Effect of preconception gamma irradiation on morphometric assessment of adult female mice and embryo / Efecto de la irradiación gamma preconcepción sobre la evaluación morfométrica de ratones hembras adultas y embriones

The aim was to study the effect of preconception gamma irradiation on the gross morphometry of the adult female mice and its embryo. Twenty-seven mice; 18 females and 9 males: subdivided into 3 groups namely (Control, Non-Irradiation and Radiation) containing 6 females and 3 male mice each in 2:1 ratio. A gamma irradiation dose of 1Gy/min was delivered to each batch of mice exposed by a Cobalt 60, Theratron 780c model, by Atomic Energy of Canada Limited (AECL) at the Radiotherapy department of the University College Hospital, Ibadan. All the animals were mated 1 week post irradiation. Vaginal plugs were confirmed, and the pregnant females were sacrificed on day 14 of gestation by chloroform inhalation. The gross morphology of the female mice and their harvested litters were assessed and statistically analysed. A total of 113 embryos were harvested in all groups; 54 for Control, 50 for Non-Irradiated and 9 for the irradiation group. The gross morphologic assessments of the fetuses were statistically significant at P value < 0.05 for all the 3 groups compared. These findings suggest that a preconception irradiation affects the morphology of the female mice and its progeny.

El objetivo fue estudiar el efecto de la irradiación gamma antes de la concepción sobre la morfometría macroscópica de ratones hembra adultos y los embriones de sus crías. Veinte y siete ratones, 18 hembras y 9 machos, divididos en 3 grupos (control, sin irradiación e irradiado) con 6 hembras y 3 machos cada uno en proporción 2:1. Una dosis de radiación gamma de 1 Gy/min fue aplicada a uno de los ratones expuestos por un equipo Cobalt 60, Theratron modelo 780c, Atomic Energy of Canada Limited (AECL) en el departamento de radioterapia del Hospital University College de Ibadan. Todos los animales se aparearon 1 semana después de la irradiación. Se confirmaron los tapones vaginales, y las hembras preñadas fueron sacrificadas en el día 14 de la gestación por inhalación de cloroformo. La morfología general de los ratones hembras y sus camadas fueron evaluadas y analizadas estadísticamente. Un total de 113 embriones se recolectaron en todos los grupos, 54 del grupo control, 50 del grupo no irradiados y 9 del grupo irradiado. Las evaluaciones morfológicas macroscópicas de los fetos fueron estadísticamente significativas (p<0,05) para los 3 grupos de comparación. Estos hallazgos sugieren que una irradiación previa a la concepción afecta a la morfología de los ratones hembra y su progenie.

Radioprotective effect of melatonin on the cervical spinal cord in irradiated rats

It has been suggested that the vascular endothelial growth factor [VEGF] gene expression plays an important role in radiation-induced injury to the spinal cord. This study assesses the radioprotective effects of N-acetyl-5-methoxytryptamine [melatonin] through its modulation of VEGF expression after localized irradiation of the cervical spinal cord. In this experimental study, we divided 192 male rats into four groups: 1. control [n=48]; 2. rats that received an intraperitoneal [IP] injection of melatonin [n=48]; 3. rats that received an IP injection of melatonin 30 minutes prior to cervical spinal cord gamma irradiation [dose: 22 Gy; [n=48]]; and 4. rats that received an IP injection of vehicle prior to spinal cord irradiation [n=48]. The changes in VEGF expression were assessed using real-time RT-PCR and enzyme-linked immunosorbent assays. Samples for light microscopy were stained with hematoxylin and eosin [H and E]. The differences among the groups were analyzed using the analysis of variance [ANOVA] test followed by Tukey's multiple comparisons test. Up-regulation of VEGF expression was observed from 8 to 22 weeks after irradiation [p<0.05]. Paralysis and other radiation-induced myelopathy manifestations developed within 22 weeks after irradiation. VEGF expression in the melatonin pre-treatment group significantly down-regulated in the 20th and 22[nd] weeks after irradiation compared to the radiation-only group. The results support the hypothesis that modulation of VEGF expression by melatonin administration may increase the survival rate of irradiated animals

O ultrassom terapêutico na medula espinhal acelera a regeneração do nervo ciático de ratos / Therapeutic ultrasound on the spinal cord accelerates regeneration of the sciatic nerve in rats

OBJETIVO: Estudar os efeitos da irradiação ultrassônica de baixa intensidade aplicada sobre a medula espinhal na regeneração do nervo ciático de ratos após lesão por esmagamento controlado, avaliando os resultados pelo índice funcional do ciático (SFI), medido nas imagens vídeo-filmadas das plantas das patas. MÉTODOS: Dezoito ratos foram submetidos a esmagamento controlado (do nervo ciático direito e divididos em dois grupos de acordo com o tratamento: Grupo 1 (n=9), irradiação simulada; Grupo 2 (n=9), irradiação efetiva. Irradiação ultrassônica de baixa intensidade foi iniciada no 7º dia pós-operatório e aplicada diariamente por 6 semanas. Imagens das plantas das patas dos animais foram vídeo-filmadas em uma esteira transparente sob velocidade controlada a intervalos semanais até a 6ª semana de irradiação e o correspondente SFI medido com um programa de computador específico. RESULTADOS: O SFI durante a 1ª e a 6ª semana de tratamento foi de -59,12 e -12,55 no Grupo 1, e -53,31 e -1,32 no Grupo 2, indicando uma melhora de 79 por cento e 97 por cento, respectivamente, mas as diferenças entre os grupos somente foram significantes (p<0,05) durante a 3ª semana de tratamento. CONCLUSÃO: Os autores concluem que o ultrassom terapêutico de baixa intensidade estimula a regeneração nervosa, com significância durante a 3ª semana de tratamento. Nivel de Evidência II, Prospectivo Comparativo.

OBJECTIVE: To study the effects of low intensity ultrasound irradiation applied on the spinal cord on the regeneration of the rat's sciatic nerve after a controlled crush injury, evaluating the functional results of the sciatic functional index as measured on the video recorded images of the foot sole. METHODS: Eighteen rats were submitted to a controlled crush injury of the right sciatic nerve and divided into two groups according to the treatment: Group 1 (n=9), simulated irradiation; Group 2 (n=9), effective irradiation. Low-intensity ultrasound irradiation was started on the 7th postoperative day and applied daily for 6 weeks. Images of the animals´ foot sole were video recorded on a see-through treadmill type walking belt machine at weekly intervals until the 6th week of irradiation and the corresponding sciatic functional index (SFI) was measured with specific software. RESULTS: The SFI during the first and last week of treatment was -59.12 and -12.55 in Group 1, -53.31 and -1.32 in Group 2, indicating a 79 percent and 97 percent improvement, respectively, but differences between groups were only significant (p<0.05) during the third week. CONCLUSION: The authors conclude that low intensity therapeutic ultrasound enhances nerve regeneration, with significance during the 3rd week of treatment. Level of Evidence: Level II, prospective comparative study.

Importance of contouring the cervical spine levels in initial intensity-modulated radiation therapy radiation for head and neck cancers: implications for re-irradiation.

Aim: To evaluate the maximum differential cervical spinal (C-spine) cord dose in intensity-modulated radiation therapy (IMRT) plans of patients undergoing radiotherapy for treatment of head and neck cancer. Materials and Methods: The C-spine of ten head and neck cancer patients that were planned using IMRT and each cervical vertebral body and the right and left sides was contoured by splitting the cord in the center. Dose-volume histograms (DVH) and maximum point doses were obtained for each contour and compared. Results: The dose to the cord varied with the location of the primary tumor but such variation was not consistently seen. This report provides information that is critical for planning reirradiation treatments. We recommend that contouring of the C-spine cord with IMRT should include outlining of each cervical cord level and identification of the right and the left sides of the cord on each plan.

Spinal cord response to altered fractionation and re-irradiation: radiobiological considerations and role of bioeffect models.

The aim of radiation oncologist is to implement an uncomplicated loco regional control of cancer by radiation therapy. The bioeffect of a physical dose depends on the nature of the tissue, fractionation scheme, dose rate and treatment time. The transformation of absorbed dose into a bioeffect dose is controlled by treatment variables and the radiobiological characteristics of the relevant tissue. Various bioeffect models have been proposed to predict the biological effect of radiotherapy treatments. Dale has proposed extrapolated response dose (ERD) equations for external beam therapy, intracavitary brachytherapy and interstitial brachytherapy. Within the context of the LQ model, the parameter which quantifies the overall biological effect on a given tissue is the biologically effective dose (BED) which is obtained by applying repopulation correction to ERD (Orton). Thames proposed the total effect (TE) concept based on the incomplete repair LQ model which accounts for the biological effect of a fractionated course of radiotherapy. Spinal cord myelitis limits the dose to tumours in the head and neck, thoracic and upper abdominal regions resulting in reduction of tumour control probability. Radiation myelopathy is one of the most devastating complications of clinical radiotherapy. Treatment techniques that are designed to minimize the risk of spinal cord injury are likely to underdose the tumour consequent failure to control the disease. Since radiation myelopathy results in severe and irreversible morbidity, it is important to establish the tolerance dose of the spinal cord. A number of patients have recently been reported to have developed radiation myelopathy following hyperfractionated accelerated radiotherapy. As the survival rates of patients increase, radiation oncologists are more frequently faced with the problem of treatment of late recurrence or second tumours situated within or close to previously treated site. A rationale for taking a decision in treating in such a condition is even more complex than the original condition and requires knowledge of the kinetics of decay of occult injury of the previous treatment. To test the validity of ERD, clinically reported data of altered fractionation to the spinal cord for 7 patients reported by Wong et al, Saunders et al and Bogaert et al, were analysed, ERD values were calculated and compared with compiled clinical literature data of 3233 patients for the incidence of spinal cord myelitis reported by Cohen and Creditor, Wara et al, Abbatucci et al and Jeremic et al for conventional fractionation. ERD values were estimated with alpha/beta of 2.5 Gy for the conventional and altered fractionation data. To test the validity of TE concept for clinical data of re-irradiation tolerance of the spinal cord, the data of the 22 patients compiled by Nieder et al were used. Clinical data compiled from the literature of Cohen and Creditor, Wara et al, Abbatucci et al and Jeremic et al, were used for comparison.

Hematological toxicities and treatment interruption due to craniospinal irradiation

To assess the frequency and severity of myelosuppression due to cranio-spinal irradiation to identify patients at high risk of haematological toxicity who may require supportive therapy. Between 1998 and 2002, 45 patients received craniospinal axis radiotherapy as part of the treatment of primary CNS tumours at departement of radiotherapeutic oncology of cancer Institute. The dose to the whole brain ranged from 30 to 40 Gy in 1.5-1.85 Gy/f. The usual dose to the posterior fossa or to the site of primary disease was 50- 55 Gy in 6-8 weeks for adults and was reduced to 45-50 Gy in 6-7 weeks for children aged, 3 years. Complete blood counts [CBC] were obtained during radiation therapy. Any interruption in treatment due hematologic toxicity [G3-4] lasting 2 days was defined as a significant treatment interruption. In 45 patients who received craniospinal irradiation [CSI] 19 patients had treatment interruption more than 2 days. The median dose at interruption was 21.6 +/- 8.7 Gy and the the frequency of grade 3,4 hematologic toxicity occurred with peack incidence in fourth week of CSI[median day of interruption was day 23,range 8-38]. The median WBC count was 1900[range 100-2140].The mean of interruption period was 7 +/- 8 days [one patient died from neutropenic fever then he didn't finish his treatment. In 19 patients who had treatment interruption,13 of them were under 12 years while 5 patients were greater than 12 years .With Mann-Whitney U test the median age of patients with treatment interruption was lower; 10.2 years and 16.2 years respectively[P=.059].].In 24 patients with dose/fraction =<1.6 Gy 12 patients [50%] had treatment interruption but in 21 patients with dose/fraction >1.6 Gy 7 [33%] had treatment interruption[P=.2] but interruption period was longer in patients with dose/ fraction >1.6 Gy .From 12 patients who had dose/fraction <=1.6Gy,7 patients had interruption period less than 5 days while in group with dose/fraction >1.6 Gy all patients had treatment interruption period more than 5 days[P=.016,CI 95% for interruption period difference =1.2-4.7]. In summary, in our study 42% of patients undergoing CSI had treatment interruption. The risk was higher in children and in patients who received higher spinal dose fraction the treatment interruption was longer, but the overall treatment-related morbidity was low. In a population at risk of hematological toxicity where further studies of HGFs should be targeted

Report of six cases of radiation myelopathy

The authors report six cases of radiation myelopathy observed after irradiation of 4 cases of cavum cancer,1 case of Hodgkin disease and 1 case of testicular seminomia. Radiation etiology of the myelopathy is diagnosed when the spinal cord is exposed to radiations, when there is coincidence between clinical signs level and irradiated medullary level, a free sufficient post radiotherapy interval and a lack of metastatic radiological signs. Chronic progressive radiation myelopathy is the most frequent with a mean beginning delay of 28.4 months clinical features of radiation myelopathy are frequently characterized by Brown sequard syndrome. This complication depend on different irradiation parameters as volume, dose and time factors, with an upper limit of 45 grays. Particular care must be taken for patients suffering from cavum cancer where irradiation ways are difficult and the other cancers where irradiation concerns an important length of the spinal cord with high doses. Systematic spinal somatosensory evoked responses for the patients who undergo spinal cord irradiation let to find infraclinical changes and modify treatment to avoid or decrease radiation myelopathy risks