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Biomedical subjects

R Alvarez

Publications and source records attributed to R Alvarez.

At least 37 records · Page 2Linked to original sources
PubMed1999

Control of cytomegalovirus disease in renal transplant patients treated with prednisone, azathioprine and cyclosporine using intensive monitoring and decreased immunosuppression.

BACKGROUND: The aim of this trial was to study the effectiveness of intensive monitoring, together with an early decrease in immunosuppression, in reducing the prevalence of CMV disease in renal transplant recipients treated with prednisone, azathioprine and cyclosporine. METHODS: From 1/95 to 11/97 a prospective, longitudinal study was conducted among 146 consecutive, unselected, renal transplant patients in our unit. Only 96 patients whose immunosuppressive regimens consisted of prednisone, azathioprine and cyclosporine and whose follow-up period was greater than 4 months were included in the study. Preemptive therapy was administered to 27 high-risk patients. CMV antigenemia (CMV-AG) and other virological tests were performed weekly for the first 4 posttransplant months. The immunosuppression was decreased when the first positive CMV-AG was detected. Azathioprine was completely withdrawn when the CMV-AG count was greater than 10 cells per 10(5) PBLs. The cyclosporine dose was gradually decreased in the next 4 weeks, but it was not withdrawn in any patient. The prednisone dose was modified according to the immunosuppressive protocol. RESULTS: 53% (51/96) of the patients had positive CMV-AG on at least one occasion. The dose of azathioprine was decreased after CMV-AG detection in 41/51 (80.4%) patients and it was completely withdrawn in 23 of these (45%). The mean decrease in the dose of azathioprine was 73 +/- 31 (25-175) mg, a mean percentage decrease of 76 +/- 27% (25-100%). The dose of cyclosporine was progressively decreased during the 4 weeks after detection of the first CMV-AG (mean cyclosporine levels: 210 +/- 66, 196 +/- 54 and 164 +/- 36 ng/ml at the time of first CMV-AG detection, 2 and 4 weeks respectively, p < 0.0001, repeated measures analysis of variance). None of the 45 patients without CMV-AG and only 2 of 51 (3.9%) patients with CMV-AG developed symptomatic CMV disease (2% of the total). CMV disease was of moderate intensity in both patients. Only 3/51 (5.8%) patients developed acute rejection after the first CMV-AG detection in the 4 posttransplant months. CONCLUSION: The results of this study suggest that intensive monitoring and an early reduction of immunosuppression, together with preemptive therapy in high-risk patients, is effective in diminishing the prevalence and severity of CMV disease.

Adult↗
PubMed1999

Comparison of custom and prefabricated orthoses in the initial treatment of proximal plantar fasciitis.

Fifteen centers for orthopaedic treatment of the foot and ankle participated in a prospective randomized trial to compare several nonoperative treatments for proximal plantar fasciitis (heel pain syndrome). Included were 236 patients (160 women and 76 men) who were 16 years of age or older. Most reported duration of symptoms of 6 months or less. Patients with systemic disease, significant musculoskeletal complaints, sciatica, or local nerve entrapment were excluded. We randomized patients prospectively into five different treatment groups. All groups performed Achilles tendon- and plantar fascia-stretching in a similar manner. One group was treated with stretching only. The other four groups stretched and used one of four different shoe inserts, including a silicone heel pad, a felt pad, a rubber heel cup, or a custom-made polypropylene orthotic device. Patients were reevaluated after 8 weeks of treatment. The percentages improved in each group were: (1) silicone insert, 95%; (2) rubber insert, 88%; (3) felt insert, 81%; (4)stretching only, 72%; and (5) custom orthosis, 68%. Combining all the patients who used a prefabricated insert, we found that their improvement rates were higher than those assigned to stretching only (P = 0.022) and those who stretched and used a custom orthosis (P = 0.0074). We conclude that, when used in conjunction with a stretching program, a prefabricated shoe insert is more likely to produce improvement in symptoms as part of the initial treatment of proximal plantar fasciitis than a custom polypropylene orthotic device.

Adult↗
PubMed1999

[The usefulness of transjugular hepatic biopsy in the evaluation of liver disease in candidates for heart transplantation].

Heart transplantation is a universally accepted procedure in the treatment of terminal heart diseases. However, the presence of advanced liver disease in the potential receptors represents a contraindication for heart transplantation. On the other hand, the true diagnosis of liver disease not secondary to heart disease may be difficult requiring confirmatory liver biopsy. Nonetheless, percutaneous liver biopsy may be difficult to perform due to presence of coagulation alterations, marked dilatation of the hepatic veins, etc. The aim of this study was to evaluate the efficacy and safety of transjugular hepatic biopsy in the presence of severe coagulopathy in potential heart transplantation receptors with suspicion of liver disease and contraindication of percutaneous liver biopsy. Over a 9-year period, 350 potential heart transplantation patients were evaluated. In 23 patients (6.7%) transjugular hepatic biopsy was performed with aspiration needle followed by a hemodynamic study in 17 cases. The transjugular hepatic biopsy was completed in 22 cases (95.6%) with adequate material for the diagnosis being obtained in 21 (91.3% of the total cases indicated). Histologic study showed significant inflammatory infiltrates or alteration of the hepatic architecture in 4 patients (18%), all being positive for some viral markers (AgHBs or anti-HCV). The obtaining of a certain histologic diagnosis modified the consideration of liver disease as a definitive contraindication and allowed the performance of heart transplantation in 17 patients (73.9%). No complications were observed in association with the procedure. The transjugular hepatic biopsy is a feasible, effective and safe alternative for obtaining liver tissue in patients under evaluation for heart transplantation with suspicion of severe liver disease. The establishment of a correct histologic diagnosis may modify the clinical decision in an important number of patients.

Biopsy↗
PubMed1999

[ Magnetic resonance imaging in the early diagnosis of bone marrow necrosis].

Bone marrow necrosis (BMN) is a rare entity characterised by fever and bone pain, accompanied by hypercalcemia and increased LDH. Amorphous eosinophilic material is present in the bone marrow aspirate, with isolated cells in different degrees of necrobiosis. These are frequently post-mortem findings, appearing in up to 19.8% of all autopsies, mostly after haematological malignancies with proliferative features (acute leukaemia, lymphoma). In general terms, BMN is regarded as a poor prognosis sign. Bone gammography with Tc has been included among the diagnostic procedures, in an attempt to carry out an early detection of BMN and to determine its spread. Magnetic resonance imaging (MRI) has recently been regarded useful to evaluate bone marrow involvement in this condition. A 53 year-old woman is presented here who, two and a half years after being diagnosed of mantle cell lymphoma, and having a relapse on her neck lymph nodes, presented severe bone pain showing no radiological evidence of osseous involvement. MRI showed ample spongy marrow involvement of her lower spine, sacrum and pelvic bones. Both femoral heads were preserved, hypointense images being observed in T1, whereas subcortical, hyperintense ones appeared in T2. Bone marrow aspirate showed poor cellularity, with different degrees of necrobiosis on a stippled background. The picture was interpreted as BMN secondary to non-Hodgkin's lymphoma.

Bone Marrow↗
PubMed1999

Evaluation of the blue formazan spot test for screening glucose 6 phosphate dehydrogenase deficiency.

Several screening tests for glucose 6 phosphate dehydrogenase (G6PD) deficiency have been reported thus far, and a standardized method of testing was proposed by the International Council for Standardization in Hematology (ICSH). The screening test used in any particular laboratory depends upon a number of factors such as cost, time required, temperature, humidity, and availability of reagents. In this study, a direct comparison between three different G6PD screening methods has been undertaken. In 71 cases (50 hematologically normal volunteers, 9 hemizygous G6PD-deficient males, and 12 heterozygous deficient females), the blue formazan spot test (BFST) was compared with the conventional methemoglobin reduction test (HiRT) and the ICSH-recommended fluorescent spot test (FST-ICSH). In all cases, the results obtained with the three screening tests were correlated with the enzyme activity assayed spectrophotometrically. In hemizygous G6PD-deficient males, all cases were equally detected with the three methods: BFST (4.7-6.64, controls: 11.1-13.4), BMRT (score +3 in all 9 cases), and FST (no fluorescence in 9 cases). In heterozygous G6PD-deficient females, two methods detected 7 out of 12 cases (BFST: 8.71-11.75, controls: 11.1-13.4; and BMRT: score +3 in 7 cases), whereas the FST-ICSH missed all 12 cases that presented a variable degree of fluorescence. Although the sensitivity for G6PD-deficient carrier detection is the same for the BMRT and the BFST, the latter has the advantage of being semiquantitative and not merely qualitative. Unfortunately, none of the three screening tests compared here allowed the detection of the 100% heterozygote carrier state of G6PD deficiency.

Evaluation Studies as Topic↗
PubMed1998

Abasic analogues of TSAO-T as the first sugar derivatives that specifically inhibit HIV-1 reverse transcriptase.

With the aim of assessing the role that the thymine base of TSAO-T may play in the interaction of TSAO compounds with HIV-1 reverse transcriptase (RT), we have designed, synthesized, and evaluated for their anti-HIV-1 activity a series of 3-spiro sugar derivatives substituted at the anomeric position with nonaromatic rings or with amine, amide, urea, or thiourea moieties that mimic parts or the whole thymine base of TSAO-T. Also, a dihydrouracil TSAO analogue and O-glycosyl 3-spiro sugar derivatives substituted at the anomeric position with methyloxy or benzyloxy groups have been prepared. Compounds substituted at the anomeric position with an azido, amino, or methoxy group, respectively, were devoid of marked antiviral activity (EC50: 10-200 microM). However, the substituted urea sugar derivatives led to an increase in antiviral potency (EC50: 0.35-4 microM), among them those urea derivatives that mimic most closely the intact TSAO-T molecule retained the highest antiviral activity. Also, the dihydrouracil TSAO derivative retained pronounced anti-HIV-1 activity. None of the compounds showed any anti-HIV-2 activity. The results described herein represent the first examples of sugar derivatives that interact in a specific manner with HIV-1 RT. Molecular modeling studies carried out with a prototype urea derivative indicate that a heteroaromatic ring is not an absolute requirement for a favorable interaction between TSAO-T and HIV-1 RT. Urea derivatives, which can mimic to a large extent both the shape and the electrostatic potential of a thymine ring, can effectively replace this nucleic acid base when incorporated into a TSAO molecular framework with only moderate loss of activity.

Animals↗
PubMed1998

[Systemic mastocytosis. Study of 14 cases].

We have analyzed the clinical, analytical and evolutive data of 14 cases of systemic mastocytosis (SM) diagnosed in our hospital between 1991-1996 and we have compared these results with those of other published series. Clinical parameters, analytical profiles, peripheral hematologic data, radiologic data and histological study were collected. Following Metcalfe's criteria, the patients were classified in 4 groups: a) group 1, indolent mastocytosis; b) group 2, hematologic disorders; c) group 3, aggressive lymphadenopathic mastocytosis with eosinophilia, and d) group 4, mastocytic leukemia. The average age at diagnosis was 52.4 years, range 25-83, and 64% were females. The mean follow-up was 2 yr. In most of the cases (71.4%) the initial complaint was urticaria pigmentosa. The predominant clinical features were pruriginous-eritematous skin lesions (in 11 cases), and digestive symptoms (in 10 patients). The most usual biochemical disorder was the rise of serum alkaline phosphatase level (in 8 patients), while lactate-dehydrogenase (LDH) was normal in all the cases. The most striking roentgenologic features were oteopenia, observed in 50% of our patients. Pheripherical hematological disorders were discovered in 8 patients (64.3%) and in one of them circulating mast-cells were observed. The bone marrow was involved in all patients (100%) and in two of them mielodysplasic features were found. The diagnostic of SM is difficult in the absence of skin lesions. The skin lesions are very common in systemic mastocytosis. Bone marrow involvement is constant, so its study has a high diagnostic rentability.

Adult↗
PubMed1998

Elevated extracellular calcium can prevent apoptosis via the calcium-sensing receptor.

The calcium-sensing receptor (CaR) is a membrane-bound, G-protein-coupled receptor present on parathyroid cells which monitors the level of extracellular calcium (Ca2+o) and transduces signals involved in serum calcium regulation. Expression of CaR protein in tissues with functions unrelated to systemic calcium homeostasis, including the brain, suggests that extracellular calcium (Ca2+o) may act as a first messenger to regulate diverse cellular functions. To test this hypothesis, we examined the effect of increasing Ca2+o on apoptosis induced by Sindbis Virus in AT-3 prostate carcinoma cells. We found a steep increase in cell survival with between 5 and 7 mM added Ca2+o (EC50 = 6.1 mM). Magnesium, a less potent agonist of the calcium sensing receptor, was also protective (EC50 = 23.4 mM). Northern and immunocytochemical analyses confirmed the presence of the CaR message and protein in AT-3 prostate carcinoma cells. Enforced expression of CaR protein by stable transfection in human embryonic kidney (HEK)-293 cells, which normally don't express the receptor, resulted in resistance to SV-induced apoptosis in the presence of elevated Ca2+o. In addition to preventing SV-induced death, elevated Ca2+o also abrogated apoptosis induced by c-Myc overexpression/serum deprivation in rat 1A fibroblasts, and these fibroblasts were shown to express CaR message and protein. Altogether, these observations suggest that Ca2+o can act with the CaR to prevent apoptosis and define a novel mechanism by which calcium ions can regulate cell survival.

Animals↗
PubMed1998

Flow cytometric DNA analysis and p53 protein expression show a good correlation with histologic findings in patients with Barrett's esophagus.

BACKGROUND: There is a considerable degree of subjectivity and, therefore, substantial interobserver and intraobserver disagreement in the diagnosis and grading of dysplastic lesions in Barrett's esophagus (BE). The aim of this study was to evaluate the usefulness of DNA flow cytometry and immunohistochemical staining for p53 protein as objective methods to complement the conventional histologic diagnosis of dysplasia in patients with this disease. The most common problems and the possible advantages of using these procedures are analyzed briefly in this article. METHODS: Formalin fixed, paraffin embedded tissue from 55 patients diagnosed with BE were processed for flow cytometric measurements (ploidy and proliferation index) and p53 immunostaining. RESULTS: Both the cytometric data and the positivity of staining for p53 revealed a statistically significant increase throughout the following sequence: no dysplasia --> indefinite for dysplasia --> low grade dysplasia --> high grade dysplasia --> adenocarcinoma. There was also a highly significant correlation between the results of the cytometric study and the positivity of staining for p53. CONCLUSIONS: In the future, the use of this procedure could play an important role in the evaluation of patients with BE. Considering that staining for p53 is technically simple, economical, and quick, and the materials required are available to most pathology laboratories, this method appears to be a firm candidate for application as a biomarker in BE. The authors have shown that it is possible to obtain adequate results for cytometric analysis with small formalin fixed, paraffin embedded biopsies if a strict protocol for the acceptance of tissue samples and/or histograms is observed.

Adenocarcinoma↗
PubMed1998

Phototransformation and proton pumping activity of the 14-fluoro bacteriorhodopsin derivatives.

The photoinduced behavior and proton pumping characteristics of some bacteriorhodopsin (BR) analogs with fluorinated chromophores (all-trans 14-fluorinated [14-F] retinal and 13-cis 14-F retinal) derived from wild type (WT) and D96N mutant BR were investigated. These analogs were characterized using spectrophotometry and a highly sensitive electrochemical technique. Similar to the white membrane JW2N, the apomembranes WT ET 1000 and D96N form photoactive pigments with the 14-F chromophores. The resulting analogs have a major absorption band at 588 nm. Red-shifted pigment (lambdamax</=680 nm) has been previously observed as a minor component of the major 587-nm pigment in 14-F BR made with white membrane JW2N. A similar red-shifted pigment is formed under yellow light (lambda>500 nm) only in the 14-F analogs derived from WT ET 1000. The measurements of the photoinduced transformation in 14-F WT analogs show that the photocycle of the major pigment occurs simultaneously with the process in the red region and is partially masked by the formation of the red-shifted species. The 14-F D96N samples have a significantly slower and more complicated photoinduced behavior. Electrochemical measurements show that the photoinduced transformation of the red species is not accompanied by proton transport.

Bacteriorhodopsins↗
PubMed1998

Sublethal damage during cryopreservation of rainbow trout sperm

Although cellular damage during cryopreservation of freshwater fish spermatozoa has been reported in several studies, there is a lack of correlation between this damage and the fertility rates of eggs using postthawed milt. The apparent lack of such correlation may be due to other undetected sublethal cryodamage, which could affect the cell functionality and viability. This may be extremely important for freshwater fish spermatozoa whose ability to fertilize the egg requires dilution in water or hypoosmotic solutions, an hazardous environment for the cells. This study tested the change in cell permeability during cryopreservation, using Hoechst 33258 to assess cell permeability. The permeability of spermatozoa at different times after dilution in several hypoosmotic media were investigated. In the first trial, fresh semen, sperm diluted in freezing media (CPT), and freeze/thawed semen were studied. Three CPT were tested (Me2SO, DMA, and methanol). In the second trial, the addition of egg yolk as a membrane stabilizer was investigated. Samples were frozen at -20 degreesC/min in a programmable cooler and thawed in a 25 degreesC water bath. Dilution in the CPTs slightly increased the susceptibility of cells to damage but freezing/thawing caused a dramatic increase in the fragility of cells, which were killed in a few seconds after their contact with the hypoosmotic solutions. Egg yolk provided a significant protection to the membrane, allowing the cells a greater and more prolonged survival in the fertilization media. Samples frozen with Me2SO displayed the best results. These results are consistent with the achieved fertility rates that demonstrated sublethal cryodamage in the function of the sperm membrane that was not detected by standard procedures. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Response to salvage treatment in recurrent ovarian cancer treated initially with paclitaxel and platinum-based combination regimens.

OBJECTIVE: The aim of this study was to evaluate the response to salvage treatment in recurrent ovarian cancer treated initially with paclitaxel-based chemotherapy. METHODS: A retrospective review of patients with recurrent ovarian cancer treated with surgical debulking and paclitaxel-based chemotherapy was performed. All cases received second-line treatment with a response evaluated by clinical or surgical means. Data analysis was conducted using the SAS statistical package. RESULTS: Fifty cases of advanced stage disease were available for review. Patients received paclitaxel and cisplatin or carboplatin with a 72.0% response rate. The median time to recurrence after primary treatment was 6 months. Second-line treatment included cisplatin or carboplatin (50%), Taxol (10%), or lutetium (22%), an intraperitoneal radiolabeled monoclonal antibody targeted to TAG-72. A 52.0% clinical response to salvage treatment was detected. With a median follow-up of 7 months, 68.0% of patients had experienced recurrence or progression of their disease. The median time to second recurrence was 5 months. Cases sensitive to initial paclitaxel-containing chemotherapy responded to any of the salvage treatments more frequently than chemotherapy-resistant tumors (88.5% versus 11.5%, P < 0.05). CONCLUSIONS: Recurrent ovarian cancer patients initially treated with paclitaxel-based chemotherapy frequently responded to salvage treatment. However, the duration of response was brief, and hospitalization for treatment-related side-effects was common. Tumor response to initial paclitaxel/platinum treatment was predictive of future response to second-line agents. Current salvage therapies appear to provide little benefit in cases of tumors resistant to primary chemotherapy.

Adult↗
PubMed1998

A new assay to asses aneuploidy in human-hamster embryos.

Fluorescent in situ hybridization using three chromosome-specific centromeric human DNA probes was used to analyze the aneuploidy frequency in human-hamster two-cell embryos. With these techniques first mitotic division errors due to the effects of physical or chemical agents on human spermatozoa, such as non-disjunction and anaphase lag, can be easily detected. In control samples the estimated frequency of non-disjunction and anaphase lag was 3.4%. This assay can also detect premeiotic or meiotic errors. We estimated the same frequency (3.4%) for disomy, whereas monosomy was not found.

Aneuploidy↗
PubMed1998

Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphisms: association with early coronary disease.

OBJECTIVE: To examine the association between coronary artery disease and polymorphisms at the angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) genes. METHODS: A total of 181 patients younger than 50 years and 240 controls from the same homogeneous Caucasian population (Asturias, Northern Spain) were genotyped (using polymerase chain reaction) for the ACE insertion/deletion (ACE-I/D) and the AT1R A/C transversion (AT1R-A/C) (3-untranslated region) polymorphisms. RESULTS: The DD-genotype was at a non-significant higher frequency among patients (50%) than in controls (41%). No difference between the two groups was found for the AT1R-genotypes. Distribution of ACE-genotypes according to AT1R-genotypes showed a significant association between ACE-DD and AT1R-CC and early coronary disease. Among the CC patients 58% were DD, compared to 21% among the controls (p = 0.02; OR = 5.32, 95% CI = 1.45, 19.51). We determined the distribution of these genotypes among the hypertensive and non-hypertensive patients. Frequencies of ACE- or AT1R-genotypes did not differ between the two groups. However, we found an interaction between the DD- and CC-genotypes in the group of normotensives. Among the CC patients, 13% of the hypertensives and 75% of the normotensives were DD (p = 0.014). CONCLUSIONS: Our results indicate a synergistic contribution of ACE and AT1R polymorphisms to the risk of coronary artery disease. This gene-gene interaction could have clinical implications. Approximately 2% of individuals in our population are CC + DD, and the genotyping of both polymorphisms could identify those with a high relative risk for coronary artery disease.

Adult↗
PubMed1998

Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors.

Four cyclic-nucleotide phosphodiesterase (PDE) genes belonging to the PDE4 family (PDE4A, 4B, 4C and 4D) have been identified. All four isogenes, including several deletions and alterations of the amino, carboxyl and central catalytic domains, were expressed in insect cells. Lysates were characterised for enzyme activity by using the Km for substrate and the EC50 for activation by the cofactor Mg2+. The catalytic domain alone appears to be sufficient for the normal enzymatic function of PDE4 proteins. Substrate affinity varied by less than 2-fold between catalytic-domain forms of the PDE4A, 4B and 4D isogenes and the long forms (PDE4A5, PDE4B1 and PDE4D3). The affinity for Mg2+ varied by less than 4-fold between long and catalytic-domain forms of PDE4A and 4B. The catalytic-domain form of PDE4D, however, had a 12-fold lower affinity for Mg2+ that was restored by including a portion of the amino-terminal domain, upstream conserved region-2 (UCR2). This result suggests that the Mg2+-binding site of PDE4D involves the UCR2 region. Inhibition of the PDE4 proteins by synthetic compounds is apparently affected differently by the domains. For PDE4B, the catalytic domain is sufficient for interactions with the inhibitors studied: IBMX, trequinsin, rolipram, TVX 2706, RP 73401 and RS-25344. For PDE4D the catalytic-domain form is less sensitive than the long form to inhibition by RS-25344, rolipram and TVX 2706, by 1463-, 11-and 12-fold, respectively. Addition of UCR2 to the catalytic-domain form of PDE4D restored all the lost sensitivities. The catalytic-domain form of PDE4A showed a reduced inhibitor affinity with RS-25344 and TVX 2706 by 77- and 90-fold, respectively. Both catalytic-domain and long forms of PDE4 isogenes interacted with equal affinity with the non-specific inhibitors IBMX and trequinsin, as well as the very potent PDE4-specific inhibitor RP 73401. Other potent and specific PDE4 inhibitors, such as rolipram, RS-25344 or TVX 2706, appear to utilize non-catalytic domain interactions with PDE4D and 4A to supplement those within the catalytic domains. These observations suggest a different relation between amino and catalytic domains in PDE4D relative to PDE4B. We therefore propose a model to illustrate these isogene-specific PDE4 domain interactions with substrate, inhibitors and the co-factor Mg2+. The model for PDE4D is also discussed in relation to changes in the activation curve for Mg2+ and sensitivity to RS-25344 that accompany phosphorylation of the long form by protein kinase A.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Molecular characterization of the PK-LR gene in pyruvate kinase deficient Spanish patients. Red Cell Pathology Group of the Spanish Society of Haematology (AEHH).

The PK-LR gene has been studied in 12 unrelated patients with red cell pyruvate kinase deficiency and hereditary nonspherocytic haemolytic anaemia (CNSHA). The entire codifying region of the R-type PK gene and the flanking intronic regions were analysed by single-stranded conformation polymorphism (SSCP) followed by direct sequencing of abnormal DNA. 10 different mutations were identified in 22/24 alleles at risk. Eight of these were missense mutations that caused the following single amino acid changes: G514C (172Glu-Gln), G1010A (337Arg-Gln), G1015C (339Asp-Gln), T1070C (357Ile-Thr), C1223T (408Thr-Ile), G1291A (431Ala-Thr), C1456T (486Arg-Trp) and G1595A (532Arg-Gln). Two were nonsense mutations: G721T (241Glu-Stop) and C1675T (559Arg-Stop). 7/22 alleles demonstrated the same C1456 --> T mutation. The study of the polymorphic site at nucleotide (nt) 1705 performed in all cases disclosed a 1705 C/C mutation in 10 and a 1705 A/C mutation in three. This is the first report on the presence of several different L-type PK gene mutations within Spanish population. Furthermore, from the PK gene mutations found, six were unique and not previously described (1015C, 1070C, 1223T, 1291A, 1595A and 1675T) and one (C1456T) seems to be predominant in Spain. Interestingly, no case with the 1529A mutation commonly found in Northern European populations was present here.

Adolescent↗