Search PubMed⌕ Search

Biomedical subjects

A Pou

Publications and source records attributed to A Pou.

At least 19 recordsLinked to original sources
PubMed2006

Dysferlin expression in monocytes: a source of mRNA for mutation analysis.

Dysferlin protein is expressed in peripheral blood monocytes. The genomic analysis of the DYSF gene has proved to be time consuming because it has 55 exons. We designed a mutational screening strategy based on cDNA from monocytes to find out whether the mutational analysis could be performed in mRNA from a source less invasive than the muscle biopsy. We studied 34 patients from 23 families diagnosed with dysferlinopathy. The diagnosis was based on clinical findings and on the absence of protein expression using either immunohistochemistry or Western blot of skeletal muscle and/or monocytes. We identified 28 different mutations, 13 of which were novel. The DYSF mutations in both alleles were found in 30 patients and only in one allele in four. The results were confirmed using genomic DNA in 26/34 patients. This is the first report to furnish evidence of reliable mutational analysis using monocytes cDNA and constitutes a good alternative to genomic DNA analysis.

DNA Mutational Analysis↗
PubMed2005

SMN2 copy number predicts acute or chronic spinal muscular atrophy but does not account for intrafamilial variability in siblings.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder that affects motor neurons. It is caused by mutations in the survival motor neuron gene 1 (SMN1). The SMN2 gene, which is the highly homologous SMN1 copy that is present in all the patients, is unable to prevent the disease. An SMN2 dosage method was applied to 45 patients with the three SMA types (I-III) and to four pairs of siblings with chronic SMA (II-III) and different phenotypes. Our results confirm that the SMN2 copy number plays a key role in predicting acute or chronic SMA. However, siblings with different SMA phenotypes show an identical SMN2 copy number and identical markers, indicating that the genetic background around the SMA locus is insufficient to account for the intrafamilial variability. In our results, age of onset appears to be the most important predictor of disease severity in affected members of the same family. Given that SMN2 is regarded as a target for potential pharmacological therapies in SMA, the identification of genetic factors other than the SMN genes is necessary to better understand the pathogenesis of the disease in order to implement additional therapeutic approaches.

Adult↗
PubMed2003

Timing of chemoradiotherapy and patient selection for locally advanced nasopharyngeal carcinoma.

AIMS: Predictors of outcome after radiotherapy alone for nasopharyngeal carcinoma (NPC) are now available from several retrospective studies. On the basis of these, it is theoretically possible to separate patients at risk of local failure from patients at risk of distant metastases (DM). According to classical principles of chemoradiotherapy timing, patients at risk of local failure would benefit mostly from concomitant chemoradiotherapy, whereas patients at risk distantly would benefit from sequential combinations. MATERIALS AND METHODS: We reviewed the literature on combined chemoradiotherapy treatment for nasopharyngeal carcinoma to assess whether timing of combined treatment matches pattern of failure. RESULTS: Available data show a significant overlap of activity, sequential treatments reducing local failure and concomitant treatments reducing DM. Therefore, in the individual patient, the strict adoption of traditional risk profiles in therapeutic decision-making may not fully exploit all the potential therapeutic effects derived from the maximal association of both sequential and concomitant therapies. CONCLUSION: Whether such combination is clinically worthwhile in every patient with locoregionally advanced nasopharyngeal carcinoma needs prospective validation, because of the high toxicity of this modality.

Chemotherapy, Adjuvant↗
PubMed2003

[Angioplasty and stenting in severe stenosis of basilar artery refractory to pharmacotherapy].

Stenoses in the posterior cerebral circulation often have a bad prognosis. There may be a high rate of morbi-mortality and recurrences of ischemic events in this territory. Currently we have no evidence or consensus about what the best pharmacological option is for these patients. We report a case of a 75 year old woman with sever stenosis of the proximal part of the basilar artery with recurrent transient ischemic events unresponsive to different combinations of antiagregant and anticoagulant treatments. A percutaneous transluminal angioplasty with the addition of a stent in the basilar artery was performed successfully. At present, there are few studies and a low number of patients treated by this technique. The results obtained are promising, with a low rate of morbi-mortality, the most frequent complications being embolization of the atherosclerotic lesion, dissection, rupture or restenosis.

Aged↗
PubMed2001

Inflammation in dysferlin myopathy: immunohistochemical characterization of 13 patients.

Inflammation was detected in 9 of 13 patients with different phenotypes of dysferlin myopathy. Endomysial or perivascular infiltrates consisted of 11.1% +/- 6.6% CD8(+) cells, 40.6% +/- 22.8% CD4(+) cells, 36.7% +/- 23.7% macrophages, and no B cells. Major histocompatibility complex class I was not upregulated in normal muscle fibers. In young patients with sporadic proximal weakness, very high creatine kinase levels, necrotic fibers and inflammation in the muscle biopsy, a diagnosis of dysferlin myopathy should be considered.

Adolescent↗
PubMed2001

Homeostasis of naive and memory T cell subpopulations in peripheral blood and lymphoid tissues in the context of human immunodeficiency virus infection.

To understand the nature of naive and memory T cell depletion in human immunodeficiency virus (HIV) immunopathogenesis, their homeostasis in peripheral blood (PB) and lymph node (LN) compartments of HIV-infected patients was examined. Although the percentage of naive CD4+ cells was higher in LN than in PB mononuclear cells (LNMC and PBMC, respectively), the memory cells were higher in PBMC than in LNMC. The ratio of naive:memory CD4+ cells from PB positively correlated with that in LNs and with the absolute CD4+ cell counts and recall antigen responses, and the ratio inversely correlated with the cellular virus load from the corresponding compartment. These findings indicate that although the pattern of naive and memory cells in the LN and PB compartments appear divergent, their relationship is nonrandom and is significant. The naive&rcolon;memory ratio in PB appears to reflect the lymphoid microenvironment and may potentially be useful as a surrogate marker for treatment efficacy and immune reconstitution.

Adult↗
PubMed2001

Chemokine/CD4 receptor density ratios correlate with HIV replication in lymph node and peripheral blood of HIV-infected individuals.

OBJECTIVES: Lymphoid tissue is a major reservoir for virus replication in HIV-infected subjects. The relationship of CCR5 and CXCR4 coreceptor density and HIV replication in peripheral blood mononuclear cells (PBMC) and lymph node (LN) mononuclear cells (LNMC) of HIV-infected subjects was examined. METHODS: PBMC and cervical LNMC from 12 HIV-infected patients were examined for virological and immunological parameters including chemokine receptor density, HIV plasma and cellular viral load, coreceptor usage and CD38/HLA-DR expression. RESULTS: The number of CCR5 and CXCR4 molecules on CD4 lymphocytes in the LN were significantly higher than in PBMC. In contrast the number of CD4 molecules/CD4 T cell was higher in PBMC than in LNMC. The CXCR4/CD4 and CCR5/CD4 ratios in the LN were significantly higher than in the PBMC. This was associated with a cellular viral load in the LN that was approximately 110-fold higher than in PBMC. The absolute number of coreceptor molecules per cell did not correlate with the viral load. However, the CCR5/CD4 and CXCR4/CD4 ratios in the LN positively correlated with HIV cellular and plasma RNA. Characterization of the viral isolates suggested an association between clinical isolates using a distinct coreceptor and the upregulation of the corresponding chemokine receptor. CONCLUSIONS: The ratios of chemokine receptors to CD4 molecules in CD4 T cells from LN is higher than in PBMC and may account for the relative difference in cellular viral load in these compartments. Additionally, the coreceptor/CD4 ratios, particularly in the lymphoid tissue, were highly related to HIV replication.

Adult↗
PubMed1999

Laryngeal framework surgery for the management of aspiration.

BACKGROUND: During the past decade, laryngeal framework surgery has become the treatment of choice for the management of adductor paralysis of the vocal fold. The primary impetus for the use of this technique has been on the rehabilitation of voice. The purpose of this study was to ascertain the effectiveness of laryngeal framework surgery, including medialization laryngoplasty with silicone (MLS), with or without arytenoid adduction (AA), on eliminating aspiration, improving diet, and aiding in the subsequent decannulation of individuals with glottic insufficiency secondary to vocal fold palsy. METHODS: A retrospective chart review was performed on all patients initially seen with vocal cord paralysis who were treated with laryngeal framework surgery from June 1992 to April 1996. The study comprised 70 patients, including 31 women and 39 men, with a median age of 57 years. Clinical information was obtained regarding the etiology of the lesion, characteristics of the vocal cord deficit, history of aspiration, the presence of other neurologic deficits or concurrent pulmonary disease, treatment, and outcome. To determine the effectiveness of MLS, with or without AA, we assessed the final outcome regarding the presence and degree of aspiration, diet, history of aspiration pneumonia, and decannulation. RESULTS: Seventy patients underwent 77 MLS (three bilateral, four revisions), and 21 AA. Decreased aspiration was obtained in 96% of our patients. Seventy-five percent of those patients who had required a tracheotomy were decannulated. CONCLUSIONS: These results support the use of laryngeal framework surgery for the effective treatment of aspiration in selected patients initially seen with deficits of the glottic closure secondary to vocal fold paralysis or paresis.

Adult↗
PubMed1998

The anterior inferior cerebellar artery infarcts: a clinical-magnetic resonance imaging study.

Acute infarcts of the anterior inferior cerebellar artery (AICA) are unusual. We report 15 cases of AICA infarcts and their correlation with the topography of the lesion by brain MRI. During 2 years we prospectively identified 7 cases of AICA infarcts among 770 acute strokes (0.9% of the acute strokes seen in our department). We studied these cases and also another 8 that we found retrospectively. Most patients (8/15) had a unilateral affectation of both middle cerebellar peduncle (MCP) and inferior lateral pontine area (ILP), in these cases the main symptoms were vertigo, ataxia, peripheral facial palsy and hypoacusia. Two other patients had isolated MCP infarcts and were characterized by peripheral vertigo and ataxia, without hypoacusia or facial palsy. Another 2 patients had isolated ILP territory infarct characterized by vertigo, left peripheral facial palsy without hypoacusia and mild or no ataxia. One patient had a Gasperini syndrome. Finally 3 patients had bilateral AICA infarcts due to basilar thrombosis. The etiology was atherosclerosis in 9 patients, lacunar due to hypertension in 1, cardiac embolism in 1, migraine in 1 and unknown in 3. Among the 15 patients only 2 died, both with AICA plus infarcts. In the remaining patients a follow-up during a mean of 31 months (3 months to 12 years) showed no recurrences.

Adult↗
PubMed1998

Multiple endocrine involvement in two pediatric patients with Kearns-Sayre syndrome.

We present 2 cases of progressively severe Kearns-Sayre syndrome (KSS) with multisystemic affectation and atypical endocrine and cutaneous features, a 16-year-old patient (case 1) and a 5-year-old patient (case 2). Endocrine studies showed high glucose and glycohemoglobin concentrations with normal pancreatic reserve and low values of ACTH, cortisol, LH and FSH in case 1. Normal ACTH values with low concentrations of cortisol and PTH were observed in case 2. Southern blot analysis and PCR amplification revealed the presence of a deletion of approximately 6.7 kb in the mitochondrial DNA of both patients. Endocrinological studies suggest that adrenal insufficiency may be an additional feature of KSS that worsens the clinical evolution of the patients. In spite of a normal pancreatic reserve, insulin therapy should be considered in patients with diabetes mellitus of mitochondrial origin.

Adolescent↗
PubMed1998

[Oral anticoagulation in the secondary prevention of cerebrovascular disease. Long-term follow-up of 169 patients].

INTRODUCTION: Although the indications for oral anticoagulation (AO) in the treatment of cerebral vascular disease (CVD) are well established, their potential side effects continue to give cause for worry. OBJECTIVES: To describe the complications and ischemic relapses in patients treated with AO for secondary prevention of CVD of cardiac embolic origin. PATIENTS AND METHODS: We included 169 patients with embologenic cardiopathy who, following an CVD, were treated with AO and followed-up at our medical centre for at least three months. We recorded their past clinical history and risk factors, occurrence of vascular relapses (VR), complications involving hemorrhage (CH), and data regarding course and follow-up. RESULTS: During an average follow-up of 50.3 months of a total of 707.9 patient/years, 20 VR (2.8% per year) were recorded; 15 of these were cerebro-vascular and mainly mild. We recorded 59 CH in 41 patients (8.3% per year) of which 6 were considered to be major. There was a 30% drop-out rate from follow-up at our centre, mainly due to death from other causes or to change of referral centre. CONCLUSIONS: There is a low incidence of relapse and of complications (usually mild) following AO for the secondary prevention of CVD of cardio-embolic origin. Efficacy and security are maintained in the long term.

Acenocoumarol↗
PubMed1996

Tracheotomy in children with juvenile-onset recurrent respiratory papillomatosis: the Children's Hospital of Pittsburgh experience.

Despite the risk of airway obstruction, tracheotomy has been viewed with trepidation in the management of recurrent respiratory papillomatosis (RRP). The literature suggests that the injury associated with the tracheotomy site may initiate the progression of disease to the distal airway. Alternatively, patients who require tracheotomy for RRP may be predisposed to distal spread because of more aggressive disease. In an effort to clarify this issue, we reviewed the Children's Hospital of Pittsburgh experience with 35 patients with RRP between 1984 and 1994; 13 patients received tracheotomies. Tracheotomy patients presented at a younger age with more widespread disease, often involving the distal airway prior to tracheotomy. Although distal spread occurred in 50% of patients, it was generally limited to the tracheotomy site. Overall, outcome in the tracheotomy group was satisfactory. Complications related to the tracheotomy were rare. We conclude that tracheotomy is an appropriate option for significantly airway compromise in patients with RRP.

Child↗
PubMed1996

[Motor neuron diseases. Present].

Recent progress in our understanding of motor neuron diseases, particularly those of degenerative pathogenesis such as spinal muscular atrophies (SMA) and amyotrophic lateral sclerosis (ALS), have to be described as historic. They are essentially of three types: 1) In first place are advances afforded by molecular genetics both in SMA (with the discovery of survival motor neurons and neuronal apoptosis inhibitor protein, which are markers of the disease and their pathogenetic mechanism) and in ALS (with the discovery of the super oxide dismutase [SOD1] gene, involved in the genesis of familial forms of ALS and other types of SMA such as certain forms of familial juvenile ALS, bulbar-spinal atrophy with gynecomasty and others). 2) In second place are biological data detailing the mechanisms of neuron death, whether programed or not, and emphasizing the importance of the so-called trophic or neurotrophin factors-whether nerve growth factor, brain-derived-neurotrophic factor, neurotrophin-3 or others whose effect of preventing neuron death has been demonstrated in vitro-as well as that of other substances such as Ca(2+)-activated neutral protease, which stabilizes synapses during development. It is assumed that one or another of these data will lead to therapeutic strategies for blocking the cascade of events that lead to neuron degeneration. 3) Finally, the strong impact of neuroimmunology in the field of neuromuscular pathology has been of interest mainly in neurogenic diseases marked purely and essentially be motor expression. As markers and pathogens, antiganglioside antibodies must necessarily be determined at this time in such entities as multifocal motor neuropathy, Guillain-Barré syndrome, acute axon motor neuropathy, Miller-Fisher syndrome and others, as their presence can inform therapeutic approaches. These three aspects and others currently under discussion will be treated in this course. At the same time the basic diagnostic aspects of motor neuron diseases will be emphasized: electrophysiologic assessment, on the one hand, and clinical features on the other. Establishing an exhaustive classification of SMA, from the earliest forms of infancy to adult types, is of great priority, as is exposing the full range of SMA according to whether distal or proximal predominance of atrophy is present. Our current understanding of the field is summarized in ten chapters on degenerative motor neuron diseases.

Amyotrophic Lateral Sclerosis↗
PubMed1996

[Juvenile and adult forms of spinal muscular atrophies].

We propose a classification system for spinal muscular atrophies (SMA) based on the distribution of clinical signs, paresis and atrophy, as well as on the location of the responsible gene and the resulting enzyme deficiency, whenever these are known. This highly practical classification system encompasses three large SMA groups, as follows. A) Generalized forms, many of which are hereditary, are generally transmitted in a recessive autosomal manner. The course of disease is more severe when symptoms manifest early. Patients whose symptoms first occur after the first year of life often reach adolescence and even adulthood, confirming a highly apparent congruence of intermediate and pseudomyopathic juvenile forms. The same genetic defect, deletion in the 5q11-13.3 locus, that is responsible for acute infantile SMA has been demonstrated in both the aforementioned forms. B) Focal forms are restricted and often isolated cases; when they are hereditary, the genetic profile is highly heterogeneous. Though the disease will not necessarily evolve, it may progress to a generalized form. Focal forms may be symetric, assymetric, spinal-bulbar or multisegmental. The genetic abnormality has been identified for only some forms, such as chronic bulbar-spinal amyotrophy linked to the X-chromosome, at whose location, Xq11, the androgenic receptor is found. C) Amyotrophic lateral sclerosis (ALS) manifests clinically in a variety of ways and may be isolated, familial, juvenile or associated. Familial ALS is related to a gene defect in the 21q22.1 location that codifies for the superoxide dismutase enzyme. One juvenile form of ALS is related to a defect in the 2q33-35 chromosome. Any type of SMA can be related to degenerative neuronal disease of the central nervous system, especially juvenile ALS with generalized SMA, although such a link is at present merely an attractive hypothesis. Specific bibliographic references are given for each SMA form. Figures are provided to illustrate most of the SMA forms included in this classification system, the patients being at this time older adolescents and adults whose disease has been in evidence over many years.

Adolescent↗
PubMed1995

Hereditary spastic paraparesis with dementia, amyotrophy and peripheral neuropathy. A neuropathological study.

Hereditary, probably autosomal recessive, spastic paraparesis in two siblings was associated with dementia of frontal lobe type, amyotrophy and peripheral sensory and motor polyneuropathy. Neuropathological findings correlate with neurological deficits, although neuron loss in the caudate and putamen, substantia nigra, and loss of Purkinje cells were clinically silent. Loss of neurons occurred in all cortical layers of the prefrontal lobe and superior temporal gyrus. Immunohistochemical studies showed reduced parvalbumin immunoreactivity in dendrites, and reduced numbers of calbindin D28k-immunoreactive cells, thus suggesting involvement of cortical local-circuit neurons. Myelin loss, ubiquitin-immunoreactive granular deposits, and nerve fibre degeneration in the white matter of the frontal lobes and corpus callosum were also observed. Cerebral and subcortical white matter abnormalities, together with atrophy of the thalamic dorsomedial complex and anterior nucleus, may have accounted for the development of severe dementia in this patient.

Brain↗