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T Billiar

Publications and source records attributed to T Billiar.

At least 19 recordsLinked to original sources
PubMed2000

Multi-variate analysis predicts clinical outcome 30 days after middle cerebral artery infarction.

BACKGROUND AND PURPOSE: To evaluate the functional prognostic value of proton magnetic resonance spectroscopy performed within the 5 days of an infarction of the middle cerebral artery territory, compared with previously demonstrated prognostic factors. METHODS: Proton magnetic resonance spectroscopy was performed on 77 consecutive non-comatosed patients during the acute stage of middle cerebral artery infarction. The functional status was determined for each patient via the Orgogozo score. Proton magnetic resonance spectroscopic data were acquired in the infarction and in contra-lateral normal tissue and the results were expressed as metabolite ratios. Correlations were evaluated between the Orgogozo score at day 1 and day 30, the age, the sex, the volume of the infarction, and the metabolic ratios. RESULTS: In a monovariate analysis, the decrease of the NAA/choline ratio was correlated with a low Orgogozo score at days 1 and 30 (P<0.05) and with a large infarction (P<0.05). A stepwise analysis showed a significant relationship between the Orgogozo score at day 30 and the Orgogozo score at day 1, the sex, the volume of infarction, and the NAA/Cho ratio within the infarction. CONCLUSIONS: Our work demonstrates that a good clinical outcome at day 30 depends on a good initial clinical score at day 1, a small volume of infarction, a small decrease of NAA/Cho, and being of the female gender.

Adult↗
PubMed2000

Muscular contractile failure in septic patients: role of the inducible nitric oxide synthase pathway.

Skeletal muscle failure is a frequent manifestation of sepsis that affects prognosis and rehabilitation by impairing respiration and ambulation. Animal studies have shown that the inducible NO synthase (NOS2) is expressed in skeletal muscles during sepsis, likely affecting muscular function, by promoting the formation of the strong oxidant peroxynitrite. In contrast, whether human skeletal muscle expresses a functional NOS2 in similar conditions is unknown. We studied NOS2 expression (mRNA and protein) and activity and its role in contractile function in samples from rectus abdominis muscle obtained during surgical procedure in 16 septic patients and in 21 controls. Peroxynitrite formation was detected by immunohistochemical detection of nitrotyrosine residues. The main results of this study are as follows: (1) A significant increase in NOS2 mRNA, protein, and activity was found in muscles from septic patients, the expression of NOS2 protein positively correlating with sepsis severity. (2) Contractile force was significantly lower in septic than in control muscles. This phenomenon was not reverted by muscle incubation ex vivo with the NOS inhibitor L-NMMA, indicating that NO was not involved in force reduction at the time of biopsy. (3) NOS2 expression in skeletal myocytes was strongly co-localized with nitrotyrosine, revealing muscular peroxynitrite generation during the septic process, before the muscle was biopsied. Exposure of control muscles to an amount of peroxynitrite similar to that generated in septic muscles during the septic process resulted in a nonreversible reduction in force generation. These results suggest that NOS2 could be involved in the decreased muscular force of septic patients via the local generation of peroxynitrite.

Adult↗
PubMed1999

Inducible nitric oxide synthase and vascular injury.

The role nitric oxide (NO) plays in the cardiovascular system is complex and diverse. Even more controversial is the role that the inducible NO synthase enzyme (iNOS) serves in mediating different aspects of cardiovascular pathophysiology. Following arterial injury, NO has been shown to serve many vasoprotective roles, including inhibition of platelet aggregation and adherence to the site of injury, inhibition of leukocyte adherence, inhibition of vascular smooth muscle cell (VSMC) proliferation and migration, and stimulation of endothelial cell (EC) growth. These properties function together to preserve a normal vascular environment following injury. In this review, we discuss what is known about the involvement of iNOS in the vascular injury response. Additionally, we discuss the beneficial role of iNOS gene transfer to the vasculature in preventing the development of neointimal thickening. Lastly, the pathophysiology of transplant vasculopathy is discussed as well as the role of iNOS in this setting.

Animals↗
PubMed1999

Survival rates of malignant gliomas in Burgundy from 1990 to 1995.

The aim of this study was to provide current data on case-fatality rates of malignant gliomas in the area of Burgundy (1,300,000 inhabitants). The ascertainment was specific according to imaging and histologic criteria, and was exhaustive because of the existence of a single University Hospital allowing both imaging and histologic diagnosis from stereotaxic cerebral biopsy. During six full years we collected 161 cases of malignant gliomas grades II to IV, 93 men (57.76%) and 68 women (42.23%). The mean age was 61 years. In all the age groups, there were a male predominance. Headache, epilepsy and motor deficit were the most frequent symptoms at onset. In most cases, the gliomas were localized within the frontal area. The post-surgical Karnofsky score was up to 70 in 40% of the cases. There were 89 glioblastomas with grade IV, 37 anaplastic astrocytomas, 13 gliomatous tumors with grade II and IV and six anaplastic oligodendrogliomas. This grading explains the very low survival rates, with a negative effect induced by age. Among the most relevant contributions of this study to the clinical features of malignant gliomas is an analysis of case-fatality rates, evaluation of health care services and therapeutic trials.

Adolescent↗
PubMed1999

Nitric oxide synthase gene transfer to the vessel wall.

A wide array of vascular disorders have been shown to benefit from gene therapy. Given the vasoprotective role that nitric oxide plays in the vasculature, it is understandable why gene therapy with the three different isoforms of nitric oxide synthase has been so successful. This review summarizes the current literature pertaining to nitric oxide synthase gene transfer to the vascular wall.

Animals↗
PubMed1998

Clinical patterns of acute stroke among the three health-care systems in France.

Data from 959 consecutive patients registered with the Dijon Stroke Registry were used to compare the characteristics of the patients who were admitted to the public hospital within the first days after their first stroke with those admitted to the private hospitals or who remained at home. Seven hundred and one patients (73%) were admitted to the public hospital, 185 (19%) were admitted to private hospitals and 73 (8%) remained in the community. The results show that the clinical patterns of the stroke are quite different among the three health-care systems. The clinical patterns of stroke managed in the public hospital are characterized by: a younger age (63-years-old vs, 77 and 76-years-old), earlier coma (29% vs 2.8 and 1.5%), more severe deficit (71% vs 15 and 5%), more hemorrhagic mechanism (23 vs 4.5% and 1.7%), more associated ischemic heart disease (31% vs 18 and 15%), more cardiac arrhythmia (38% vs 11 and 8%), higher case fatality rate (39% vs 8 and 2%). Therefore, we have identified three clinical patterns among the three health-care facilities. These three clinical patterns are quite different on the point of view of the clinical severity, and the associated co-morbidities. The socio-economic status is not a criteria in the choice of the health-care facility. This observed distribution is not the consequence of a voluntary policy. Copyright 1998 Lippincott Williams & Wilkins

Journal Article↗
PubMed1998

Epilepsy in patients with multiple sclerosis: radiological-clinical correlations.

PURPOSE: To determine potential mechanisms of epilepsy in patients with multiple sclerosis (MS). METHODS: Among 402 patients with clinically and radiologically defined MS, including de novo cases, presenting to the Neurology Service, University Hospital of Dijon, we identified 17 with epileptic seizures (4.25%). Among them, the percentage with partial seizures (50%) was greater than that in the reference population. RESULTS: In most of the patients with MS, plaques were localized in the frontal region, associated with frontal and callosal atrophy, a frontal syndrome, and severe disability status (as assessed by a standard scale). Magnetic resonance imaging (MRI) showed numerous subcortical plaques. Seizures generally were well controlled with antiepileptic drugs (AEDs). CONCLUSIONS: Our data suggest that the subcortical plaques of MS underlie seizure activity in patients with MS and epilepsy.

Adult↗
PubMed1998

Incidence of transient ischemic attacks in Dijon, France. A 5-year community-based study.

The aim of this study was to determine the incidence of first-ever TIA and the distribution of risk factors in those patients with TIA in Dijon. We performed a prospective population-based study in Dijon City with 135,000 inhabitants, from 1990 to 1994, using several case-collection sources. Over a 5-year period, we recorded 258 cases of first-ever TIA, giving a crude annual incidence rate of 38.68/100,000 for men and 32.70/100,000 for women. The mean age of first-ever TIA was higher in women (71.75 years) than in men (70.35 years). A CT scan was performed in 97% of the cases and silent lacunes were discovered in 17% of cases. In our 5-year study in Dijon of first-ever TIA, we found incidence rates similar to those of previous population-based studies. Our results also support the hypothesis that risk factors for TIA are similar to those for stroke.

Adult↗
PubMed1997

Unilateral lenticular infarcts: radiological and clinical syndromes, aetiology, and prognosis.

OBJECTIVES: To analyse the clinical features induced by lenticular infarction found in 20 patients, and to analyse the radiological and clinical correlations. METHODS: Eight women and 12 men, mean age 73 years, were included in this study, which was carried out from 1 January 1994 to 30 November 1996. They were characterised by the onset of a lenticular infarction, shown by CT and MRI. A complete neurological and neurocognitive examination, and photon emission computed tomography (SPECT), were performed in all the patients and there was a long clinical follow up. RESULTS: Two distinct clinical syndromes were identified corresponding to the two anatomical areas of the lenticular nucleus: behavioural and cognitive disorders were associated with infarcts within the globus pallidus, whereas both motor disorders (dystonia) and cognitive disorders were associated with infarcts within the putamen. Outcome was excellent in all the patients for motor function, but slight cognitive disorders, problems with short term memory, and dysphasia persisted for several months. The size of the lesion did not explain these symptoms. By contrast, the slight reduction in cerebral blood flow found in the adjacent frontotemporal area may explain them by a deafferentation or a diaschisis phenomenon. CONCLUSION: It is possible to identify the clinical symptoms of a single lesion in the pallidus nucleus and in the putaminal nucleus, in which behavioural, cognitive, and movements disorders are important. After an acute and spectacular onset, outcome is in general excellent. A disease of the small arteries must be involved.

Aged↗
PubMed1995

[Value of gadolinium magnetic resonance imaging of the lumbosacral roots in acute polyradiculoneuritis].

Four patients with acute inflammatory polyradiculoneuropathy were evaluated with MRI. In 3 of 4 cases, gadolinium enhancement was observed in the nerve roots of cauda equina, on frontal and horizontal slices. This enhancement was correlated with the severity of the clinical picture and the cerebrospinal-fluid inflammatory protein concentration and supports the inflammatory nature of this forms of acute polyradiculoneuropathy.

Acute Disease↗
PubMed1995

High doses of dietary arginine during repletion impair weight gain and increase infectious mortality in protein-malnourished mice.

There is considerable evidence for the beneficial effects of dietary arginine, a conditionally-essential amino acid that enhances anabolism and T-cell function. However, the safety and efficacy of higher doses of arginine supplementation following infection have not been investigated completely. These issues were explored therefore, in a murine model of malnutrition and infection. Severe protein malnutrition was induced by feeding mice for 6 weeks on an isoenergetic diet containing only 10 g protein/kg. Mice were then allowed to consume diets with normal amounts of protein (200 g/kg) with 50 g/kg provided as amino acid mixtures of glycine and arginine in which the arginine content ranged from 0 to 50 g/kg. During the repletion period a significant weight gain was noted in the groups fed on diets with either 10 or 20 g arginine/kg, but not in the group fed on the diet with 50 g arginine/kg, compared with the diet with 0 g arginine/kg. Mortality rates after infection with Salmonella typhimurium were not decreased by the addition of 10 or 20 g arginine/kg to the diet, and were in fact worsened by supplementation with 50 g arginine/kg. The results of the present study showed that not only are the beneficial effects of arginine supplementation after infection lost when high doses are administered, but also that these high doses become toxic. Mice fed on higher doses showed significant impairment of weight gain and an increase in mortality rates.

Animals↗
PubMed1994

Inhaled nitric oxide in congenital diaphragmatic hernia.

Pulmonary hypertension is a major complication of congenital diaphragmatic hernia (CDH). Inhaled nitric oxide (NO) is a selective pulmonary vasodilator because it produces vasodilatation of the pulmonary vasculature without systemic hypotension. In experimental and clinical studies, inhaled NO ameliorates pulmonary hypertension and improves gas exchange. The goal of the present study was to determine the extent to which infants with CDH respond to inhaled NO. Four newborn infants with CDH complicated by severe respiratory insufficiency and right-to-left shunting received inhaled NO. In three patients, postductal oxygenation improved in response to small concentrations of NO (5 to 10 ppm); two received NO after operative repair, and the third both before and after repair. However, tachyphylaxis developed in all cases within 1 to 6 days. A fourth patient received inhaled NO in an attempt at weaning from ECMO. He did not respond, remaining hypoxic despite 80 ppm NO, and continued to require ECMO. In the three patients who responded to inhaled NO, plasma nitrites and nitrates (stable oxidative end products of NO) accumulated over time, but not in the patient who did not respond. The accumulation of nitrite and nitrate in plasma may reflect alveolar-capillary NO absorption, and may identify patients who will respond to continued inhaled NO. Methemoglobin remained below 1.9% in all four babies. Selected infants with CDH may respond to NO, but the benefit may be temporary.

Administration, Inhalation↗
PubMed1991

Vasospasm and platelet deposition in human arteries: effects of topical methylene blue.

Vasodilation of small blood vessels is controlled in part by the endothelium-derived relaxing factor (EDRF), which also inhibits platelet adhesion. Methylene blue (MB), which is occasionally applied directly to blood vessels during microsurgery to provide orientation and prevent torsion, is an irreversible inhibitor of the effects of endothelium-derived relaxing factor and may thereby augment both vasospasm and platelet responses. We have investigated the effects of the extravascular adventitial application of methylene blue on platelet deposition to human placental arteries (HPA) in the presence and absence of surgically induced vasospasm. A trend toward increased platelet deposition to human placental arteries was seen in each group but did not reach significance. The degree of platelet deposition to control human placental arteries suggests that the effects of methylene blue on platelet deposition may be dwarfed by the effects of surgical trauma and ischemia.

Administration, Topical↗
PubMed1989

Inhibition of chemotaxis Ng-monomethyl-L-arginine: a role for cyclic GMP.

The metabolism of L-arginine to nitric oxide (NO) has been shown to be important for the effector functions of many cell types, including polymorphonuclear (PMN) leukocytes. Its effect appears to be mediated at least in part by NO stimulation of soluble guanylate cyclase. We evaluated the role of this pathway in two PMN effector functions: cell movement and microbial killing, using the competitive inhibitor of L-arginine conversion to NO, NG-monomethyl-L-arginine (NMA). We also evaluated the effect of additional L-arginine and dibutyryl cyclic guanosine monophosphate (cGMP) on any NMA-associated changes. Human peripheral blood neutrophils were used and the cells were incubated with and without NMA. Chemotaxis was evaluated using a 48-well micro-Boyden chamber. Microbial killing was evaluated using S aureus strains D2C and 502A. These studies demonstrated that chemotaxis to formyl-methionyl-leucyl-phenylalanine was markedly inhibited in NMA-treated cells. This inhibition could be overcome if L-arginine or dibutyryl cGMP were added with the NMA. In contrast, microbial killing of S aureus was unaffected by NMA. These observations support the hypothesis that the L-arginine metabolism to NO and its effect on the cGMP level may be important for the dynamic changes required for neutrophil chemotaxis.

Arginine↗
PubMedDate not supplied

Pro- and anti-apoptotic effects of nitric oxide in irradiated keratinocytes: the role of superoxide.

Ultraviolet radiation (UV) induces apoptosis in keratinocytes by both p53- and death receptor-dependent pathways. It also generates free radicals in keratinocytes, including the synthesis of nitric oxide (NO) by constitutive and inducible NO synthases (NOS). NO has both pro- and anti-apoptotic effects. We wished to determine which of these was predominant in keratinocytes. Human CCD1106 keratinocytes were irradiated with UVB in the presence and absence of several NOS antagonists. Apoptosis was measured by flow cytometry with annexin V binding. NOS antagonism consistently altered UVB-induced apoptosis measured 18 h after irradiation. In 9 of 13 experiments, NOS antagonism increased apoptosis. However, in 4 of 13 experiments, NOS antagonism reduced apoptosis. We postulated that the variable effects of NO might be due to a critical balance between UVB-induced NO and superoxide production. We predicted that NO would be anti-apoptotic in the presence of low O(-)(2), but pro-apoptotic when NO combined with O(-)(2) to form peroxynitrite. Though superoxide dismutase reduced apoptosis after UVB, addition of peroxynitrite did not affect apoptosis. We conclude that NO released by UV irradiation is anti-apoptotic; however, the levels of O(-)(2) may be a determinant of NO action.

Animals↗