Characterization of inflammatory bowel disease in Colombia: Results of a national register. / Caracterización de la enfermedad inflamatoria intestinal en Colombia: resultados de un registro nacional.

AIM: To determine the clinical, sociodemographic, and treatment characteristics of inflammatory bowel disease (IBD) in a Colombian population register. METHODS: A descriptive, analytic, observational, cross-sectional, multicenter study on patients with IBD from 17 hospital centers in 9 Colombian cities was conducted. RESULTS: A total of 2,291 patients with IBD were documented, 1,813 (79.1%) of whom presented with ulcerative colitis (UC), 456 (19.9%) with Crohn's disease (CD), and 22 with IBD unclassified (0.9%). The UC/CD ratio was 3.9:1. A total of 18.5% of the patients with UC and 47.3% with CD received biologic therapy. Patients with extensive UC had greater biologic therapy use (OR = 2.78, 95% CI: 2.10-3.65, p = 0.000), a higher surgery rate (OR = 5.4, 95% CI: 3.5-8.3, p = 0.000), and greater frequency of hospitalization (OR = 4.34, 95% CI: 3.47-5.44, p = 0.000). Patients with severe UC had greater biologic therapy use (OR = 5.04, 95% CI: 3.75-6.78, p = 0.000), a higher surgery rate (OR = 8.64, 95% CI: 5.4-13.78, p = 0.000), and greater frequency of hospitalization (OR = 28.45, 95% CI: 19.9-40.7, p = 0.000). CD patients with inflammatory disease behavior (B1) presented with a lower frequency of hospitalization (OR = 0.12, 95% CI: 0.07-0.19, p = 0.000), a lower surgery rate (OR = 0.08, 95% CI: 0.043-0.15, p = 0.000), and less biologic therapy use (OR = 0.26, 95% CI: 0.17-0.41, p = 0.000). CONCLUSION: In Colombia, there is a predominance of UC over CD (3.9:1), as occurs in other Latin American countries. Patients with extensive UC, severe UC, or CD with noninflammatory disease behavior (B2, B3) have a worse prognosis.

Espectro mutacional de la distrofia muscular de Duchenne en España: estudio de 284 casos / Mutational spectrum of Duchenne muscular dystrophy in Spain: Study of 284 cases

Introducción: La distrofia muscular de Duchenne (DMD) es una enfermedad neuromuscular grave que afecta a uno de cada 3.500 varones nacidos y sigue un patrón de herencia ligada al cromosoma X. En esta enfermedad se observa una ausencia total de la distrofina, generalmente debida a mutaciones en el gen DMD, que altera la pauta de lectura y en torno al 80% de los casos son debidos a deleciones y duplicaciones de uno o más exones. Métodos: Se han revisado 284 casos de varones diagnosticados genéticamente de DMD entre los años 2007 y 2014. Estos pacientes provienen de 8 hospitales españoles de referencia que cubren la mayor parte del territorio español. Para la identificación de las mutaciones se realizaron las técnicas de reacción en cadena de la polimerasa multiplex, MLPA y secuenciación. Resultados: Los pacientes con DMD presentan en su mayoría grandes deleciones (46,1%) o grandes duplicaciones (19,7%) en el gen de la distrofina. El restante 34,2% corresponde al conjunto de mutaciones puntuales, destacando las sustituciones nucleotídicas tipo nonsense que aparecen en la mitad de los casos. Este estudio permitió identificar 23 nuevas mutaciones en DMD: 7 grandes deleciones y 16 mutaciones puntuales. Conclusiones: El algoritmo de diagnóstico genético aplicado por los centros participantes es el más adecuado para genotipificar a los pacientes con DMD. La especificidad genética de las distintas terapias en desarrollo pone de manifiesto la importancia de conocer la mutación de cada paciente, siendo un 38,7% de ellos susceptibles de participar en los ensayos clínicos actuales (AU)

Introduction: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMD patients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons. Methods: We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations. Results: Most of these DMD patients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations. Conclusions: The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials (AU)

Mutational spectrum of Duchenne muscular dystrophy in Spain: Study of 284 cases. / Espectro mutacional de la distrofia muscular de Duchenne en España: estudio de 284 casos.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMD patients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons. METHODS: We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations. RESULTS: Most of these DMD patients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations. CONCLUSIONS: The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials.

Artrodesis tibiotalocalcánea con placa humeral bloqueada / Tibiotalocalcaneal arthrodesis using a humeral locking plate

Objetivo. Describir los resultados obtenidos en la artrodesis tibiotalocalcánea (TTC) con placa humeral bloqueada. Métodos y materiales. Estudio descriptivo observacional, retrospectivo tipo serie de casos, entre enero de 2007 y diciembre de 2013 en el Hospital Militar Central de Bogotá. Se incluyó a pacientes con artrosis TTC sintomática diagnosticada tanto clínica como radiológicamente tratados mediante artrodesis TTC con placa humeral bloqueada con seguimiento mínimo de 6 meses. Resultados. Un total de 35 pacientes: 7 (20%) mujeres y 28 (80%) hombres. Edad promedio 36,3 años (19,77). Etiología: 74% con artrosis de origen postraumático, en la mayoría de los casos, secundaria a heridas por arma de fragmentación y heridas por proyectil de arma de fuego; neuropáticas 20%. El injerto utilizado fue autógeno en 13 casos y combinado en 14 casos, con un tiempo de fusión promedio de 4,37 meses. Respecto a complicaciones, se presentó retraso en la consolidación en 3 casos e infección del sitio operatorio en 4. La puntuación postoperatoria promedio en la escala AOFAS fue: 66,7/100 puntos con un puntaje en la Escala Visual Análoga del dolor de 2,35. Conclusión. La artrodesis TTC con placa humeral bloqueada es una adecuada opción para la fijación de este tipo de artrodesis con una baja tasa de complicaciones y con resultados postoperatorios satisfactorios en cuanto a mejoría de dolor y consolidación (AU)

Objective. To describe the results of tibiotalocalcáneal arthrodesis (TTC) using a humeral locking plate. Methods and materials. A retrospective, observational study was conducted between January 2007 and December 2013 in the Hospital Militar Central de Bogotá. The study included patients with symptomatic osteoarthritis diagnosed clinically and radiologically, and who underwent TTC arthrodesis using a humeral locking plate with a minimum follow up of 6 months. Results. The total number patients was 35, of whom 7 (20%) were women and 28 (80%) men, with a mean age 36.3 years (19.77). Aetiology: 74% with post-traumatic arthritis, most of them secondary to gunshot wounds and fragmentation weapons, and neuropathic in 20%. An autogenous graft was used in 13 cases, and 14 cases using both, with a mean consolidation time of 4.37 months. Complications include, delayed union in 3 cases, and surgical site infection in 4. The postoperative functionality (AOFAS) mean was 66.7/100 points, with a score of 2.35 on a visual analogue pain scale. Conclusion. TTC arthrodesis using a humeral locking plate is a suitable option for fixing this type of arthrodesis, with a low rate of complications, and postoperative results that revealed satisfactory improvement in pain and consolidation (AU)

[Tibiotalocalcaneal arthrodesis using a humeral locking plate]. / Artrodesis tibiotalocalcánea con placa humeral bloqueada.

OBJECTIVE: To describe the results of tibiotalocalcáneal arthrodesis (TTC) using a humeral locking plate. METHODS AND MATERIALS: A retrospective, observational study was conducted between January 2007 and December 2013 in the Hospital Militar Central de Bogotá. The study included patients with symptomatic osteoarthritis diagnosed clinically and radiologically, and who underwent TTC arthrodesis using a humeral locking plate with a minimum follow up of 6 months. RESULTS: The total number patients was 35, of whom 7 (20%) were women and 28 (80%) men, with a mean age 36.3 years (19.77). AETIOLOGY: 74% with post-traumatic arthritis, most of them secondary to gunshot wounds and fragmentation weapons, and neuropathic in 20%. An autogenous graft was used in 13 cases, and 14 cases using both, with a mean consolidation time of 4.37 months. Complications include, delayed union in 3 cases, and surgical site infection in 4. The postoperative functionality (AOFAS) mean was 66.7/100 points, with a score of 2.35 on a visual analogue pain scale. CONCLUSION: TTC arthrodesis using a humeral locking plate is a suitable option for fixing this type of arthrodesis, with a low rate of complications, and postoperative results that revealed satisfactory improvement in pain and consolidation.

Valoración de la implementación de programa de ahorro de sangre en cirugía ortopédica / Assessment of the introduction of a blood management program in orthopaedic surgery

Objetivo. Describir el impacto de la introducción de un programa de ahorro de sangre (PAS) en las transfusiones, estancias hospitalarias y complicaciones debidas a la artroplastia total de cadera (ATC) y artroplastia total de rodilla (ATR). Material y métodos. Estudio observacional retrospectivo en el Hospital Universitario Araba, de 2006 a 2011. Se recogieron todas las ATR y ATC. La variable principal fue el porcentaje de pacientes transfundidos con sangre alogénica. Como variables secundarias se recogió la media de bolsas transfundidas, transfusiones totales (alogénica y/o autóloga), las complicaciones (totales y específicas), la edad y el sexo de los pacientes, hemoglobina prequirúrgica y al alta y la estancia hospitalaria. Resultados. Se incluyeron un total un total de 825 ATC y 875 ATR. Tanto en ATC (47,6% en 2006 y 30,6% en 2011; p = 0,013) como ATR (33,6% en 2006 y 16,2% en 2011; p < 0,001) se produjo una disminución significativa en las transfusiones alogénicas. Las transfusiones totales también disminuyeron en ATC (65,7% en 2006 y 39,5% en 2011; p < 0,001) y ATR (38,3% en 2006 y 17,2% en 2011; p < 0,001). La estancia disminuyó en ambas cirugías (p = 0,038 en ATC y p < 0,0001 en ATR). En 2006 fue de 9,2 ± 2,9 días en ATC y 11,1 ± 4,7 días en ATR, mientras que en 2011 fue de 8,7 ± 4,2 y 9,5 ± 3,4 días para ATC y ATR respectivamente. Conclusiones. La implementación del PAS, y sus aportaciones consecutivas, ha reducido significativamente el porcentaje de pacientes que requieren transfusiones, tanto alogénicas como autólogas. La estancia media disminuyó aunque no pueda establecerse el impacto del PAS en las mismas (AU)

Objective. To assess the impact of implementing a Patient Blood management program (PBM) on transfusion rates, hospital stay, and complications for total hip arthroplasty (THA) and total knee arthroplasty (TKA). Material and methods. A retrospective, observational study was conducted in Araba University Hospital from 2006 to 2011. All THA and TKA were included. The percentage of patients transfused with allogeneic blood was the primary endpoint. The mean of transfused blood bags, overall transfusion, complications (both overall and specific), patient age and sex, pre-operative and discharge hemoglobin, and hospital stay were recorded. Results. A total of 825 THA and 875 TKA were included. Both THA (47.6% in 2006 and 30.6% in 2011; P = .013) and TKA (33.6% in 2006 and 16.2% in 2011; P < .001) showed a significant decrease of allogeneic transfusion. The overall transfusion rate was also reduced in THA (65.7% in 2006 and 39.5% in 2011; P < .001) and TKA (38.3% in 2006 and 17.2% in 2011; P < .001). Hospital stay was reduced in both types of surgeries (P < .038 in THA and P < .0001 in TKA). In 2006 it was 9.2 ± 2.9 days for THA and 11.1 ± 4.7 days for TKA, whereas in 2011 it was 8.7 ± 4.2 and 9.5 ± 3.4 days for THA and TKA, respectively. Conclusions. Our patient blood management has decreased the percentage of patients that need both allogeneic and autologous transfusion in a statistically significant way. Although the mean hospital stay decreased, the impact of the PBM cannot be established (AU)

Assessment of the introduction of a blood management program in orthopaedic surgery.

OBJECTIVE: To assess the impact of implementing a Patient Blood management program (PBM) on transfusion rates, hospital stay, and complications for total hip arthroplasty (THA) and total knee arthroplasty (TKA). MATERIAL AND METHODS: A retrospective, observational study was conducted in Araba University Hospital from 2006 to 2011. All THA and TKA were included. The percentage of patients transfused with allogeneic blood was the primary endpoint. The mean of transfused blood bags, overall transfusion, complications (both overall and specific), patient age and sex, pre-operative and discharge hemoglobin, and hospital stay were recorded. RESULTS: A total of 825 THA and 875 TKA were included. Both THA (47.6% in 2006 and 30.6% in 2011; P=.013) and TKA (33.6% in 2006 and 16.2% in 2011; P<.001) showed a significant decrease of allogeneic transfusion. The overall transfusion rate was also reduced in THA (65.7% in 2006 and 39.5% in 2011; P<.001) and TKA (38.3% in 2006 and 17.2% in 2011; P<.001). Hospital stay was reduced in both types of surgeries (P<.038 in THA and P<.0001 in TKA). In 2006 it was 9.2±2.9 days for THA and 11.1±4.7 days for TKA, whereas in 2011 it was 8.7±4.2 and 9.5±3.4 days for THA and TKA, respectively. CONCLUSIONS: Our patient blood management has decreased the percentage of patients that need both allogeneic and autologous transfusion in a statistically significant way. Although the mean hospital stay decreased, the impact of the PBM cannot be established.

PLP1 gene analysis in 88 patients with leukodystrophy.

Pelizaeus-Merzbacher disease (PMD) is caused in most cases by either duplications or point mutations in the PLP1 gene. This disease, a dysmyelinating disorder affecting mainly the central nervous system, has a wide clinical spectrum and its causing mutations act through different molecular mechanisms. Eighty-eight male patients with leukodystrophy were studied. PLP1 gene analysis was performed by the Multiplex Ligation-dependent Probe Amplification technique and DNA sequencing, and, in duplicated cases of PLP1, gene dosage was completed by using array-CGH. We have identified 21 patients with mutations in the PLP1 gene, including duplications, short and large deletions and several point mutations in our cohort. A customized array-CGH at the Xq22.2 area identified several complex rearrangements within the PLP1 gene region. Mutations found in the PLP1 gene are the cause of PMD in around 20% of the patients in this series.

Fluid-percussion brain injury induces changes in aquaporin channel expression.

Edema, the accumulation of excess fluid, is a major pathological change in the brain that contributes significantly to pathology and mortality after moderate to severe brain injury. Edema is regulated by aquaporin (AQP) channels which transport water across cellular membranes. Six AQPs are found in the brain (1, 3, 4, 5, 8, and 9), and previous studies have found that AQP4 is regulated after traumatic brain injury (TBI). To further understand how AQPs contribute to brain edema, we investigated whether expression of AQP1, 3, and 9 are also regulated after TBI. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury (FPI) or sham surgery. After induction of FPI, the injured, ipsilateral parietal cortex and hippocampus were dissected and analyzed by Western blotting. We observed a small decrease in AQP3 and 4 levels at 7 days after FPI in the ipsilateral, parietal cortex. Both AQP1 and 9 significantly increased within 30 min post-injury and remained elevated for up to 6 h in the ipsilateral, parietal cortex. Aqp1 and 9 mRNA levels were also significantly increased at 30 min post-FPI. Administration of an AQP1 and 4 antagonist, AqB013, non-significantly increased brain water content in sham, non-injured animals, and did not prevent edema formation 24 h after trauma in either the parietal cortex or hippocampus. These results indicate that Aqp1 and 9 mRNA and protein levels increase after moderate parasagittal FPI and that an inhibitor of AQP1 and 4 does not decrease edema after moderate parasagittal FPI.

Efectos de la intercambiabilidad de fentanilo transdérmico / Effects of the interchangeability of transdermal fentanyl products

Introducción: el uso de medicamentos genéricos es una práctica cada vez más frecuente, encaminada fundamentalmente al control del gasto sanitario. Los genéricos, al serbio equivalentes con la marca original, en general son intercambiables. No obstante, hay excepciones con los medicamentos de margen terapéutico estrecho. En el caso de los opiáceos potentes, y concretamente del fentanilo transdérmico, se cuestiona la intercambiabilidad de la prescripción inicial por parte de otros médicos o farmacéuticos, ya que podría incidir en un cambio en la analgesia o en la aparición de efectos secundarios y modificar la seguridad del fármaco para un determinado paciente. Material y métodos: se han revisado las comunicaciones recibidas en nuestra unidad del dolor de pacientes previamente controlados con una marca específica de fentanilo (en todos los casos Durogesic®) que fueron cambiados a otra presentación de fentanilo transdérmico por un médico distinto al prescriptor inicial o en la propia oficina de farmacia. Resultados: en un período de 2 meses se recibieron 20 comunicaciones de pérdida o disminución de la analgesia o de la presencia de efectos secundarios, previamente inexistentes bajo el tratamiento con Durogesic®, tras el cambio por una especialidad genérica de fentanilo transdérmico. Conclusión: sin entrar a discutir la política del uso de genéricos, consideramos que dada la potencia de fentanilo y los posibles cambios en la concentración plasmática al intercambiar una presentación por otra, la intercambiabilidad sólo debería realizarse bajo el control del médico que inició el tratamiento o por el médico responsable del paciente, al objeto de mantener la analgesia conseguida y evitar la aparición de efectos adversos (AU)

Introduction: the use of generic drugs is becoming increasingly wide spread, a practice mainly aimed at controlling health expenditure. Because generic drugs are bioequivalent with the original make, these products are generally interchangeable. Nevertheless, drugs with a narrow therapeutic margin are exceptions to this rule. In the case of potent opioids, and specifically, of transdermal fentanyl, the interchangeability of the initial prescription by other physicians or by pharmacists is questionable, since substitution could result in a change in analgesia or in the development of adverse effects, compromising the safety of the drug in individual patients. Material and methods: we reviewed the reports received in our pain unit of patients previously controlled with a specific brand of fentanyl (Durogesic® in all patients) who were switched to another brand of transdermal fentanyl by a physician other than the physician initially prescribing the drug or in the pharmacy. Results: in a 2-month period, we received 20 reports of loss of analgesic effect or of the presence of adverse effects, which were absent under Durogensic® treatment, after’s witching this brand for a generic transdermal fentanyl product. Conclusion: irrespective of the policy of generic drug use and given the potency of fentanyl and the possible changes in plasma concentration when one brand is changed to another, we believe that, to maintain analgesic effect and avoid the development of adverse effects, any change should be authorized by the physician originally prescribing the drug or by the physician responsible for the patient’s care (AU)

Domain interactions in the yeast ATP binding cassette transporter Ycf1p: intragenic suppressor analysis of mutations in the nucleotide binding domains.

The yeast cadmium factor (Ycf1p) is a vacuolar ATP binding cassette (ABC) transporter required for heavy metal and drug detoxification. Cluster analysis shows that Ycf1p is strongly related to the human multidrug-associated protein (MRP1) and cystic fibrosis transmembrane conductance regulator and therefore may serve as an excellent model for the study of eukaryotic ABC transporter structure and function. Identifying intramolecular interactions in these transporters may help to elucidate energy transfer mechanisms during transport. To identify regions in Ycf1p that may interact to couple ATPase activity to substrate binding and/or movement across the membrane, we sought intragenic suppressors of ycf1 mutations that affect highly conserved residues presumably involved in ATP binding and/or hydrolysis. Thirteen intragenic second-site suppressors were identified for the D777N mutation which affects the invariant Asp residue in the Walker B motif of the first nucleotide binding domain (NBD1). Two of the suppressor mutations (V543I and F565L) are located in the first transmembrane domain (TMD1), nine (A1003V, A1021T, A1021V, N1027D, Q1107R, G1207D, G1207S, S1212L, and W1225C) are found within TMD2, one (S674L) is in NBD1, and another one (R1415G) is in NBD2, indicating either physical proximity or functional interactions between NBD1 and the other three domains. The original D777N mutant protein exhibits a strong defect in the apparent affinity for ATP and V(max) of transport. The phenotypic characterization of the suppressor mutants shows that suppression does not result from restoring these alterations but rather from a change in substrate specificity. We discuss the possible involvement of Asp777 in coupling ATPase activity to substrate binding and/or transport across the membrane.

Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in thirteen Spanish families.

We have determined the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT; HPRT1) deficiency in eight Lesch-Nyhan patients and in five partially HPRT deficient patients with mild to severe neurologic symptoms. Eight of these thirteen mutations have not been previously described. HPRT Zaragoza II (a GG insertion in exon 2), HPRT Murcia (an AG deletion in exon 4), HPRT Asturias (a A deletion in exon 4) and HPRT Cartagena (a A insertion in exon 6) cause a frame-shift resulting in a premature stop codon. HPRT Sevilla is a splice-site mutation resulting in exon 8 skipping in the HPRT mRNA. HPRT Huelva, Madrid II and Zaragoza I are point mutations that result in single amino-acid changes in the mutated HPRT protein (118G-->A, G40R; 143G-->A, R 48 H; 397G-->A, V133 M, respectively). Three mutations have been previously described in unrelated families, and two mutations have been already published. All mutations that resulted in truncated proteins corresponded to patients with the Lesch-Nyhan phenotype. Characterization of the HPRT mutation allowed us to make carrier detection in 33 women and prenatal diagnosis in two fetuses. Hum Mutat 15:383, 2000.

Functional domain analysis of the yeast ABC transporter Ycf1p by site-directed mutagenesis.

The yeast cadmium factor (Ycf1p) is a vacuolar protein involved in resistance to Cd(2+) and to exogenous glutathione S-conjugate precursors in yeast. It belongs to the superfamily of ATP binding cassette transporters, which includes the human cystic fibrosis transmembrane conductance regulator and the multidrug resistance-associated protein. To examine the functional significance of conserved amino acid residues in Ycf1p, we performed an extensive mutational analysis. Twenty-two single amino acid substitutions or deletions were generated by site-directed mutagenesis in the nucleotide binding domains, the proposed regulatory domain, and the fourth cytoplasmic loop. Mutants were analyzed phenotypically by measuring their ability to grow in the presence of Cd(2+). Expression and subcellular localization of the mutant proteins were examined by immunodetection in vacuolar membranes. For functional characterization of the Ycf1p variants, the kinetic parameters of glutathione S-conjugated leukotriene C(4) transport were measured. Our analysis shows that residues Ile(711), Leu(712), Phe(713), Glu(927), and Gly(1413) are essential for Ycf1p expression. Five other amino acids, Gly(663), Gly(756), Asp(777), Gly(1306), and Gly(1311), are critical for Ycf1p function, and two residues, Glu(709) and Asp(821), are unnecessary for Ycf1p biogenesis and function. We also identify several regulatory domain mutants in which Cd(2+) tolerance of the mutant strain and transport activity of the protein are dissociated.

[Myotonic dystrophy: DNA instability in monozygotic twins]. / Distrofia miotónica: inestabilidad del ADN en gemelas monocigóticas.

INTRODUCTION: Myotonic dystrophy is an autosomal dominant hereditary disorder with variable expression, associated with expansion of the CTG triplet on the gene which codifies myotonia situated on chromosome 19q. We present an unusual case of myotonic dystrophy in a pair of monozygotic twin sisters, determination of CTG expansion in lymphocytes of members of their family and in their father's spermatozoids. CLINICAL CASE: The patients presented the phenomenon of anticipation of paternal transmission with an expansion of triplet CTG of lymphocyte DNA in a range of 300-1,400 identical repetitions in both. DNA of the paternal lymphocytes and spermatozoids showed a similar expansion of 75 repetitions. CONCLUSIONS: CTG expansion is not due to previous expansion of DNA in the paternal gametes but to instability of DNA in the cellular mitoses following formation of the zygote.

Electroretinogram in Duchenne/Becker muscular dystrophy.

The authors studied all cases with dystrophinopathy consecutively reviewed between May 1995 and December 1996 by means of electroretinography (ERG), which was recorded using skin eyelid electrodes and with standard flash stimulation. This methodology can detect the functional abnormalities associated with dystrophinopathies. The most valuable parameter is the ratio of B-wave amplitude to A-wave amplitude (B/A amplitude ratio), which was greater than 2 in all normal control patients (n = 10) and nondystrophinopathic muscular dystrophy (MD) patients (n = 2). It was less than 2 in 100% (n = 16) of Duchenne muscular dystrophy (DMD) patients (mean ratio 0.73; range 0.4-1.26). It was less than 2 in 71% (n = 7) of Becker muscular dystrophy (BMD) patients (mean ratio 1.12; range 0.88-1.37), and less than 2 in 50% (n = 4) of definitive DMD carriers. Twenty-nine percent of BMD, 50% of DMD carriers, and the only case with asymptomatic dystrophinopathy had normal ratios (greater than 2). The differences between the mean ratios of control, DMD, and BMD groups were statistically significant, all of them with P < 0.001. ERG abnormalities of dystrophinopathies were associated with the more severe muscular phenotype but not with the presence or location of gene deletion. ERG is an easy and simple technique that is useful in cases of suspected dystrophinopathy with a nonconclusive molecular study. It is less useful in patients who are DMD carriers.

[A retrospective study of delta F508 mutation in 22 patients operated on for meconium ileus]. / Estudio retrospectivo de la mutación delta F508 en 22 pacientes intervenidos por ileo meconial.

Meconium ileus is the earliest clinical manifestation of cystic fibrosis. We report 22 neonates with meconium ileus who had clinical evidence of cystic fibrosis. Patients were categorized as simple with inspissated meconium in the ileum with dilated loops proximally or complicated with volvulus or atresia and/or a perforation resulting in meconium peritonitis. Histopathology of the surgically resected specimens of small bowel revealed lesions typical of cystic fibrosis. Genetic studies were performed on all subjects, this study analyzes the usefulness in the detection of delta F508 mutation in formalin-fixed paraffin-embedded tissues obtained from patients with meconium ileus, ten of whom had the delta F508/delta F508 mutation.

Detection of delta F508 cystic fibrosis mutation by polymerase chain reaction from old paraffin-embedded tissues: a retrospective autopsy study.

This study analyzes the usefulness of the polymerase chain reaction technique in the detection of delta F508 mutation in 11- to 25-yr-old formalin-fixed paraffin-embedded tissues obtained from the autopsy of 38 cystic fibrosis patients (nine with meconium ileus). Two different pairs of oligonucleotide primers were used: C16 B/C16 D that amplify 98 and/or 95 bp and FQ1/FQ2 that amplify 50 and/or 47 bp. After two independent rounds of polymerase chain reactions with the two sets of primers, amplification products were obtained in 67.5% of the cases when using C16 B/C16 D primers and in all cases when using FQ1/FQ2 primers. Fifty percent of the chromosomes analyzed in the 29 patients without meconium ileus had the delta F508 mutation, which was present in 13 heterozygous and 8 homozygous patients. The remaining eight cystic fibrosis patients did not carry that mutation. These results are similar to those reported in cystic fibrosis patients from Spain. In the meconium ileus group, we found a higher than expected proportion of delta F508 mutation; all patients showed the delta F508 mutation in at least one chromosome, seven patients (77.8%) being homozygous and two (22.2%) heterozygous. Present results indicate that delta F508 mutation can be detected by polymerase chain reaction in old paraffin-embedded tissues when appropriate primers are used.(ABSTRACT TRUNCATED AT 250 WORDS)