Tumor induction by ras and myc oncogenes in fetal and neonatal brain: modulating effects of developmental stage and retroviral dose

Introduction into fetal rat brain cells of a replication-defective retroviral vector harboring v-Ha-ras and v-gag-myc rapidly causes the induction of highly malignant undifferentiated neuroectodermal tumors following transplantation into the brains of syngeneic hosts [Wiestler, et al. (1992) Cancer Res. 52: 3760–3767]. In the present study, we have investigated the modulating effect of the developmental stage of neural target cells and of the dose of the retroviral vector used in the grafting experiments. Exposure of fetal cells from embryonic day (E)12 or E14 produced a 100% incidence of malignant neuroectodermal tumors which led to the death of recipient animals after a median latency period of 32 days. A 100-fold reduction of the virus dose from 2.062×10⁶ to 2.062×10⁴ focus-forming units/ml resulted in a lower tumor incidence of 25%. Of six neural grafts exposed to v-Ha-ras and v-myc at E16, only one showed evidence of tumorigenesis (low-grade astrocytoma and hemangioma). All other transplants were morphologically normal for observation periods of 26 weeks, indicating a marked loss of transforming activity of ras and myc in more advanced stages of brain development. In retrovirus-exposed donor cells which caused the development of neural tumors in recipient rats, malignant transformation was also evident during culture in vitro, usually after 9–12 days. Oncogene complementation was also studied in the newborn rat brain. After microinjection of the retroviral vector into the brain at postnatal day (P)0, P1 and P3, 5 out of 20 animals (25%) developed a total of seven brain tumors. Histopathologically, three of these neoplasms were malignant neuroectodermal tumors which, in contrast to those induced in fetal brain transplants showed evidence of focal glial and/or neuronal differentiation. In addition, we observed one oligodendroglioma, two hemangiomas and a malignant hemangioendothelioma. These data indicate that neural precursor cells and endothelia of the rat brain represent the major target cells for the complementary action of ras and myc and that the use of target cells from later developmental stages (E16 and postnatal) leads to the induction of both primitive and more differentiated neoplasms.These studies were supported by the Fonds zur Förderung der wissenschaftlichen Forschung in Österreich (Erwin Schrödinger fellowship, JO501-MED), by the Swiss National Science Foundation and by the Cancer League of the Kanton of Zürich     

Acoustic rhinometry in pre-school children

Acoustic rhinometry was performed in 35 normal nose-breathing children between 3 and 6 years. The average cross-sectional areas at the nasal valve, at the anterior end of the turbinates, and in the nasopharynx were 0.34±0.06 cm², 0.35±0.08 cm² and 1.37±0.48 cm² respectively. The average minimal cross-sectional area was 0.29±0.06 cm². The minimal cross-sectional area was located at the nasal valve in 14 and at the anterior end of nasal tubinates in 21 of the 35 children. As would be expected, the cross-sectional areas at different sites of the nasal cavity increased with increasing age of the children. But, whereas the minimal cross-sectional area increased by 0.024 cm² per year, the nasopharyngeal cross-sectional area increased by 0.20 cm² per year. No significant differences were found between boys and girls. Measurements of the posterior nasal and nasopharyngeal cross-sectional areas were unreliable, whenever the minimal cross-sectional area was less than 0.2 cm². Furthermore, assessment of the nasopharynx may be difficult because of involuntary movements of the soft palate.     

Location and geometric description of carpal bones in CT images

The carpal regions of ten cadaver extremities were imaged by CT. The images were combined into a 3-dimensional model of the carpus using a technique based on a dynamic programming algorithm to find an optimal estimate of the location of the bone boundaries in the CT images. The resulting set of surface points on each bone was used to compute volumes and principal and antipodal axes for the bones. A spatial coordinate system was established based on the positions of the centroids of three bones in the distal carpal row. The angular orientations of all carpal bones were determined with respect to this system. The principal axes for the same bone among ten wrist specimens proved to be more widely dispersed than the antipodal axes for the same bones. The antipodal axes also correspond more closely to an intuitive notion of the “longest axis” of the bones. We conclude that the antipodal axis is a more reliable and useful measure of bone orientation than the principal axis.     

Results of arthroscopic acromioplasty related to rotator cuff lesions

Summary Seventy-nine patients with a history of the subacromial impingement syndrome were treated by arthroscopic acromioplasty. The results were evaluated with a new scoring system designed to assess subjective symptoms before and after operation. The outcome was related to the pathological lesions of the rotator cuff seen at arthroscopy and graded by our modification of the Neer classification. The overall results were satisfactory in 67%, with men having better results than women. Those with a history of injury did better than those without, and the results in those with partial or total cuff tears were better than those with intact cuffs. Since the state of the cuff affects the result, arthroscopy should precede acromioplasty.

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Résumé Soixante dix-neuf patients, présentant depuis 3.5 ans (±1.8) un syndrome de conflit sousacromial, ont été traités par acromioplastie arthroscopique. Les résultats ont été évalués au moyen d'une nouvelle cotation, mesurant la symptomatologie subjective avant et 17 mois en moyenne après l'intervention chirurgicale. On a étudié le rapport entre ces résultats et la morphologie pathologique de la coiffe des rotateurs, constatée lors de l'arthroscopie et classée conformément à notre version modifiée, décrite précédemment, de la classification de Neer. Les résultats globaux étaient satisfaisants dans 67% des cas. Les résultats étaient nettement meilleurs chez les hommes que chez les femmes. Ils étaient significativement meilleurs chez les patients pour qui la symptomatologie était apparue après un traumatisme violent, de même lorsqu'il existait une rupture totale ou partielle de la coiffe des rotateurs. L'état de la coiffe influence les résultats de l'acromioplastie, pour pouvoir le déterminer il faut pratiquer une arthroscopie préalable.

     

Quantifying how location and dose of botulinum toxin injections affect muscle paralysis

Despite the widespread use of botulinum toxin to treat muscle dystonias, no method exists to quantify muscle paralysis in either human or nonhuman models. In this study we examined how the location, dose, and volume of botulinum injection affects paralysis in the rat tibialis anterior muscle. Paralysis was quantified by electrically stimulating the nerve to the tibialis anterior and then staining sections of the muscle for glycogen. The areas of glycogen-containing fibers represented regions of botulinum action. The results showed that the most important injection technique is to inject botulinum directly into the motor endplate region of a muscle. Injections only 0.5 cm from the motor endplate resulted in a 50% decrease in paralysis. Increases in dose increased paralysis, however, some of that increase was simply due to the increased volume of injection. Thus, delivering toxin in small volumes near the MEP band of a muscle should produce the most effectiveparalysis. © 1993 John Wiley & Sons, Inc.     

Secondary correction of the unilateral cleft nose deformity with an endonasal technique

Summary Malposition of the nasal bone, septum and the alar cartilage are striking features of the unilateral cleft nose deformity. An endonasal technique (the extramucosal) was used in 26 patients, aged 13–38 (median 19), to correct aesthetic and functional problems. Twenty-four patients were secondary and two were tertiary. The patients were followed from 1–9 years. The pathological anatomy of the septum varied considerably, so different types of septoplasties had to be done. In 20 patients, satisfactory aesthetic and functional results were obtained in one operation. Secondary corrections were indicated in six patients. In cases with no gross scarring in or around the alar cartilage, the form and position of this cartilage will be more normal once the alar cartilages have been undermined and the deviation of the nasal bone and the septum is corrected.     

The in vitro fertilisation programme at Tygerberg Hospital and the University of Stellenbosch. Five years' experience, April 1983-January 1988

The results of the in vitro fertilisation programme at Tygerberg Hospital for the period April 1983 to January 1988 are presented. Of the 1117 laparoscopies performed, 825 patients reached the transfer stage. A live-birth rate of 9.3% was achieved. The pregnancy rate after transfer of 4 embryos was 25.9% compared with 15.4% after 2 embryos and 10.8% after 3 embryos (P = less than 0.0001). The multiple pregnancy rate was 2.8% in the group receiving 2 embryos and 11.7% and 10.4% in those receiving 3 and 4 embryos, respectively. Of the 77 successful pregnancies (90 babies), 1 baby died at 34 weeks' gestation as the result of abruptio placentae due to preeclampsia and 1 cot death occurred. The only congenital abnormality encountered was a cleft palate.     

Failure of coconut oil to accelerate psoriasis clearance in narrow-band UVB phototherapy or photochemotherapy

Despite a widely held belief that the use of emollients prior to broad-band UVB irradiation accelerates clearance of psoriasis, only one single-blind controlled study exists in support of this. No similar study has been carried out with photochemotherapy (PUVA) or narrow-band UVB (311–313 nm) phototherapy. As some emollients absorb UV radiation, and thereby inhibit psoriasis clearance, there is a need to identify emollients suitable for pre-irradiation use. Coconut oil may be useful in this respect. In two randomized groups of patients with chronic plaque psoriasis undergoing either routine PUVA(n=14) or narrow-band UVB phototherapy (n=15), a single-blind controlled (half-body) study was undertaken to assess the died of pre-irradiation application of coconut oil. Patients were given PUVA twice weekly, or TL-01 therapy thrice weekly. The initial UV dose was 70% of previously determined minimal phototoxic (MPD) or minimal erythema doses (MED), with 40% incremental steps at each visit (reduced if adverse effects occurred). Psoriasis severity was scored on each side after every three treatments. No significant acceleration of psoriasis clearance was seen in either group. We do not, therefore, recommend the routine use of emollients prior to PUVA or TL-01 therapy when using near erythemogenic irradiation regimens.     

The nature and extent of aggressive behaviour amongst people with learning difficulties (mental handicap) in a single health district

ABSTRACT. This paper describes the method and results of a survey of aggressive behaviour amongst people with learning difficulties. The study was confined to a single health district in the South Western Region of the UK with a general population of about 370000. At the time of the survey, the Handicap Register for the district recorded 1362 people as having a learning difFiculty. The overall prevalence of aggressive behaviour amongst people with learning difficulties for whom base population data was available was 17.6%. The lowest rate was identified amongst day facilities (9.7 %) and the highest in hospitals within the district (38.2%). The prevalence rate amongst those attending schools for children with severe learning difSculties was 12.6%. Proportionately more males than females were reported to present problems of aggressive behaviour. The gender difference appeared to be largely accounted for by the disproportionate number of men identified within day facilities. There was no significant evidence of an association between the person's gender and the presence aggressive behaviour within schools or hospitals. The results indicated that, although physical and verbal aggression were the most frequently reponed behaviours, many of the sample were also said to engage in other forms of challenging behaviour, particularly self-injurious, ritualistic, stereotypical and withdrawn behaviour. The risk of a serious or very serious injury to another person was very low; 0.7% or six people with learning difiSculties firom the district were reponed to be currently presenting such a risk. Similarly, only 2% of the base population (n=18) were reponed to be extremely difficult to manage. The implications of the findings are discussed.