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Biomedical subjects

R Vidal

Publications and source records attributed to R Vidal.

At least 73 records · Page 4Linked to original sources
PubMed2000

Isoniazid prophylaxis in lung transplantation.

The incidence of tuberculous disease (TD) is higher in lung-transplant patients than in the general population. During a 7-year period, we included 61 patients who underwent lung transplantation in a prospective isoniazid prophylaxis protocol. Isoniazid was prescribed to infected and anergic patients not previously treated when added to the waiting list. Six of 61 patients (10%) developed tuberculosis. We observed no differences in tuberculous disease incidence between infected-anergic and non-infected patients. In our tuberculous-endemic area, isoniazid prophylaxis is safe and offers protection from TD to infected and anergic patients who must be enrolled in a lung transplantation program.

Adolescent↗
PubMed2000

Simple method for alpha1-antitrypsin deficiency screening by use of dried blood spot specimens.

The use of dried blood spot (DBS) specimens in quantitative alpha1-antitrypsin (alpha1-AT) detection or genetic analysis is limited because protein levels in the samples are low and they contain components that can interfere with polymerase chain reaction amplification. A methodological adaptation was developed to overcome these drawbacks which is discussed here. The study population consisted of 200 healthy volunteers and 300 patients with chronic obstructive pulmonary disease (COPD). DBS specimens were tested for alpha1-AT concentration using a modified nephelometric assay and phenotyped with an isoelectric focusing method. Genetic diagnosis was established by deoxyribonucleic acid sequencing using a simple purification procedure to remove contaminants. The nephelometric method showed a detection limit of 0.284 mg x dL(-1), corresponding to a serum concentration of 13 mg x dL(-1). The correlation coefficient between alpha1-AT concentrations in DBS versus serum samples was R2=0.8674 (p<0.0001). All 200 healthy individuals had DBS alpha1-AT concentrations >1.9 mg x dL(-1), corresponding to 114 mg x dL(-1) in serum samples. One hundred and twenty-five COPD patients (42%) showed alpha1-AT values <1.8 mg x dL(-1). Twenty patients with the PIZ phenotype had alpha1-AT values lower than 0.64 mg x dL(-1). On the basis of genotyping, one COPD patient was classified as heterozygous (PIMM(heerlen)). Selective elution of contaminants resulted in optimal alpha(1)1-antitrypsin genotyping. Because of its sensitivity and excellent correlation with the standard method, the dried blood spot quantitative assay is a reliable tool for routine measurement of alpha1-antitrypsin.

Blood Specimen Collection↗
PubMed2000

Diagnosis of Chlamydia pneumoniae in community-acquired pneumonia in children in Chile.

UNLABELLED: The incidence of Chlamydia pneumoniae in community-acquired pneumonia in children was studied prospectively in 112 children aged 1 mo to 14 y. Diagnosis of C. pneumoniae was performed by polymerase chain reaction (PCR) on nasopharyngeal aspirates and serology by the microimmunofluorescence test on a single serum specimen. Three (2.7%) cases of pneumonia due to this agent were diagnosed by both PCR and serology. C. pneumoniae was not found in any of 62 children below 5 y of age. In the age group 5-8 y, only 1/30 (3%) was found positive, and in the age group 9-14 y, C. pneumoniae was diagnosed in 2/20 (10%) children. CONCLUSION: Although the number of enrolled patients is small, and the diagnostic techniques used may have some limitations, the results of this study suggest that C. pneumoniae.plays a minor role in the aetiology of pneumonia in children less than 9 y of age in our country. However, it should be considered as a potential agent in pneumonia in older children.

Adolescent↗
PubMed2000

Familial cerebral amyloid angiopathies and dementia.

Amyloidosis is a disorder of protein conformation leading to aggregation. The term defines a diverse group of proteins normally present in body fluids as soluble precursors that can be deposited as insoluble amyloid fibrils in different tissues producing organ dysfunction and cell death. These fibrils are composed of self-assembled, low molecular weight mass peptides adopting beta-pleated sheet structure, the conformation responsible for their physicochemical properties and tinctoreal characteristics. So far, 20 different proteins have been identified as subunits of amyloid fibrils (Westermark et al., 1999). Collectively, they are products of normal genes; however, several amyloid precursors contain abnormal amino acid substitutions that can impose an unusual potential for self-aggregation. The molecular mass of the amyloid peptides is within the 4 to 30-kDa range, with heterogeneity at the amino- and carboxyl-terminal portions found in most amyloid proteins. Increased levels of amyloid precursors, either in the circulation or locally in sites of deposition, are usually the result of overexpression or defective clearance, or both. Of the 20 amyloid proteins identified, few of them are known to cause amyloid deposition in the central nervous system, which in turn results in cognitive deficits, dementia, stroke, cerebellar and extrapyramidal signs, or a combination of them.

Amyloid beta-Protein Precursor↗
PubMed2000

A newly formed amyloidogenic fragment due to a stop codon mutation causes familial British dementia.

Familial British dementia (FBD) is an early-onset autosomal dominant disorder characterized by progressive cognitive impairment, spasticity, and cerebellar ataxia. Hippocampal neurofibrillar degeneration and widespread parenchymal and vascular amyloid deposits are the main neuropathological lesions. Amyloid fibrils are composed of a novel 34 amino acid subunit (ABri) with no sequence identity to any known amyloid molecule. The peptide derives from a larger precursor protein codified by a single gene BRI on chromosome 13. Affected family members have a single base substitution at the stop codon of the BRI gene that generates a longer open-reading frame resulting in a larger precursor protein. The release of the 34 C-terminal amino acids from the mutated precursor originates the ABri amyloid subunit. Our discovery of a new amyloid associated with the development of dementia supports the concept that amyloid peptides may be of primary importance in the initiation of neurodegeneration.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Amyloidogenesis in familial British dementia is associated with a genetic defect on chromosome 13.

Familial British dementia (FBD) is a disorder characterized by the presence of amyloid deposits in cerebral blood vessels and brain parenchyma coexisting with neurofibrillary tangles in limbic areas. The amyloid subunit (ABri) is a 4 kDa fragment of a 266 amino acid type II single-spanning transmembrane precursor protein encoded by the BRI gene located on chromosome 13. In FBD patients, a single base substitution at the stop codon of this gene generates a larger 277-residue precursor (ABriPP-277). Proteolytic processing by a furin-like enzyme at the C-terminus of the elongated precursor generates the 34 amino acid ABri that undergoes rapid aggregation and fibrillization. ABri is structually unrelated to all known amyloids including A beta, the main component of the amyloid lesions in Alzheimer's disease (AD), indicating that cerebral deposition of amyloid molecules other than A beta can trigger similar neuropathological changes leading to neuronal loss and dementia. These data support the concept that amyloid deposition in the vascular wall and brain parenchyma is of primary importance in the initiation of neurogeneration.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Inclusion body myositis, muscle blood vessel and cardiac amyloidosis, and transthyretin Val122Ile allele.

Typical of sporadic inclusion body myositis muscle biopsies are vacuolated muscle fibers containing intracellular amyloid deposits and accumulations of "Alzheimer-characteristic" proteins. There is no muscle blood vessel or cardiac amyloidosis. We report on a 70-year-old African-American man homozygous for the transthyretin Val122Ile allele who has both sporadic inclusion body myositis and cardiac amyloidosis. His unique pathological features included transthyretin immunoreactivity in prominent muscle blood vessel amyloid and congophilic amyloid deposits within vacuolated muscle fibers.

Aged↗
PubMed1999

[Tuberculous infection in nursing students: prevalence and conversion during a 3-year follow-up].

BACKGROUND: The aim of this study was to ascertain the positive tuberculin prevalence among the nursing students at the beginning of their studies; to assess the annual tuberculin conversion rate during their studies; to obviate the possibility of false conversions, studying the booster effect. PATIENTS AND METHODS: Cohort study, prospective, 3 groups not parallels (n = 316), 32 months follow-up in all students. Mean age 21 years (SD = 4; range = 17-39). First phase: before beginning clinical practice, a tuberculin test was undertaken by Mantoux technique with PPD type RT-23 with Tween 80 of 2 TU; this was repeated after 7-10 days, to BCG vaccinated and PPD negative on the first one, to study the booster effect. Second phase: at 18 months we repeated the tuberculin test to PPD negatives including the vaccinates with booster effect but PPD negative. The end of the study was at 32 months, repeating the test to PPD negatives at the end of their nursing studies. RESULTS: Tuberculin prevalence of 12% (38/316); CI 95%: 8.4%-15.6%. There were no significant differences of prevalence between vaccinated and unvaccinated nurse students. The prevalence in women was 8.9% (24/267) and 28.6% (14/49) in men. The only variables with statistical significance for being tuberculin positive were, age (p = 0.002) and sex (p = 0.003). 3/42 vaccinated with BCG (7%) had initial PPD (+); 2/39 of the remaining (5%) showed to be tuberculin positive after the booster effect and 37 tuberculin negative and booster negative. In the conversion study there were 259 valid students at the end of 3 years; there were 14 (5.4%) converters in the second year and 9 (3.5%) in the third year. Tuberculin conversion annual rate was 3.8 per 100 people/year. CONCLUSIONS: The tuberculous infection prevalence in nursing students was 12% (38/316). The annual frequency of tuberculin conversion (3.8 per 100 people/year) was higher in our students than in the general population, reinforcing the suitability of making periodical tuberculin control tests in PPD negative student nurses with continuous hospital contact.

Adolescent↗
PubMed1999

A stop-codon mutation in the BRI gene associated with familial British dementia.

Familial British dementia (FBD), previously designated familial cerebral amyloid angiopathy-British type, is an autosomal dominant disorder of undetermined origin characterized by progressive dementia, spasticity, and cerebellar ataxia, with onset at around the fifth decade of life. Cerebral amyloid angiopathy, non-neuritic and perivascular plaques and neurofibrillary tangles are the predominant pathological lesions. Here we report the identification of a unique 4K protein subunit named ABri from isolated amyloid fibrils. This highly insoluble peptide is a fragment of a putative type-II single-spanning transmembrane precursor that is encoded by a novel gene, BRI, located on chromosome 13. A single base substitution at the stop codon of this gene generates a longer open reading frame, resulting in a larger, 277-residue precursor. Release of the 34 carboxy-terminal amino acids from the mutated precursor generates the ABri amyloid subunit. The mutation creates a cutting site for the restriction enzyme XbaI, which is useful for detecting asymptomatic carriers. Antibodies against the amyloid or homologous synthetic peptides recognize both parenchymal and vascular lesions in FBD patients. A point mutation at the stop codon of BRI therefore results in the generation of the ABri peptide, which is deposited as amyloid fibrils causing neuronal disfunction and dementia.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Somatic mutations of the L12a gene in V-kappa(1) light chain deposition disease: potential effects on aberrant protein conformation and deposition.

Light chain deposition disease (LCDD) and light chain amyloidosis (AL) are disorders of monoclonal immunoglobulin deposition in which normally soluble serum precursors form insoluble deposits in tissues. A common feature in both is the clonal proliferation of B-cells that produce pathogenic light chains. However, the deposits in LCDD differ from those in AL in that they are ultrastructurally granular rather than fibrillar and do not bind Congo red or colocalize with amyloid P component or apolipoprotein E. The reason(s) for their differences are unknown but are likely multifactorial and related to their protein conformation and their interaction with other molecules and tissue factors in the microenvironment. Knowledge of the primary structure of the light chains in LCDD is very limited. In the present study two new kappa(1) light chains from patients with LCDD are described and compared to seven other reported kappa-LCDD proteins. The N-terminal amino acid sequences of light chain GLA extracted from the renal biopsy and light chain CHO from myocardial tissue were each identical to the respective light chains isolated from the urines and to the V-region amino acid sequences translated from the cloned cDNAs obtained from bone marrow cells. The germline V-region sequences, determined from the genomic DNA in both and in MCM, a previously reported kappa(1) LCDD light chain, were identical and related to the L12a germline gene. The expressed light chains in all three exhibit amino acid substitutions that arise from somatic mutation and result in increased hydrophobicity with the potential for protein destabilization and disordered conformation.

Amino Acid Sequence↗
PubMed1999

Atherosclerosis of the thoracic aorta and aortic debris as a marker of poor prognosis: benefit of oral anticoagulants.

OBJECTIVES: Our aim was to confirm the poor prognosis related to thoracic aortic plaques, in particular aortic debris, diagnosed by transesophageal echocardiography (TEE) and to evaluate patients' prognosis as a function of the antithrombotic treatment. BACKGROUND: Aortic atheroma (AA) has been widely studied. However, it is still not known which antithrombotic treatment should be adopted in this disease. METHODS: Patients referred for TEE and diagnosed with AA were followed. All thromboembolic events and deaths were recorded during a follow-up of 22+/-10 months. The antithrombotic treatment to be adopted was left to the discretion of the practitioner in charge of the patient. RESULTS: Aortic atheroma was found in 12% of all TEE performed and in 27.5% of TEE performed for stroke. This prevalence was higher when no other etiology existed to explain the stroke (p < 0.001). During follow-up, an end point occurred in 22.5% of patients. The more severe the AA the greater the incidence of events (p = 0.007). A higher mortality rate is shown in patients with aortic debris (p = 0.049). Compared with those treated with oral anticoagulants, patients with aortic plaques >4 mm thick treated with antiplatelets had more embolic events and combined events (p = 0.01 and p = 0.007, relative risk [RR] = 5.9, 95% confidence interval [CI] = 1.4 to 15, respectively); patients with aortic debris had more combined events and a higher mortality rate (p = 0.001, RR = 7.1, 95% CI = 1.2 to 19 and p = 0.019, RR = 9.1, 95% CI = 1.2 to 25, respectively). CONCLUSIONS: We confirm the high incidence of vascular events and deaths in patients with AA. We have demonstrated, for the first time in this condition, a better outcome among patients treated with oral anticoagulants versus antiplatelets.

Administration, Oral↗
PubMed1999

pH-dependent fibrillogenesis of a VkappaIII Bence Jones protein.

Disorders of immunoglobulin (Ig) synthesis that occur in malignant plasma-cell proliferation may result in either granular (LCDD) or fibrillar (AL) tissue deposition of light-chain monoclonal components. The structural features that govern the transition from soluble polypeptides to either fibrillar or granular conformational states remain undefined. Among the many factors presumed to play a role in these transitions the net charge of the molecule has been associated with folding conformation changes. The majority of the proteins involved in AL amyloidosis show acidic isoelectric points (pI 3.8-5.2), whereas most L chains with basic pIs deposit in granular patterns. In our studies a 12 kD VkappaIII fragment was purified as the main component of the fibrils isolated from myocardium and adipose tissue of the pericardium obtained post-mortem from an individual with systemic AL amyloidosis. An apparently identical 12 kD VL fragment with the same N-terminal sequence constituted the BJ protein present in the urine. This urinary protein exhibited strikingly cathodic electrophoretic mobility on agarose gels and lacked retention by anionic exchange chromatography matrices, indicative of a highly basic pI (>10). When it was subjected to in vitro fibril-formation experiments, the BJ protein adopted a fibrillar conformation only at acidic pHs, remaining aggregated but not fibrillar at physiological pH. The data indicate that a specific tissue deposition pattern involves not only structural properties of the protein but rather more complex mechanisms in which acidic micro-environments may contribute to the stabilization of amyloidogenic conformations.

Aged↗
PubMed1999

Esophageal dysplasias are detected by endoscopy with Lugol in patients at risk for squamous cell carcinoma in southern Brazil.

Diagnosis of squamous cell carcinoma of the esophagus is usually late. Staining of the mucosa with Lugol's solution during endoscopy has been suggested to identify early cancer/dysplasia and may improve prognosis. Lugol was tested during endoscopy in 96 asymptomatic subjects at risk for this tumor, who were found to have atypias after exfoliative cytology in southern Brazil. Biopsies were obtained in Lugol's 'stained' and 'unstained' areas in the esophageal mucosa and the histologic results were compared. 'Unstained' areas were present in 64 (66.7%) instances: 44 'unstained' areas over mucosa with normal appearance revealed seven dysplasias (four high and three low grade), whereas 20 'unstained' areas with visible lesions contained only one dysplasia (low grade). 'Stained' areas in 96 (100%) subjects showed two additional dysplasias (one high and one low grade). In this study, Lugol 'unstained' areas were of great value for detection of dysplasias (sensitivity = 80%; specificity = 63%; p = 0.01, Fisher's exact test; CI = 95%; odds ratio = 6.7).

Aged↗
PubMed1999

Immunochemical microanalysis of amyloid proteins in fine-needle aspirates of abdominal fat.

Diagnosis of systemic amyloidosis by fine-needle aspiration biopsy of abdominal fat is well established. A complete diagnosis now must include determination of the chemical type of amyloid. Microextracts of amyloid proteins from 11 Congo red-positive aspirate samples were analyzed with immunochemical methods. There was correspondence of the results obtained by immunohistologic and Western blotting analyses in 3 of 4 specimens with kappa light chain amyloid, 5 of 6 with lambda amyloid, and 1 with amyloid A. The method provides rapid and reliable diagnostic information necessary for classification of the chemical type of amyloid required for initiation of specific modes of therapy, with little discomfort to the patient.

Abdomen↗