolite in ovine plasma. The sample clean-up was performed by solid-phase extraction (SPE) on C18 disposable extraction cartridges (DECs). All the sample handling operations were effected by a robotic auto-sampler. The DEC was first conditioned with methanol and phosphate buffer pH 7.4. After loading 1.0 ml of plasma sample onto the DEC, the latter was washed with the same buffer. The elution step was performed with methanol (0.25 ml) and the eluate was then diluted by adding 0.75 ml volume of phosphate buffer pH 6.4. A 20-microliters volume of the resultant solution was injected onto an octadecyl silica column preceded by a short guard column. The HPLC mobile phase was methanol-phosphate buffer pH 6.4 (25:75, v/v). Sulfamethazine and N4-acetylsulfamethazine were determined photometrically at 262 nm. Under these conditions, linear calibration curves ranging from 2 to 250 micrograms ml-1 have been obtained for both compounds. Drug recoveries were higher than 90% and typical relative standard deviation values were 0.7% (within-day) and 2.0% (between-day) at a plasma concentration of 50 micrograms ml-1.

Animals↗
PubMed1993

Tyrosine phosphorylation and association with phospholipase C gamma-1 of the GAP-associated 62-kD protein after CD2 stimulation of Jurkat T cell.

Numerous substrates are tyrosine phosphorylated upon CD2 stimulation of human Jurkat T cells using a mitogenic pair of CD2 monoclonal antibodies, including the phospholipase C (PLC)gamma-1-p35/36 complex. Most of these substrates are identically tyrosine phosphorylated after CD3 ligation, suggesting that both stimuli share the same biochemical pathway. We show, however, in this report that a 63-kD protein is specifically phosphorylated on tyrosine residues after ligation of the CD2 molecule. The tyrosine phosphorylation of p63 can be induced independently of other substrates when using a single CD2 mAb recognizing the D66 epitope of the molecule. Importantly, this CD2-induced tyrosine phosphorylation of p63 can also occur in the absence of the CD3 zeta chain membrane expression, and is also distinct from the protein tyrosine kinases p56lck and p59fyn. We demonstrate, moreover, that p63 is physically linked with PLC gamma-1 and p35/36 upon CD2 stimulation. Finally, we also show that a 62-kD protein coimmunoprecipitating with the p21ras GTPase activating protein (GAP) is heavily tyrosine phosphorylated only after CD2 stimulation. This ultimately suggests that p63 may represent in fact the 62-kD protein that associates with GAP after tyrosine phosphorylation. Taken together, these results demonstrate the occurrence in Jurkat cells of a tyrosine kinase pathway specifically coupled to the CD2 molecule. They also suggest a function of the p62-GAP-associated protein as a link between PLC gamma-1 and p21ras activation pathways after CD2 activation.

Antibodies, Monoclonal↗
PubMed1993

Reconstitution studies of lipid effects on insulin-receptor kinase activation.

Insulin receptors extracted from human placenta were reconstituted by dialysis into well-characterized lipid vesicles. For all types of lipids studied, vesicles were shown to be unilamellar, about 120 nm in diameter. The incorporation of lectin-purified insulin receptors was assessed by cosedimentation of 125I-insulin binding and [32P]phospholipids in a sucrose gradient. The insulin-binding activity was not modified by the composition of the lipid vesicles. However, tyrosine kinase activation appeared to be more sensitive to its lipid environment. Mixtures of phosphatidylcholine/phosphatidylserine or phospholipids/phosphatidylserine, in ratios of 1-4, increased the insulin-induced tyrosine kinase activation in a dose-dependent manner. In contrast, experiments performed in the presence of phosphatidylinositol showed a decrease in the enzyme stimulation. These results indicate an opposing involvement of these two anionic phospholipids in the kinase activation. Inclusion of cholesterol (10-30%) into phosphatidylcholine vesicles reduced kinase activation, which was drastically inhibited by 30% cholesterol. The effect of a total extract of brain gangliosides was biphasic, stimulatory at low concentration (5-10%), but with a reverse effect at higher concentrations. These results stress the importance of the lipid environment for insulin-receptor signaling, particularly for the insulin-induced activation of its beta-subunit kinase.

Animals↗
PubMed1993

Intravenous nicardipine in hypertensive children.

Fourteen hypertensive patients hospitalized in a paediatric intensive care unit were studied to evaluate safety and hypotensive efficacy of intravenous nicardipine. Systolic and diastolic blood pressure significantly decreased 1 h after the beginning of the treatment (1 microgram/kg per minute). Mean decrease in systolic blood pressure during the first 24 h was between 9.9% and 13.4% of the initial value. Mean lowering of diastolic blood pressure was between 16.7% and 25.6%. Nicardipine did not significantly affect heart rate with dose of 1 microgram/kg per minute. No clinical side-effects were observed. Nicardipine could be a first line drug for the treatment of hypertension in paediatric intensive care units.

Blood Pressure↗
PubMed1993

Serious childhood angiomas: unsuccessful alpha-2b interferon treatment. A report of four cases.

Over a 4-year period, we managed four children with alarming haemangiomas (two cases of Kasabach-Merritt syndrome and two life-threatening haemangiomas). Systemic steroid therapy was ineffective. Other treatments (radiotherapy, anti-platelet drugs) were also ineffective in the Kasabach-Merritt patients. On the basis of recent reports on the effects of interferon on endothelial cells, we used alpha-2 interferon therapy, but obtained no response.

Arm↗
PubMed1993

Recurrent oligodendroglioma diagnosed with 11C-L-methionine and PET: a case report.

A benign oligodendroglioma was removed in a young patient who had temporal epileptic seizures. He then became free of any fit until 15 months after the operation, when he developed seizures progressively less controlled by therapy. All investigations were normal (including CT scan and MRI) except a PET study which showed a high uptake of 11C-L-methionine in the area of the previous tumor. The second operation revealed that this area was indeed a tumor recurrence. We briefly discuss the potential usefulness of PET for the follow-up of low grade gliomas.

Adolescent↗
PubMed1993

Influence of cholesterol derivatives on cytoskeletal organization of human carcinoma cells.

Recent developments of immunotherapeutic approaches have shown that artificial ordering of tumor cell membranes with cholesterol hemisuccinate (CHS) or 25-hydroxycholesterol (25-OH) may significantly enhance the immunogenicity of human renal adenocarcinoma cells. To gain further insight into the molecular mechanism of these sterols, we investigated cytoskeletal modification, which is related to the cell membrane. After treatment of human renal carcinoma cells with these cholesterol (at 10(-6) and 10(-7) M) for 5 days, we observed a disorganization of the submembrane end of the cytoplasmic actin stress fibers by cytofluorescence. The microtubule network was not affected. Thus, in the present study, we found that changes in membrane physicochemical properties impaired the anchorage of actin microfilaments in the plasma membrane of human renal cancer cells. Under the same experimental conditions, such modifications were not observed in normal cells (human fibroblasts) or in human hepatoma cells. We suggest that incubation of cancer cells with these sterols induced a redistribution of the cholesterol-rich membrane microdomains which are linked to the cytoskeleton through submembrane proteins.

Actins↗
PubMed1993

[Sudden crib death. Experience in a referral center 1986-1991].

BACKGROUND: Sudden infant death syndrome (SIDS) may have several etiologies, all of which must be identified in order to recognize those infants believed to be at risk. One of the best ways to do this is by prospective studies on a large population of infants who died of SIDS. METHODS: A total of 171 infants who died from SIDS between January 1, 1986 and June 30, 1991, were studied. 154 infants were completely investigated, including a post mortem examination. They were assigned to one of 4 groups, according to whether death was due to diseases of poor prognosis (group A), diseases that are occasionally fatal but potentially treatable (group B), minor diseases not normally fatal (group C), or was essentially unexplained (group D). RESULTS: The classical risk factors for SIDS were found in this population: incidence peaked in males (sex-ratio 1.5), during the cold seasons (62%), between 1 and 6 months of age (94%), mainly between 1 and 4 months of age (84%). Symptoms were definitely present during the 2 days before death in 50%. 20% of cases had clinical histories of congenital disease, complicated or recurrent postnatal disease, or fulminant recent disease. Group A included 107 infants (69% of the 154 completely investigated patients). Premature birth (17.5%) and low birth weight for gestational age (10.5%) were more frequent in our series than in the normal population. CONCLUSION: The cause of death was identified in about 75% of cases. This possibility improves management of further siblings of SIDS victims even though the variety of risk factors makes prevention of SIDS difficult.

Autopsy↗