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Biomedical subjects

B Fernandez

Publications and source records attributed to B Fernandez.

At least 19 recordsLinked to original sources
PubMed2007

A new strategy based on recombinant viruses as a tool for assessing drug susceptibility of human immunodeficiency virus type 1.

The emergence of drug-resistant variants during antiretroviral therapy is a serious obstacle to sustained suppression of the human immunodeficiency virus type 1 (HIV-1). For that reason, resistance assays are essential to guide clinicians in the selection of optimal treatment regimens. Genotypic assays are less expensive and results are available faster than phenotypic assays. However, in heavily experienced patients with multiple treatment failures interpretation of complex mutation patterns remains difficult, and in these cases phenotypic assays are recommended. This report describes a novel recombinant virus assay where protease (PR) and reverse transcriptase (RT) sequences derived from the plasma isolated from patients are introduced into the back-bone of an HIV molecular clone that expresses Renilla luciferase protein in the place of nef gene. All drug resistance profiles analyzed correlate with previously reported data and showed high reproducibility. This assay, in addition to a fast (completed in 10 days), precise, reproducible and automated method, presents several advantages as compared to other phenotypic assays. The system described below allows the generation of recombinant viruses with multiples cycles of replication carrying a reporter gene in their genomes. These features increase the sensitivity of the test, an important aspect to be considered in the evaluation of less fit viral isolates. In conclusion, the assay permits the quantitation of the level of resistance of clinical HIV-1 isolates to PR and RT inhibitors.

Animals↗
PubMed2006

An inversion inv(4)(p12-p15.3) in autistic siblings implicates the 4p GABA receptor gene cluster.

INTRODUCTION: We describe the case of two brothers diagnosed with autism who both carry a paracentic inversion of the short arm of chromosome 4 (46,XY, inv(4)(p12-p15.3)). We have determined that this inversion is inherited from an apparently unaffected mother and unaffected maternal grandfather. Methods/ RESULTS: Using fluorescence in situ hybridisation analysis and Southern blot hybridisation we identified the breakpoints. The proximal breakpoint (4p12) maps to a region containing a cluster of gamma-aminobutyric acid A (GABA(A)) receptor genes, and directly interrupts the GABRG1 gene, the distal-most gene of the cluster. We also identified an insertion/deletion polymorphism for a approximately 2 kb LINE1 (L1) element that occurs within intron 7 of GABRG1. Our genotype analysis amongst autism families indicated that the L1 deletion allele did not show increased transmission to affected individuals. No linkage disequilibrium was evident between the L1 and single nucleotide polymorphisms in adjacent GABA(A) receptor genes on 4p, where a recent study has identified significant association with autism. DISCUSSION: Despite this, the identification of an inversion breakpoint disrupting GABRG1 provides solid support for the genetic involvement of the short arm of chromosome 4 in the genetic aetiology of autism, and for the hypothesis of disrupted GABA neurotransmission in autism.

Adult↗
PubMed2006

Discrete time piecewise affine models of genetic regulatory networks.

We introduce simple models of genetic regulatory networks and we proceed to the mathematical analysis of their dynamics. The models are discrete time dynamical systems generated by piecewise affine contracting mappings whose variables represent gene expression levels. These models reduce to boolean networks in one limiting case of a parameter, and their asymptotic dynamics approaches that of a differential equation in another limiting case of this parameter. For intermediate values, the model present an original phenomenology which is argued to be due to delay effects. This phenomenology is not limited to piecewise affine model but extends to smooth nonlinear discrete time models of regulatory networks. In a first step, our analysis concerns general properties of networks on arbitrary graphs (characterisation of the attractor, symbolic dynamics, Lyapunov stability, structural stability, symmetries, etc). In a second step, focus is made on simple circuits for which the attractor and its changes with parameters are described. In the negative circuit of 2 genes, a thorough study is presented which concern stable (quasi-)periodic oscillations governed by rotations on the unit circle - with a rotation number depending continuously and monotonically on threshold parameters. These regular oscillations exist in negative circuits with arbitrary number of genes where they are most likely to be observed in genetic systems with non-negligible delay effects.

Algorithms↗
PubMed2005

[Ultrastructural study of epiretinal membrane stained by trypan blue: 15 case reports].

INTRODUCTION: Idiopathic epiretinal membrane results from detachment of the posterior hyaloid and is believed to be related to naturally occurring defects in the internal limiting membrane (ILM) of the retina. Vitrectomy and peeling are the treatment of choice. Trypan blue 0.15% (TB) stains epiretinal membrane and internal limiting membrane. It allows selective and complete removal, facilitating surgery, with less retinal damage. An ultrastructural study was conducted showing ultrastructural features of idiopathic epiretinal membranes (ERM) and those of the internal limiting membrane and its connections with the retinal side. MATERIAL AND METHODS: After pars plana vitrectomy and induction of posterior vitreous detachment, 0.2 ml TB 0.15% was injected over the ERM in an air-filled eye. The stained tissue was peeled with intraocular forceps. Specimens were at once collected in 4% glutaraldehyde for a transmission electron microscopy study. RESULTS: TB may allow complete and easier ERM and ILM peeling. The staining does not present toxic effects. The major cellular contingent is represented by glial cells, participating actively in neocollagen synthesis. Their presence supports the hypothesis of a migratory movement of retinal cells toward the vitreoretinal side. CONCLUSION: The presence of an intact internal limiting membrane, the absence of optical fibers belonging to the under retina, and the absence of any sign of apoptosis make TB a useful staining agent for ERM and ILM peeling.

Aged↗
PubMed2004

Evaluation of functional improvement in older patients with cognitive impairment, depression and/or delirium admitted to a geriatric convalescence hospitalization unit.

Cognitive impairment, depression and delirium are problems of high prevalence in older patients. The geriatric convalescence unit (GCU) is a hospitalization facility offering an interdisciplinary geriatric intervention program that may be more appropriate for these patients. This study intended to analyze the functional improvement (FI) in older patients with cognitive impairment, depression and/or delirium admitted to a GCU. A group of 107 patients received specific nurse care, habitually performed in GCU and they also were included in a rehabilitation program. Cognitive impairment, depression and delirium were diagnosed according to standardized protocols. The analyzed variables were: age, functional status (Barthel index) before admission (BBA), at admission (BA) and at discharge(BD), diagnostic categories, cognitive function (mini mental state examination: MMSE) and post-discharge destination. The corrected Heinemann index (CHI) was used to evaluate FI obtained during GCU-stay, where CHI = 100 x (BD-BA)/(BBA-BA), and the efficiency index(El) was used to analyze the relationship between FI and the length of stay in the GCU,where El = (BD-BA)/(days in GCU). According to CHI, patients were divided in three groups. Group I: CHI = 0 or negative (patients who lost functional capacity during hospitalization,those who died or were transferred to hospital owing to acute deterioration. Group II: CHI < 35 % (high FI). Mean age was 77.6 +/- 9.1 years, the diagnostic categories were: fractures/orthopedics 49 (45.7 %), neurological 27(25.2 %), pulmonary/cardiologic 6 (5.6 %) and other cases 25 (23.3 %). Mean MMSE and BA scores were 16.9 +/- 9.4 and 29.6 +/- 18.9, respectively. Post-discharge destinations were:63 patients (58.8 %) returned home, 28 (26.1 %) were definitively institutionalized, 11 (10.2%) died and finally 5 (4.6 %) were transferred to acute care hospital. In-Group I, there were 35 patients (32.7 %) with a mean value of the El = 0.12 +/-1.1; in Group II, 13 (12.1 %) and 0.26 +/- 0.38; in Group III, 59 (55.1 %) and 0.94 +/- 0.97, respectively. In spite of the presence of cognitive impairment, depression and/or delirium, a high proportion of patients (67.2 %)obtained a significant improvement in their functional capacity.35 % (moderate FI). Group III: CHI >/=

Aged↗
PubMed2003

Receptor-independent role of the urokinase-type plasminogen activator during arteriogenesis.

To define the role of the plasminogen activators (PAs) urokinase PA (uPA) and tissue PA (tPA) as well as the uPA receptor (uPAR) in arteriogenesis, we investigated their impact in a rabbit and mouse model of adaptive collateral artery growth. Collateral artery growth was induced by occlusion of the femoral artery in rabbit and wild-type (WT) mice and in mice with targeted inactivation of uPA (uPA-/-), tPA (tPA-/-), or uPAR (uPAR-/-). Northern blot results revealed a significant up-regulation of uPA but not uPAR or tPA in the early phase of arteriogenesis in rabbit and WT mice. This up-regulation on RNA level was followed by an increased protein level and enzymatic activity. Impaired perfusion recovery upon femoral artery ligation was observed by laser Doppler analysis in vivo in uPA-deficient mice but not in uPAR or tPA deficiency compared with WT mice. Immunohistochemical studies revealed an association of leukocyte infiltration with arteriogenesis in WT mice that was strongly reduced in uPA-/- but not in uPAR- or tPA-deficient mice. We conclude that arteriogenesis is promoted by an uPA-mediated infiltration of leukocytes that is not dependent on uPAR.

Animals↗
PubMed2003

[Botulinum toxin and traumatic brain injury].

Botulinum toxin is a successful focal spasticity therapy. The aim of this article is to study the data of the literature concerning its utilisation in traumatic brain injured patients, whom motor and tonus disturbances are polymorphic, in their clinical presentation as well as in their evolution. Although there are few studies concerning its utilisation in such patients, none of them being controlled, its use seems interesting in focal spasticity treatment. It can contribute to improve functional abilities and comfort for these patients.

Anti-Dyskinesia Agents↗
PubMed2003

Predictive, pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000.

Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.

Adolescent↗
PubMed2001

Role of ischemia and of hypoxia-inducible genes in arteriogenesis after femoral artery occlusion in the rabbit.

Vascular endothelial growth factor (VEGF) is known to play an important role in angiogenesis. Its place in collateral artery growth (arteriogenesis), however, is still debated. In the present study, we analyzed the expression of VEGF and its receptors (Flk-1 and Flt-1) in a rabbit model of collateral artery growth after femoral artery occlusion. Hypoxia presents the most important stimulus for VEGF expression. We therefore also investigated the expression level of distinct hypoxia-inducible genes (HIF-1alpha, LDH A) and determined metabolic intermediates indicative for ischemia (ATP, creatine phosphate, and their catabolites). We found that arteriogenesis was not associated with an increased expression of VEGF or the mentioned hypoxia-inducible genes. Furthermore, the high-energy phosphates and their catabolites were entirely within normal limits. Despite the absence of an increased expression of VEGF and its receptors, collateral vessels increased their diameter by a factor of 10. The speed of collateral development could be increased by infusion of the chemoattractant monocyte chemotactic protein-1 but not by infusion of a 30 times higher concentration of VEGF. From these data, we conclude that under nonischemic conditions, arteriogenesis is neither associated with nor inducible by increased levels of VEGF and that VEGF is not a natural agent to induce arteriogenesis in vivo.

Adenosine Triphosphate↗
PubMed2001

Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1.

Dominantly inherited progressive hearing loss DFNA38 is caused by heterozygosity for a novel mutation in WFS1, the gene for recessively inherited Wolfram syndrome. Wolfram syndrome is defined by juvenile diabetes mellitus and optic atrophy and may include progressive hearing loss and other neurological symptoms. Heterozygotes for other Wolfram syndrome mutations generally have normal hearing. Dominant deafness defined by DFNA38 is more severe than deafness of Wolfram syndrome patients and lacks any syndromic features. In a six-generation kindred from Newfoundland, Canada, WFS1 Ala716Thr (2146 G-->A) was shared by all deaf members of the family and was specific to deaf individuals. The causal relationship between this missense mutation and deafness was supported by two observations based on haplotype and mutation analysis of the kindred. First, a relative homozygous for the mutation was diagnosed at age 3 years with insulin-dependent diabetes mellitus, the central feature of Wolfram syndrome. Second, two relatives with normal hearing had an identical haplotype to that defining DFNA38, with the exception of the base pair at position 2146. Other rare variants of WFS1 co-inherited with deafness in the family could be excluded as disease-causing mutations on the basis of this hearing-associated haplotype. The possibility that 'mild' mutations in WFS1 might be a cause of non-syndromic deafness in the general population should be explored.

Amino Acid Sequence↗
PubMed2001

Ultrastructural study of rat hippocampus after chronic administration of aluminum L-glutamate: an acceleration of the aging process.

An ultrastructural study of rat hippocampus was performed on young (group 1) and old (group 4) rats receiving daily subcutaneous injections of aluminum L-glutamate and on old untreated rats (group 5). Young controls were treated with sodium L-glutamate (group 2) and physiological saline (group 3). Group 1 showed vacuolated astrocytes with numerous lipofuscin deposits, mitochondrial swelling, a thinning of the myelin sheath, and many multivesicular bodies invading the cytoplasm. Cellular structure did not appear to be affected in groups 2 and 3. Group 4 showed swollen mitochondria, a demyelination process in axonal regions, sizable perivascular oedema with vessel retraction and gliofilament bundles. In this group, lipofuscin deposits in astrocytes were associated with multivesicular bodies that thinned the myelin sheath to the breaking point; however, no excitotoxic glutamate-induced effects were observed. In group 5, extreme cytoplasmic vacuolation was observed, with massive mitochondrial swelling, considerable thinning of the myelin sheath (at times to the breaking point), sizable vacuolar degeneration and gliofilament bundles. These results indicate that ultrastructural alterations in the hippocampus, such as cell vacuolization, massive mitochondrial swelling and the demyelination process, occur with aging and independently of aluminum intoxication. Similar alterations were observed in aluminum L-glutamate-intoxicated young rats, but not in controls. These results are consistent with aluminum-induced acceleration of the aging process.

Aging↗
PubMed2001

Cadmium-containing granules in kidney tissue of the Atlantic white-sided dolphin (Lagenorhyncus acutus) off the Faroe Islands.

Top predators from the northern sub-polar and polar areas exhibit high cadmium concentrations in their tissues. In the aim to reveal possible adverse effects, samples of five Atlantic white-sided dolphins Lagenorhyncus acutus have been collected on the occasion of the drive fishery in the Faroe Islands, for ultrastructural investigations and energy dispersive X-ray microanalyses. Cadmium concentrations were less than the limit of detection in both immature individuals and ranged from 22.7 to 31.1 microg x g(-1) wet weight in the mature individuals. Two individuals with the highest cadmium concentrations exhibited electron dense mineral concretions in the basal membranes of the proximal tubules. They are spherocrystals made up of numerous strata mineral deposit of calcium and phosphorus together with cadmium. Cadmium has been detected with a molar ratio of Ca:Cd of 10:1 in the middle of these concretions. To our knowledge, this is the first report of such granules in a wild vertebrate. The role of these granules in the detoxification of the metal and the possible pathological effects are considered.

Animals↗
PubMed2001

The pituitary response to ovine corticotropin-releasing hormone is enhanced in obese men and correlates with insulin resistance.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in central obesity has been demonstrated in women. We studied the corticotropin (ACTH) and cortisol response to ovine corticotropin releasing hormone (oCRH) and its association to parameters of adiposity and insulin resistance in a group of 19 healthy obese (BMI > 25 kg/m2) and 9 non-obese men. Relative insulin resistance was assessed by the homeostatic model assessment (HOMA IR). Baseline ACTH was similar, while cortisol was lower in the obese group. The ACTH response to oCRH was significantly higher in the obese group. ACTH incremental area under the curve (iAUC) correlated with age, HOMA IR, and sagittal diameter but not with leptin. In multiple regression analysis, only HOMA IR was an independent predictor of ACTH iAUC. In conclusion, obese men have hyperactivity of the HPA axis at the pituitary level, which appears to be linked to insulin resistance.

Adrenocorticotropic Hormone↗
PubMed2000

Transgenic myocardial overexpression of fibroblast growth factor-1 increases coronary artery density and branching.

Fibroblast growth factor (FGF)-1 plays important roles during myocardial and coronary morphogenesis. FGF-1 is also involved in the physiological response of the adult heart against ischemia, which includes cardiomyocyte protection and vascular growth. In the present study, we have generated transgenic mice with specific myocardial overexpression of the gene. Transgene expression was verified by Northern blot, and increased FGF-1 protein content was assessed by Western blot and immunoconfocal microscopy. Anatomic, histomorphological, and ultrastructural analyses revealed no major morphological or developmental abnormalities of transgenic hearts. Capillary density was unaltered, whereas the density of coronary arteries, especially arterioles, was significantly increased, as was the number of branches of the main coronary arteries. In addition, the coronary flow was significantly enhanced in transgenic mice ex vivo. These differences in the anatomic pattern of the coronary vasculature are established during the second month of postnatal life. The present findings demonstrate an important role of FGF-1 in the differentiation and growth of the coronary system and suggest that it is a key regulatory molecule of the differentiation of the arterial system.

Animals↗
PubMed2000

Total hysterectomy for benign pathologies: direct costs comparison between laparoscopic and abdominal hysterectomy.

OBJECTIVES: The aim of this study is a direct costs comparison between laparoscopic and abdominal total hysterectomy when theses procedures are indicated for benign pathologies. STUDY DESIGN: To this end we compared the direct costs of total laparoscopic hysterectomy (TLH) calculated from a series of 105 patients with that obtained for a comparable series of 30 patients who underwent hysterectomy by laparotomy. RESULTS: The direct costs of total hysterectomy for a benign pathology by laparoscopic surgery and laparotomy are comparable (respectively 7693 French francs (FF) and 7759 FF). Whatever the type of operation the cost for staff represents 60% of the total cost. Expenditure for staff during the operation represents 41.0% of the total cost of TLH (3154 FF/7693 FF) whereas it represents only 31.0% of the cost of the operation when carried out by laparotomy (2406 FF/7759 FF) (P<0.0001). Inversely the expenditure due to staff during the post operative phase represents 24.1% of the total cost of the operation when laparotomy is used (1875 FF/7759 FF) and only 13.4% of the cost of the operation by laparoscopic surgery (1029 FF/7693 FF) (P<0.0001). When the operation uses laparoscopic surgery the increase in expenditure during the surgical act is compensated by the statistically significant shortening in the hospital stay. Expenditure connected with the laparoscopic surgery equipment is minimal compared to the costs connected with the staff. CONCLUSION: Provided that TLH is carried out with reusable laparoscopic surgery equipment, by skilled surgeons working in suitable hospital structures making the particularly heavy investment in laparoscopic surgery equipment economically viable, TLH is an economically viable technique as an alternative to laparotomy.

Adult↗
PubMed2000

AT-1 receptor and phospholipase C are involved in angiotensin III modulation of hypothalamic noradrenergic transmission.

1. We previously reported that angiotensin III modulates noradrenergic neurotransmission in the hypothalamus of the rat. In the present work we studied the effects of angiotensin III on norepinephrine release and tyrosine hydroxylase activity. We also investigated the receptors and intracellular pathways involved in angiotensin III modulation of noradrenergic transmission. 2. In rat hypothalamic tissue labeled with [3H]norepinephrine 1, 10, and 100 nM and 1 microM losartan (AT1 receptor antagonist) had no effect on basal neuronal norepinephrine release, whereas 10 and 100 nM and 1 microM losartan partially diminished norepinephrine secretion evoked by 25 mM KCl. The AT2 receptor antagonist PD 123319 showed no effect either on basal or evoked norepinephrine release. The increase in both basal and evoked norepinephrine output induced by 1 microM angiotensin III was blocked by 1 microM losartan, but not by 1 microM PD 123319. 3. The phospholipase C inhibitor 5 microM neomicin inhibited the increase in basal and evoked norepinephrine release produced by 1 microM angiotensin III. 4. Tyrosine hydroxylase activity was increased by 1 microM angiotensin III and this effect was blocked by 1 microM LST and 5 microM neomicin, but not by PD 123319. On the other hand, 1 microM angiotensin III enhanced phosphatidyl inositol hydrolysis that was blocked by 1 microM losartan and 5 microM neomicin. PD 123319 (1 microM) did not affect ANG III-induced phosphatidyl inositol hydrolysis enhancement. 5. Our results confirm that angiotensin III acts as a modulator of noradrenergic transmission at the hypothalamic level through the AT1-phospholipase C pathway. This enhancement of hypothalamic noradrenergic activity suggests that angiotensin III may act as a central modulator of several biological processes regulated at this level by catecholamines, such as cardiovascular, endocrine, and autonomic functions as well as water and saline homeostasis.

Angiotensin III↗
PubMed2000

Lumbar disc herniation in a 27-month-old child. Case report.

The occurrence of disc herniation is rare in children. A 27-month-old child fell from his cradle and developed, in the following 2 weeks, irritability, low-back pain, and difficulty in walking. On physical examination a compensatory gait, paravertebral muscle spasm, and a restricted right straight-leg raising test were demonstrated. Plain x-ray films revealed a narrowed L4-5 intervertebral space. Magnetic resonance imaging of the lumbosacral spine demonstrated decreased signal in the L4-5 disc, with posterior disc protrusion. At surgery, blood infiltrating the subperiosteal plane was observed. Via a left hemilaminectomy and under microscopic magnification, the left L-5 nerve root was found to be intact, and on the right side significant nerve root compression was identified. During dissection an accidental dural tear occurred. A right L-4 hemilaminectomy was performed, and the disc fragments were removed until a complete nerve root decompression was obtained and the dura was repaired. The child recovered uneventfully and was asymptomatic 7 years postsurgery. This child is one of the youngest patients with a herniated disc reported in the world literature. The authors discuss the diagnostic difficulties and management of this entity in children.

Accidental Falls↗