Biomedical subjects
E Douek
Publications and source records attributed to E Douek.
In situ hybridisation analysis of a homogeneously staining region at 11q23-24 in an acute myeloid leukaemia (M5) using yeast artificial chromosomes.
An example of a homogeneously staining region (hsr), occurring in an acute myeloid leukaemia (M5) on chromosome 11 in the region of bands q23-q24, has been analysed. In situ hybridisation using yeast artificial chromosome (YAC) DNA demonstrated that the amplification did not include the CD3 gene cluster and did not affect the human trithorax gene known to be disrupted by translocations at 11q23. In contrast, the amplification was shown to include the sequence D11S543 which has been previously mapped to chromosome band 11q24. High resolution analysis using confocal microscopy allowed the individual amplicons to be visualised, and it was shown that the hsr consisted of an 8-fold amplification of the region surrounding the probe D11S543. From previous estimates of human chromosome size it was possible to calculate that the hsr was composed of amplicons approximately 10 megabases in length. It was concluded that the region amplified did not extend as far as the translocation breakpoints occurring at 11q23 in acute leukaemias.
Intracranial germ cell tumours: I. Experience with platinum based chemotherapy and implications for curative chemoradiotherapy.
The results of treatment with platinum based combination chemotherapy in ten patients with intracranial germ cell tumours (GCT) are presented. Two patients, treated for relapse within the central nervous system (CNS), attained partial responses of short duration. One patient with systemic relapse was successfully salvaged with chemotherapy. Seven patients received primary chemotherapy, six of whom received a 'CNS friendly' regimen consisting of vincristine, etoposide, carboplatin (VEJ) prior to craniospinal axis (CSA) irradiation. Three complete and three partial responses, and one patient with stable disease, were seen prior to irradiation. All seven patients are alive and remain disease-free at a median time of 12 months after treatment. Current treatment policy for germinomas attaining complete response to two courses of VEJ is a lowered CSA dose prescription, while non-germinomatous germ cell tumours (NGGCT) receive standard total dose CSA irradiation.
The generation of DNA probes to chromosome 11q23 by Alu PCR on small numbers of flow-sorted 22q- derivative chromosomes.
A strategy for the isolation of DNA probes from small numbers of flow-sorted human chromosomes has been developed. A lymphoblastoid cell line carrying the 22q- derivative chromosome product of the constitutional t(11;22) translocation was used as the source of chromosomes. Synthetic oligonucleotide primers, based on the consensus Alu sequence, were used to amplify inter-Alu sequence from 500 flow-sorted 22q- derivative chromosomes. The amplified sequences were cloned into a plasmid vector by blunt-end ligation, yielding clones with inserts in the range of 400 to 1000 bp. Approximately 70% of these clones hybridized to human DNA as single-copy probes. To identify clones derived from chromosome 11, the library was screened with a heterogeneous probe prepared by Alu-PCR amplification from the DNA of a somatic cell hybrid containing one homology of chromosome 11. All the positive clones found were mapped to within the q23-q25 region of chromosome 11 known to be translocated onto the 22q- derivative chromosome. Further mapping studies showed that most of these probes (7/8) lay between the breakpoints for the t(4;11) translocation of acute lymphocytic leukemia and the t(11;22) of Ewing sarcoma. Thus, the use of Alu-PCR on the small derivative chromosome 22q- has provided a greatly enriched source of probes to region 11q23, a part of the genome that is currently of great interest. This approach will be particularly appropriate to small numbers of chromosomes when high specificity rather than total representation is required.
Screening for deafness in children.
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Platinum-based chemotherapy for recurrent CNS tumours in young patients.
Twenty nine patients (median age 12 years) with a CNS tumour, received platinum-based chemotherapy for assessable disease. In 23 patients there was an objective response with improvement lasting for a median duration of 11 months. There was little difference in the response to cisplatinum or carboplatin therapy. The response rates in specific disease groups were: medulloblastoma 8/10, two with a complete response (CR) and six with a partial response (PR); ependymoma 1/5 PR; pineal retinoblastoma 5/5 with three CR and two PR; primitive neurectodermal tumours (PNET) 2/2 PR and pineal germ cell tumours 6/6 with four CR and two PR. It is concluded that platinum-based chemotherapy has a beneficial effect on CNS tumours of the CNS, especially medulloblastoma, ectopic intracranial retino-blastoma and pineal germ cell tumours.
Sensorineural deafness.
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Workshop: direct electrical stimulation of the inner ear for the relief of tinnitus.
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Workshop: cochlear implants in children.
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Speech pattern element stimulation in electrical hearing.
A sensation of hearing is provided for the otherwise totally deaf adult by the use of an electrode arrangement, placed external to the cochlea, which provides only larynx frequency speech pattern information. This is normally obtained by acoustic analysis and is presented so that, although its pattern is preserved, its physical form is matched to the patient's auditory capacity. Speech-receptive improvement has been shown using interactive synthetic speech techniques, video-recorded lipreading tests, and interactive conversational-type presentations. Speech production skills are also enhanced by self-monitoring, and examples of voice range improvement and jitter reduction are given. The particular electrode system used is especially suitable for promontory stimulation in adult patients without a tympanic membrane. The work as a whole is relevant, however, to the design of other conservative prostheses for both deaf adults and children.
Clinical aspects of extracochlear electrical stimulation.
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Classification of tinnitus.
Classification in general serves a number of purposes. In relation to tinnitus there are particular problems because the cause in only rarely known and the mechanism is not known at all. This means that firm classifications tend to be misleading and serve little purpose other than to delude the doctor and the patient. The aim in this paper therefore is to examine the various ways in which information (whether scientific or clinical) about tinnitus can be organized so as to help diagnosis, management or research towards recognition of the fundamental abnormalities. Attempts at classification based on the site of the lesion and on speculation about its cause are described. Classification is analysed according to (1) patients' own reports, (2) doctors' clinical observations, (3) various techniques of measurement, (4) associated phenomena and (5) results of treatment. From these various aspects a pattern emerges which, though incomplete, at least exposes rather than obscures the gaps in our knowledge.
Cochleo-vestibular correlates of tinnitus: tinnitogram.
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Development surveillance at 8 months.
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A new approach to the cochlear implant.
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Effects of incubator noise on the cochlea of the newborn.
The possible effects of incubator noise on the hearing of premature babies have long been debated. The type of hearing loss found in 12 low-birthweight children was examined; and the variable noise level in regularly used incubators was measured. This noise, applied to guinea pigs continuously during their second week after birth, was shown histologically to destroy a proportion of the sensory cells in the cochlea. Adult guinea pigs, however, were not vulnerable in this way. The conclusion is that there is definite circumstantial evidence of the damaging effect of many incubators on the hearing of premature infants.