RESUMO
Ultrasound activated resorbable pin osteosynthesis (UARPO) has recently shown favourable results in operations on children suffering for craniosynostosis. However, data on complications coming with this new technique in children suffering from craniosynostoses are scarce and have only been assessed retrospectively so far. It has been the aim of the present study to prospectively follow up children undergoing craniosynostosis surgery with a focus on complications related to UARPO materials. Ten pediatric patients (3 female/7 male) were operated due to craniosynostosis at an average age of 9.1±3.8 months using UARPO (SonicWeld/Resorb-X, KLS Martin, Tuttlingen, Germany). Clinical followup evaluations were carried out 1, 3, 6, 9, 12 and 18 months after surgery according to signs of local infection, stability of the remodeled cranial vault and the palpability of the osteosynthesis material. If secondary surgery was necessary, the indication was documented and evaluated by histological and wound smear examinations. No intra-operative or postoperative complications during the inpatient period occurred. 3 patients needed secondary operation due to a localized chronic swelling at the former incision site which developed 3, 9 and 12 months after the operation. Histological examinations yielded a giant cell formation surrounding the resorbable materials in all cases. Additionally, the wound smear showed a bacterial infection in one site. The current prospective study is the first in the field. It reveals a high percentage of delayed foreign body reactions with UARPO, bearing the need of secondary surgery. It seems that this high complication rate found in the present prospective study may weigh out the advantages of UARPO.
Assuntos
Implantes Absorvíveis/efeitos adversos , Craniossinostoses/cirurgia , Fixadores Internos/efeitos adversos , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/instrumentação , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/cirurgia , Criança , Feminino , Seguimentos , Reação a Corpo Estranho/complicações , Reação a Corpo Estranho/cirurgia , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/etiologia , Estudos ProspectivosRESUMO
We report the cloning and characterization of the entire AFX gene which fuses to MLL in acute leukemias with a t(X;ll)(q13;q23). AFX consists of two exons and encodes for a protein of 501 amino acids. We found that normal B- and T-cells contain similar levels of AFX mRNA and that both the MLL/AFX as well as the AFX/MLL fusion transcripts are present in the cell line and the ANLL sample with a t(X;11)(q13;q23). The single intron of the AFX gene consists of 3706 nucleotides. It contains five simple sequence repeats with lengths of at least 12 bps, a chi-like octamer sequence (GCA/TGGA/TGG) and several immunoglobulin heptamer-like sequences (GATAGTG) that are distributed throughout the entire AFX intron sequence. In the KARPAS 45 cell line the breakpoints occur at nucleotides 2913/2914 of the AFX intron and at nucleotides 4900/4901 of the breakpoint cluster region of the MLL gene. The AFX protein belongs to the forkhead protein family. It is highly homologous to the human FKHR protein, the gene of which is disrupted by the t(2;13)(q35;q14), a chromosome rearrangement characteristic of alveolar rhabdomyosarcomas. It is noteworthy that the t(X;11)(q13;q23) in the KARPAS 45 cell line and in one acute nonlymphoblastic leukemia (ANLL) disrupts the forkhead domain of the AFX protein exactly at the same amino acids as does the t(2;13)(q35;q14) in case of the FKHR protein. In addition, the 5'-part of the AFX protein contains a conserved hexapeptide motif (QIYEWM) that is homologous to the functionally important conserved hexapeptide QIYPWM upstream of the homeobox domain in Hox proteins. This motif mediates the co-operative DNA binding of Pbx family members and Hox proteins and, therefore, plays an important role in physiologic and oncogenic processes. In acute leukemias with a t(X;11)(q13;q23), this hexapeptide motif is separated from the remaining forkhead domain within the AFX protein. The predicted amino acid sequence of AFX differs significantly from the partial AFX protein sequence published previously (Genes, Chromosomes and Cancer, 1994, 11, 79-84). This discrepancy can be explained by the occurrence of two sequencing errors in the earlier work at nucleotide number 783 and 844 (loss of a cytosine residue or guanosine residue, respectively) that lead to two reading frame shifts.
Assuntos
Proteínas Sanguíneas/genética , Cromossomos Humanos Par 11 , Genes/genética , Íntrons/genética , Leucemia/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Cromossomo X , Doença Aguda , Sequência de Aminoácidos , Sequência de Bases , Proteínas de Ciclo Celular , Clonagem Molecular , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead , Histona-Lisina N-Metiltransferase , Humanos , Leucemia-Linfoma de Células T do Adulto/genética , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , Células Tumorais CultivadasRESUMO
Some chromosomal translocations involved in the origin of leukemias and lymphomas are due to malfunctions of the recombinatorial machinery of immunoglobulin and T-cell receptor-genes. This mechanism has also been proposed for translocations t(4;11)(q21;q23), which are regularly associated with acute pro-B cell leukemias in early childhood. Here, reciprocal chromosomal breakpoints in primary biopsy material of fourteen t(4;11)-leukemia patients were analysed. In all cases, duplications, deletions and inversions of less than a few hundred nucleotides indicative of malfunctioning DNA repair mechanisms were observed. We concluded that these translocation events were initiated by several DNA strand breaks on both participating chromosomes and subsequent DNA repair by 'error-prone-repair' mechanisms, but not by the action of recombinases of the immune system.
Assuntos
Dano ao DNA , Reparo do DNA , Leucemia de Células B/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Adolescente , Adulto , Sequência de Bases , Linfoma de Burkitt/etiologia , Linfoma de Burkitt/genética , Criança , Pré-Escolar , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Proteínas de Ligação a DNA/genética , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Leucemia de Células B/etiologia , Masculino , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , Proteínas Nucleares/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Fatores de Elongação da TranscriçãoRESUMO
Derivative chromosomes of 40 patients diagnosed with t(4;11) acute lymphoblastic leukemia (ALL) were analysed on the genomic DNA level. Chromosomal breakpoints were identified in most cases within the known breakpoint cluster regions of the involved MLL and AF4 genes. Due to our current knowledge of the primary DNA sequences of both breakpoint cluster regions, specific features were identified at the chromosomal fusion sites, including deletions, inversions and duplications of parental DNA sequences. After separation of all t(4;11) leukemia patients into two age classes (below and above 1 year of age), the analysis of chromosomal fusion sites revealed significant differences in the distribution of chromosomal breakpoints and led to the definition of two hotspot areas within the MLL breakpoint cluster region. This may point to the possibility of different age-linked mechanisms that were leading to t(4;11) chromosomal translocations.
Assuntos
Quebra Cromossômica , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Proteínas de Ligação a DNA/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes , Fatores de Transcrição , Adulto , Criança , Inversão Cromossômica , Reparo do DNA/genética , Histona-Lisina N-Metiltransferase , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , Translocação GenéticaRESUMO
Chromosomal rearrangements constitute a significant feature of leukemogenesis and malignant transformation in general. Nucleotide patterns in the immediate vicinity of the break point may provide important information about the underlying causalities, eg illegitimate recombination events mediated by topoisomerase II, Alu repeats, or VDJ recombinase. In order to facilitate the determination of those DNA patterns, we developed a new fingerprint approach. In a first step, two DNA fragments were independently amplified by long distance PCR: the genomic region carrying the break point and the normal nonrearranged counterpart. Subsequently, both PCR products were digested with restriction enzymes, end-labelled with a fluorescent dye, and subjected to high resolution polyacrylamide gel electrophoresis. By comparing the restriction patterns of the rearranged and the nonrearranged PCR fragments, the break points could be easily localized within a size range coverable by a single sequencing reaction. Finally, the exact DNA sequence across the break point was directly determined. The 'fingerprint' technique is fast, reliable and enables the assay of multiple samples in parallel.
Assuntos
Impressões Digitais de DNA/métodos , DNA/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Sequência de Bases , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 9 , DNA/metabolismo , Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Genoma Humano , Histona-Lisina N-Metiltransferase , Humanos , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , Reação em Cadeia da PolimeraseRESUMO
In this project we developed a social support and health education intervention meant to answer whether or not a program of this kind, within the present medical system, can improve perinatal outcomes. A multicenter randomized controlled trial was conducted in four Latin American countries. In Mexico, the project was carried out in a third level obstetric hospital. Patients were screened between the 15th and 22nd week of gestation. Inclusion criteria were factors associated with high risk of low birthweight. A total of 620 women were recruited, randomized and followed up during pregnancy and up to the 40th day post partum. Women in the intervention group were visited four to six times during pregnancy, could use a telephone hot line and a consultation service. A poster and a pamphlet meant to reinforce health education were handed out in the first visit. A "guided tour" for women at the end of pregnancy was organized periodically. Outcomes were measured in both groups at the 36th week of gestation, post partum and 40 days after delivery. Neonatal outcomes were obtained by blind interviewers from the clinical records. Neither in the multicenter nor in the Mexican sample were we able to modify the incidence of low birthweight and prematurity. However, in Mexico we obtained positive effects on birthweight and gestational age in the whole sample and in some specific strata. These results strongly suggest the convenience of replicating the study in Mexico.
Assuntos
Promoção da Saúde/métodos , Bem-Estar do Lactente , Cuidado Pré-Natal/métodos , Apoio Social , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido Pequeno para a Idade Gestacional , GravidezRESUMO
To compare the predictive value of "cognitive map" and "working memory" theories of hippocampal function, the performance of rats with dorsal hippocampal lesions was compared to that of control rats in a series of experiments. In Experiment I, experimental rats learned a spatial alternation task with normal ease, but in Experiment II, they were significantly impaired on an elevated 8-arm radial maze. In Experiment III, the performance of the same experimental and control rats was compared on two versions of a 16-arm enclosed radial maze. In the first version, carpet inserts served as cues to mark eight unbaited arms and each of the remaining arms contained one food pellet. While both experimental and control rats successfully avoided the set of cued arms, experimental rats reentered uncued baited arms more frequently than did control rats. In the second version no intramaze cues were provided, but the spatial distribution of baited and unbaited arms remained the same as that used in the first version. In this uncued version, experimental rats both entered unbaited arms and reentered baited arms more frequently than did control rats, i.e., they were impaired in both "reference" and "working" memory. These findings are compatible with the hypothesis that hippocampal lesions result in an impaired capacity to form cognitive maps but they are not compatible with the working memory hypothesis. Furthermore, twelve separate evaluators classed experimental rats as using fewer mapping and more orientation strategies than control rats in the 8-arm maze.