Diagnóstico de la infección por Treponema pallidum en pacientes con sífilis temprana y neurosífilis mediante reacción de la polimerasa en cadena / Laboratory diagnosis of Treponema pallidum infection in patients with early syphilis and neurosyphilis through a PCR-based test

Syphilis is a sexually transmitted disease caused by Treponema pallidum. The diagnosis is based mainly in clinical presentation and non-specific assays. PCR-based diagnosis has been suggested as an attractive alternative method. The aim of this study was the validation of a PCR-based test for the diagnosis of early syphilis (ES) and neurosyphilis (NS). Clinical samples of mucocutaneous lesions and cerebrospinal fluid (CSF) specimens from patients previously diagnosed for ES and NS respectively using an enlarged gold standard, were tested by PCR. The reaction was done using primers targeting the tpN47gene. Twenty out of 21 mucocutaneous samples from patients diagnosed with ES were positive by PCR, with a clinical sensitivity of 95 percent. Four out of 8 CSF samples from patients previously diagnosed with NS were positive by PCR, with a clinical sensitivity of 50 percent. The clinical specificity for both ES and NS was 100 percent. The PCR sensitivity and specificity for mucocutaneous samples allowed us to implement this assay in our laboratory for routine diagnosis. Although the sensitivity of the PCR in CSF was low, it may be useful to support clinical diagnosis.

La sífilis es una enfermedad de transmisión sexual producida por Treponema pallidum, cuyo diagnóstico se realiza presuntivamente basándose en aspectos clínicos y análisis de especificidad limitada. La reacción de la polimerasa en cadena (RPC) ha sido planteada como una alternativa diagnóstica de mayor sensibilidad y especificidad. El objetivo de este trabajo fue validar una RPC para el diagnóstico de sífilis temprana (ST) y neurosífilis (NS). Se utilizaron muestras de lesiones muco-cutáneas y de LCR de pacientes con sospecha de cursar ST y NS respectivamente, previamente diagnosticados, utilizando un estándar de oro ampliado. La RPC fue realizada con partidores dirigidos al gen tpN47. De las 21 muestras de pacientes con ST, la RPC resultó positiva en 20, lo que resulta en una sensibilidad clínica de 95 por ciento. De las 8 muestras de pacientes con NS, la RPC resultó positiva en 4, obteniéndose una sensibilidad clínica de 50 por ciento. La especificidad clínica para ST y NS fue de 100 por ciento. La excelente sensibilidad y especificidad de la RPC para muestras muco-cutáneas permitió la exitosa implementación de este análisis en nuestro laboratorio para el diagnóstico de rutina. Si bien la sensibilidad de la RPC en LCR es baja, es muy útil para apoyar el diagnóstico clínico.

[Epidemiologial profile of invasive candidiasis in intensive care units at a university hospital]. / Perfil epidemiológico de la candidiasis invasora en unidades de pacientes críticos en un hospital universitario.

UNLABELLED: Invasive candidiasis (IC) epidemiology has changed in critically ill patients and limited data are available in Chile. OBJECTIVE: To describe the epidemiological and microbiological profile of IC in critically ill patients. METHODS: Observational prospective study conducted from October 2001 to August 2003 in critically ill adults with suspected or confirmed IC. RESULTS: 53 patients met criteria for IC, finding 18 (33.9%) candidemias, 22 (41.5%) disseminated IC, and 13 (24.5%) local IC. We identified 8 (44.4%) C. albicans and 10 (55.6%) non-albicans Candida in candidemias. C. tropicalis was the predominant non-albicans species (27.7%). An 88.8 % of Candidas sp recovered in candidemias were fluconazole susceptible. Overall hospital mortality was 24.5%. Mortality in candidemia was significantly lower than in disseminated IC (16.6 vs 31.8%, p = 0.02). CONCLUSIONS: A higher proportion of non-albicans Candida was observed in candidemias from critically ill patients. However, most of these strains were fluconazole susceptible. A lower overall mortality was observed in candidemias.

Perfil epidemiológico de la candidiasis invasora en unidades de pacientes críticos en un hospital universitario / Epidemiologial profile of invasive candidiasis in intensive care units at a university hospital

Invasive candidiasis (IC) epidemiology has changed in critically ill patients and limited data are available in Chile. Objective: To describe the epidemiological and microbiological profile of IC in critically ill patients. Methods: Observational prospective study conducted from October 2001 to August 2003 in critically ill adults with suspected or confirmed IC. Results: 53 patients met criteria for IC, finding 18 (33.9 percent) candidemias, 22 (41.5 percent) disseminated IC, and 13 (24.5 percent) local IC. We identified 8 (44.4 percent) C. albicans and 10 (55.6 percent) non-albicans Candida in candidemias. C. tropicalis was the predominant non-albicans species (27.7 percent). An 88.8 percent of Candidas sp recovered in candidemias were fluconazole susceptible. Overall hospital mortality was 24.5 percent. Mortality in candidemia was significantly lower than in disseminated IC (16.6 vs 31.8 percent, p = 0.02). Conclusions: A higher proportion of non-albicans Candida was observed in candidemias from critically ill patients. However, most of these strains were fluconazole susceptible. A lower overall mortality was observed in candidemias.

La epidemiología de candidiasis invasora (CI) ha cambiado, lo cual no ha sido suficientemente estudiado en Chile. Objetivo: Describir el perfil epidemiológico y microbiológico de CI en pacientes críticos. Métodos: Estudio observacional prospectivo entre octubre 2001 y agosto 2003, en pacientes críticos adultos con sospecha o confimnación de CI. Resultados: 53 pacientes cumplieron criterios de CI. De ellos, 18 (33,9 por ciento) tuvieron candidemia, 22(41,5 por ciento) CI diseminada y 13(24,5 por ciento) CI local. Entre las candidemias, hubo 8 C. albicans (44,4 por ciento) y 10 Candida no albicans (55,6 por ciento), predominando C. tropicalis (27,7 por ciento). Un 88,8 por ciento de las candidemias fueron susceptibles a fluconazol. La mortalidad hospitalaria global fue 24,5 por ciento, significativamente menor en pacientes con candidemias vs CI diseminada (16,6 vs 31,8 por ciento, p = 0,02). Conclusiones: Se observó una mayor proporción de Candida no albicans en candidemias de pacientes críticos. Sin embargo, la mayoría de estas cepas fue susceptible a fluconazol. La mortalidad global fue menor en candidemias.

Conceptos básicos sobre el estudio de paternidad / Basic concepts about paternity testing

Nowadays, the analysis of genetic markers is a very important and validated tool for the identification of individuals, and for paternity testing. To do so, highly variable regions of the human genome are analyzed, making it possible to obtain the genetic profle of an individual, and to distinguish between different individuals. The methodology used is basically the same all over the world, consisting in the analysis of 13 to 15 markers. To assign biological paternity the child must have inherited the characteristics from the alleged father in each of the genetic markers analyzed. This analysis achieves a certainty higher than with any other test, which is expressed as the probability of paternity. This probability has to be at least 99.9 percent, but greater probabilities are usually obtained, especially if the mother is included in the analysis. If the characteristics of two or more genetic markers from the alleged father are absent in the child, biological paternity is excluded.

El análisis de marcadores genéticos se ha convertido en una herramienta muy importante y ampliamente reconocida para la identificación de individuos y para el estudio de paternidad. Para esto se estudian distintas regiones del genoma humano que son altamente variables en la población y que permiten obtener el perfil genético y distinguir entre distintos individuos. La metodología que se utiliza es básicamente la misma en todo el mundo y consiste en el análisis de entre 13 a 15 marcadores. La paternidad biológica se asigna cuando el hijo/a presenta las características que debe heredar del presunto padre en cada uno de los marcadores genéticos estudiados. A través de este análisis es posible asignar paternidad con un grado de certeza más alto que con cualquier otro sistema, el que se expresa como probabilidad de paternidad. Esta probabilidad debe alcanzar al menos 99,9 por ciento. Sin embargo, es posible obtener probabilidades mucho más altas, sobre todo si se incluye a la madre en el estudio. Si las características genéticas del supuesto padre están ausentes en el hijo/a en al menos dos marcadores, se excluye la paternidad biológica.

[Genetic tests: definition, methods, validity and clinical utility]. / Tests genéticos: Definición, métodos, validación y utilidad clínica.

The knowledge of the human genome has led to an explosion of available genetic tests for clinical use. The methodologies used in these tests vary widely, allowing the study from chromosomes to the analysis of a single nucleotide. Prior to its use in the clinical setting, these tests should have an evaluation that includes analytical and clinical validation and determination of the clinical utility, as any other tests, including requirements for quality assurance. Recently, the CDC (Centers for Disease Control and Prevention, USA) published a guideline for Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions, covering the pre-analytical, analytical and post-analytical phases of the tests. The document covers the importance of proper selection of tests, the availability of information on the performance of the techniques used, the quality control practices, the training of personnel involved and the report of results, to allow the adequate interpretation, including sensitivity and specificity. Considering that recent advances in genetics have changed and will continue to affect clinical practice, genetic tests must meet quality and safety requirements to enable optimal use of them.

Tests genéticos: Definición, métodos, validación y utilidad clínica / Genetic tests: Definition, methods, validity and clinical utility

The knowledge of the human genome has led to an explosion of available genetic tests for clinical use. The methodologies used in these tests vary widely, allowing the study from chromosomes to the analysis of a single nucleotide. Prior to its use in the clinical setting, these tests should have an evaluation that includes analytical and clinical validation and determination of the clinical utility, as any other tests, including requirements for quality assurance. Recently, the CDC (Centers for Disease Control and Prevention, USA) published a guideline for Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions, covering the pre-analytical, analytical and post-analytical phases of the tests. The document covers the importance of proper selection of tests, the availability of information on the performance of the techniques used, the quality control practices, the training of personnel involved and the report of results, to allow the adequate interpretation, including sensitivity and specificity. Considering that recent advances in genetics have changed and will continue to affect clinical practice, genetic tests must meet quality and safety requirements to enable optimal use of them.

El conocimiento del genoma humano ha dado lugar a un aumento explosivo de los test genéticos disponibles para uso clínico. Las metodologías utilizadas en este tipo de tests son muy variadas, permitiendo desde el estudio de los cromosomas hasta el análisis de una base nucleotídica. Previo a su utilización en el ámbito clínico, estos tests deben tener una evaluación que incluya su validación analítica y clínica y determinación de la utilidad clínica, además de cumplir, como cualquier otro examen, con requisitos para el aseguramiento de la calidad. Recientemente, el CDC (Centersfor Disease Control and Prevention, EE. UU) hapublicado recomendaciones para las buenas prácticas de laboratorio de tests moleculares que se utilizan para el diagnóstico de enfermedades genéticas, que abarcan la fase pre- analítica, analítica y post-analítica. Dentro de éstas destacan: la importancia de la selección adecuada de los tests, la disponibilidad de la información sobre el desempeño de las técnicas utilizadas, las prácticas de control de calidad, la capacitación del personal involucrado y la elaboración de un informe de resultados que permita al clínico interpretarlos adecuadamente, incluyendo sensibilidad y especificidad. Tomando en cuenta que los recientes avances en genética han modificado y seguirán modificando la práctica clínica, los test genéticos deben cumplir con las exigencias de calidady seguridad que permitan su uso óptimo.

[Laboratory alert value reporting by the clinical laboratory at an academic medical network]. / Aviso de valores de alerta por parte del laboratorio clínico en una red de salud universitaria.

BACKGROUND: An alert value is a result suggesting that the patient is at imminent danger unless appropriate remedial actions begin promptly. Report of alert values (AV) by the clinical laboratories has taken special relevance in recent years due to its contribution to patient's care. AIM: To report results of AV informed during 2007 within the Health Network of the Pontificia Universidad Católica de Chile. MATERIAL AND METHODS: Analysis of AV recorded in a centralized database of the laboratories of the health network, between January and December, 2007. RESULTS: Total number of AV was 5.366, which represented 0.3% of total examinations and corresponded mainly to the clinical chemistry area. Potassium levels generated the higher number of AV detected, followed by positive blood cultures. Eighty two percent of AV corresponded to hospitalized patients. The greater number of AV was reported to intermediate and intensive care services. Thirty two percent of AV was informed to the physician or professional in charge of the patient within 5 minutes of obtaining the results and 79% within 30 minutes. CONCLUSIONS: To obtain a real impact on patient management, it is fundamental to shorten the lapse between the obtainment of tests results and the warning, supported on appropriate computerized systems, and to spread the procedure to all personnel involved in patient's care.

Análisis retrospectivo del rendimiento de Amplicor-PCR® para la detección de Mycobacterium tuberculosis en muestras respiratorias y no respiratorias con baciloscopia negativa: A retrospective analysis / Assessment of the Amplicor PCR® for the detection of Mycobacterium tuberculosis in smear negative respiratory and non respiratory specimens

Background: Commercial polymerase chain reaction (PCR) kits are widely accepted for analysis of smear positive respiratory specimens, but the sensitivity is variable for smear negative ones. Objective: To assess the PCR method usefulness in smear negative respiratory and non respiratory specimens. Methods: We compared the PCR results (AMPLICOR MTB test™, Roche) of 235 specimens subjected to culture in Loewenstein-Jensen agar (as the gold standard). Results: 181 (76 percent) were respiratory and 54 (24 percent) extra-respiratory specimens. The sensitivity was 88 percent) and 50 percent>, respectively, specificity and PPV was 100 percent> in both cases. NPV was 99.4 percent> in respiratory specimens and 96.1 percent in non-respiratory specimens. Conclusions: The good performance of this PCR in smear negative respiratory specimens allows the clinician to take decisions based on the result of this exam. In extra-respiratory specimens the contribution is important only when the PCR result is positive.

[Universal or broad-range polymerase chain reaction (PCR): a contribution to the detection and identification of bacteria and fungi in clinical practice]. / "PCR universal o de amplio espectro": un aporte a la detección e identificación de bacterias y hongos en la práctica clínica.

The use of techniques for the detection of nucleic acids such as the polymerase chain reaction (PCR) has had a major impact on microbiological analysis, playing an important role in the clinical laboratory. Most of the techniques currently used are designed for specific detection of a particular microorganism. However, infectious agents can also be identified even if genus or species are unknown, using universal primers to amplify bacterial or fungal DNA and then identify the species by sequence (universal or wide spectrum PCR). This methodology is applied in cultures that are difficult to identify using phenotypic techniques, and more recently it is also being used directly in clinical samples, where the detection and identification of the infectious agent by traditional techniques is difficult or not possible.

Aviso de valores de alerta por parte del laboratorio clínico en una red de salud universitaria / Laboratory alert value reporting by the clinical laboratory at an academic medical network

Background: An alert value is a result suggesting that the patient is at imminent danger unless appropriate remedial actions begin promptly. Report of alert values (AV) by the clinical laboratories has taken special relevance in recent years due to its contribution to patient's care. Aim: To report results of AV informed during 2007 within the Health Network of the Pontificia Universidad Católica de Chile. Material and methods: Analysis of AV recorded in a centralized database of the laboratories of the health network, between January and December, 2007. Results: Total number of AV was 5.366, which represented 0.3 percent of total examinations and corresponded mainly to the clinical chemistry area. Potassium levels generated the higher number of AV detected, followed by positive blood cultures. Eighty two percent of AV corresponded to hospitalized patients. The greater number of AV was reported to intermediate and intensive care services. Thirty two percent of AV was informed to the physician or professional in charge of the patient within 5 minutes of obtaining the results and 79 percent within 30 minutes. Conclusions: To obtain a real impact on patient management, it is fundamental to shorten the ¡apse between the obtainment of tests results and the warning, supported on appropriate computerized systems, and to spread the procedure to all personnel involved in patient's care (RevMéd Chile 2009; 137: 1137-44).

PCR universal o de amplio espectro: Un aporte a la detección e identificación de bacterias y hongos en la práctica clínica / Universal or broad-range polymerase chain reaction (PCR): A contribution to the detection and identification of bacteria and fungi in clinical practice

The use of techniques for the detection of nucleic acids such as the polymerase chain reaction (PCR) has had a major impact on microbiological analysis, playing an important role in the clinical laboratory. Most of the techniques currently used are designed for specific detection of a particular microorganism. However, infectious agents can also be identified even if genus or species are unknown, using universal primers to amplify bacterial or fungal DNA and then identify the species by sequency (universal or wide spectrum PCR). This methodology is applied in cultures that are difficult to identify usingphenotypic techniques, and more recently it is also being used directly in clinical samples, where the detection and identification of the infectious agent by traditional techniques is difficult or not possible.

El uso de técnicas para la detección de ácidos nucleicos como la reacción en cadena de la polimerasa (PCR) ha tenido un gran impacto en el diagnóstico microbiológico, ocupando un lugar importante en el laboratorio clínico. La mayoría de ¡as técnicas en uso han sido diseñadas para la detección específica de un microorganismo. Sin embargo, también es posible identificar el agente etiológico aunque se desconozca la especie o el género, utilizando partidores universales para amplificar el ADN de bacterias y hongos, y luego secuenciar para identificar la especie (PCR universal o de amplio espectro). Esta metodología se aplica en cultivos difíciles de clasificar por técnicas fenotípicas, pero también se ha comenzado a utilizar directamente en muestras clínicas, en las que la detección e identificación del agente infeccioso por técnicas tradicionales resulta difícil o no es posible.

[Presence of metallo beta-lactamases in imipenem-resistant Pseudomonas aeruginosa]. / Presencia de metalo-beta-lactamasas en Pseudomonas aeruginosa resistente a imipenem.

BACKGROUND: Metallo-beta-lactamases (MBL) confer high resistance to carbapenems in Pseudomonas aeruginosa (Psae). They are encoded in mobile elements of different genes (VIM, IMP, SMP, GIM), along with other resistance genes. AIM: To detect the presence of MBL in imipenem resistant Psae strains. MATERIAL AND METHODS: Fifty-nine imipenem resistant Psae strains isolated from January 2004 to August 2005 in a University Clinical Hospital, were included. The presence of MBL was studied by Etest (phenotypic) and genotypic polymerase chain reaction (PCR) methods. To rule out a nosocomial outbreak, MBL positive strains were studied by pulse field gel electrophoresis. RESULTS: The presence of MBL was detected in eleven strains. AH were type VIM and were not clonally related. There was no concordance between phenotypic and genotypic MBL detecting methods. All the strains were also multiresistant. CONCLUSIONS: The presence of MBL was detected in 19% of imipenem resistant Psae strains.

Hiperplasia suprarrenal no clásica, características clínicas y genéticas / Clinical and genetic features of non classical adrenal hyperplasia

Background: The non classical form of congenital adrenal hyperplasia (NCAH) is increasingly recognized inhyperandrogenic patients, with variable phenotypic expression. Aim: To determine the clinical, hormonal, andgenetic characteristics of a group of patients with NCAH. Patients and methods: The medical records of 57NCAH patients were retrospectively reviewed. The diagnosis was established by basal or post-ACTH-stimulation 17-hydroxyprogesterone (17-OHP) levels >7 ng/mL and > 15 ng/mL, respectively. Patients with post-ACTH 17-OHP levels between 10-15 ng/mL, and with one identified allele o without genetic tests, were consideredas heterozygous. Genotyping for 10 mutations was performed by PCR. Results: The average age of diagnosis was 12.4 +/- 0.9 years. Six patients were male. Pubarche and hirsutism were the clinical signs more frequently described in patients below 10 years of age (25/29) and over 10 years of age (11/24), respectively. A basal 17-OHP > 7 ng/mL was observed in 36 patients; the post ACTH 17-OHP was between 10-15 and > 15 ng/mL in 5 and 17 patients, respectively. Genotype analyses were performed in 38 patients. V281L was carried on approximately 68.4 percent of all alleles and 29 percent of patients carried severe mutations. Only one of five possible carrier patients, was diagnosed as NCAH after the genetic test (V281L/ In2splice). Conclusions: Males with NCAH were apparently sub-diagnosed. Pubarche and hirsutism were the more frequently reported signs. The genetic test is complementary in the diagnosis of NCAH. One third of the patients carried a classic mutation and could have an increased risk to have siblings with Classical CAH.

Presencia de metalo-ß-lactamasas en Pseudomonas aeruginosa resistente a imipenem / Presence of metal lo ß-lactamases in imipenem-resistant Pseudomonas aeruginosa

Background: Metallo-ß-lactamases (MBL) confer high resistance to carbapenems in Pseudomonas aeruginosa (Psae). They are encoded in mobile elements of different genes (VIM, IMP, SMP, GIM), along with other resistance genes. Aim: To detect the presence of MBL in imipenem resistant Psae strains. Material and methods: Fifty-nine imipenem resistant Psae strains isolated from January 2004 to August 2005 in a University Clinical Hospital, were included. The presence of MBL was studied by Etest (phenotypic) and genotypic polymerase chain reaction (PCR) methods. To rule out a nosocomial outbreak, MBL positive strains, were studied by pulse field gel electrophoresis. Results: The presente of MBL was detected in eleven strains. AH were type VIM and were not clonally related. There was no concordance between phenotypic and genotypic MBL detecting methods. AH the strains were also multiresistant. Conclusions: The presence of MBL was detected in 19 percent of imipenem resistant Psae strains.

[Bacillary angiomatosis caused by Bartonella quintana in an human immunodeficiency virus positive patient]. / Angiomatosis bacilar por Bartonella quintana en un paciente con infección por virus de inmunodeficiencia humana.

We report the first case of bacillary angiomatosis due to Bartonella quintana affecting a Chilean a HIV positive patient in Chile. He was a 27 years old, heterosexual male, indigent man known to be HIV positive serological status known from September, 2003, under irregular medical control. On April, 2005, he presented a progressive abscess in the frontal region and erythematous papules in the extremities, that extended to face, thorax and mucoses, becoming nodular and violaceous lesions. Bacillary angiomatosis diagnosis was initially sustained on account of the clinical manifestations, and was confirmed by serology and Warthin Starry staining from a skin biopsy. The etiological agent was identified as Bartonella quintana through universal RPC performed from a cutaneous nodule to detect 16S rRNA gen. Azithromycin plus ciprofloxacin was started, besides of anti retroviral therapy antiretroviral, with the lesions being progressively disappearing.

Angiomatosis bacilar por Bartonella quintana en un paciente con infección por virus de inmunodeficiencia humana / Bacillary angiomatosis caused by Bartonella quintana in an human immunodeficiency virus positive patient

We report the first case of bacillary angiomatosis due to Bartonella quintana affecting a Chilean a HIV positive patient in Chile. He was a 27 years old, heterosexual male, indigentman known to be HIV positive serological status known from September, 2003, under irregular medical control. On April, 2005, he presented a progressive abscess in the frontal region and erythematous papules in the extremities, that extended to face, thorax and mucoses, becoming nodular and violaceous lesions. Bacillary angiomatosis diagnosis was initially sustained on account of the clinical manifestations, and was confirmed by serology and Warthin Starry staining from a skin biopsy. The etiological agent was identified as Bartonella quintana through universal RPC performed from a cutaneous nodule to detect 16S rRNA gen. Azithromycin plus ciprofloxacin was started, besides of anti retroviral therapy antiretroviral, with the lesions being progressively disappearing.

Reportamos el primer caso de angiomatosis bacilar por Bartonella quintana en un paciente con infección por VIH en nuestro país. Este corresponde a un hombre de 27 años, heterosexual, indigente, seropositivo para VIH conocido desde septiembre de 2003, en control irregular. En abril de 2005, el paciente desarrolló un aumento progresivo de volumen en la región frontal y aparición de pápulas eritematosas en las extremidades, que luego se extendieron a la cara, tórax y mucosas, tornándose nodulares y violáceas. El diagnóstico de angiomatosis bacilar se planteó inicialmente por el cuadro clínico del paciente, siendo confirmado por serología y tinción de Warthin Starry positiva en la biopsia de piel. El agente causal se identificó como Bartonella quintana por RPC universal para el gen del 16S ARNr de un nódulo cutáneo. Se inició terapia antimicrobiana con azitromicina y ciprofloxacina, además de terapia antiretroviral, con desaparición de las lesiones en forma progresiva.

Mutaciones del gen del receptor 3 del factor de crecimiento de fibroblasto (FGFR3) en pacientes chilenos con talla baja idiopática, hipocondroplasia y acondroplasia / Mutations in the fibroblast growth factor receptor 3 gene (FGFR3) in chilean patients with idiopathic short stature, hypochondroplasia and achondroplasia

Background: Achondroplasia and hypochondroplasia are skeletal dysplasias of autosomal dominant inheritance that represent different degrees of severity of the same pathological entity. Both dysplasias are caused by mutations in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene. In achondroplasia more than 95% of the cases studied to date carry the same mutation (G380R). Hypochondroplasia represents a greater clinical and genetic heterogeneity, possibly being confused with "idiopathic short stature". The N540K mutation has been detected in 50-70% of cases of hypochondroplasia and mutations at the 650 locus in approximately 2.8%. Aim: To assess the frequency of N540K and G380R mutations, and changes at the 650 locus in Chilean patients with idiopathic disproportionate short stature, hypochondroplasia and achondroplasia. Patients and Methods: We studied 21 patients referred for idiopathic short stature, 5 with clinically suspected hypochondroplasia and 4 with achondroplasia. The G1138A, G1138C (G380R), and C1620, C1620A (N540K) mutations and the nucleotide changes at the 650 locus were studied using PCR and restriction analysis of genomic DNA. Results: Three out of five hypochondroplasia patients were heterozygous for the N540K mutation. All of the 4 patients with achondroplasia presented the G1138A mutation. None of these mutations were found in patients with idiopathic short stature. Conclusion: Chilean patients with hypochondroplasia and achondroplasia have the same mutations described in other ethnic groups. The identification of mutations in 3 out of 5 patients with hypochondroplasia shows that this analysis is a useful tool for its diagnostic confirmation. In short stature the molecular study should only be indicated in those cases presenting other clinical and/or radiological features of hypochondroplasia (Rev Méd Chile 2003; 131: 1405-10).

Correlación genotipo fenotipo de un grupo de pacientes con fibrosis quística / Correlation between phenotype and genotype in a group of patients with cystic fibrosis

Background: Cystic fibrosis (CF) is the most common lethal autosomic disease in Caucasians, with a global incidence of 1:3000 newborns. More than 900 mutations have been described, involving the Cystic Fibrosis Transmembrane Regulator (CFTR). The ÆF508 mutation is present in 60 percent of alleles studied worldwide. Aim: To report 25 patients with cystic fibrosis in whom a genetic study was done. Material and methods: Twenty five patients (14 men, aged between 18 months and 25 years) with a diagnosis of cystic fibrosis based on clinical features plus two abnormal sweat tests are reported. The genetic study considered the 20 most common mutations in cystic fibrosis and was done in genomic DNA of peripheral lymphocytes, by polymerase chain reaction. Results: A mutation was found in 75 percent of analyzed alleles. ÆF508 was present in 50 percent of cases (ÆF508/ÆF508 in 8 and ÆF508/other in 11). When ÆF508 was present, pancreatic insufficiency was always a feature and nutritional status was worse. Respiratory involvement was variable, both for homozygous and heterozygous cases. Other severe mutations such as W1282X and G542X were related to clinical manifestations similar to those found in ÆF508 mutation. Diagnosis was made before six months of age in 12 patients. The clinical presentation was meconium ileus and there was a family history of the disease in most cases. The majority of cases of early diagnosis presented severe mutations, but milder respiratory symptoms and lesser nutritional compromise at the time of assessment. Conclusions: Most patients studied had a severe cystic fibrosis mutation, which was associated with more severe respiratory, pancreatic and nutritional involvement. The early diagnosis of the disease, which would allow to improve the prognosis and the quality of life, must be emphasized

Anticuerpos anti-tiroglobulina en el seguimiento de pacientes con cáncer diferenciado de tiroides: ¿marcadores de enfermedad residual o recidivante? / Anti thyroglobulin antibodies in the follow up of patients with differentiated thyroid cancer

Background: Anti thyroglobulin antibodies are present in 25 percent of patients treated for a differentiated thyroid cancer, invalidating thyroglobulin determination. Those patients subjected to total thyroidectomy and free of disease, should reduce the production of these antibodies, due to the lack of antigenic stimulus. Therefore, anti thyroglobulin antibodies could be useful to detect early relapses. Aim: To assess the relationship between anti thyroglobulin antibodies and the evolution of the disease in patients treated for thyroid cancer. Material and methods: Retrospective analysis of 26 patients treated for thyroid cancer with positive anti thyroglobulin antibodies, followed for three years. These were divided in those with or without lymphocytic thyroiditis (19 and 7 respectively). Results: At the first year of follow up, anti thyroglobulin antibody concentration was 401ñ94.9 UI/ml (xñsem) in patients with thyroiditis and 38.9ñ8.9 UI/ml in those without thyroiditis (p < 0.005). During the three years of follow up, no differences in anti thyroglobulin antibodies were observed between patients with or without tumor relapse. Conclusions: Concentration of anti thyroglobulin antibodies was higher in patients with thyroiditis and did not differentiate patients with tumor relapse