Pion radiotherapy of unresectable soft tissue sarcomas at the Swiss Institute for Nuclear Research

The Swiss Institute for Nuclear Research SIN at Villigen is one of the three centres in the world (LAMPF, Los Alamos; TRIUMF, Vancouver) where pion therapy is possible. A dynamic, tumour conforming spot scan technique for the treatment of deep-seated tumours has been in use since November 1981. With this technique with a favorable integral dose distribution, curative irradiation also of advanced tumours in the retroperitoneum and pelvis is possible. Only at SIN, the treatment of non-resectable soft tissue sarcomas with pions is part of the clinical program. Between 1983 and 1985 totally nine patients were treated, 1/9 with three manifestations, 1/9 with palliative intent. In 20 fractions over five weeks (four fractions a week) total doses of 30 to 36 Gy (90% isodose) were applied. In a follow-up period of eleven to 43 months (median 18 months) only 1/10 tumour manifestations treated with greater than or equal to 30 Gy failed locally. The two-year survival rate (Kaplan-Meier) is 56%. Metastases were the cause of death in 3/5 patients, 1/5 heart disease, 1/5 local tumour progression. Even though 9/11 tumours were located in the retroperitoneum or pelvis, no radiogenic morbidity of the bowel was found. These preliminary results stimulate the intensification of this clinical program. 1986 the same number of patients with non-resectable soft tissue sarcomas was treated as in the whole period 1982 to 1985 before.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Primitive Neuroectodermal Tumors of the Central Nervous System

Controversial issues relating to the pathobiology and classification of central nervous system primitive neuroectodermal tumors (PNETs) have plagued neuropathologists for more than 70 years. Hypotheses advanced in the mid-1920's have remained as fixed concepts in contemporary literature, largely consequent to repetitious support by a small number of neuropathologists despite a growing body of information discrediting these ideas from neuroembryologists, oncologists, neuroscien-tists and pathologists.
Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul-loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.
The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.
Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers.     

Temporal prominence of auditory evoked potentials (N1 wave) in 4-8-year-old children

Cortical auditory evoked potentials (N1 wave) were studied in 24 adults (12 men, 12 women) and 20 children (12 boys, 8 girls; age: 4-8 years). In adults, this wave was recorded with maximal amplitude at frontocentral sites, peaking at about 100 ms poststimulation, whereas in children the auditory response displayed maximal amplitude at the midtemporal sites, with a positive wave at about 100 ms and a large negative wave at approximately 170 ms. Moreover, the modulatory effects of intensity on N1 amplitude were prominent at frontocentral sites in adults and at temporal sites in children. Frontocentral negative response was also recorded in children but was smaller in amplitude and longer in peak latency (around 140 ms) than in adults; responses were of greater amplitude at the frontal site than at the vertex before 6 years of age, whereas the reverse was more often found after this age. These data suggest great differences with age in the neural generators contributing to auditory evoked potentials recorded in the N1 latency range.     

Comparing sulindac with indomethacin for closure of ductus arteriosus in preterm infants

Objectives: A prospective study comparing the efficiacy and side-effects of oral sulindac with intravenous indomethacin in clinically stable preterm infants (<1750 g) requiring non-invasive closure of haemodynamically significant patent ductus arteriosus.
Methodology: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (± 1 week) and birthweight (±100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group.
Results: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment ( P >0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups ( P <0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group.
Conclusions: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental.     

Androgen metabolism in thymus of fetal and adult rats.

Cytochrome P450 (P450) monooxygenases play a role in target tissue metabolic activation of xenobiotics and/or endogenous compounds, such as vasoactive molecules or hormones. Indeed, tissue-specific metabolism of steroids is important in a variety of organs, including thymus, and may alter tissue-specific functions. Steroids have been shown to regulate thymus growth and function, but surprisingly little is known about expression of the responsible enzyme systems in thymus tissue, nor is the thymus-specific biotransformation of testosterone known. We therefore investigated gene and protein expression, total protein content, and enzyme activity of major P450 isoforms and other key steroid-metabolizing enzymes in thymus tissue of adult and fetal rats. We detected 6 beta-hydroxytestosterone (HT), 7 alpha-HT, 16 alpha-HT, 2 alpha-HT, and androstenedione to be major testosterone metabolites in the adult thymus. The high production of 7 alpha-HT and 16 alpha-HT correlated well with the gene and protein expression of CYP2A1/2 and CYP2B1/2 in thymus of adult animals. When compared with fetal thymic tissue, CYP2A1/2, 17beta-hydroxysteroid dehydrogenase isoform 1 (17 beta-HSDH1) and the androgen receptor were 8-, 3-, and 3-fold more highly expressed in adult rats, whereas 17 beta-HSDH2, 17 beta-HSDH3, and 5 alpha-reductase were reduced to 12%, 0%, and 32% of those in fetal thymus. In conclusion, we demonstrated that rat thymus expresses a variety of cytochrome P450 monooxygenases and other steroid-metabolizing enzymes, and it successfully metabolizes testosterone. Changes of the underlying steroid-metabolizing enzyme systems may aid in understanding the role of androgens in altering biological functions of the thymus.     

A systematic review investigating psychosocial aspects of egg sharing in the United Kingdom and their potential effects on egg donation numbers

This review aims to provide an up-to-date knowledge of the psychosocial aspects of egg donation from the perspectives of the egg share donor and their recipient. It explores the motives, experiences and attitudes of egg sharers and their views towards donor anonymity and disclosure. Conclusions are made on how these findings can guide clinical practice and improve egg sharing numbers. A systematic search of peer-reviewed journals of four computerized databases was undertaken. Eleven studies were included in the review. Psychosocial aspects towards donation were positive from the egg share donor and recipient. Concerns raised were whether participating in the egg sharing scheme would impact on their success rates, as well as frustration expressed by a minority regarding the lack of knowledge of egg sharing outside of fertility clinics. The 2005 legislative changes in the UK have not caused the anticipated dramatic decrease in egg donation; however, oocyte donation still falls short of demand. Egg sharing provides a practical option for more patients to access IVF, whilst also providing more donor oocytes. Improved information provision will result in greater awareness of egg sharing, with the potential to recruit more donors and meet the needs of recipients currently on long waiting lists.     

Brain Metabolic Abnormalities Associated with Developmental Venous Anomalies

BACKGROUND AND PURPOSE:Developmental venous anomalies are the most common intracranial vascular malformation and are typically regarded as inconsequential, especially when small. While there are data regarding the prevalence of MR imaging findings associated with developmental venous anomalies, FDG-PET findings have not been well-characterized.MATERIALS AND METHODS:Clinical information systems were used to retrospectively identify patients with developmental venous anomalies depicted on MR imaging examinations who had also undergone FDG-PET. Both the MR imaging and FDG-PET scans were analyzed to characterize the developmental venous anomalies and associated findings on the structural and functional scans. Qualitative and quantitative assessments were performed, including evaluation of the size of the developmental venous anomaly, associated MR imaging findings, and characterization of the FDG uptake in the region of the developmental venous anomaly.RESULTS:Twenty-five developmental venous anomalies in 22 patients were identified that had been characterized with both MR imaging and FDG-PET, of which 76% (19/25) were associated with significant metabolic abnormality in the adjacent brain parenchyma, most commonly hypometabolism. Patients with moderate and severe hypometabolism were significantly older (moderate: mean age, 65 ± 7.4 years, P = .001; severe: mean age, 61 ± 8.9 years, P = .008) than patients with developmental venous aberrancies that did not have abnormal metabolic activity (none: mean age, 29 ± 14 years).CONCLUSIONS:Most (more than three-quarters) developmental venous anomalies in our series of 25 cases were associated with metabolic abnormality in the adjacent brain parenchyma, often in the absence of any other structural abnormality. Consequently, we suggest that developmental venous anomalies may be better regarded as developmental venous aberrancies.

Adevelopmental venous anomaly (DVA) is a transparenchymal vein of greater than usual size into which coalesces a network of smaller veins, a configuration described as a caput medusa. DVAs may drain into either the superficial or deep venous systems and may occur in the cerebrum, cerebellum, brain stem, and spinal cord. DVAs are the most common intracranial vascular malformation, with a reported incidence of 2.6%.^1,2 The mechanism of DVA formation is still controversial. The term “developmental venous anomaly” was first coined by Lasjaunias et al³ to emphasize their belief that these are embryologic variants of venous drainage rather than true vascular anomalies.Brain parenchymal lesions have been widely reported in association with DVAs, with abnormalities apparent on angiography,⁴ CT⁵ and MR structural imaging,^6–8 and functional imaging methods such as perfusion and diffusion-weighted imaging.^9–12 Several case reports further exemplify how DVAs can be associated with clinical pathologies such as hemorrhagic transformation, ischemic complications, and epileptogenic foci.^13–16 Recent studies also indicate the possible role of DVAs in the formation of cavernous malformations.⁹ These findings suggest that the clinical significance of abnormal brain anatomy and activity near a DVA is uncertain and has yet to be accurately evaluated. Furthermore, our clinical experience has revealed metabolic abnormality associated with DVAs, as determined by FDG-PET. These findings led us to the hypothesis that the metabolic activity in brain parenchyma in the region of a DVA is abnormal. In this study, we sought to better understand metabolic activity in the region of DVAs as assessed by FDG-PET.