Factores de riesgo y protección de la conducta antisocial en adolescentes / Risk and protective factors for antisocial behavior used by adolescents

Existe un amplio consenso entre los investigadores y el público en general acerca de la naturaleza multicausal de la conducta antisocial. Cualquier abordaje preventivo y/o de intervención de estas conductas debe asentarse necesariamente en la identificación y evaluación de cuáles son los factores de riesgo responsables del inicio y el mantenimiento de las mismas. Es necesario realizar una integración de los diferentes factores implicados, tanto ambientales como individuales (factores psicológicos y de socialización) para apreciar la idoneidad de un abordaje multidimensional de los determinantes de la conducta antisocial en adolescentes. Se discuten, además, las implicaciones preventivas de la revisión realizada para la población adolescente escolar y en riesgo (AU)

Marcadores bioquímicos de cromosomopatía durante el embarazo / Biochemical marked of chromosomopathy during pregnancy

La edad materna como único criterio se utilizó para seleccionar las gestaciones de alto riesgo de aneuploidía en los inicios de la amniocentesis para diagnóstico prenatal. La introducción del cribado bioquímico de segundo trimestre (alfafetoproteína + hCG) permitió en la década de 1990 duplicar la detección prenatal del síndrome de Down del 30 al 65 por ciento, manteniendo la misma tasa de falsos positivos, según han mostrado los amplios estudios prospectivos poblacionales. Aumentar hasta el 90 por ciento los diagnósticos parece estar a nuestro alcance si se combina la translucencia nucal con los marcadores bioquímicos de primer trimestre (PAPP-A+ hCG) (AU)

Responsabilidad por lesiones prenatales. Fundamento, Wrongful Life y tendencias. (Especial atención al derecho suizo) / Responsibility for prenatal injuries. Bases, wrongful life and trends

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Chromosomal changes pattern and gene amplification in T cell non-Hodgkin's lymphomas.

T cell non-Hodgkin's lymphomas are a heterogeneous group of lymphomas with poor prognosis, and whose genetic alterations are not well understood. Comparative genomic hybridization (CGH) is a technique that allows the identification of DNA imbalances without cytogenetic studies. We have studied 37 samples from 29 T cell non-Hodgkin's lymphomas (25 peripheral and four lymphoblastic lymphomas) by CGH in order to detect DNA sequence copy number changes of putative importance in the biology and prognosis of these neoplasms. We detected abnormal CGH profiles in 16/27 (59%) of samples at diagnosis, a ratio that increased to 66% (23/37) when we included the relapsed samples. The most common recurrent changes were gains related to the X chromosome, either the whole chromosome or partially the Xq26-27 bands (19%). Other recurrent changes included gains of bands 9q34, gains of chromosomes 17, 19, and 20, and complete or partial deletions of chromosome 13 (10%). Cancer-related genes located at Xq26-28 region were analyzed by Southern blot and fluorescence in situ hybridization (FISH). Low level amplification of some of these genes was detected by this technique confirming the results obtained by CGH in this region. The detection of abnormal CGH profiles in these T cell lymphomas could have clinical implications. Patients with abnormal CGH profiles showed significant associations with advanced stage of disease, overexpression of P53, and higher proliferative index.

Genes and inheritance.

The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in healthcare practice. It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic genetics. This article provides the oncology nurse with an overview of basic genetic concepts, including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, and the multifactorial basis underlying the common diseases of adulthood. Normal gene structure and function are introduced and the biochemistry of genetic errors is described.

[Preimplantation genetic diagnosis. The first experiences in Denmark]. / Praeimplantations genetisk diagnostik. De første erfaringer i Danmark.

INTRODUCTION: Preimplantation genetic diagnosis (PGD) is a possible alternative to prenatal diagnosis, whereby families with serious inherited diseases can avoid having children with the disease. The genetic diagnosis is performed on embryos before implantation and therefore implies IVF. Hence, PGD offers the possibility of transferring embryos without disease, thereby avoiding termination of pregnancy owing to an affected fetus. MATERIAL AND METHODS: Activities at the Centre for Preimplantation Genetic Diagnosis at Aarhus University Hospital since its opening in February 1999 are described. The fluorescent in situ hybridisation (FISH) technique was used for sex selection (hemophilia A and Duchenne's muscular dystrophy) and translocations. The polymerase chain reaction (PCR) was used for cystic fibrosis. RESULTS: Of 20 PGD cycles started, 15 were successful in terms of transference of healthy or carrier embryos. A positive pregnancy test was found after six of 15 embryo transfers (40%) with two subsequent clinical pregnancies. CONCLUSIONS: The present pregnancy rates with PGD are comparable to those following IVF; the clinical pregnancy rate may seem low, but the cycle numbers are small. Preimplantation genetic diagnosis seems to be a realistic alternative for selected genetic diseases, in cases where the couple find abortion unacceptable.

[Problems posed by the diagnosis and prenatal management of facial clefts]. / Problèmes posés par le diagnostic et la prise en charge prénatale des fentes faciales.

OBJECTIVE: To identify the difficulties in relation to prenatal diagnosis of cleft lip and/or palate. To provide useful clue to the clinician in order to evaluate prognosis and for prenatal management of this malformation. PATIENTS AND METHODS: Retrospective study of all cases managed in our fetal medicine unit between January 1991 and December 1999. During this study period 64 cases of fetal cleft lip and/or palate were retrospectively reviewed. From June 1995, all cases were prospectively recorded, giving us the opportunity to compare the performance of three ultrasound signs for associated secondary cleft palate. RESULTS: The mean gestational age at diagnosis was 26 weeks. Associated ultrasound abnormalities were detected in 42% of cases. Chromosome analysis was performed in all fetuses with associated ultrasound findings and in 39% of fetuses with isolated facial clefts. All fetuses with isolated cleft were chromosomally normal, whereas 15 of the 26 with additional abnormalities had chromosomal defects. Prospective assessment of three ultrasound signs of associated secondary cleft palate was considered possible in 57% of facial clefts. Sensitivity of these signs was respectively 78% (interruption of the secondary palate midline linear echo in a sagittal view), 87% (abnormal oro-nasopharyngeal fluid flow with color Doppler imaging) and 31% for ancillary signs (amniotic fluid excess and non-visualized fetal stomach) for the prediction of associated cleft palate. Only the absence of the three signs to rule out secondary cleft palate. CONCLUSION: Prenatal diagnosis of cleft lip and/or palate must draw attention to associated sonographic malformations. When cleft lip and/or palate is isolated, amniocentesis is recommended apart from selected cases. Secondary palate involvement is difficult to ascertain during pregnancy.

[Detection of submicroscopic chromosome abnormalities by comparative genomic hybridization]. / Påvisning af submikroskopiske kromosomfejl med komparativ genomisk hybridisering.

INTRODUCTION: The purpose was to detect chromosome abnormalities in dysmorphic and mentally retarded individuals with normal karyotypes by means of comparative genomic hybridisation (CGH). MATERIAL AND METHODS: One hundred and forty-four individuals with normal karyotype underwent CGH analysis with a new detection technique where fixed limits are replaced by dynamic standard reference intervals. This method provides improved resolution and thereby detects minor chromosome abnormalities. RESULTS: Fifteen minor abnormalities (10%) and one trisomy 9 mosaic were found. Eleven were interstitial deletions or duplications, which cannot be detected by screening with other cytogenetic techniques. Three were terminal deletions or duplications and one was a terminal unbalanced translocation. DISCUSSION: CGH analysis with dynamic standard reference intervals is a new objective and quantitative method, which is suitable for screening for small chromosome abnormalities that can not be detected by conventional chromosome analysis. The method is recommended for use in the investigation of dysmorphic and mentally retarded individuals, in whom abnormalities are not found by ordinary karyotyping.

Translocaciones cromosómicas en los linfomas no-Hodking (Parte II) / Chromosomal translocations in non-Hodking`s lymphomas. Part II

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Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family.

OBJECTIVE: To describe an unusual kindred with adult-onset ataxia and thalamic lesions detected by brain MRI. METHODS: The authors characterized clinical, laboratory, and pathologic features of the disease and sought linkage to previously recognized ataxia loci. RESULTS: Two sisters and a brother developed progressive ataxia, dysarthria, mild cognitive impairment, and sensorimotor neuropathy at age 30, combined with epilepsy in one sibling. MRI showed symmetric thalamic lesions, changes in brainstem gray matter, and white matter changes in the cerebellum. Autopsy in one of the patients revealed neuronal degeneration with a peculiar vacuolar change in thalamus, probably representing transsynaptic degeneration in response to deafferentation. Neuronal and secondary tract degeneration was observed in the spinal cord, cerebellum, and brainstem suggesting a spinocerebellar degeneration. The disorder appears to be transmitted as an autosomal recessive trait. Genetic and sequence analysis of the FRDA gene and comprehensive laboratory examinations excluded Friedreich's ataxia and other similar recessive diseases. CONCLUSION: Adult-onset recessive ataxia with bilateral thalamic lesions in this family may represent a distinct hereditary spinocerebellar ataxia.

Atypical presentation of dopa-responsive dystonia: generalized hypotonia and proximal weakness.

Dopa-responsive dystonia (DRD) is an autosomal dominant disorder typically presenting as dystonia with diurnal variability. Described is an 8-year-old boy who had had waddling gait, generalized hypotonia, and proximal weakness since early childhood. He responded well to low-dose L-dopa. He had a point mutation of the GTP cyclohydrolase I gene. The patient's father and sister had the same mutation but did not have proximal weakness. GTP cyclohydrolase I deficiency can present with hypotonia and weakness.

Genetic imbalances revealed by comparative genomic hybridization in Ewing tumors.

Ewing tumors are characterized by reciprocal translocations involving the EWS gene on 22q12 fused to ETS transcription-factor family members. Little is known about further aberrations contributing to tumor development and progression. Sixty-two frozen tumors with known EWS rearrangements (52 primary tumors, 10 relapses) of ET patients registered in the EICESS protocol were analyzed by comparative genomic hybridization (CGH). The median number of changes in 52 primary and 10 relapsed cases was 2.5 and 5.0 per tumor (P = 0.153). Frequent abnormalities included gains of chromosomes 8, 12, 20, and 1q and losses of 16q and 19q. Neither number nor type of aberration was associated with histology, tumor size, disease stage, tumor localization, or histologic tumor response to chemotherapy. Among the 52 primary tumors, 26 with Type I fusion (EWS exon 7 to FLI1 exon 6) and 26 with other fusion types had a median of 2.0 and 3.0 aberrations per tumor, respectively (P = 0.031). Combinations of gains of chromosomes 8 and 12, gains of chromosome 20, and either gains of 8q or 18q and losses of 16q and 17p frequently occurred. The cumulative overall survival (OAS) was different between 35 patients with <5 aberrations and 13 patients with > or =5 aberrations (P = 0.009). Univariate analysis showed that patients with gains of 1q, 2q, 12, and 20 or losses of 16q and 17p had significantly lower OAS than those without aberrations. By multivariate analysis, loss of 16q (relative risk [RR] = 5.3; P = 0.0006) was an independent prognostic factor.

Aspects of biopsy procedures prior to preimplantation genetic diagnosis.

Today, preimplantation genetic diagnosis (PGD) is offered in over 40 centres worldwide for an expanded range of genetic defects causing disease. This very early form of prenatal diagnosis involves the detection of affected embryos by fluorescent in situ hybridization (FISH) (sex determination or chromosomal defects) or by polymerase chain reaction (PCR) (monogenic diseases) prior to implantation. Genetic analysis of the embryos involves the removal of some cellular mass from the embryos (one or two blastomeres at cleavage-stage or some extra-embryonic trophectoderm cells at the blastocyst stage) by means of an embryo biopsy procedure. Genetic analysis can also be performed preconceptionally by removal of the first polar body. However, additional information is then often gained by removal of the second polar body and/or a blastomere from the embryo. Removal of polar bodies or cellular material from embryos requires an opening in the zona pellucida, which can be created in a mechanical way (partial zona dissection) or chemical way (acidic Tyrode's solution). However, the more recent introduction of laser technology has facilitated this step enormously. Different biopsy procedures at different preimplantation stages are reviewed here, including their pros and cons and their clinical applications. The following aspects will also be discussed: safety of zona drilling by laser, use of Ca2+/Mg2+-free medium for decompaction, and removal of one or two cells from cleavage-stage embryos.

Supernumerary ring chromosomes in dermatofibrosarcoma protuberans may contain sequences from 8q11.2-qter and 17q21-qter: a combined cytogenetic and comparative genomic hybridization study.

Dermatofibrosarcoma protuberans (DFSP) presents with characteristic cytogenetic features such as reciprocal t(17;22)(q22;q13) or, more commonly, supernumerary ring chromosomes containing sequences from chromosomes 17 and 22. Here, we report the identification of a novel abnormality in a 43-year-old woman with DFSP. Cytogenetic analysis of tumor cells showed the presence of a supernumerary ring chromosome as the sole anomaly. Amplification of 8q11.2 approximately qter and 17q21 approximately qter sequences was confirmed by comparative genomic hybridization (CGH); the present case apparently lacked amplification of chromosome 22. To our knowledge, this is the first case indicating that the ring chromosome in DFSP is possibly associated with amplified material from chromosomes 8 and 17.

An hsr on chromosome 7 was shown to be an insertion of four copies of the 11q23 MLL gene region in an HIV-related lymphoma.

A 45-year-old male with AIDS presented with a cecal diffuse large B-cell lymphoma. Cytogenetic and flourescence in situ hybridization (FISH) studies revealed a complex karyotype with multiple aberrations that included a translocation, t(8;14) involving MYC on chromosome 14. This is specific to B-cell lymphomas. There were also frequently observed secondary changes such as chromosome 1 rearrangement leading to trisomy of 1q and loss of tp53 from the deleted chromosome 17. A unique secondary abnormality was an hsr on chromosome 7, which by FISH and SKY investigations was shown to originate from chromosome 11 involving 4 copies of the MLL gene region.

Clonal chromosome rearrangements in hairy cell leukemia: personal experience and review of literature.

Cytogenetic studies in hairy cell leukemia (HCL) are rare. In the present report, cytogenetic investigations were performed on marrow cells obtained from 21 HCL male patients with a mean age of 57 years and active disease. Karyotypic analysis was successful in 18 of the 21 patients, either at diagnosis or in relapse after treatment with IFNa. Clonal chromosome abnormalities were detected in eight of 18 cases. The chromosome most frequently involved in the rearranged karyotypes was chromosome 14. Results are discussed with respect to 79 abnormal HCL cases obtained from an extensive review of the literature from 1978 to 2000.

Aneurysmal bone cyst with chromosomal changes involving 7q and 16p.

An aneurysmal bone cyst was submitted to cytogenetic analysis. The modal chromosome number was 46. The composite karyotype was 40 approximately 48,XY,-Y[4],-6[3],del(7)(q32)[3],-9[3],+12[2],+13[2], inv(16)(p13.1q24)[4],-17[3],-19[4],-20[3][cp13]. The clonal structural changes detected were del(7)(q32) and inv(16)(p13.1q24). The breakpoints involved affected areas to which important genes for cell cycle regulation have been mapped. There is only one report in the literature of three aneurysmal bone cysts presenting clonal karyotypic alterations. The cytogenetic study of the aneurysmal bone cyst reported here showed different results when compared to those previously described in the literature.

Smoking and acute myeloid leukemia: associations with morphology and karyotypic patterns and evaluation of dose-response relations.

This case-control study of tobacco smoking and acute myeloid leukemia (AML), emphasizing specific associations with morphologic and cytogenetic subtypes, comprised smoking histories for 333 cases and 351 controls. Smoking status (ever smokers versus life-long non-smokers) showed no evident effect on AML risk. However, an effect of smoking was indicated at high cumulative smoking doses (pack-years), e.g. 40 pack-years was associated with an odds ratio (OR) of 1.5 [95% confidence interval (CI) 1.0-2.3]. Among morphologic subtypes, the smoking associated OR for acute erythroleukemia was 8.9 (95% CI 1.0-76). No clear associations between smoking and cytogenetic subtypes of AML were observed.