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Biomedical subjects

C Ayuso

Publications and source records attributed to C Ayuso.

At least 37 records · Page 2Linked to original sources
PubMed2003

Huntington disease-unaffected fetus diagnosed from maternal plasma using QF-PCR.

The discovery of fetal DNA in maternal plasma from early pregnancies has led to new opportunities for clinical application. In the last few years there have been numerous reported applications, mainly fetal gender and RhD genotyping. The prenatal diagnosis of some inherited genetic diseases such as Huntington disease is also very frequently required in the prenatal diagnosis routine. We have successfully diagnosed, with a non-invasive procedure, an unaffected HD fetus at the 13th week of gestation using fetal DNA from maternal plasma and the quantitative fluorescent PCR method, which is one of the most sensitive ways to detect fetal DNA in maternal plasma at such an early time of gestation.

Alleles↗
PubMed2003

Is there a role for (99m)Tc-anti-CEA monoclonal antibody imaging in the diagnosis of recurrent colorectal carcinoma?

AIM: To evaluate the usefulness of immunoscintigraphy with an anti-CEA monoclonal antibody fragment labelled with (99m)Tc for early detection of colorectal recurrence in patients with rising serum CEA levels. METHODS: Fifty-one consecutive patients (27 women, 24 men) with colorectal cancer (mean age 68.9+/-10.2 years) and rising CEA levels (16.2+/-18.2 ng/ml) were prospectively studied. Two immunoscintigraphy studies were performed in 8 patients (n=59). Immunoscintigraphy was performed after i.v. injection of 925 MBq of anti-CEA monoclonal antibody. Planar images of the thorax, abdomen and pelvis, as well as SPECT of the abdomen and pelvis were obtained at 4 and 24 hours after injection. In all cases an abdominal CT scan was previously performed. Findings were validated by histopathological analysis (28 cases) or by imaging and clinical follow-up of at least 6 months following the immunoscintigraphy (31 cases). RESULTS: Forty-one patients did not show recurrence during follow-up. We found 18 cases with confirmed diagnosis of extrahepatic abdominal or pelvic diseases, 11 cases with liver metastases, 9 in the thorax and 2 in the bone. In patients with pelvic and extrahepatic abdominal disease, immunoscintigraphy was positive in 18 cases (14 true positive, 4 false positive). From the 14 true positive only 7 cases had been detected by CT. Immunoscintigraphy was negative in the remaining 41 cases (37 true negative, 4 false negative). Therefore, the sensitivity and specificity for immunoscintigraphy in extrahepatic abdominal and pelvic disease were 78% and 90%, respectively. CT results showed a lower sensitivity of 61% (p<0.05) and specificity of 83%. Liver metastases were detected by CT in 9 cases, but only 2 of these were identified using immunoscintigraphy. CONCLUSION: Scintigraphy with anti-CEA monoclonal antibody fragment labelled with (99m)Tc is superior to CT for the detection of pelvic and extrahepatic abdominal recurrence of colorectal cancer, while CT is more sensitive in the detection of liver and lung metastases. Immunoscintigraphy has a limited usefulness in the detection of distant metastases, but it may be helpful in the diagnosis of suspected colorectal recurrence in patients with non-conclusive CT findings, when FDG-PET is not available.

Aged↗
PubMed2002

CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.

Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. Usher syndrome type ID, one of seven Usher syndrome type I genetic localizations, have been mapped to a chromosomal interval that overlaps with a nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, a gene that encodes a putative cell-adhesion protein with multiple cadherin-like domains, are responsible for both Usher syndrome and DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects have been identified that differentiate these two phenotypes. Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. In the present study, a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness were screened for the presence of mutations in the entire coding region of CDH23, by heteroduplex, single-strand conformation polymorphism, and direct sequence analyses. A total of 36 different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. A total of seven mutations were common to more than one family. Numerous exonic and intronic polymorphisms also were detected. Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP-like manifestations, indicating that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 display a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia.

Adolescent↗
PubMed2002

Prenatal detection of a cystic fibrosis mutation in fetal DNA from maternal plasma.

OBJECTIVES: Maternal plasma and serum are being used to detect fetal DNA by PCR in order to determine certain conditions such as fetal gender and RhD without invasive procedures. Because of the presence of maternal DNA in plasma, these approaches are limited to paternally inherited disorders or those de novo present in the fetus. We have assessed the possibility of performing the detection of a single-gene disorder such as a fetal paternally inherited Cystic Fibrosis mutation (Q890X) in maternal plasma. METHODS: The analysis was performed at 13 weeks of gestation using DNA extracted from maternal plasma. We used a PCR amplification of the Q890X mutation and a posterior restriction analysis of the PCR product. RESULTS: We were able to detect the presence of the mutation and thus the fetal condition of being a carrier of the paternal mutation. CONCLUSIONS: We have made evident the possibility of detecting an inherited paternal mutation in a non-invasive way at the 13t(hr) weeks of pregnancy. This methodology could be very useful in cases of paternally inherited dominant disorders. The technical improvements in fetal DNA detection and analysis might lead to the development of new applications in the non-invasive prenatal diagnosis field.

Cystic Fibrosis↗
PubMed2002

[Evaluation of the efficacy and efficiency of a multidisciplinary unit for the treatment of patients with colorectal cancer].

INTRODUCTION: Because of the increased complexity of the diagnostic-therapeutic approach to colorectal cancer (CRC), these patients should be managed in specialized multidisciplinary units. The aim of this study was to evaluate the efficacy and efficiency of a CRC unit (CRCU) in the diagnostic-therapeutic management of these patients. PATIENTS AND METHODS: Two groups of 50 patients with colon cancer treated in our center before and after the implementation of the CRCU were selected. Fulfillment with the protocol in terms of tumoral staging, surgical and adjuvant treatment, follow-up, interval until treatment, hospital stay, morbidity and early mortality, and the overall duration of the diagnostic-therapeutic process was analyzed. In addition, clinical workload was evaluated and a cost-minimization analysis was performed. RESULTS: The CRCU reduced the interval until surgery (20.3 12.0 vs 28.0 20.4 days; p = 0.05), hospital stay (9.8 7.7 vs 14.5 9.3 days: p = 0.01), the time to the start of adjuvant treatment (29.4 10.2 vs 39.7 19.8 days; p = 0.03) and the overall duration of the process (60.4 23,8 vs 82.1 46.1 days; p = 0.05), representing a saving of 978.85 E per patient. This improvement took place despite an increase in clinical workload (24% in 5 years in relation to the number of admissions) and had no effect on morbidity (26 vs 24%; NS) or immediate mortality (6 vs 4%; NS). CONCLUSION: Specialized multidisciplinary units increase the efficacy and efficiency of the management of patients with CRC.

Aged↗
PubMed2002

Aniridia as part of a WAGR syndrome in a girl whose brother presented hypospadias.

Aniridia can arise as part of the WAGR syndrome (Wilms tumour. aniridia, genitourinary anomalies, and mental retardation), due to a deletion or chromosomal region 11p13. We report a girl with a complete WAGR syndrome, whose brother presented hypospadias. Cytogenetic, FISH and molecular studies showed a deletion in one chromosome 11 of the patient. No cytogenetic rearrangement or deletion affecting the genes included in this region (PAX6 and WT1) were observed in her brother and parents. This excludes a higher risk than that of the general population for developing Wilms tumour in the brother and supports that the presence of WAGR syndrome in the patient and hypospadias in her brother is a chance association. We conclude that the identification and definition of the deletions in the WAGR region, which include the WT1 locus are important in order to identify a high tumour risk in infant patients with aniridia including those without other WAGR anomalies.

Aniridia↗
PubMed2001

Identification of three novel mutations of the noggin gene in patients with fibrodysplasia ossificans progressiva.

We report noggin mutations in three Spanish families with fibrodysplasia ossificans progressiva (FOP). The three propositi have typical FOP findings; in the first and third families the parents are unaffected, while in the second family the father is partially affected. DNA of the three propositi and their parents was screened by sequencing for mutations in the noggin gene (NOG). Sequencing indicated a G to C mutation at nucleotide 274 of the NOG gene in the first propositus, encoding for the G92R substitution at the peptide level; this first mutation is de novo, the corresponding change not being observed in parents. In the second propositus, a G to T mutation at nucleotide 271 encodes for the G91C substitution, transmitted in the corresponding family by the partially affected father. In the third propositus, sequencing indicated a G to A mutation at nucleotide 275, encoding for the G92E substitution; this third mutation is de novo. All three mutations, as well as the Delta42 deletion already reported, resulted in the alteration of the portion of the NOG gene at positions 265-282, encoding for the potential N-myristoylation site at residues 89-GGGGGA-94.

Binding Sites↗
PubMed2001

[Molecular analysis of the RPE65 gene in 72 Spanish families with autosomal recessive retinitis pigmentosa].

BACKGROUND: Autosomal recessive retinitis pigmentosa (arRP) is the most common form of retinitis pigmentosa (RP). It is characterized by a high degree of allelic and non-allelic genetic heterogeneity. Previously,it has been demonstrated that the RPE65 gene is responsible for 2% recessive or isolated RP cases and 16% Leber's congenite amaurosis cases. Although the concrete function of RPE65 is unknown as yet, it has been found to be involved in vitamin A metabolism and rhodopsin regeneration. PATIENTS AND METHOD: We studied the involvement of the RPE65 gene in 72 arRP Spanish families by means of indirect molecular and mutation analysis. RESULTS: The results obtained using the intragenic microsatellite marker D1S2803 allowed us to exclude RPE65 as the causative gene of the disease in 80.5% of the families studied. Three new variants of the RPE65 gene have been identified: IVS6-43delA, IVS6-42delT and IVS6-33CG. We found that IVS6-33C-->G was a common polymorphism. The other variants, namely IVS6-43delA and IVS6-42delT, were not identified in 150 control chromosomes studied. The segregation analysis of IVS6-42delT variant seemed to exclude it as being involved in the disease. CONCLUSIONS: Our results argue against the involvement of RPE65 gene in the families studied, indicating that the prevalence of RPE65 abnormalities in arRP Spanish families may be lower than that observed in other populations.

Carrier Proteins↗
PubMed2001

Prenatal diagnosis on fetal cells from maternal blood: practical comparative evaluation of the first and second trimesters.

Objectives- Several attempts have been made to determine the gestational period in which the maximum number of fetal cells can be found in maternal blood and consequently which is the best week in which to perform a reliable non-invasive prenatal diagnosis. Most studies conclude that the number of nucleated red blood cells (NRBC) increases in line with gestation, but the number of cells that are fetal in origin (FNRBC) decreases in the third trimester. The aim of the present study was to make a practical comparative evaluation of the first and second trimesters to ascertain the period in which a greater number of FNRBC can be found of the total number of NRBC identified. Methods- Double density gradient and a posterior positive selection (CD71) by magnetic activated cell sorting (MACS) were employed. In the final fraction, erythroblasts were identified using Kleihauer staining and were studied using the fluorescence in situ hybridization (FISH) interphasic technique. Results- There was a significant difference (p<0.05) between the mean number of FNRBC found in the first and second trimesters. Conclusions- The number of FNRBC increases from the first to the second trimester. It appears that the optimum week in which to perform a reliable non-invasive prenatal diagnosis is around the 15th week.

Adult↗
PubMed2001

Mutations P51U and G122E in retinal transcription factor NRL associated with autosomal dominant and sporadic retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most frequent form of inherited retinopathy. RP is genetically heterogeneous with autosomal dominant, autosomal recessive and X-linked forms. Autosomal dominant retinitis pigmentosa (adRP) accounts for about 20-25% of all RP cases. At least ten adRP loci have so far been mapped. However, mutations causing adRP have been identified only in four retina-specific genes: RHO (encoding rhodopsin) in approximately 20% of adRP families, peripherin/RDS (3-5% of adRP) and recently RP1 (Pierce et al., 1999, Sulivan et al., 1999) and NRL gene. Only one mutation in the NRL gene causing adRP has so far been reported (Bessant et al., 1999). Here we report a novel mutation Pro51Leu in an adRP Spanish family supporting that mutation in NRL is the cause of adRP. A second missense mutation Gly122Glu has been observed in a simplex RP patient that may represent a sporadic case of retinitis pigmentosa. Hum Mutat 17:520, 2001.

Base Sequence↗
PubMed2001

Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains.

X-linked Retinitis Pigmentosa (XLRP) shows a huge genetic heterogeneity with almost five distinct loci on the X chromosome. So far, only two XLRP genes have been identified, RPGR (or RP3) and RP2, being mutated in approximately 70% and 10% of the XLRP patients. Clinically there is no clearly significative difference between RP3 and RP2 phenotypes. In the attempt to assess the degree of involvement of the RP2 gene, we performed a complete mutation analysis in a cohort of patients and we identified five novel mutations in five different XLRP families. These mutations include three missense mutations, a splice site mutation, and a single base insertion, which, because of frameshift, anticipates a stop codon. Four mutations fall in RP2 exon 2 and one in exon 3. Evidence that such mutations are different from the 21 RP2 mutations described thus far suggests that a high mutation rate occurs at the RP2 locus, and that most mutations arise independently, without a founder effect. Our mutation analysis confirms the percentage of RP2 mutations detected so far in populations of different ethnic origin. In addition to novel mutations, we report here that a deeper sequence analysis of the RP2 product predicts, in addition to cofactor C homology domain, further putative functional domains, and that some novel mutations identify RP2 amino acid residues which are evolutionary conserved, hence possibly crucial to the RP2 function.

Amino Acid Sequence↗
PubMed2001

Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma.

Radiofrequency (RF) ablation is an alternative to percutaneous ethanol injection (PEI) for single nonsurgical hepatocellular carcinoma (HCC) and is currently used as adjuvant therapy before liver transplantation. This phase II study assesses the treatment-related complications and response rate of RF for the treatment of single HCC < or = 5 cm. Percutaneous RF was performed under conscious sedation and ultrasound (US) guidance with an electrical generator connected to a single cooled-tip electrode. Neoplastic cells in peripheral blood (reverse transcription-polymerase chain reaction for alpha fetoprotein [AFP] messenger RNA) were analyzed before and after RF. Treatment response was assessed by spiral computed tomography (CT) at 1 month and every 3 months by US or spiral CT thereafter. Thirty-two patients (20 men; age 67 +/- 4 years; 78% hepatitis C virus; 24 Child-Pugh A) with a mean tumor size of 2.8 cm (25 patients < or = 3 cm) were treated by RF (1.25 sessions; mean time, 22.1 +/- 2 minutes). Adjuvant PEI was performed in 9 cases. Complete response was achieved in 21 patients (65%), being significantly higher for HCC < or = 3 cm (76% vs. 29%, P = .03). After a median follow-up of 10 months, 8 patients showed treatment-related morbidity. Four of them (12.5%) showed biopsy-proven needle-track seeding detected between 4 to 18 months. Neoplastic seeding was related to subcapsular location (P = .009), poor differentiation degree (P = .02), and baseline AFP levels (P = .02). Thus, RF ablation with cooled-tip needle for HCC is associated with a high risk of neoplastic seeding. Iatrogenic dissemination was related to subcapsular location or an invasive tumoral pattern, and has to be considered when selecting curative treatments for HCC or adjuvant therapies before liver transplantation.

Aged↗
PubMed2001

Evaluation of RLBP1 in 50 autosomal recessive retinitis pigmentosa and 4 retinitis punctata albescens Spanish families.

Defects in retinal vitamin A metabolism or in genes expressed in the retinal pigment epithelium (RPE) are related to nonsyndromic retinitis pigmentosa (RP). The RLBP1 gene encodes the cellular retinaldehyde-binding protein which, in the RPE and Müller cells of the retina, is thought to play a role in retinoid metabolism and visual pigment regeneration. We describe a study of the involvement of the RLBP1 gene in 50 autosomal recessive retinitis pigmentosa (ARRP) and four retinitis punctata albescens Spanish families. Cosegregation and homozygosity studies using an intragenic polymorphism and three close markers (D15S116, D15S127, and D15S130) ruled out RLBP1 as the cause of ARRP in 26 pedigrees. In the remaining families, SSCP analysis of the coding region and sequencing of the abnormal migrating bands did not detect any disease-causing mutation. These results indicate that mutations in the RLBP1 gene are not responsible for the ARRP or retinitis punctata albescens in this set of Spanish families. We did, however, identify two frequent polymorphisms (3'UTR + 167 G > T, T: 0.23 and G: 0.77; IVS6 + 20 T > C, T: 0.36 and C: 0.64), a silent substitution (S218S), and a rare variant (5'UTR-101 G > A).

Carrier Proteins↗