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P Carbonell

Publications and source records attributed to P Carbonell.

At least 19 recordsLinked to original sources
PubMed2006

[Hereditary pancreatitis caused by a new mutation in the trypsinogen gene. Report of a family].

Hereditary pancreatitis is an uncommon autosomal dominant disease secondary to a mutation normally located in the trypsinogen gene, preventing trypsin deactivation. This mutation translates clinically into recurrent attacks of acute pancreatitis and an increased risk of pancreatic cancer. We report a case of acute hereditary pancreatitis due to a trypsinogen mutation that has previously been described in only one family.

Child↗
PubMed2004

Novel HMBS founder mutation and significant intronic polymorphism in Spanish patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis, caused by a partial deficiency of hydroxymethylbilane synthase (HMBS). Knowledge of the nature of the HMBS mutations causing AIP in Spanish families is very limited. Here we report a novel 669_698del of the HMBS gene in twenty-two individuals from five independent Spanish AIP families, settled in Murcia (southeastern region of Spain). All mutation carriers shared a common disease associated haplotype indicating an ancestral founder effect. Identification of the 669_698del founder mutation allowed rapid and simple molecular diagnosis of AIP in families from this region in Spain. In addition, 771 + 58C>T in intron 12 on the non-669_698del allele was identified in six AIP patients, which promoted homozygous AIP misdiagnosis.

Adult↗
PubMed2001

Long-term response to interferon plus ribavirin in patients with chronic hepatitis C refractory to interferon.

OBJECTIVE: A sustained response (SR) to interferon (IFN) is only observed in 15-20% of patients with chronic hepatitis C (CHC). The aim of this study was to determine the long-term effectiveness and safety of the treatment with IFN plus ribavirin (RIB) over two years in CHC patients without SR to IFN. DESIGN: A prospective and open longitudinal follow-up study was conducted over 3 years. PATIENTS AND METHODS: A total of 77 CHC patients were included: 63 non-responders (NR) and 14 relapsers (R) to IFN. Patients were treated with IFN (3 MU s.c. three times a week) and RIB (1,000-1,200 mg p.o. daily) for 12 months. Treatment tolerance and viral response (HCV-RNA in serum < 1,000 copies/ml) were assessed after 1, 3, 6 and 12 months of treatment. SR and relapsing rates were subsequently evaluated 6, 12 and 24 months after the end of the treatment, together with those variables capable of predicting SR. RESULTS: At the end of the treatment, 19/77 patients responded (24.7%), 9/63 (14.3%) were non-responders and 10/14 (71.4%) relapsers, and these same patients exhibited SR after 6 months. The SR rate two years after treatment was 22.1% [8/63 (12.7%) NR and 9/14 (64.3%) R]. The relapse rate after 6 months and two years was respectively 0 and 10.5% (2/77). Independent variables capable of predicting SR were negative viremia conversion within the first month of treatment, maintenance of such negative viremia after 6 months, and R status to IFN. Side effects were recorded in 90.9% of cases (70/77), the most frequent being pseudoinfluenza syndrome. Treatment had to be discontinued in 33.8% of patients (26/77). CONCLUSIONS: Combined IFN-RIB therapy for 12 months in CHC patients without SR to IFN obtains a long-term SR of 22.1%, this rate being higher in relapsers to prior IFN therapy (64.3% in R versus 12.7% in NR).

Adult↗
PubMed2001

[Diagnosis of fragile X syndrome].

The fragile X syndrome (FXS) is the main cause of hereditary mental retardation. Although a lower frequency has been demonstrated in latest population studies, FXS constitutes the most frequent cause of hereditary mental retardation. FXS was historically diagnosed, firstly, only in clinically affected patients, but it was not possible to detect carriers with no symptoms. Once the mechanisms that specifically induced X chromosomal fragility were beginning to be understood, it became possible to confirm clinically diagnosed patients and detect some of asymptomatic carriers. But, the discovery of FMR1 gene has allowed us to reliable know the genetic status of anyone with respect to fragile X syndrome, independently of whether one belongs to a fragile X family. In this respect a combination of molecular and cytogenetic techniques may be used to detect expansions in the repeat region of the FMR1 gene. Three classes of alleles are found, normal with 5-60 repeats, premutated with repeats between 60 and 200 copies and full mutated with expansion greater than 200 copies.

Alleles↗
PubMed2000

Interferon alfa-2b plus ribavirin for chronic hepatitis C patients who have not responded to interferon monotherapy.

BACKGROUND: The role of combination therapy is poorly defined in chronic hepatitis C patients who are non-responders to interferon. AIM: To assess the efficacy, safety and tolerance of interferon alfa-2b plus ribavirin in chronic hepatitis C patients who do not respond to interferon monotherapy. METHODS: A total of 127 non-responder patients with chronic hepatitis C received 3 mU t.i.w. of interferon alfa-2b plus 1000-1200 mg ribavirin daily for 48 weeks. Effects of therapy were evaluated by serum aminotransferases and hepatitis C virus (HCV) RNA levels. RESULTS: Twenty-nine (23%) patients had an end-of-treatment response. Six months after treatment, 20 (16%) patients were sustained responders. Early loss of HCV RNA was the strongest predictor of a sustained response (P < 0.0001). Remission was also more frequent in patients with genotype 1b (P < 0.02), elevated alanine aminotransferase (P < 0.03) and low gamma glutamiltranspeptidase (P < 0.002). Treatment was discontinued in 21 (17%) patients: in 14 for intolerance and in seven due to side-effects. CONCLUSIONS: Combination therapy with interferon plus ribavirin produced a sustained response in 16% of chronic hepatitis C patients who were non-responders to interferon. This combination was safe and well tolerated.

Adult↗
PubMed1998

Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis.

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are caused by the loss of function of imprinted genes in proximal 15q. In approximately 2%-4% of patients, this loss of function is due to an imprinting defect. In some cases, the imprinting defect is the result of a parental imprint-switch failure caused by a microdeletion of the imprinting center (IC). Here we describe the molecular analysis of 13 PWS patients and 17 AS patients who have an imprinting defect but no IC deletion. Heteroduplex and partial sequence analysis did not reveal any point mutations of the known IC elements, either. Interestingly, all of these patients represent sporadic cases, and some share the paternal (PWS) or the maternal (AS) 15q11-q13 haplotype with an unaffected sib. In each of five PWS patients informative for the grandparental origin of the incorrectly imprinted chromosome region and four cases described elsewhere, the maternally imprinted paternal chromosome region was inherited from the paternal grandmother. This suggests that the grandmaternal imprint was not erased in the father's germ line. In seven informative AS patients reported here and in three previously reported patients, the paternally imprinted maternal chromosome region was inherited from either the maternal grandfather or the maternal grandmother. The latter finding is not compatible with an imprint-switch failure, but it suggests that a paternal imprint developed either in the maternal germ line or postzygotically. We conclude (1) that the incorrect imprint in non-IC-deletion cases is the result of a spontaneous prezygotic or postzygotic error, (2) that these cases have a low recurrence risk, and (3) that the paternal imprint may be the default imprint.

Angelman Syndrome↗
PubMed1997

FMR2 expression in families with FRAXE mental retardation.

Normal individuals express the two alternative transcripts, FMR2 and Ox19, from the FRAXE-associated CpG island. Molecular analysis of the Ox19 transcript suggests that it is a truncated isoform of the FMR2 gene with an alternative 3' end. Both isoforms showed a similar pattern of expression, with the Ox19 isoform expressed at a much lower level. Fibroblasts, chorionic villi and hair roots showed the highest level of FMR2 expression, whole blood cells and amniocytes showed very low expression, and the transcript was not detected in lymphoblasts. Fibroblasts of 11 individuals from seven families segregating FRAXE were assayed for FMR2 expression and FRAXE CpG island methylation. A man with an unmethylated expansion of 0.6 kb expressed FMR2 and represents a pre-mutation carrier. All chromosomes with FRAXE CCG expansions of 0.8 kb or greater were fully methylated and did not express the FMR2 gene, analogous to the mechanism of silencing the FMR1 gene in carriers of the FRAXA full mutation. The boundary between FRAXE pre-mutation and FRAXE full mutation is between 0.7 and 0.8 kb. Two men with absence of FMR2 expression in fibroblasts were not mentally impaired, suggesting that IQ in some men with FRAXE full mutation may remain within the normal range. Although molecular tools to study FRAXE non-specific mental retardation are now available, further psychometric and molecular studies are needed to characterize the effect of the FRAXE full mutation for the purpose of genetic counselling.

Base Sequence↗
PubMed1997

Prophylactic intravenous ondansetron in patients undergoing cataract extraction under general anesthesia.

During the past decade the demand for outpatient surgery has grown rapidly. Postoperative nausea and vomiting is one of the more common undesirable consequences of surgery, which may significantly delay the patient's discharge from the ambulatory surgery center. None of the currently used antiemetic drugs is considered totally effective in abolishing nausea or vomiting. The purpose of this study was to compare the efficacy of ondansetron, a highly selective 5-hydroxytryptamine subtype-3 receptor antagonist, with that of metoclopramide for the prevention of postoperative emesis in patients undergoing cataract surgery. The incidence of postoperative nausea was significantly less in the ondansetron group than that in the metoclopramide group (p = 0.046). Although the incidence of vomiting was clinically less frequent in the ondansetron group, there were no significant differences between both treatment groups. To our knowledge, this is the first study to demonstrate that ondansetron is effective to prevent postoperative emesis after extracapsular cataract extraction.

Adolescent↗
PubMed1997

[Cytomegalovirus retinitis in a pediatric AIDS patient].

INTRODUCTION: Cytomegalovirus retinitis (CMV) is the most frequently found opportunistic eye infection in adults with AIDS, with mean incidence of 20%-50%. However, only 5% of children with AIDS have this infection. CLINICAL CASE: We present the case of a six year old girl with stage C3 AIDS diagnosed at the age of 20 months, who developed unilateral diffuse retinitis due to CMV. The infection involved the posterior pole of the right eye, with retinal atrophy along the temporal vascular arcodes, and an active advance front in the temporal macula. The optic nerve was not found to be involved although the peripheral areas of the retina were involved leading to rhegmatogenous detachment of the superotemporal retina. In view of the systemic deterioration of the patient, no specific anti-CMV treatment was given. The patient died of respiratory insufficiency a few weeks later. CONCLUSIONS: CMV retinitis in paediatric AIDS patients is usually associated with more severe illness and a poorer general health than the adult population. In view of the absence of symptoms in these patients, periodic ophthalmoscopic examinations should be done in those who have severe immunological deterioration.

Acquired Immunodeficiency Syndrome↗
PubMed1996

FRAXE mutation analysis in three Spanish families.

Very little is known about the phenotype of FRAXE-positive individuals and the relation between the genotype/phenotype and genotype/ cytogenetic expression. We describe three families with normal and mildly affected individuals and a severely retarded male expressing fragility at the FRAXE locus or presenting different expansions at the CGG FRAXE triplet. In addition, we analyze the FRAXE mutation in sperm DNA from a retarded male carrier with a handicapped daughter expressing fragility at the FRAXE locus. Mental status in FRAXE individuals is highly variable and, although mild mental retardation is observed in most cases, several carrier males are apparently normal. It seems that methylation is not as strictly associated with size of CGG triplets in the FRAXE locus as in FRAXA, and it is possible that normal carrier individuals with fully methylated increments in lymphocytes have a certain proportion of unmethylated alleles in the critical (i.e., neural) tissues, FRAXE mutation is apparently similar to FRAXA in that males with somatic large methylated increments are carriers of small unmethylated ones in germinal cells.

Adolescent↗
PubMed1996

Intrafamily transmission of hepatitis C virus: sexual and non-sexual contacts.

BACKGROUND/METHODS: As a high number of patients with antibodies to hepatitis C (anti-HCV) do not have a known history of parenteral acquisition, other non-parenteral means of hepatitis C virus transmission must be studied. We investigated 1451 household contacts of 535 anti-HCV positive, human immunodeficiency virus-negative index patients. RESULTS: Overall, the prevalence of anti-HCV in household contacts was 4.5%. Thirty (7.6%) out of the 394 heterosexual stable partners were anti-HCV positive as compared to 35 (3.3%) out of 1057 non-sexual contacts (p < 0.01). The prevalence of anti-HCV was lowest in children of the index cases (1.8%). In this group, the prevalence of anti-HCV was 3% (10/330) when the mother was the index case, as opposed to 0.6% (2/328) when the father was the index case (p < 0.05). The prevalence of anti-HCV increased with age, being highest (18.6%) in family contacts older than 60 years. CONCLUSIONS: Transmission of hepatitis C virus may occur among household contacts of anti-HCV positive patients. Sexual contact or the use of non-disposable medical material in the past might explain the higher prevalence of anti-HCV found in sexual partners and in family contacts older than 60 years of age. Anti-HCV screening should be performed in family contacts of anti-HCV positive patients, particularly in those contacts older than 20.

Adolescent↗
PubMed1995

FRAXE and mental retardation.

Mental impairment and instability of the CCG repeat at FRAXE is described in six kindreds. Cosegregation of FRAXA and FRAXE was found within one of these kindreds. Cytogenetic expression of FRAXE was shown to skip a generation when associated with a reduction in size of the CCG expansion when transmitted through a male; however, in general, transmission occurred through females and a copy number increased from one generation to the next. In these respects the behaviour of FRAXE paralleled that of FRAXA. A relationship between FRAXE and non-specific mental impairment is strongly suggested by the occurrence in these families of more mentally impaired male and female carriers, after removal of index cases, than could reasonably be expected by chance.

Adolescent↗
PubMed1994

Molecular analysis of the (CGG)n expansion in the FMR-1 gene in 59 Spanish fragile X syndrome families.

The fragile X mental retardation syndrome is caused by an expansion of a trinucleotide repeat (CGG)n in the FMR-1 gene. Molecular genetic study of fragile X provides accurate diagnosis and facilitates genetic counseling in families with affected members. We present here the molecular study of 59 Spanish fragile X syndrome families using probe StB 12.3 and the polymerase chain reaction (PCR) of the (CGG)n repeat sequence of the FMR-1 gene. The results obtained have allowed us to characterize 455 individuals, including eight prenatal diagnoses. The clinical diagnosis of fragile X in 89 affected males was confirmed, 137 female carriers were identified (48 of whom were mentally retarded), 176 individuals "at risk" were found not to have the expansion, and 12 cases of normal transmitting males (NTM) were detected. In the sample studied, no de novo mutations were detected, nor any mutation different from that described for the (CGG)n expansion. One nonmentally retarded male was detected as having an unmethylated CpG island for the FMR-1 gene, but with more than 200 CGG repeats (high functioning male). The analysis of the (CGG)n repeat in 208 normal chromosomes gave an allele distribution similar to that in other Caucasoid population groups, with alleles of 29 and 30 CGG repeats accounting for 46% of the chromosomes. The combination of Southern analysis and PCR of the (CGG)n repeat is highly efficient for diagnosis, compared with cytogenetic techniques, especially in the detection of female carriers, NTMs, and prenatal diagnosis, enabling accurate genetic counseling to be provided in all cases.

Blotting, Southern↗
PubMed1994

Fragile X syndrome and the (CGG)n mutation: two families with discordant MZ twins.

The fragile X phenotype has been found, in the majority of cases, to be due to the expansion of a CGG repeat in the 5'-UTR region of the FMR-1 gene, accompanied by methylation of the adjacent CpG island and inactivation of the FMR-1 gene. Although several important aspects of the genetics of fragile X have been resolved, it remains to be elucidated at which stage in development the transition from the premutation to the full mutation occurs. We present two families in which discordance between two sets of MZ twins illustrates two important genetic points. In one family, two affected MZ brothers differed in the number of CGG repeats, demonstrating in vivo mitotic instability of this CGG repeat and suggesting that the transition to the full mutation occurred postzygotically. In the second family, two MZ sisters had the same number of repeats, but only one was mentally retarded. When the methylation status of the FMR-1 CpG island was studied, we found that the majority of normal chromosomes had been inactivated in the affected twin, thus leading to the expression of the fragile X phenotype.

Adolescent↗
PubMed1989

[Superficial gastric carcinoma. Clinical analysis].

While in Japan the incidence of superficial gastric cancer (CGS) is very high (35%), with a mean 5-year survival rate of 95%, in our environment it is infrequent. Although the global incidence of gastric cancer is declining, recently, since endoscopy became routine, an increase has been seen in the diagnosis of superficial gastric cancer. In the period between 1976-1982 two cases were diagnosed in our service, but between 1982-1986 the total number of cases found was 23, representing 0.37% of all the endoscopies performed (approx. 6,800) and 8.6% of those diagnostic of gastric cancer (266 cases). Of the lesions, 60.8% were located in the antral region and the most common accompanying symptomatology was ulcerative syndrome (47.3%). The predominant tumoral type was ulcerative (73.9%) (classification of the Japanese Endoscopy Society). The benefits of radiological study were nil, while endoscopic biopsy was diagnostic in 100% after an average of 1.8 (1-4) endoscopies per patient with 6-12 biopsy samples obtained in each endoscopy. Of these 23 patients, 8 underwent total gastrectomy, 14 partial gastrectomy and one refused surgical treatment. The survival was 91.3%, with a follow-up of 6 to 60 months, and two deaths were due to nontumoral causes.

Adult↗