Load-Sharing and Kinematics of the Human Cervical Spine Under Multi-Axial Transverse Shear Loading: Combined Experimental and Computational Investigation.

The cervical spine experiences shear forces during everyday activities and injurious events yet there is a paucity of biomechanical data characterizing the cervical spine under shear loading. This study aimed to (1) characterize load transmission paths and kinematics of the subaxial cervical spine under shear loading, and (2) assess a contemporary finite element cervical spine model using this data. Subaxial functional spinal units (FSUs) were subjected to anterior, posterior, and lateral shear forces (200 N) applied with and without superimposed axial compression preload (200 N) while monitoring spine kinematics. Load transmission paths were identified using strain gauges on the anterior vertebral body and lateral masses and a disc pressure sensor. Experimental conditions were simulated with cervical spine finite element model FSUs (GHBMC M50 version 5.0). The mean kinematics, vertebral strains, and disc pressures were compared to experimental results. The shear force-displacement response typically demonstrated a toe region followed by a linear response, with higher stiffness in anterior shear relative to lateral and posterior shear. Compressive axial preload decreased posterior and lateral shear stiffness and increased initial anterior shear stiffness. Load transmission patterns and kinematics suggest the facet joints play a key role in limiting anterior shear while the disc governs motion in posterior shear. The main cervical spine shear responses and trends are faithfully predicted by the GHBMC cervical spine model. These basic cervical spine biomechanics and the computational model can provide insight into mechanisms for facet dislocation in high severity impacts, and tissue distraction in low severity impacts.

Technique and preliminary findings for in vivo quantification of brain motion during injurious head impacts.

Computational models of the human brain are widely used in the evaluation and development of helmets and other protective equipment. These models are often attempted to be validated using cadaver tissue displacements despite studies showing neural tissue degrades quickly after death. Addressing this limitation, this study aimed to develop a technique for quantifying living brain motion in vivo using a closed head impact animal model of traumatic brain injury (TBI) called CHIMERA. We implanted radiopaque markers within the brain of three adult ferrets and resealed the skull while the animals were anesthetized. We affixed additional markers to the skull to track skull kinematics. The CHIMERA device delivered controlled, repeatable head impacts to the head of the animals while the impacts were fluoroscopically stereo-visualized. We observed that 1.5 mm stainless steel fiducials (∼8 times the density of the brain) migrated from their implanted positions while neutral density targets remained in their implanted position post-impact. Brain motion relative to the skull was quantified in neutral density target tests and showed increasing relative motion at higher head impact severities. We observed the motion of the brain lagged behind that of the skull, similar to previous studies. This technique can be used to obtain a comprehensive dataset of in vivo brain motion to validate computational models reflecting the mechanical properties of the living brain. The technique would also allow the mechanical response of in vivo brain tissue to be compared to cadaveric preparations for investigating the fidelity of current human computational brain models.

Assessing the performance of motorcyclists' impact protectors in simulated ATD knee and shoulder impacts.

OBJECTIVE: Fractures are a common injury among motorcycle riders and can have serious health implications. Impact protection (IP) has been designed to help prevent fractures, yet there are conflicting opinions as to whether this IP does in fact help prevent fractures in real-world crashes. This work aimed to (1) use simulated dummy impacts to examine whether existing types of IP could reduce the force transferred to the underlying bone to below fracture tolerance levels and (2) investigate whether current European Standard (EN 1621-1) test procedures for impact protectors designed for motorcyclists are sufficient to ensure fracture protection. METHOD: Twenty-three shoulder and 7 knee IP specimens were tested using a 23-kg impactor contacting axially along the clavicle and femur of an anthropomorphic test device (ATD) at an energy level corresponding to the fracture tolerance of these bones. Sixteen IP specimens were the same as those worn by motorcycle riders involved in crashes where injury outcome was known (knee: n = 3; shoulder: n = 13) and the IP had been previously tested to EN 1621-1. Other IP tested represented a wide range of IP available for purchase at a motorcycle accessory store. Double and triple layers of IP were also tested. Energy attenuated during the dummy impacts was compared to energy attenuated when tested to EN 1621-1. RESULTS: Of the 23 shoulder IP tested, the average percentage reduction of transferred force to the shoulder from the baseline test was 7.6 ± 4.8%. The percentage reduction of transferred force to the knee from the baseline was 43.9 ± 7.5%. The entire group of knee IP tested reduced the transferred force to the knee to below the 10-kN injury threshold for the femur. There was a positive but nonsignificant correlation between the ATD test and the EN 1621-1 impact test performance, suggesting that the European standard test method likely provides a good indication of IP performance. However, given the low correlation coefficient, the relationship between IP performance in the European standard test method and injury protection remains unclear. CONCLUSION: Though the energy attenuation test method in the European standard may be an appropriate approach, distinct differences in injury protection performance observed between knee and shoulder IP indicate that there may be a need for different performance criteria for IP designated to protect different body regions.

Radiography used to measure internal spinal cord deformation in an in vivo rat model.

Little is known about the internal mechanics of the in vivo spinal cord during injury. The objective of this study was to develop a method of tracking internal and surface deformation of in vivo rat spinal cord during compression using radiography. Since neural tissue is radio-translucent, radio-opaque markers were injected into the spinal cord. Two tantalum beads (260 µm) were injected into the cord (dorsal and ventral) at C5 of nine anesthetized rats. Four beads were glued to the lateral surface of the cord, caudal and cranial to the injection site. A compression plate was displaced 0.5 mm, 2 mm, and 3 mm into the spinal cord and lateral X-ray images were taken before, during, and after each compression for measuring bead displacements. Potential bead migration was monitored for by comparing displacements of the internal and glued surface beads. Dorsal beads moved significantly more than ventral beads with a range in averages of 0.57-0.71 mm and 0.31-0.35 mm respectively. Bead displacements during 0.5 mm compressions were significantly lower than 2 mm and 3 mm compressions. There was no statistically significant migration of the internal beads. The results indicate the merit of this technique for measuring in vivo spinal cord deformation. The pattern of bead displacements illustrates the complex internal and surface deformations of the spinal cord during transverse compression. This information is needed for validating physical and finite element spinal cord surrogates and to define relationships between loading parameters, internal cord deformation, and biological and functional outcomes.

Re-exposure to the hypobaric hypoxic brain injury of high altitude: plasma S100B levels and the possible effect of acclimatisation on blood-brain barrier dysfunction.

Hypobaric hypoxic brain injury results in elevated peripheral S100B levels which may relate to blood-brain barrier (BBB) dysfunction. A period of acclimatisation or dexamethasone prevents altitude-related illnesses and this may involve attenuation of BBB compromise. We hypothesised that both treatments would diminish the S100B response (a measure of BBB dysfunction) on re-ascent to the hypobaric hypoxia of high altitude, in comparison to an identical ascent completed 48 h earlier by the same group. Twelve healthy volunteers, six of which were prescribed dexamethasone, ascended Mt Fuji (summit 3700 m) and serial plasma S100B levels measured. The S100B values reduced from a baseline 0.183 µg/l (95 % CI 0.083-0.283) to 0.145 µg/l (95 % CI 0.088-0.202) at high altitude for the dexamethasone group (n = 6) and from 0.147 µg/l (95 % CI 0.022-0.272) to 0.133 µg/l (95 % CI 0.085-0.182) for the non-treated group (n = 6) [not statistically significant (p = 0.43 and p = 0.82) for the treated and non-treated groups respectively]. [These results contrasted with the statistically significant increase during the first ascent, S100B increasing from 0.108 µg/l (95 % CI 0.092-0.125) to 0.216 µg/l (95 % CI 0.165-0.267) at high altitude]. In conclusion, an increase in plasma S100B was not observed in the second ascent and this may relate to the effect of acclimatisation (or hypoxic pre-conditioning) on the BBB. An exercise stimulated elevation of plasma S100B levels was also not observed during the second ascent. The small sample size and wide confidence intervals, however, precludes any statistically significant conclusions and a larger study would be required to confirm these findings.

Immunogenicity of a prophylactic quadrivalent human papillomavirus L1 virus-like particle vaccine in male and female adolescent transplant recipients.

Organ TX recipients are at an increased risk of developing cancers of the lower genital tract related to HPV. The quadrivalent HPV vaccine has high efficacy in preventing these diseases, but response to many vaccines is suboptimal after organ transplantation. Liver and kidney TX recipients received quadrivalent HPV vaccine. Serum samples were tested for anti-HPV levels. Of 20 renal transplant recipients screened, 14 received vaccine. Of these, seven completed the vaccine series and seven had incomplete vaccination. Of five liver TX children, three received vaccines (two complete and one incomplete). All eight kidney and liver TX children with complete vaccination and available results were seronegative at baseline and had seroconversion at month 7 for all four HPV types. Six of 14 (42.8%) kidney TX recipients developed AR. During the same time period, eight of 28 (28.5%) non-vaccine renal transplant recipients developed AR (p = ns). Transplant adolescents developed 100% seroconversion to all four HPV serotypes with HPV vaccine with serologic titers similar to historic controls. A non-significant increased incidence of AR was noted among kidney transplant vaccine recipients. A much larger study would be needed to evaluate whether HPV vaccination increases AR in transplant adolescents.

Challenging behaviour and sleep cycle disorder following brain injury: a preliminary response to agomelatine treatment.

BACKGROUND: Sleep disturbances are common after acquired brain injury. Sedatives can exacerbate behavioural disorders. OBJECTIVES: This study reports the case of a severely brain damaged man (TM) who developed a non-24 hour sleep cycle disorder that was effectively managed by the administration of a melatonin receptor agonist, agomelatine. METHOD: TM suffered significant brain damage as a result of a large subarachnoid haemorrhage of his right anterior cerebral artery complicated by midline shift and subsequent infarction of his left middle cerebral artery. In addition to challenging behaviour and cognitive impairment, TM presented with a recurrent disturbed sleep-wake pattern that significantly worsened his quality-of-life. He was diagnosed as suffering of non-24 hour sleep-wake disorder. Challenge was recorded using the Overt Aggression Scale Modified for Neuro-Rehabilitation (OASMNR). RESULTS: Typical hypnotics had no or ill effects. Agomelatine prescription (25 mg) led to significant OASMNR and sleep efficiency change with effects apparent at 1.5 years later. CONCLUSIONS: Administration of the melatonin receptor (MT1 and MT2) agonist agomelatine each night resulted in an immediate and sustained improvement on sleep and on indices of challenging behaviour.

Varicella zoster virus vasculopathy: analysis of virus-infected arteries.

OBJECTIVE: Varicella zoster virus (VZV) is an under-recognized yet treatable cause of stroke. No animal model exists for stroke caused by VZV infection of cerebral arteries. Thus, we analyzed cerebral and temporal arteries from 3 patients with VZV vasculopathy to identify features that will help in diagnosis and lead to a better understanding of VZV-induced vascular remodeling. METHODS: Normal and VZV-infected cerebral and temporal arteries were examined histologically and by immunohistochemistry using antibodies directed against VZV, endothelium, and smooth muscle actin and myosin. RESULTS: All VZV-infected arteries contained 1) a disrupted internal elastic lamina; 2) a hyperplastic intima composed of cells expressing α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SM-myosin) but not endothelial cells expressing CD31; and 3) decreased medial smooth muscle cells. The location of VZV antigen, degree of neointimal thickening, and disruption of the media were related to the duration of disease. CONCLUSIONS: The presence of VZV primarily in the adventitia early in infection and in the media and intima later supports the notion that after reactivation from ganglia, VZV spreads transaxonally to the arterial adventitia followed by transmural spread of virus. Disruption of the internal elastic lamina, progressive intimal thickening with cells expressing α-SMA and SM-MHC, and decreased smooth muscle cells in the media are characteristic features of VZV vasculopathy. Stroke in VZV vasculopathy may result from changes in arterial caliber and contractility produced in part by abnormal accumulation of smooth muscle cells and myofibroblasts in thickened neointima and disruption of the media.

Effects of feeding triticale dried distillers grains plus solubles as a nitrogen source on productivity of lactating dairy cows.

The objective of this study was to compare triticale dried distillers grains plus solubles (TDDGS) as a source of dietary N with other high-protein feeds commonly used in North America: corn dried distillers grains plus solubles (CDDGS), canola meal (CM), and soybean meal (SBM). Rumen degradable protein (% of crude protein, CP) after 16h of incubation in the rumen was higher for CDDGS and TDDGS (69.3% and 64.5%, respectively) than for CM (62.2%) and SBM (53.0%). For the lactation study, experimental diets were formulated to supply 30% of dietary CP from TDDGS, CDDGS, CM, or SBM. These diets contained 22.3% forage neutral detergent fiber and approximately 19.2% CP and were fed to 12 multiparous Holstein cows (130+/-40 d in milk) in a 4 x 12 Latin rectangle design with 21-d periods. Neither dry matter intake nor milk yield was affected by treatment, averaging 25.5 and 35.5kg/d, respectively. Plasma concentrations of Arg, Lys, and Thr were greater for cows fed CM or SBM compared with those fed TDDGS or CDDGS, whereas plasma concentrations of Leu and Phe were lower for cows fed CM or SBM compared with those fed TDDGS or CDDGS. Cows fed CDDGS had lower milk CP yield compared with cows fed CM (1.07 vs. 1.16kg/d). Contrarily, milk CP and milk lactose yields were not different for cows fed TDDGS compared with CM or SBM. These data suggest that TDDGS can replace CM or SBM in the diets of lactating dairy cows without adverse effects on production. Furthermore, although dried distillers grain has been generally accepted as a feed high in ruminal undegradable protein, CDDGS and TDDGS used in the present study had high in situ ruminal degradable crude protein. Further investigation is warranted to determine the extent of variation in ruminal protein degradation among different types of dried distillers grains.

Effects of addition of essential oils and monensin premix on digestion, ruminal fermentation, milk production, and milk composition in dairy cows.

Four ruminally cannulated, lactating Holstein cows were used in a 4 x 4 Latin square design (28-d periods) with a 2 x 2 factorial arrangement of treatments to study the effects of dietary addition of essential oils (0 vs. 2 g/d; EO) and monensin (0 vs. 350 mg/d; MO) on digestion, ruminal fermentation characteristics, milk production, and milk composition. Intake of dry matter averaged 22.7 kg/d and was not significantly affected by dietary additives. Apparent digestibilities of dry matter, organic matter, neutral detergent fiber, and starch were similar among treatments. Apparent digestibility of acid detergent fiber was increased when diets were supplemented with EO (48.9 vs. 46.0%). Apparent digestibility of crude protein was higher for cows fed MO compared with those fed no MO (65.0 vs. 63.6%). Nitrogen retention was not changed by additive treatments and averaged 27.1 g/d across treatments. Ruminal pH was increased with the addition of EO (6.50 vs. 6.39). Ruminal ammonia nitrogen (NH3-N) concentration was lower with MO-supplemented diets compared with diets without MO (12.7 vs. 14.3 mg/100 mL). No effect of EO and MO was observed on total volatile fatty acid concentrations and molar proportions of individual volatile fatty acids. Protozoa counts were not affected by EO and MO addition. Production of milk and 4% fat-corrected milk was similar among treatments (33.6 and 33.4 kg/d, respectively). Milk fat content was lower for cows fed MO than for cows fed diets without MO (3.8 vs. 4.1%). The reduced milk fat concentration in cows fed MO was associated with a higher level of trans-10 18:1, a potent inhibitor of milk fat synthesis. Milk urea nitrogen concentration was increased by MO supplementation, but this effect was not apparent when MO was fed in combination with EO (interaction EO x MO). Results from this study suggest that feeding EO (2 g/d) and MO (350 mg/d) to lactating dairy cows had limited effects on digestion, ruminal fermentation characteristics, milk production, and milk composition.

Evaluation of antigen-capture ELISA and immunohistochemical methods for avian surveillance of West Nile virus.

Accurate detection of West Nile virus (WNV) in corvids is essential for monitoring the spread of virus during the mosquito season. Viremia in corvids is very high, with titers approaching 10(8) viral particles/ml. In the presence of such marked viremia, the sensitivity of real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis is unnecessary, and more cost-effective methods should be assessed. To this end, antigen-capture ELISA (ACE) and immunohistochemical (IHC) assays were evaluated. Skin, cloacal swab specimens, and feathers from corvids were tested by use of ACE, and results were compared with results obtained from use of real-time RT-PCR analysis. Of the 3 sample types, skin gave the best sensitivity (98%) and specificity (100%). Skin, brain, kidney, and spleen from corvids were analyzed by IHC, and results were compared with real-time RT-PCR results. Kidney and spleen were more often positive by use of IHC than were brain and skin tissue; however, IHC did not perform as well as ACE in the identification of virus-positive birds. Results of this study support the use of a skin sample in an ACE format as an effective surveillance method for corvids.

Trial introduction of the Willis dropped ovary technique for spaying cattle in northern Australia.

OBJECTIVE: To compare the Willis dropped ovary technique with traditional spaying methods in extensive beef cattle herds in northern Australia. PROCEDURE: Three field trials were conducted simultaneously at different sites in northern Australia in 1996-97. Brahman and Brahman-Shorthorn cross heifers (n = 219, 2 years, 250 to 378 kg) and cows (n = 211, 3 to 16 years, 256 to 540 kg) were allocated by stratified randomisation to three treatments: spaying using the Willis dropped ovary technique (WDOT); spaying using traditional paralumbar and vaginal methods; and unspayed. Following these procedures, these nonpregnant, nonlactating cattle were then exposed to bulls (4 per 100 females) under extensive rangeland conditions for 12 months during which time weight, body condition, pregnancy and ovarian function were monitored and compared. RESULTS: Pregnancy rates varied from 60 to 90% for entire heifers and 80 to 100% for entire cows depending on site. The traditional spay methods were 100% successful in preventing pregnancy; the WDOT was 92 to 97% effective, depending on operator experience. The number of deaths was the same or higher in Willis spayed animals than other groups. Weight changes were similar in all groups at the three sites over the trial period. The time taken to spay using the WDOT was similar to or less than that required for the traditional methods. Uterine abnormalities were not observed in animals spayed with the WDOT, there were however 30 (12.4%) animals where excision of the ovary was incomplete; the still-attached ovarian remnant presumably accounting for the three pregnant animals in this group. CONCLUSION: The WDOT suffers from requiring a high degree of skill in transrectal ovarian manipulation. There were more deaths and more pregnancies than with traditional spay methods. More experienced operators can be expected to achieve lower mortalities, better contraception and higher processing rates. Pregnancy will occur as a consequence of ovarian remnants unless care is taken to ensure removal of the entire ovary.

Contraceptive efficacy of an intra-uterine device in Brahman cattle.

The contraceptive efficacy of an intra-uterine device was evaluated using 218 heifers and 212 cows on three north Australian cattle stations. The heifers were aged approximately 2 years and weighed 250-378 kg; the cows were aged 3-16 years and weighed 256-540 kg. All cattle were non-pregnant, non-lactating Brahmans. At the end of the monsoon (wet) season (April-June 1997), the cattle were allocated by stratified randomisation to the three treatments which were untreated controls (n=59), surgical ovariectomy (n=105), or implantation with a bovine intra-uterine device (BIUD; n=266). All cattle grazed and were managed as one group within each station. They were exposed to bulls (4 per 100 females) from soon after treatment until slaughter approximately 12 months later. The BIUD could not be implanted in 25% of heifers and 8% of cows due to narrow or twisted cervices. Correct placement of the BIUDs appeared to be achieved in 57% of heifers and 72% of cows. At slaughter, the devices were incorrectly positioned in 73% of heifers and 49% of cows into which BIUDs had been inserted and that remained non-pregnant. Uterine perforations by the BIUD were observed in 35 and 45% of these heifers and cows, respectively; most perforations appeared to occur during implantation. Low-grade endometritis was observed at slaughter in most BIUD-implanted animals; 2% had pyometra.BIUD animals did not have significantly different growth to that of control or ovariectomised animals, other than when ovariectomy suppressed growth following surgery. Most animals implanted with BIUDs appeared to have normal ovarian function and animals were observed mating. All ovariectomised animals remained non-pregnant. Over 80% of controls were pregnant within 8 months of exposure to bulls, except heifers at one station where pregnancy rate was restricted to 25% as a result of severe nutritional conditions. Pregnancy was diagnosed in 21% of heifers and 33% of cows with implanted BIUDs. The device remained correctly positioned and with no pregnancy diagnosed in the year following implantation in only 2% of heifers and 14% of cows originally allocated. Because of the difficulties of implanting BIUDs, the high frequency of associated uterine injury, the high pregnancy rate in implanted animals, and that growth was unaffected by the presence of a BIUD, it was concluded that the device had poor contraception efficacy and no growth-promotant effect in Brahman cattle.

Comparison of BACTEC MGIT 960 and BACTEC 460 for culture of Mycobacteria.

We have compared the BACTEC 460 system with the BACTEC MGIT 960 system for culture of mycobacteria from 1800 routine clinical specimens. Rate of isolation of M. tuberculosis and time to detection of positive culture was comparable for both systems (BACTEC 460, 35 isolates, BACTEC MGIT 960, 34 isolates). Contamination of cultures was more common with the BACTEC MGIT 960 system. With intensification of the decontamination process an acceptable contamination rate was achieved in the BACTEC MGIT 960 system but time to detection of positive culture was increased by 1 to 2 days.

Reproductive responses of cattle to GnRH agonists.

The response in cattle to treatment with gonadotrophin releasing hormone (GnRH) agonist includes downregulation of GnRH receptors on gonadotrophe cells, desensitisation of the anterior pituitary gland to endogenous GnRH, and the abolition of pulsatile release of LH. In bulls, a tonic pattern of LH release is associated with increased secretion of testosterone, which persists for the duration of treatment with GnRH agonist. The mechanism for this response in bulls has not been elucidated, but clearly pulsatile release of LH is not required to stimulate the synthesis of steroidogenic enzymes that sustain elevated secretion of testosterone. In heifers, desensitisation to endogenous GnRH prevents the occurrence of the pre-ovulatory surge release of LH, thus blocking ovulation. The latter provided the opportunity to evaluate the potential of a GnRH agonist bioimplant to control fertility in heifers under extensive management. Bioimplants that contained graded amounts of GnRH agonist prevented pregnancies in heifers for periods of 3 to 12 months. Zebu crossbred heifers treated with GnRH agonist from 14 to 23 months of age failed to conceive, but showed normal conception patterns when introduced into mating herds at around 26 months of age. After treatment with GnRH agonist for 4 to 6 weeks, ovarian follicular growth in heifers is restricted to relatively small (2-4 mm) antral follicles. Suppressed follicular growth in heifers treated long-term with GnRH agonist is due to a lack of gonadotrophin support, rather than a direct action of agonist at the ovaries. This was demonstrated by the ability to induce apparently normal follicular growth and ovulation by acute treatment with FSH for 4 days, followed by an injection of LH, in heifers that had been exposed to GnRH agonist for around 6 months, and which had only small (2-4 mm) antral follicles at the start of FSH treatment. GnRH agonist bioimplants have been incorporated into new multiple ovulation and embryo transfer protocols that allow control of the time of ovulation subsequent to superstimulation of ovarian follicular growth with FSH. In these protocols, the endogenous surge release of LH is blocked by treatment with agonist and ovulation is timed by injection of exogenous LH, allowing fixed-time AI. It can be concluded from recent studies that GnRH agonist bioimplants have considerable potential for both pro-fertility and anti-fertility applications in cattle. It is likely that commercial bioimplants will be available within the next 3 to 5 years.

Limitations of the World Health Organization classification of childhood supratentorial astrocytic tumors. Children Brain Tumor Consortium.

BACKGROUND: In the context of many implied but not rigorously stated histologic feature combinations, the World Health Organization (WHO) classification of astrocytic tumors specifies only the presence or absence of endothelial proliferation, necrosis, and mitosis to distinguish astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. METHODS: The authors examined the effects of these and other reliably recognized histologic features on survival in the Childhood Brain Tumor Consortium (CBTC) sample of 340 children with supratentorial astrocytic tumors. RESULTS: Overall, the WHO criteria distinguished only two prognostically distinct classes of astrocytomas. When the specific combinations of the three features were unambiguously designated, three diagnostic categories resulted. These revised diagnostic categories are consistent with WHO guidelines and have significantly different survival distributions. However, neither the original WHO diagnoses nor the revised categories adequately separated these tumors prognostically, because histologic features other than those specified by WHO were significantly associated with improved or worsened survival. CONCLUSIONS: Classifications based on small numbers of specified histologic features may not be feasible because they inadequately separate childhood astrocytic tumors into prognostically homogeneous groups. Preferable classification techniques are those that simultaneously account for all reliably recognized histologic features.

[The role of radiotherapy in the treatment of malignant meningiomas]. / Die Rolle der Strahlentherapie in der Behandlung maligner Meningiome.

PURPOSE: Most malignant meningiomas will recur following surgical resection only. The role of irradiation and radiation dose levels is poorly defined. This study reviews a single institution experience using both, conventional and high doses > or = 60 Gy/CGE radiation regimen. PATIENTS AND METHODS: Between 1974 and 1995 16 patients with histologically proven malignant meningioma underwent radiation therapy (RT). Age at diagnosis ranged between 6 and 79 years (median: 49 years). Three patients reported previous irradiation to the head at least 14 years prior to diagnosis. Ten patients were treated for primary, and 6 patients for recurrent disease. Six patients underwent gross total and 10 patients subtotal resection (Table 1). RT was delivered using conventional, megavoltage photons or combined 160 MeV proton and photon irradiation. Except 1 patient, who died during RT, the radiation doses ranged between 40 and 70 Gy/CGE (= Cobalt Gray Equivalent) (median: 58 Gy/CGE, Table 2). RESULTS: With median observation time of 59 months (range: 10 to 155 months), actuarial local control rates at 5 and 8 years were 52% and 17%, respectively. Target doses > or = Gy/CGE resulted in significantly improved tumor control (100%) compared to < 60 Gy/CGE (17%) (p = 0.0006, Table 3 and Figure 1). Improved local control translated also in increased overall survival: 87% (> or = 60 Gy/CGE) versus 15% (< 60 Gy/CGE) at 5 years (p = 0.025, Figure 2). At time of analysis, 6/16 patients (38%) were alive. Two patients developed symptomatic brain damage at doses of 59.3 and 72 Gy/CGE. CONCLUSION: Conformal, radiation therapy with target doses > or = 60 Gy/CGE, in this study by use of combined proton and photon irradiation, can significantly improve chances of long-term local control and survival for patients diagnosed with these challenging tumors.

Treatment with progesterone and 17 beta-oestradiol to induce emergence of a newly-recruited dominant ovulatory follicle during oestrus synchronisation with long-term use of norgestomet in Brahman heifers.

The aim of this study was to determine the effect on ovarian follicular growth and atresia, of acute treatment with either 100 mg of progesterone (n = 10), 200 mg of progesterone (n = 10), 10 mg of oestradiol + 100 mg of progesterone (n = 10), 10 mg of oestradiol (n = 10) or no treatment (n = 10), given on Day 10 of a 17-day treatment with a norgestomet implant in randomly cycling Bos indicus heifers. The fate of the dominant follicle on Day 10, emergence of the new cohort of follicles and the intervals from implant removal to ovulation were recorded by ultrasonography. Plasma concentrations of Luteinizing hormone (LH), progesterone and oestradiol were determined during the time when the norgestomet implant was in place. All treatments resulted in the emergence of a new cohort of follicles within 5 days of administration. The day of emergence of the ovulatory follicle tended to be delayed after treatment with 100 mg of progesterone (2.7 +/- 0.3 days after treatment), 200 mg of progesterone (3.7 +/- 0.5 days after treatment), 10 mg of oestradiol + 100 mg of progesterone (4.4 +/- 0.2 days after treatment) and 10 mg of oestradiol (4.6 +/- 0.4 days after treatment) compared to control heifers (1.4 +/- 1.4 days after time of treatment). The mean interval from implant removal to onset of oestrus was significantly shorter after treatment with 100 mg of progesterone (38.4 +/- 2.6 h) than after treatment with 200 mg of progesterone (61.5 +/- 3.9 h) but otherwise, the mean interval from implant removal to onset of oestrus did not differ. Oestrus synchrony, measured by the sample standard deviation of oestrus onset, was tighter in all treatment groups compared to untreated control heifers. The mean interval from implant removal to ovulation did not differ significantly between groups. The synchrony of ovulation, measured by the sample standard deviation of the interval from implant removal to ovulation, was significantly tighter after treatment with 100 mg of progesterone, 200 mg of progesterone and 10 mg of oestradiol compared to control heifers. Treatment with 10 mg of oestradiol resulted in ovulation in seven of 10 heifers before implant removal, three of which failed to ovulate after implant removal. Progesterone administered on Day 10 lowered plasma LH concentrations (P < 0.05), whereas treatment with oestradiol caused a surge of LH and ovulation. Progesterone administered with oestradiol prevented the LH surge. A combination treatment of oestradiol and progesterone given on Day 10 of a 17-day norgestomet treatment in a range of follicular states resulted in the consistent emergence of a new cohort of follicles which included the eventual ovulatory follicle.