[Imaging of side effects after radiation therapy]. / Nebenwirkungen nach Strahlentherapie in der Bildgebung.

BACKGROUND: Peritumoral normal tissue is inevitably also irradiated during radiotherapy, depending on the location and size of the target volume as well as the cumulative dose. Depending on the temporal course after irradiation acute, subacute, and chronic alterations are described in co-irradiated normal tissue that can be detected by imaging. Radiation damage can be transient or persistent. OBJECTIVE: This article gives an overview of the most important signs of radiation-induced radiogenic alterations to tissue in various organ systems. FINDINGS: Frequent radiation-induced tissue alterations found by imaging are pneumonitis, disturbance of the blood-brain barrier, radionecrosis of brain tissue, radiogenic liver damage, mucositis, colitis, osteitis, osteoradionecrosis and myositis. The combination with systemic chemotherapy or immunotherapy can increase the severity of radiogenic reactions of normal tissue. RECOMMENDATIONS FOR AFTERCARE: The most important differential diagnosis for radiogenic alterations to normal tissue is post-therapeutic tumor recurrence. Besides typical latency periods, location and matching with the radiation field are important differentiation criteria, depending on the tumor biology and the radiation technique. The follow-up schedule should follow the current guidelines and the clinical condition of the patient should be additionally considered. The radiologist needs to be familiar with the typical imaging morphology of radiogenic tissue changes to avoid false interpretation during follow-up investigations.

Bilateral bifid mandibular condyles diagnosed with three-dimensional reconstruction.

Bifid mandibular condyles (BMCs) are rare anomalies. The overwhelming majority of prior reports described their predominantly unilateral occurrence diagnosed by panoramic radiography. We present an even rarer case of bilateral BMC initially identified by panoramic radiography and confirmed with colour-enhanced three-dimensional CT. These images substantiate the theory that the secondary condyles arise from the neck of the mandible (Lopez-Lopez et al. Bifid condyle: review of the literature of the last 10 years and report of two cases. Cianio 2010; 28: 136-140).

Cell analysis with the new Leipzig high-energy ion nanoprobe.

The high-energy ion nanoprobe LIPSION at the University of Leipzig has been in operation since 1998. The ultrastable, 3.5 MV SINLETRON accelerator supplies the H+ or He+ ion beam. A magnetic scanning system moves the focused beam across the sample. At present, a resolution of 41 +/- 4 nm in the low current mode and 300 nm at 5 pA can be achieved. The experimental chamber is equipped with electron-, energy dispersive X-ray-, and particle detectors. They can be used simultaneously to analyse the sample by means of PIXE (particle induced X-ray emission), RBS (Rutherford backscattering), and in the case of thin sections or monolayer samples STIM (scanning transmission ion microscopy). A goniometer allows the application of channeling measurements in single crystals in combination with these methods. In contrast to previous publication describing microbeam facility at LIPSION, the current biomedical research has concentrated on microscopy and tomography on chondrocytes in pig cartilages and fixed single endothelial cells (HUVEC). For the irradiation of single living cells, an external beam facility with irradiation platform, fast beamgate and mini-Petri dishes is under construction.

The growth and development of the Annals of Human Biology: a 25-year retrospective.

The history of the founding in 1958 of the Society for the Study of Human Biology is outlined, and the circumstances in which the Annals of Human Biology began publication in 1974. The contents of the papers published 1974-1997 are reviewed; about 40% concern Population Biology, 40% Auxology and 20% Population Physiology. Some outstanding contributions in the first two of these fields are mentioned. Many consist of groups of papers from an ongoing study: 11 papers from the Otmoor villages study by Harrison and colleagues, and 11 concerning the growth of children in the Zurich Longitudinal Study, by Gasser and colleagues. Papers concerning the analysis of growth data and modelling of the growth curve, especially by Healy, are noted, and papers giving evidence of mini-spurts in growth and the saltation-stasis growth model are recalled. Wilson's papers on catch-up and growth regulation in twins are reviewed; also the contribution to growth-as-a-mirror of social conditions by workers at the Stockholm Institute of Education. The National Study of Health and Growth, led by Rona, contributed 13 papers over 14 years to the Annals, and there were outstanding one-off papers from the National Child Development Study, and the Cuban National Growth Study of 1972, and concerning the secular trend towards greater leg length in Japan, the upward social mobility of the taller of pairs of brothers, the growth of 18th century children in Vienna and Stuttgart and the measurements of 19th century slaves in the USA.

Growth velocity monitoring of the efficacy of different therapeutic protocols in a group of thalassaemic children.

Since intensive chelating therapy for thalassaemic children was introduced, growth rates appear to have diminished. To investigate what factors were responsible we compared velocities of growth in length over a period of 1 year between groups distinguished by different strategies of treatment. Forty-two thalassaemic patients, 30 males aged 4-12 years, and 12 females, 4-10 years old, were assigned from their current treatment into subgroups based upon blood ferritin levels, daily dose of desferrioxamine and urinary zinc levels. CONCLUSION The results confirm that a reduction in desferrioxamine results in greater growth. If blood ferritin is low, the change effect may be greater. Secondly, any zinc deficiency should be treated. The changes in treatment convert a growth velocity of -2 to -3 SDS to a velocity of about -1 SDS.

Somatostatin analog treatment slows growth and the tempo of reproductive maturation in female rhesus monkeys.

The present study tested the hypothesis that a reduction in serum GH during adolescence would result in slower growth and delayed puberty. Skeletal growth and maturation as well as indices of reproductive development were studied in juvenile female rhesus monkeys receiving a constant sc infusion of a somatostatin analog, Sandostatin, at a dose of approximately 4.50 micrograms/kg BW.day (Ssa; n = 6) and in untreated females (Con; n = 6) from 18 months of age through the luteal phase of the second ovulation. Although age at menarche was similar in Con and Ssa females, first ovulation was delayed significantly in Ssa females, such that the interval between menarche and first ovulation was significantly longer in Ssa females. Serum concentrations of GH, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 were reduced in Ssa females, particularly after menarche. Although changes in body weight were similar between Ssa and Con females, growth in height was significantly greater in Con females. Furthermore, peak growth velocity in height occurred at a significantly later age in SSa females, but at a similar degree of skeletal maturity. Serum insulin and glucose levels in response to iv glucose were similar in the two groups; however, fasting levels of serum glucose decreased significantly in both groups with advancing age, but the decrease was greater in Con. During the luteal phase of the first 2 ovulatory cycles, there were diminished serum progesterone in 16.7% (2 of 12) of the Con and 41.7% (5 of 12) of the Ssa females. Serum estradiol was significantly lower throughout the first 2 ovulatory cycles in Ssa females, whereas serum LH and IGF-I were similar to those in Con females. Multiple regression analyses revealed that age at menarche was best predicted from the amount of growth in height before menarche, whereas those females who had higher serum IGF-binding protein-3 levels before menarche had an earlier growth spurt, and those who grew faster had a shorter interval between menarche and first ovulation. These data indicate that treatment with a long-acting somatostatin analog, which produces a relative deficiency in the GH axis, slows growth and delays the tempo of puberty. The data suggest that this delay may be due to a reduction in gonadal sensitivity to LH.

Automatic bone age measurement using computerized image analysis.

In 1992 we described a computer-assisted method for assigning Tanner-Whitehouse RUS skeletal maturity scores to hand-wrist radiographs. An operator positions each epiphysis in turn beneath a video camera, views the image on the computer screen and corrects the position of the radiograph by matching to templates of the TW stages displayed on the screen. The process is then automatic; the computer, not the operator, rates the bone. The image is digitized and then represented by a large number of mathematical coefficients. These coefficients are then compared to those generated by each stage of the TW standards, and the closest match is sought. Since the comparison is quantitative the system produces continuous stage scores instead of the old discrete ones such as B, C, D, etc. Thus in longitudinal data a much smoother progression of skeletal maturity scores with age is achieved. The reliability of the computer-assisted skeletal age score (CASAS) is considerably greater than that of the usual manual method. Differences between duplicate readings of a bone by a single observer average about 0.25 stage, and reach 1.0 stage or more only in about 3% of instances, compared with 15-20% characteristic of manual ratings.

A computerized image analysis system for estimating Tanner-Whitehouse 2 bone age.

A method for assigning Tanner-Whitehouse 2 skeletal maturity scores (or bone ages) to hand-wrist X-rays by an image analysis computer system is described. An operator positions the relevant area of the X-ray on a light box beneath a video camera. Correct positioning is assured by computer templates of each bone stage. Thereafter the process is automatic; the computer, not the operator, rates the bones. The system produces continuous stage scores, not discrete ones such as B, C or D. Data are given which show that the computer-assisted skeletal age score is more repeatable than the usual manual (or unassisted) rating. The absolute difference between duplicates averaged 0.25 stages; differences of as much as 1.0 stage occurred in only 3% of duplicates compared with 15% obtained in manual ratings.

Reliability and validity of computer-assisted estimates of Tanner-Whitehouse skeletal maturity (CASAS): comparison with the manual method.

Three observers rated 57 X-rays from normal healthy children in Project HeartBeat! twice each by CASAS, the computer-assisted version of the TW2 RUS bone age method. Differences between duplicates of individual bone ratings which reached or exceeded 1.0 unit (or 1 stage) were 5% within observer and 8% between observers for CASAS, and 17 and 33%, respectively, for the unassisted MANUAL method. In children followed longitudinally, CASAS scores increased much more steadily than MANUAL scores, largely because the bones were rated, in the former system, on a continuous rather than a discrete-integer scale. We conclude that CASAS is a more reliable and probably a more valid estimator of skeletal maturity than the MANUAL version of the TW2 RUS method.

Constant low-dose oestradiol replacement accelerates skeletal maturation and growth in ovariectomized adolescent rhesus monkeys.

The effects of oestradiol (OE2) on adolescent growth in female rhesus monkeys were evaluated by testing the hypothesis that, upon removal of the ovary, the increase in growth normally seen at the time of puberty would be abolished and that treatment with OE2 would restore it. Juvenile monkeys (n = 12) were ovariectomized and were given either an OE2-bearing silicone elastomer capsule implanted subcutaneously to simulate mid-pubertal concentrations ('treated =', n = 8) or no steroid treatment ('control =', n = 4). Females were studied from 18 to 42 months of age which, in intact females, typically encompasses the prepubertal period to the occurrence of first ovulation. Over the whole period, growth in body weight, crown-rump (CR) length and tibia length for control females were less than the 95% confidence limits of females treated with OE2. However, significant spurts of growth in both CR and tibia length occurred in the control as well as treated animals, although the peak velocities were somewhat lower for non-OE2-treated animals. Peak growth velocities occurred at an earlier chronological age in treated females, although at the same degree of skeletal maturity as found in control females. Skeletal maturity was significantly advanced in treated females from 27 months onward. Serum concentrations of nocturnal GH increased significantly with advancing age in both groups, with greater increases observed in treated females. Serum concentrations of IGF-I were higher in treated females until some 30 months of age, at which point concentrations increased in a similar fashion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal treatment of male monkeys with a gonadotropin-releasing hormone agonist alters differentiation of central nervous system centers that regulate sexual and skeletal development.

Male rhesus monkeys treated continuously with a GnRH agonist for the first 4 months of postnatal life exhibited a delay in the onset of puberty and an attenuated peripubertal rise in testosterone (T) secretion. The objectives of the current study were to determine whether these effects on sexual development were permanent and whether the hypothalamic-pituitary-testicular axis was functioning normally in these animals as adults. Neonatal GnRH agonist treatment delays but does not permanently block sexual maturation in male monkeys. Treated animals that did not show a pubertal rise in serum T during the breeding season of their 4th year exhibited a seasonal but subnormal elevation of serum T during the subsequent breeding season. Growth of the skeleton was diminished as evidenced by shorter adult crown-rump, tibia, and femur length and reduced bone mineral density of the humerus and lumbar spine. The magnitude of the serum LH and T response to iv pulses of GnRH [50 ng/kg body weight (BW)] and naloxone (1 mg/kg BW) did not differ between control and treated animals during the nonbreeding or breeding season at 6 yr of age. Conversely, treated animals showed a subnormal serum LH and T response to N-methyl-D,L-aspartic acid (5 mg/kg BW iv) during the nonbreeding season. These data suggest that adult monkeys treated neonatally with a GnRH agonist exhibit subnormal sensitivity of the central nervous system to one or more excitatory amino acids (e.g. aspartate or glutamate). Thus, abolishing neonatal activation of the pituitary-testicular axis with a GnRH agonist may permanently alter differentiation of central nervous system centers that are either involved in GnRH secretion or govern this process.