[Protective effects of the growth hormone (GH) on the irradiated spinal cord in rats]. / Radioprotección de la médula espinal mediante la hormona de crecimiento (GH). Estudio experimental en ratas.

Radiotherapy or irradiation of SNC AVM's or tumors also presents a high risk for provoking lesions in adjacent surrounding tissue. The objective of our study is to demonstrate radiotherapy induced alterations in a rat spinal cord model and evaluate the protective effect of Growth Hormone (GH) on rats exposed to high radiotherapy doses. The experimental study employed two groups of Wistar rats: Group A (control group):10 rats, which received 30 Gy at the spinal cord . Group B: 10 rats, these animals received 30 Gy and dose of 2mg/kg/day GH. Growth hormone administration was begun three days before radiotherapy and continued until two days after radiotherapy for a total of six days. At 14 days postradiotherapy, all the rats were sacrificed and the spinal cord extracted immediately. Hematoxyline-eosine histologic studies showed that control animals only exposed to radiotherapy had severe alterations with hemorrhage and vacuolisation of the entire irradiated segment while these alterations were much less severe in the GH-treated group. In conclusion, 30 Gy irradiation produced morphological changes including vascular endothelial oedema, necrosis, hemorrhage, and inflammatory exudates. A 2 mg/kg/day dose of GH protected the rat spinal cord against the noxious effects of the radiotherapy, decreasing the clinical, macro and microscopic damage in the treated animals.

Radioprotección de la médula espinal mediante la hormona de crecimiento (GH). Estudio experimental en ratas / Protective effects of the growth hormone (GH) on the irradiated spinal cord in rats

La radioterapia empleada en el tratamiento de los tumores o malformaciones vasculares del SNC presenta riesgo de causar lesiones en los tejidos adyacentes. El objetivo de nuestro estudio es demostrar las alteraciones provocadas por la radioterapia en la medula espinal de ratas a altas dosis y el valorar el efecto protector de la hormona de crecimiento (GH). El estudio experimental fue realizado con dos grupos de ratas Wistar. Grupo A (grupo control): Constó de 10 ratas que se irradiaron con 30 Gy en la medula espinal. Grupo B: Fue un grupo de 10 ratas irradiadas con 30Gy a las que se administró 2mg/kg/día de GH tres días previos a la radioterapia, el día de la radioterapia, y dos días después. A los 14 días de la radioterapia fueron perfundidas mostrando el estudio histológico de la médula espinal de las ratas tratadas sólo con radioterapia de forma intensa, hemorragias y trombosis de capilares. Al grupo a las que se administró GH mostró una importante disminución de las lesiones. En resumen la radioterapia administrada en dosis de30 Gy causa cambios morfológicos como edema lesión del endotelio vascular, necrosis, hemorragias, exudado inflamatorio. La dosis de 2mg/kg/día ejerce un efecto protector en la medula espinal de ratas tras la administración de radioterapia disminuyendo el daño macro y microscópico en las ratas estudiadas

Radiotherapy or irradiation of SNC AVM's or tumors also presents a high risk for provoking lesions in adjacent surrounding tissue. The objective of our study is to demonstrate radiotherapy induced alterations in a rat spinal cord model and evaluate the protective effect of Growth Hormone(GH) on rats exposed to high radiotherapy doses. The experimental study employed two groups of Wistar rats: Group A (control group):10 rats, which received 30 Gy at the spinal cord . Group B: 10 rats, these animals received 30 Gy and dose of 2mg/kg/day GH. Growth hormone administration was begun three days before radiotherapy and continued until two days after radiotherapy for a total of six days. At 14 days postradio therapy, all the rats were sacrificed and the spinal cord extracted immediately. Hematoxy line-eosine histologic studies showed that control animals only exposed to radiotherapy had severe alterations with hemorrhage and vacuolisation of the entire irradiated segment while these alterations were much less severe in the GH-treated group. In conclusion, 30 Gy irradiation produced morphological changes including vascular endothelial oedema, necrosis, hemorrhage, and inflamantory exudates. A2 mg/kg/day dose of GH protected the rat spinal cord against the noxious effects of the radiotherapy, decreasing the clinical, macro and microscopic damage in the treated animals

[A comparative study of the treatment of high grade gliomas]. / Estudio comparativo en el tratamiento de los gliomas de alto grado.

INTRODUCTION: The influence of surgery, radiotherapy and/or chemotherapy on the outcome on the results in patients with malignant gliomas is controversial. PATIENTS AND METHODS: We studied 44 patients (26, women; 18 men; age 38 72 years) diagnosed with grades III and IV astrocytoma who had been operated and then received adjuvant radiotherapy and either BCNU or temozolamyde chemotherapy. Survival time and adverse effects of the chemotherapy were analysed. CONCLUSION: Aggressive surgery associated with radiotherapy and temozolamyde chemotherapy prolonged survival in our patients with malignant astrocytomas.

Estudio comparativo del tratamiento de los gliomas de alto grado / A comparative study of the treatment of high grade gliomas

Introducción. En los pacientes con astrocitomas malignos se pueden emplear distintos tratamientos, como cirugía, radioterapia y quimioterapia, y es muy controvertida la influencia de estos tratamientos. Pacientes y métodos. Valoramos 44 pacientes diagnosticados de astrocitoma de grado III y IV intervenidos quirúrgicamente, que recibieron como tratamiento adyuvante radioterapia y quimioterapia con BCNU y temozolamida; 26 eran mujeres y 18 hombres, con edades comprendidas entre 38 y 72 años. Valoramos la supervivencia alcanzada por los enfermos y los efectos adversos de los distintos quimioterápicos, y correlacionamos el tratamiento administrado y los resultados. Conclusión. La cirugía agresiva asociada a radioterapia y quimioterapia con temozolamida prolonga la supervivencia de los pacientes con astrocitomas malignos (AU)

Introduction. The influence of surgery, radiotherapy and/or chemotherapy on the outcome on the results in patients with malignant gliomas is controversial. Patients and methods. We studied 44 patients (26, women; 18 men; age 38-72 years) diagnosed with grades III and IV astrocytoma who had been operated and then received adjuvant radiotherapy and either BCNU or temozolamyde chemotherapy. Survival time and adverse effects of the chemotherapy were analysed. Conclusion. Aggressive surgery associated with radiotherapy and temozolamyde chemotherapy prolonged survival in our patients with malignant astrocytomas (AU)

Aerosol orgotein (Ontosein) for the prevention of radiotherapy-induced adverse effects in head and neck cancer patients: a feasibility study.

Orgotein is an anti-inflammatory superoxide dismutase agent successfully used in treating several inflammatory diseases. It is also used in treating radiation-induced adverse effects in difference malignancies, notably breast, lung, bladder, prostate, cervix, and head and neck cancers. It is administered either topically or parenterally. To our knowledge, it has never been used before for prophylaxis of radiation-induced adverse effects or in aerosol form. Here we report on the results from a feasibility study on aerosol orgotein (Ontosein) for prevention of acute and deferred radiation-induced adverse effects in patients treated for head and neck malignancies. Our results show that aerosol orgotein administered before each radiation therapy session may impart some benefits in both incidence and severity of acute and deferred radiation-induced adverse effects in head and neck cancer patients, when compared with historical controls. In addition, aerosol orgotein administration is easy and convenient for both the patient and the radiotherapist.

Neoadjuvant therapy of rectal carcinoma with UFT-leucovorin plus radiotherapy.

BACKGROUND: The object of this phase II study was to assess the impact of preoperative external radiation therapy combined with UFT and leucovorin on tumor response, sphincter preservation and tumor control in patients with rectal carcinoma. PATIENTS AND METHODS: Forty-one patients with resectable extraperitoneal rectal adenocarcinoma received radiation therapy and two courses of chemotherapy. Chemotherapy consisted of a 2-h infusion of 6S-steroisomer of leucovorin (6SLV) 250 mg/m2 on day 1, oral 6SLV 7.5 mg every 12 h on days 2-14, and UFT either 350 or 300 mg/m2 on days 1 to 14 every 28 days. Six additional courses of chemotherapy were given after surgery. RESULTS: Seven of 16 patients (43%) who received 350 mg/m2/day of UFT had grade 3-4 diarrhea and two other patients (12%) had grade 3-4 dermatitis. The next 25 patients received 300 mg/m2/day of UFT and only 14% of them had grade 3-4 diarrhea. Surgery consisted of low-anterior resection in 26 patients (63%) and abdominal-perineal amputation in 15 (37%). There were six histological complete responses (15%). Downstaging occurred in 25 patients (63%). The overall survival at 3 years was 90% and the pelvic disease-free survival 92%. CONCLUSIONS: Preoperative therapy with radiotherapy and UFT-6SLV downstaged 63% of tumors and allowed a sphincter-preserving procedure in some patients. Toxicity was moderate. This scheme is convenient because of the oral administration of chemotherapy.

[Protective effects of growth hormone en cell cultures of the central nervous system]. / Efecto protector de la hormona de crecimiento en cultivos de células del sistema nervioso central.

OBJECTIVE: We examine a possible protective effect from growth hormone (GH) against radiation in cell cultures of rat embryon brain cortex. MATERIALS AND METHODS: Brain cortexes were removed from rat embryos of 17 days development and prepared for cell culture. The culture medium of half the plates was enriched with 500 ng/ml GH. All plates received a radiation dose of 3 Gy per plate and were again incubated for 24 hours. The TUNEL technique was employed to verify cell apoptosis in the irradiated plates and compare its level in plates with and without GH. CONCLUSIONS: We observed that irradiated cultures with GH had significantly less cell apoptosis than those without GH and concluded that this hormone excercised a protective effect on the cell cultures. The present study demonstrated the protective effect from GH in rat embryonary cells and suggests the need for future in vitro and in vivo studies using central nervous system cells.

Efecto protector de la hormona del crecimiento en cultivos de células del sistema nervioso central / Growth hormone protects rat embryon SNC cell cultures from radiation

Objetivo. Estudiar el efecto protector de la hormona del crecimiento (GH) in vitro en los cultivos de células de cortezas de embriones de ratas cuando se administra radioterapia. Material y métodos. Se han realizado cultivos de las células de las cortezas de embriones de ratas en el 17º día. Después de 24 horas de incubación de los cultivos con la GH (dosis, 500 ng/mL) sin sueros, las placas con los cultivos recibieron tratamiento radioterápico en una dosis de 3 Gy por placa, y se mantuvieron a continuación en estufa durante más de 24 horas para observar el efecto comparativo de la radioterapia en los cultivos irradiados con y sin la GH. Por medio de la técnica de TUNEL para verificación de la apoptosis celular hicimos un estudio comparativo para valorar si había diferentes grados de apoptosis en las placas de cultivos celulares con y sin la GH tras la administración de radioterapia. Conclusión. La GH, en la dosis empleada, causa un significativo aumento de la celularidad en las células cultivadas al ser una hormona proliferativa, factor comprobado por otros estudios realizados previamente. A través de la realización de la técnica de apoptosis en los cultivos de las células de la corteza de embriones de ratas apreciamos que, en las placas irradiadas que recibieron GH, hubo significativamente menos apoptosis celular que en los cultivos sin GH, la cual ejerce un efecto protector sobre estas células. Creemos que la GH ejerce un efecto protector sobre las células del SNC de embriones de ratas in vitro, y puede ser objeto de estudio su efecto protector in vivo (AU)

Clinical features of pharyngeal cancer: a retrospective study of 258 consecutive patients.

Pharyngeal cancer still presents an unsatisfactory mortality (30-40 per cent in most series, with a slightly better prognosis for nasopharyngeal cancer relative to both oropharyngeal and hypopharyngeal cancers) despite advances in treatment. Therefore, it is critical to know the clinical features of pharyngeal cancer. The purpose of this study was to investigate the most relevant clinical features of pharyngeal cancer (oropharyngeal, hypopharyngeal, and nasopharyngeal) in order to improve knowledge of this malignancy with the aim of ameliorating diagnosis and treatment. The retrospective study was based on a review of medical records from 258 consecutive patients with pharyngeal cancer (oropharyngeal, hypopharyngeal and nasopharyngeal) diagnosed at La Paz University Hospital, Madrid, Spain, between January 1 1991 and and December 31 1995. Medical records were provided by the Departments of Otorhinolaryngology, Head and Neck Surgery, Radiation Oncology, and Medical Oncology. All medical records were analysed for the following clinical variables: 1) incidence, 2) sociodemographics, 3) sites (oropharynx, hypopharynx, nasopharynx) and subsites, 4) clinical and histological staging, 5) pathology, 6) presenting symptoms, 7) time to diagnosis, 8) patients' general performance status at diagnosis, 9) personal cancer history and synchronous head and neck tumours, 10) premalignant lesions, and 11) paediatric cases. Our most outstanding finding was the excessively long time that elapsed between first clinical manifestation appearance and conclusive diagnosis of pharyngeal cancer (4.7 months for pharynx, 4.5 for oropharynx, 4.4 for hypopharynx and 6.5 for nasopharynx cancers). It was found that nasopharyngeal cancer was quite different from both oropharyngeal and hypopharyngeal cancers with respect to its potential aetiology, risk factors and clinical presentation. In addition it has a better prognosis.

Intramedullary spinal cord metastasis. A case report.

This 54-year-old patient with a breast carcinoma of one year's evolution presented a progressive paraparesis and sphincter disregulation of a week evolution; MRI image showed a tumor in the medullary conus. She improved after removal of the conus mass. The histologic diagnosis was metastasis of adenocarcinoma. Metastasis at this level is infrequent and represents less than 1% of all spinal metastases. When the patients' general condition is good, surgery can relieve the neurologic deficit produced by the medullary mass.

Growth hormone reduces bacterial translocation in radiation enteritis in the rat.

BACKGROUND: Radiotherapy may be considered as one of the most effective treatments for digestive tumours. This procedure has major side effects, especially in fast growing tissues like intestinal mucosa. The administration of drugs that reduce or avoid radiation injury of the intestinal mucosa may be clinically advantageous. Growth hormone is a peptide suitable for this purpose by modifying cell proliferation within the intestinal crypt. MATERIAL AND METHOD: Adult male Wistar rats were used in a model of abdominal irradiation. Each irradiated animal received 1200 cGy under anaesthesia and was sacrificed four and seven days later. The animals were treated with either saline or growth hormone (1 mg/kg/day) beginning immediately after the irradiation treatment. On the day of sacrifice, intestinal samples were taken for morphometric measurements and mesenteric lymph nodes for bacterial translocation. RESULTS: Mortality was of 50% approximately and was not affected by growth hormone treatment in irradiated animals. Bacterial translocation increased (p < 0.05) in irradiated animals whereas no significant increase was observed in rats treated with growth hormone. Growth hormone promotes an earlier growth of intestinal villi in irradiated animals (p < 0.05). CONCLUSIONS: Growth hormone promotes the morphologic adaptation of intestinal mucosa after abdominal irradiation, reducing bacterial translocation in rat.

Morphometric and proliferative effects of growth hormone on radiation enteritis in the rat.

UNLABELLED: Radiation enteritis is a common occurrence after radiotherapy in patients with abdominal tumors. Growth hormone may modify the response of the intestinal mucosa to radiation through its effects on the cell cycle or by increasing cell mass. The aim of this study is to determine the effects of growth hormone in the radiation-induced morphoproliferative changes in the intestinal mucosa. MATERIAL AND METHODS: An intestinal mucosal lesion was induced in adult male Wistar rats by means of abdominal irradiation with a lethal dose (LD50) of 1200 cGy. All animals received treatment with either saline or growth hormone for 7 days after irradiation. The animals were sacrificed on day 7. Body weight was determined the morphoproliferative status of the intestinal mucosa was assessed and the disaccharidase activity was measured. RESULTS: Growth hormone reduced body weight loss and increased mucosal length in irradiated rats. Mucosal proliferation was incremented in both irradiated and nonirradiated growth hormone-treated rats. Disaccharidase activity levels were similar to or higher than control values in all treated groups. CONCLUSION: Administration of growth hormone to irradiated rats reduces intestinal injury, probably as a consequence of an earlier recovery of intestinal morphology and functional status.

Brain tumor and pregnancy.

OBJECTIVE: To establish the indications for surgical intervention, at the appropriate gestational duration, for brain tumors in pregnant women, and to evaluate any association pregnancy hormones may have with the rate of growth or development of complications of brain tumors. METHODS: We observed seven women with brain tumors associated with pregnancy in a series of 126,413 pregnancies from 1983 to 1995. One woman presented with symptoms of intracranial hypertension, and neurologic signs were the first symptoms in two other women. One woman presented with a sudden hemorrhagic lesion, and three had focal seizures. All were evaluated with computed tomography, magnetic resonance imaging, or both. RESULTS: Six of the seven women had surgery; the seventh was treated with radiotherapy because the neuroradiologic studies suggested a quickly growing brainstem glioma. Diagnoses were confirmed on histology in six women: two with meningiomas, two with ependymomas, and two with low-grade astrocytomas (one of these had multiple astrocytomas). Estrogen and progesterone receptors were studied in two cases (one meningioma and one astrocytoma) and were present in both. CONCLUSION: Management of brain tumors should be tailored to the individual patient. There may be a relation between pregnancy hormones and the rate of brain tumor growth mediated through specific intracellular receptors.