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A Oliver

Publications and source records attributed to A Oliver.

At least 37 records · Page 2Linked to original sources
PubMed2002

Gene conversion (655G splicing mutation) and the founder effect (Gln318Stop) contribute to the most frequent severe point mutations in congenital adrenal hyperplasia (21-hydroxylase deficiency) in the Spanish population.

This study addresses the contributions of gene conversion and a founder effect to the distribution of the two most frequent severe point mutations of the 21-hydroxylase (21OH) gene causing congenital adrenal hyperplasia: the 655G splicing mutation at intron 2, and Gln318Stop in a Spanish population. Direct and indirect analyses of segregated mutant and normal 21OH genes in 200 Spanish families (classic and nonclassic 21OH deficiency) were performed. Both mechanisms were found to contribute to different degrees to the defective investigated alleles. The 655G splicing mutation (62 alleles, 15.5%) seemed to be almost exclusively related to recent conversion events, whereas Gln318Stop (33 alleles, 8.3%) is more likely to be due to the dissemination of remotely generated mutant alleles. Other severe defective alleles, 8 bp-deletion (13 alleles, 3.3%), 306insT (5 alleles, 1.3%), and gene deletions (43 alleles, 11%), as well as the mild mutation Val281Leu (120 alleles, 30%), also appear to be strongly associated with particular D6S273 alleles. Although gene conversion contributes to the generation of severe 21OH alleles, the high frequency of some severe mutations in different geographic areas is consistent with a founder effect.

Adrenal Hyperplasia, Congenital↗
PubMed2002

Non-classical 21-hydroxylase deficiency in children: association of adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone with the risk of compound heterozygosity with severe mutations.

AIM: To investigate the association between levels of 17-hydroxyprogesterone (17-OHP) and the risk of being compound heterozygous for severe mutations in children with non-classical 21-hydroxylase deficiency (NC21OHD). METHODS: In 86 Spanish NC21OHD children (75 families) an analysis of the 21-hydroxylase (21-OH) gene was performed by CYP21B-specific polymerase chain reaction amplification, allele-specific oligonucleotide hybridization and Southern blotting. Familial analysis established how the alleles segregated, and allowed the selection of 21-OH-genotyped normal and carrier children, which proved useful in determining a more precise definition of the cut-off for diagnosis. Receiver operating characteristics (ROC) curve analyses were performed to determine the potential value of 17-OHP in predicting compound heterozygosity for severe mutations. RESULTS: Thirty-four of the 86 children (39%) were found to carry one severe 21-OH mutation (7.3% deletions or conversions, 2.7% 655G, 2.7% Q318X, 1.3% 1172N, 1.3% R356W, and 3.3% double microconversions or small conversions involving single exons). The predominant mutation was V281L (56.7%). P453S and P30L were less frequent (3.3 and 2%). No patient showed two severe mutations. The degree of enzymic deficiency, as measured by basal or adrenocorticotropic hormone (ACTH)-stimulated 17-OHP levels in fully genotyped patients, but not clinical severity (age and number of symptoms at diagnosis), was found to be significantly greater in children with the severe/mild genotype. ROC curve analyses revealed a strong association between ACTH-17-OHP and genotype (area under the curve 0.908, SE 0.057). CONCLUSION: ACTH-stimulated 17-OHP may predict the risk of severe mutations in compound heterozygosity in children (maximum predictive value 93% sensitivity and 83% specificity for a cut-off at 151 nmol l(-1)), although a certain overlap in individual values is observed and performance of molecular analysis should never be obviated in the genetic counselling of these patients.

17-alpha-Hydroxyprogesterone↗
PubMed2001

Nontuberculous mycobacteria in patients with cystic fibrosis.

The prevalence and clinical implications of colonization with nontuberculous mycobacteria were prospectively studied in 37 patients who had cystic fibrosis. Sputum samples were cultured on Coletsos and Löwenstein-Jensen selective media after decontamination with sodium hydroxide and oxalic acid. Oxalic acid-decontaminated fractions were also cultured in selective liquid medium. Nontuberculous mycobacteria were isolated from 6 patients (16.1%). Mycobacterium chelonae and Mycobacterium avium-intracellulare complex were the most common species. Three patients with positive results of culture had at least 1 positive result by acid-fast smear. Oxalic acid decontamination and culture in liquid medium had the lowest contamination rate (6.7%). Colonization with nontuberculous mycobacteria was associated with humoral response to mycobacteria (immunoglobulin G titers against antigen A60) in patients with samples that tested positive by acid-fast smear. An improvement in pulmonary function was observed in 2 patients after they received a course of antimycobacterial therapy. Screening for nontuberculous mycobacteria in patients with cystic fibrosis will contribute to understanding the relevance of these pathogens with regard to deterioration of pulmonary function in patients with cystic fibrosis.

Adolescent↗
PubMed2001

Performance of the VITEK2 system for identification and susceptibility testing of routine Enterobacteriaceae clinical isolates.

The VITEK2 system was evaluated with 138 fresh consecutive routine clinical Enterobacteriaceae isolates. Susceptibility results to 10 beta-lactams, three aminoglycosides and a quinolone were compared with those obtained following the NCCLS standard microdilution. API20E was used as reference method for identification. All but three isolates were correctly identified in 3 h at species level (97.8%), two isolates (1.4%) at genus level and only one isolate was misidentified. Overall essential agreement for susceptibility testing was 97.1%. Discrepancies were mainly observed with piperacillin (1.1%), cefuroxime (0.6%) and amoxycillin/clavulanate (0.3%). Discrepancies for aminoglycosides and ciprofloxacin were low (<0.1%). Minor, major and very major errors (NCCLS categories) were 4.1%, 0.2% and 6.1%, respectively. Very major errors were due to piperacillin (4.5%), ampicillin (0.8%) and amoxycillin/clavulanate (0.8%). The VITEK2 system gave accurate identification and susceptibility testing results of routine Enterobacteriaceae clinical isolates.

4-Quinolones↗
PubMed2001

The impact of improved safety on maintaining a sufficient blood supply.

The impact of improved safety on maintaining a sufficient blood supply is becoming an increasingly real issue facing the National Blood Service in England and North Wales. This paper shows the extent of the impact that safety measures can have on reducing collection levels, without making any value judgement on the safety critera themselves. It demonstrates that underlying trends in collection are making it increasingly difficult to meet demand. Further potential restrictions, perhaps associated with variant Creutzfeldt-Jacob disease (vCJD), will require a reassessment of the safety-sufficiency trade-off. The analysis strongly suggests that continual enhancement of safety criteria, for both individual donor and patient benefit, will lead to insufficient supply to meet current levels of hospital demand. New approaches are needed to effectively manage blood throughout the supply chain, thereby ensuring sufficient supply.

Blood Banks↗
PubMed2001

Developing a UK health equity network.

The UK Health Equity Network (HEN) was established in 1999 to encourage and facilitate multidisciplinary and multi-stakeholder collaboration in health inequalities research. This paper briefly details the history, objectives and location of HEN.

Cooperative Behavior↗
PubMed2001

Increasing National Health Service funding: implications for welfare and justice.

Two of the fundamental purposes for establishing the National Health Service (NHS) were to increase social welfare and improve social justice. Decisions to increase NHS investment should ideally be taken with these fundamental objectives in mind. Given that society faces resource constraints, increased financial investment in the NHS will always involve forgone investment elsewhere, and it may never be possible to determine with any degree of certainty whether further real investment in the NHS will increase overall social welfare. If the Government decides to increase NHS investment for political reasons, it should therefore at least try to ensure that the methods by which it raises extra revenue improve social justice. The introduction of an NHS premium payment for high earners would be a progressive measure consistent with this objective.

Financing, Government↗
PubMed2001

Nucleotide sequence and characterization of a novel cefotaxime-hydrolyzing beta-lactamase (CTX-M-10) isolated in Spain.

A cefotaxime-resistant, ceftazidime-susceptible Escherichia coli isolate was obtained from a patient with sepsis in 1997, from which a beta-lactamase with a pI of 8.1 was cloned. Cephaloridine and cefotaxime relative hydrolysis rates were 167 and 81, respectively (penicillin G rate = 100), whereas ceftazidime hydrolysis was not detected. The nucleotide sequence revealed a bla gene related to that coding for CTX-M-3. Despite 21 nucleotide substitutions, only 2 determined amino acid changes (Ala27Val and Arg38Gln). The amino acid sequence identity between this enzyme, designated CTX-M-10, and the chromosomal beta-lactamase of Kluyvera ascorbata was 81%.

Cefotaxime↗
PubMed2001

Characterization of clinical isolates of Klebsiella pneumoniae from 19 laboratories using the National Committee for Clinical Laboratory Standards extended-spectrum beta-lactamase detection methods.

Extended-spectrum beta-lactamases (ESBLs) are enzymes found in gram-negative bacilli that mediate resistance to extended-spectrum cephalosporins and aztreonam. In 1999, the National Committee for Clinical Laboratory Standards (NCCLS) published methods for screening and confirming the presence of ESBLs in Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli. To evaluate the confirmation protocol, we tested 139 isolates of K. pneumoniae that were sent to Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology) from 19 hospitals in 11 U.S. states. Each isolate met the NCCLS screening criteria for potential ESBL producers (ceftazidime [CAZ] or cefotaxime [CTX] MICs were > or =2 microg/ml for all isolates). Initially, 117 (84%) isolates demonstrated a clavulanic acid (CA) effect by disk diffusion (i.e., an increase in CAZ or CTX zone diameters of > or =5 mm in the presence of CA), and 114 (82%) demonstrated a CA effect by broth microdilution (reduction of CAZ or CTX MICs by > or =3 dilutions). For five isolates, a CA effect could not be determined initially by broth microdilution because of off-scale CAZ results. However, a CA effect was observed in two of these isolates by testing cefepime and cefepime plus CA. The cefoxitin MICs for 23 isolates that failed to show a CA effect by broth microdilution were > or =32 microg/ml, suggesting either the presence of an AmpC-type beta-lactamase or porin changes that could mask a CA effect. By isoelectric focusing (IEF), 7 of the 23 isolates contained a beta-lactamase with a pI of > or =8.3 suggestive of an AmpC-type beta-lactamase; 6 of the 7 isolates were shown by PCR to contain both ampC-type and bla(OXA) genes. The IEF profiles of the remaining 16 isolates showed a variety of beta-lactamase bands, all of which had pIs of < or =7.5. All 16 isolates were negative by PCR with multiple primer sets for ampC-type, bla(OXA), and bla(CTX-M) genes. In summary, 83.5% of the K. pneumoniae isolates that were identified initially as presumptive ESBL producers were positive for a CA effect, while 5.0% contained beta-lactamases that likely masked the CA effect. The remaining 11.5% of the isolates studied contained beta-lactamases that did not demonstrate a CA effect. An algorithm based on phenotypic analyses is suggested for evaluation of such isolates.

Algorithms↗
PubMed2001

Recording and analyzing high-density event-related potentials with infants. Using the Geodesic sensor net.

This article provides an overview of the use of the Geodesic sensor net system for high-density event-related potential (ERP) recording in infants. Some advantages and disadvantages of the system, as applied to infants, are discussed. First, we illustrate that high-density data can be recorded from infants at comparable quality to that observed with conventional (low density) ERP methods. Second, we discuss ways to utilize the greater spatial information available by applying source separation and localization procedures. In particular, we focus on the application of one recent source separation method, Independent Component Analysis (ICA). Finally, we show that source localization can be applied to infant high-density data, although this entails adopting a number of assumptions that remain to be verified. In the future, with improved source separation algorithms, we suggest that single-trial or single-subject analyses may become feasible.

Adult↗
PubMed2001

Risk of thrombosis associated with oral contraceptives of women from 97 families with inherited thrombophilia: high risk of thrombosis in carriers of the G20210A mutation of the prothrombin gene.

BACKGROUND AND OBJECTIVES: Oral contraceptives (OC) and inherited thrombophilia are well-known risk factors associated with venous thromboembolism (VTE). However, there are only few studies on the risk of VTE in women with inherited thrombophilia who use oral contraceptives. DESIGN AND METHODS: We performed a retrospective family cohort study of 325 women belonging to 97 families with inherited thrombophilia, including antithrombin, protein S and C deficiencies, the factor V Leiden mutation (FVL) and the G20210A mutation of the prothrombin gene (PT20210A) to determine the risk of VTE associated with OC intake. RESULTS: For carriers of the PT20210A mutation, the risk of VTE in OC users was 3-fold higher (95% CI 1.3-6.8) than that in non-carriers. Carriers of FVL mutation taking OC showed an OR of 1.4 (95% CI 0.6-3.3), indicating a tendency to increase the risk of VTE. INTERPRETATION AND CONCLUSIONS: Because of the high prevalence of the PT20210A (6.5%) and FVL (2%) mutations in the general Spanish population and the increased risk of VTE associated with OC intake, genetic screening for these mutations should be considered in potential OC users belonging to families with thrombophilia.

Adolescent↗
PubMed2001

Contribution of prothrombin 20210A allele and factor V Leiden mutation to thrombosis risk in thrombophilic families with other hemostatic deficiencies.

BACKGROUND AND OBJECTIVES: The aims of this study were to compare the lifetime probability of developing thrombosis in 722 relatives of 132 thrombophilic families of symptomatic probands with recognized thrombophilic defects and to determine the prevalence of the factor V Leiden (FVL) mutation and the 20210A allele of the prothrombin gene (PT20210A) in these families. DESIGN AND METHODS: The study included 722 members belonging to 132 unrelated families. The propositi were patients who had been referred to our Thrombosis Unit. The families were selected through a symptomatic proband. Once a patient with a deficiency or mutation was identified, family members were screened for the same defect. RESULTS: The prevalence of FVL and PT20210A in families with other thrombophilic defects was higher than expected. Compared with non-deficient individuals, the risk of venous thrombosis was increased in subjects with antithrombin (AT), protein S (PS) and protein C (PC) deficiencies, and in carriers of FVL and PT20210A mutations. The risk of thrombosis was significantly increased for individuals with combined genetic defects (PC-FVL, PS-FVL, PS-PT20210A and FVL-PT20210A). The ages at the time of 50% thrombosis-free survival were as follows: 34 years for AT deficiency, (19 years with FVL, 21 years with PT20210A), 62 years for PC deficiency (33 years with FVL, 44 years with PT20210A), 37 years for PS deficiency (24 years with FVL, 36 years with PT20210A), 50 years for the FVL mutation (52 years with PT20210A), and 65 years for the PT20210A mutation. As for clinical characteristics, no differences were observed except for the higher frequency of oral contraceptive-related thrombosis in women who were carriers of PT20210A or FVL. INTERPRETATION AND CONCLUSIONS: Based on these results, screening for FVL and PT20210A mutation is recommended in patients with other thrombophilic defects. To the best of our knowledge, this is the first family study, including the PT20210A mutation, that compares genetic risk factors for thrombosis and the lifelong probability of developing thrombosis.

Adolescent↗
PubMed2001

[Cystinuria and cystine kidney lithiasis. Diagnosis and therapeutic approach].

OBJECTIVE: Cystine renal stone is the only clinical consequence of cystinuria, an autosomal recessive hereditary disease that affects an average of 1 out of 7,000 newborns, and whose geographical distribution varies significantly. The diagnosis and treatment of this condition is reviewed in the light of the advances in genetics and molecular biology. METHODS: The evolution of current knowledge about this disease is reviewed. RESULTS/CONCLUSIONS: The advances over the last 8 years have led to the characterization, at the present time, of two genes responsible for this disease, which demonstrates its polygenic origin. By phenotype, cystinuria can be classified into two types: type 1 and non-type 1. Both types show genetic and biochemical, but not clinical differences. From the therapeutic viewpoint, the main objective is to eliminate existing calculi and, above all, prevent recurrence by acting on the pathophysiologic mechanisms of renal cystine. Experience shows that despite the correct use of our current therapeutic armamentarium and the application of the general guidelines discussed in this paper, some cystinuric patients still maintain an important stone-forming activity. Patient clinical evaluation and a genetic study of both patient and family will be decisive for phenotyping.

Cystine↗
PubMed2000

High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection.

The lungs of cystic fibrosis (CF) patients are chronically infected for years by one or a few lineages of Pseudomonas aeruginosa. These bacterial populations adapt to the highly compartmentalized and anatomically deteriorating lung environment of CF patients, as well as to the challenges of the immune defenses and antibiotic therapy. These selective conditions are precisely those that recent theoretical studies predict for the evolution of mechanisms that augment the rate of variation. Determination of spontaneous mutation rates in 128 P. aeruginosa isolates from 30 CF patients revealed that 36% of the patients were colonized by a hypermutable (mutator) strain that persisted for years in most patients. Mutator strains were not found in 75 non-CF patients acutely infected with P. aeruginosa. This investigation also reveals a link between high mutation rates in vivo and the evolution of antibiotic resistance.

Adaptation, Physiological↗