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Biomedical subjects

M Ruiz

Publications and source records attributed to M Ruiz.

At least 91 records · Page 5Linked to original sources
PubMed1999

Malignant brain tumour mortality among children and adolescents: geographical distribution in Spain.

Log-linear Poisson mixed models were used to study provincial malignant brain tumour (MBT) mortality among children and adolescents in Spain (1975-1992) in order to investigate the influence of specific socio-economic factors and to produce smoothed estimators of standardised mortality ratios (SMRs). Interdependence between geographical units was taken into account by including provinces as random effect terms nested with the corresponding Autonomous Region (Spain's administrative divisions). MBT mortality showed a positive association with three variables: non-cancer-related infant mortality; percentage of provincial land surface area devoted to agriculture; and industrial/construction activity. According to the final model, SMRs increased by 4% with every 10% rise in the area devoted to agriculture, with a 4% excess risk predicted for every increase in non-cancer-related infant mortality of 1 per 1000 person-years, and a 7% excess risk for contiguous categories of industrial/construction activity. By smoothing extreme values caused by random variability, the regression model yielded a reasonable estimation of SMRs. While infant mortality may be linked to the quality of medical care available, the relationship seen between MBT mortality and agricultural area accords with the excess risk reported for farmers' offspring. Finally, industrial activity might be regarded as a risk factor or as a marker of other conditions also associated with these tumours.

Adolescent↗
PubMed1999

Spiny calretinin-immunoreactive neurons in the hilus and CA3 region of the rat hippocampus: local axon circuits, synaptic connections, and glutamic acid decarboxylase 65/67 mRNA expression.

We have used the Golgi method and Golgi electron microscopic techniques to analyze the axonal arborization and efferent connections of spiny calretinin-immunoreactive neurons in the CA3 region and hilus of the rat hippocampal formation. In the hilus, the axons of spiny calretinin-immunoreactive neurons sent out numerous collaterals that arborized in the hilar region and the molecular layer. In the CA3 region, these axons extended mainly to the stratum radiatum and pyramidal layer but also to the stratum oriens and stratum lacunosum-moleculare. Axonal varicosities were distributed widely throughout the axonal collaterals. Electron microscopic studies revealed that the axon terminals of spiny calretinin-immunoreactive neurons established synaptic contacts mainly with dendritic shafts. We next analyzed the expression of glutamic acid decarboxylase (GAD65/67) mRNAs in spiny nonpyramidal neurons that were identified by calretinin immunoreactivity. We found that spiny calretinin-positive neurons in the CA3 region and hilus of the rat hippocampal formation expressed the two isoforms of GAD: GAD65 and GAD67 mRNAs. These findings show that the spiny calretinin-immunoreactive neurons of hippocampus give rise to local axonal arborizations, suggesting that they are inhibitory.

Animals↗
PubMed1999

Development of commissural connections in the hippocampus of reeler mice: evidence of an inhibitory influence of Cajal-Retzius cells.

Reelin is a large, extracellular matrix protein involved in neuronal migration and axonal growth. To analyze the contribution of Reelin to the development of the commissural projection in the hippocampus, we analyzed the ontogeny of this projection in the reeler mutant mouse. Injections of the lipophilic tracer DiI revealed many commissural fibers in the hippocampus of both reeler and control mice at P1-P2. At P5, at P12, and in the adult, the topography of commissural connections was normal in the CA1 region of reeler mice, with axons innervating the stratum radiatum and stratum oriens. In contrast, in the CA3/CA2 region, commissural fibers abnormally innervated the stratum lacunosum-moleculare and, in the dentate gyrus, some fibers were observed in the outer molecular layer. Next, we monitored the distribution of Cajal-Retzius cells in the hippocampus of reeler mutant mice and noted that the stratum lacunosum-moleculare of the CA3/CA2 region was largely devoid of Cajal-Retzius (CR) cells. Taken together, the above results indicate that in the absence of CR cells in the CA3/CA2, commissural axons abnormally grow to the stratum lacunosum-moleculare. To test this hypothesis a series of coculture experiments was performed in collagen gels, in which the CA3 axonal growth was monitored when confronted to the marginal zone. These experiments showed that the marginal zone containing CR cells exerts short-range inhibitory influences for commissural axonal growth.

Age Factors↗
PubMed1999

Opening mechanism of a cyclic nucleotide-gated channel based on analysis of single channels locked in each liganded state.

Cyclic nucleotide-gated channels contain four subunits, each with a binding site for cGMP or cAMP in the cytoplasmic COOH-terminal domain. Previous studies of the kinetic mechanism of activation have been hampered by the complication that ligands are continuously binding and unbinding at each of these sites. Thus, even at the single channel level, it has been difficult to distinguish changes in behavior that arise from a channel with a fixed number of ligands bound from those that occur upon the binding and unbinding of ligands. For example, it is often assumed that complex behaviors like multiple conductance levels and bursting occur only as a consequence of changes in the number of bound ligands. We have overcome these ambiguities by covalently tethering one ligand at a time to single rod cyclic nucleotide-gated channels (Ruiz, ML., and J.W. Karpen. 1997. Nature. 389:389-392). We find that with a fixed number of ligands locked in place the channel freely moves between three conductance states and undergoes bursting behavior. Furthermore, a thorough kinetic analysis of channels locked in doubly, triply, and fully liganded states reveals more than one kinetically distinguishable state at each conductance level. Thus, even when the channel contains a fixed number of bound ligands, it can assume at least nine distinct states. Such complex behavior is inconsistent with simple concerted or sequential allosteric models. The data at each level of liganding can be successfully described by the same connected state model (with different rate constants), suggesting that the channel undergoes the same set of conformational changes regardless of the number of bound ligands. A general allosteric model, which postulates one conformational change per subunit in both the absence and presence of ligand, comes close to providing enough kinetically distinct states. We propose an extension of this model, in which more than one conformational change per subunit can occur during the process of channel activation.

Affinity Labels↗
PubMed1999

T(h)1 but not T(h)0 cell help is efficient to induce cytotoxic T lymphocytes by immunization with short synthetic peptides.

Immunization of BALB/c mice with peptide HVSGHRMAWDMMMNWA, encompassing residues 121-135 from hepatitis C virus E1 protein, induced CD4(+) T(h)1 cells as well as a long-lasting CD8(+) cytotoxic T lymphocyte (CTL) response in vivo when the peptide was administered s.c. with or without incomplete Freund's adjuvant. Using truncated peptides from this sequence it was shown that the determinant recognized by cytotoxic T cells was encompassed by residues SGHRMAWDM. Deletion of residues from the N-terminus or the C-terminus of the wild-type peptide abrogated its helper character. When Val122 of the wild peptide was replaced by Ala, the ability to induce a cytotoxic response was lost concomitantly with the loss of the T(h)1 pattern of cytokine production. Interestingly, the Ala-modified peptide, when co-immunized with a peptide encompassing residues 323-329 from ovalbumin (OVA), which is able to induce a T(h)1 response in BALB/c mice, restored the capacity of the modified peptide to induce CTL. However, co-immunization of the Ala-modified peptide with a peptide encompassing residues 106-118 from sperm whale myoglobin, which induces a T(h)0 cytokine profile in BALB/c mice, was much less efficient than the OVA peptide to restore CTL induction. These results demonstrate that CTL induction with a short synthetic peptide requires that this peptide contains domains recognized by T(c) cells as well as by T(h)1 cells. For those peptides that do not contain this type of T(h) domain, competent T cell help can be provided by co-immunization with a distinct peptide that is able to stimulate a T(h)1 response.

Amino Acid Sequence↗
PubMed1999

Immunogenicity of variable regions of hepatitis C virus proteins: selection and modification of peptide epitopes to assess hepatitis C virus genotypes by ELISA.

The immunogenicity of variable regions of hepatitis C virus (HCV) proteins was studied by ELISA by using 543 synthetic peptides from 120 variable regions and 90 sera from HCV-infected patients. Some regions from certain genotypes were less immunogenic, or even non-immunogenic, compared with their equivalents in other genotypes. However, the mean recognition of all peptides from genotypes 1a, 1b and 3 by sera infected with genotypes 1a, 1b and 3, respectively, showed no significant differences, suggesting a similar overall immunogenicity of variable regions from these genotypes. Proteins NS4a, NS4b and NS5a were found to be the most immunogenic. Recognition of individual peptides by the sera of infected patients showed that the humoral response against HCV is patient-dependent. The work shows that 15-mer peptides may encompass several B-cell epitopes. These epitopes may lie in slightly different positions in different genotypes. Thirty-one percent of the 543 peptides were recognized by some of the 35 healthy donors. This may be a reflection of the large number of antigens to which they had been exposed, but it may also reflect a strategy of HCV to respond to immune pressure. After selection and modification, a set of 40 peptides was used to assess genotypes 1a, 1b, 1, 2 and 3 in the sera of HCV-infected patients, with sensitivities of 34.1, 48.5, 68.8, 58.3 and 48.9% and specificities of 100, 99.1, 97.1, 99.5 and 99%, respectively. The overall sensitivity and specificity for the assessment of genotypes 1, 2 and 3 were 64 and 98%, respectively.

Amino Acid Sequence↗
PubMed1999

The human immunoglobulin heavy diversity (IGHD) and joining (IGHJ) segments.

The 'Human Immunoglobulin Heavy Diversity (IGHD) and Joining (IGHJ) segments', fifth report of the 'IMGT Locus on Focus' section, comprises six tables entitled: (1) 'Human germline IGHD segments at 14q32.33'; (2) 'Human IGHD alleles'; (3) 'Human germline IGHJ segments at 14q32.33'; (4) 'Human IGHJ alleles'; (5) 'Human germline IGHD orphons on chromosome 15 (15q11.2)'; (6) 'Correspondence between the different human IGHD nomenclatures', and two figures: (1) 'Protein display of human IGH D-REGIONs'; (2) 'Protein display of human IGH J-REGIONs'. These tables and figures are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cnusc.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.

Alleles↗
PubMed1999

Protein displays of the human immunoglobulin heavy, kappa and lambda variable and joining regions.

'Protein displays of the Human Immunoglobulin Heavy, Kappa and Lambda Variable and Joining Regions', the 6th report of the 'IMGT Locus on Focus' section, comprises 4 figures: (1) 'Protein display of human IGH V-REGIONs'; (2) 'Protein display of human IGK V-REGIONs'; (3) 'Protein display of human IGL V-REGIONs and V-PREB REGION'; (4) 'Protein display of human IGH, IGK and IGL J-REGIONs', and 1 table entitled: 'FR-IMGT and CDR-IMGT length of the human IGHV, IGKV, IGLV and V-PREB genes'. These figures and table are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cnusc.fr: 8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.

Amino Acid Sequence↗
PubMed1999

Pneumonia acquired in the community through drug-resistant Streptococcus pneumoniae.

The aim of the study was to determine the incidence of and risk factors for drug resistance of Streptococcus pneumoniae, and its impact on the outcome among hospitalized patients of pneumococcal pneumonia acquired in the community. Consecutive patients with culture-proven pneumococcal pneumonia were prospectively studied with regard to the incidence of pneumococcal drug resistance, potential risk factors, and in-hospital outcome variables. A total of 101 patients were studied. Drug resistance to penicillin, cephalosporin, or a macrolide drug was found in pneumococci from 52 of the 101 (52%) patients; 49% of these isolates were resistant to penicillin (16% intermediate resistance, 33% high resistance), 31% to cephalosporin (22% intermediate and 9% high resistance), and 27% to a macrolide drug. In immunocompetent patients, age > 65 yr was significantly associated with resistance to cephalosporin (odds ratio [OR]: 5.0; 95% confidence interval [CI]: 1.3 to 18.8, p = 0. 01), and with the presence of > 2 comorbidities with resistance to penicillin (OR: 4.7; 95% CI: 1.2 to 19.1; p < 0.05). In immunosuppressed patients, bacteremia was inversely associated with resistance to penicillin and cephalosporin (OR: 0.04; 95% CI: 0.003 to 0.45; p < 0.005; and OR: 0.46; 95% CI: 0.23 to 0.93; p < 0.05, respectively). Length of hospital stay, severity of pneumonia, and complications were not significantly affected by drug resistance. Mortality was 15% in patients with any drug resistance, as compared with 6% in those without resistance. However, any drug resistance was not significantly associated with death (relative risk [RR]: 2. 5; 95% CI: 0.7 to 8.9; p = 0.14). Moreover, attributable mortality in the presence of discordant antimicrobial treatment was 12%, as compared with 10% (RR: 1.2; 95% CI: 0.3 to 5.3; p = 0.67) in the absence of such treatment. We conclude that the incidence of drug-resistant pneumococci was high. Risk factors for drug resistance included advanced age, comorbidity, and (inversely) bacteremia. Outcome was not significantly affected by drug resistance.

Adult↗
PubMed1999

Etiology of community-acquired pneumonia: impact of age, comorbidity, and severity.

The aim of this study was to determine the etiology of community-acquired pneumonia (CAP) and the impact of age, comorbidity, and severity on microbial etiologies of such pneumonia. Overall, 395 consecutive patients with CAP were studied prospectively during a 15-mo period. Regular microbial investigation included examination of sputum, blood culture, and serology. Sampling of pleural fluid, transthoracic puncture, tracheobronchial aspiration, and protected specimen brush (PSB) sampling were performed in selected patients. The microbial etiology was determined in 182 of 395 (46%) cases, and 227 pathogens were detected. The five most frequent pathogens were Streptococcus pneumoniae (65 patients [29%]), Haemophilus influenzae (25 patients [11%]), Influenza virus A and B (23 patients [10%]), Legionella sp. (17 patients [8%]), and Chlamydia pneumoniae (15 patients [7%]). Gram-negative enteric bacilli (GNEB) accounted for 13 cases (6%) and Pseudomonas aeruginosa for 12 cases of pneumonia (5%). Patients aged < 60 yr were at risk for an "atypical" bacterial etiology (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.2 to 4.5), especially Mycoplasma pneumoniae (OR: 5.3; 95% CI: 1.7 to 16.8). Comorbid pulmonary, hepatic, and central nervous illnesses, as well as current cigarette smoking and alcohol abuse, were all associated with distinct etiologic patterns. Pneumonia requiring admission to the intensive care unit was independently associated with the pathogens S. pneumoniae (OR: 2.5; 95% CI: 1.3 to 4.7), gram-negative enteric bacilli, and P. aeruginosa (OR: 2.5; 95% CI: 0.99 to 6.5). Clinical and radiographic features of "typical" pneumonia were neither sensitive nor specific for the differentiation of pneumococcal and nonpneumococcal etiologies. These results support a management approach based on the associations between etiology and age, comorbidity, and severity, instead of the traditional syndromic approach to CAP.

Adult↗
PubMed1999

Severe community-acquired pneumonia. Risk factors and follow-up epidemiology.

The aim of the study was to determine risk factors for severe community-acquired pneumonia (CAP) as well as to compare microbial patterns of severe CAP to a previous study from our respiratory intensive care unit (ICU) originating from 1984 to 1987. Patients admitted to the ICU according to clinical judgment were defined as having severe CAP. For the study of risk factors, a hospital-based case-control design was used, matching each patient with severe CAP to a patient hospitalized with CAP but not requiring ICU admission. Microbial investigation included noninvasive and invasive techniques. Overall, 89 patients with severe CAP were successfully matched to a control patient. The presence of an alcohol ingestion of >/= 80 g/d (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.4 to 10.6, p = 0.008) was found to be an independent risk factor for severe CAP and prior ambulatory antimicrobial treatment (OR 0.37, 95% CI 0.17 to 0.79, p = 0.009) to be protective. Streptococcus pneumoniae (24%) continued to be the most frequent pathogen; however, 48% of strains were drug-resistant. "Atypical" bacterial pathogens were significantly more common (17% versus 6%, p = 0.006) and Legionella spp. less common (2% versus 14%, p = 0.004) than in our previous study, whereas gram-negative enteric bacilli (GNEB) and Pseudomonas aeruginosa continued to represent important pathogens (6% and 5%, respectively). Our findings provide additional evidence for the importance of the initiation of early empiric antimicrobial treatment for a favorable outcome of CAP. Variations of microbial patterns are only in part due to different epidemiological settings. Therefore, initial empiric antimicrobial treatment will also have to take into account local trends of changing microbial patterns.

Adolescent↗
PubMed1999

Diagnosis and follow-up of a case of peroxisomal disorder with peroxisomal mosaicism.

Peroxisomal disorder phenotypes are the result of mutations that cause defective peroxisomal assembly or alterations in the import mechanism of peroxisomal proteins that lead to multiple peroxisomal dysfunctions, or the result of a peroxisomal enzymatic deficiency with a single peroxisomal dysfunction. With complementation analysis, 16 groups have been found. Assignment of the genetic defect has been described for some of the complementation groups. We describe the clinical evolution and follow-up over 10 years of a patient who belongs to complementation group 4, although he showed a milder clinical course. It has been found in fibroblasts different peroxisome populations, normal processing and expression of beta-oxidation PTS1 and PTS2 proteins, abnormal ALD protein distribution and normal plasmalogen biosynthesis; abnormal beta-oxidation metabolites have also been detected in serum. Ultrastructural studies in liver showed peroxisomal mosaicism as in fibroblasts. It has been taken into account that peroxisomal mosaicism may lead to variability in peroxisomal diagnostic parameters, making difficult the final diagnosis in these patients.

Adolescent↗
PubMed1999

Assessment of myocardial viability using 123I-labeled iodophenylpentadecanoic acid at sustained low flow or after acute infarction and reperfusion.

UNLABELLED: 123I-labeled iodophenylpentadecanoic acid (IPPA) is a synthetic fatty acid that may be useful for determination of myocardial viability. We investigated the uptake and clearance kinetics of this tracer in canine models of ischemia and infarction. METHODS: In protocol 1, 185 MBq (5 mCi) 123I-IPPA were injected intravenously in 19 dogs with 50% left anterior descending artery (LAD) flow reduction. In 9 dogs, 201TI was coinjected. In protocol 2, 5 dogs underwent LAD occlusion for 3 h, and 123I-IPPA was injected 60 min after reperfusion. All dogs had flow measured by microspheres, regional systolic thickening by ultrasonic crystals and measurements of postmortem risk area and infarct size. Tracer activities were quantified by gamma well counting and by serial imaging. RESULTS: In protocol 1 dogs with sustained low flow (50% +/- 4%) and absence of systolic thickening (-3.2% +/- 1%), 123I-IPPA defect magnitude (LAD/left circumflex artery [LCX] count ratios) decreased from 0.65 +/- 0.02 to 0.74 +/- 0.02 at 30 min and to 0.84 +/- 0.03 at 2 h (P < 0.01), indicative of rest redistribution. Final transmural 123I-IPPA LAD/LCX activity ratio (0.99 +/- 0.05) was significantly greater than the flow ratio (0.53 +/- 0.04) at injection, confirming complete rest redistribution. The final 123I-IPPA activity ratio was significantly greater than the 201TI ratio over the 2-h period (P < 0.01). In protocol 2 dogs that underwent 3 h of total LAD occlusion and reflow (infarct size = 51% +/- 13% of risk area), viability was overestimated with 123I-IPPA, because uptake averaged 64% of normal in the central necrotic region, where flow averaged < 10% of normal. CONCLUSION: These findings suggest that serial 123I-IPPA imaging may be useful for assessing myocardial viability under conditions of sustained low flow and myocardial asynergy, such as appears to exist in patients with chronic coronary artery disease and depressed left ventricular function. In contrast, 123I-IPPA given early after reperfusion following prolonged coronary occlusion overestimates the degree of viability and therefore may not provide useful information pertaining to the degree of myocardial salvage after reflow in the setting of acute myocardial infarction.

Animals↗
PubMed1999

Community-acquired pneumonia in the elderly.

The incidence of community-acquired pneumonia (CAP) in the elderly is higher compared to younger populations. In addition, pneumonia in the elderly is a life-threatening problem. As our demographics have changed, clinicians have developed a heightened interest in managing pneumonia in the elderly. The development of pneumonia in elderly patients differs from that in younger individuals due to a complex array of factors. (1) The organisms involved depend on the setting in which the pneumonia developed: either the nonhospitalized elderly patient with CAP or the institutionalized patient who develops nursing-home-acquired pneumonia. (2) Underlying comorbid conditions commonly exist in the elderly that affect the etiology and outcome of pneumonia. Overall, Streptococcus pneumoniae and Haemophilus influenzae are still the most common etiologies of pneumonia in the elderly. The true role of gram-negative bacilli remains unclear although these micro-organisms may be more common etiologic agents in nursing-home pneumonia. Some recent studies from Mediterranean areas have reported high rates of infection by Chlamydia pneumoniae, but the real role of this micro-organism has to be confirmed. Another important issue is that the presenting symptoms of pneumonia in the elderly can be subtle and sometimes difficult to recognize. Fever is frequently absent, and delirium or alteration of functional physical capacity may be the only manifestations. Mortality in the elderly with CAP is higher when compared to younger populations. However, this may be explained by the concomitant presence of comorbid conditions more than by age per se. This statement has to be kept in mind when considering hospital and, particularly, intensive care unit admissions. Finally, antibiotic pharmacokinetics in the elderly populations with CAP ought to be considered to avoid frequent side-effects and complications. Overall, antibiotic regimens in hospitalized elderly patients with CAP do not differ from other hospitalized CAP populations. An organized approach to assessing elderly patients with suspicion of pneumonia and an awareness of common pitfalls in the management of this pulmonary infection in this population are essential to improving outcomes.

Aged↗
PubMed1999

Metabolic and hormonal changes during aerobic exercise in distance runners.

A group of long-distance runners is studied in order to clarify aspects concerning neuroendocrine mechanisms regulating organic adaptation to maximum effort, with special interest in the function of the growth hormone in fat metabolism and the possible use of ketone bodies as an alternative source of energy. A test is designed on a treadmill with a gradient of 3% and progressive increases in speed of 2 Km/h every 10 min, starting at 6 Km/h, and continuing until exhaustion. Masks are worn to enable the breath by breath measurement of expired gases and the subjects are monitored electrocardiographically using V5. For blood sample collection an antecubital vein is catheterized with a system enabling the replacement of the blood volume extracted by means of perfusion with physiological saline solution, and the increasing concentration of hormones in the blood is evaluated. The results obtained, indicate that epinephrine as well as GH hormones increase significatively from 20 min of exercise in runners promoting changes from carbohydrates to lipids as fuels to carry out exercise. The concomitant variations in energy substrates support the former hypothesis of work. Moreover, the muscle could employ acetylCoA originating from acetoacetate as an alternative metabolic source of fuel during maximum effort.

Adipose Tissue↗
PubMed1999

Leukemia, lymphomas, and myeloma mortality in the vicinity of nuclear power plants and nuclear fuel facilities in Spain.

Mortality due to hematological tumors in towns near Spain's seven nuclear power plants and five nuclear fuel facilities during the period 1975-1993 was ascertained. The study was based on 610 leukemia-, 198 lymphoma-, and 122 myeloma-induced deaths in 489 towns situated within a 30-km radius of such installations. As control areas, we used 477 towns lying within a 50- to 100-km radius of each installation, matched by population size and a series of sociodemographic characteristics (income level, proportion of active population engaged in farming, proportion of unemployed, percentage of illiteracy, and province). Relative risk (RR) for each area and the trends in risk with increasing proximity to an installation were analyzed using log-linear models. None of the nuclear power plants registered an excess risk of leukemia-induced mortality in any of the surrounding areas. Excess risk of leukemia mortality was, however, observed in the vicinity of the uranium-processing facilities in Andújar [RR, 1.30; 95% confidence interval, 1.03-1.64] and Ciudad Rodrigo (RR, 1.68; 95% confidence interval, 0.92-3.08). Excess risk of multiplemyeloma mortality was found in the area surrounding the Zorita nuclear power plant. Statistical testing revealed that, with the single exception of multiple myeloma, none of the tumors studied showed evidence of a rise in risk with proximity to an installation. No study area yielded evidence of a raised risk of leukemia mortality among persons under the age of 25 years. More specific studies are called for in areas near installations that have been fully operational for longer periods. In this connection, stress should be laid on the importance of using dosimetric information in all future studies.

Adolescent↗
PubMed1999

[The diagnosis of peroxisomal disorders in Spain during the period 1987-1997].

INTRODUCTION: Peroxisomal disorders are divided into two groups: a) Those with alterations in multiple peroxisomal functions, and b) With alterations in only one peroxisomal function. DEVELOPMENT: During the period 1987-1997, using very long chain fatty acids, plasmalogens and phytanic acid as diagnostic parameters, we diagnosed 116 cases of peroxisomal disorders in Spain. The most frequent (76%) was found to be X-linked adrenoleukodystrophy (X-ALD). Of the five phenotypes described in this condition, the adult cerebral form is seen in a higher percentage in the Spanish population (14%) than in other populations studied (1-3%). Defects in the assembly of peroxisomes made up 18%; the commonest phenotype was that of Zellweger's syndrome (13 cases), followed by neonatal adrenoleukodystrophy (5 cases) and infantile Refsum (2 cases). In the latter two patients, study of the hepatic peroxisomes showed a mosaic distribution. Rhizomelic punctate chondroplasia made up 3%, isolated beta-oxidation defects 2% and defects of plasmalogen synthesis 1%. In X-ALD, diagnosis of an initial case led to the detection of 12 presymptomatic and 70 heterozygote persons. Prenatal diagnoses were made on 10 occasions and 7 fetuses found to be affected. The introduction of the study of ALDP expression in the fibroblasts and the profile of the organic acids in the urine has led to improved diagnosis of these disorders.

Adult↗