Mechanical loading of intervertebral disc modulates microglia proliferation, activation, and chemotaxis.

OBJECTIVE: The aim of the study is to assess the effects of the neuroinflammatory microenvironment of a mechanically-induced degenerating intervertebral disc (IVD) on neuroinflammatory like cells such as microglia, in order to comprehend the role of microglial cells in degenerative disc disease. METHODS: Bovine caudal IVDs were kept in culture in an ex vivo bioreactor under high frequency loading and limited nutrition or in free swelling conditions as control samples. Conditioned media (CM) were collected, analysed for cytokine and neurotrophin content and applied to microglial cells for neuroinflammatory activation assessment. RESULTS: Degenerative conditioned medium (D-CM) induced a higher production of interleukin (IL)-8, nerve growth factor (NGF), interferon (IFN)-γ, IL-17 from IVD cells than unloaded control conditioned medium (U-CM). Upon 48 h of co-incubation with microglia, D-CM stimulated microglia proliferation, activation, with increased expression of ionized calcium binding adaptor molecule 1 (IBA1) and CD68, and chemotaxis. Moreover, an increment of nitrite production was observed. Interestingly, D-CM caused an upregulation of IL-1ß, IL-6, tumour necrosis factor α (TNFα), inducible NO synthase (iNOS), IBA1, and vascular endothelial growth factor (VEGF) genes in microglia. Similar results were obtained when microglia were treated with the combination of the measured cytokines. CONCLUSIONS: Our findings show that in IVD degenerative microenvironment, IL-8, NGF, IFN-γ, IL-17 drive activation of microglia in the spinal cord and increase upregulation of neuroinflammatory markers. This, in turn, enhances the inflammatory milieu within IVD tissues and in the peridiscal space, aggravating the cascade of degenerative events. This study provides evidence for an important role of microglia in maintaining IVD neuroinflammatory microenvironment and probably inducing low back pain.

Glucosylceramide synthase protects glioblastoma cells against autophagic and apoptotic death induced by temozolomide and Paclitaxel.

Glioblastoma is a deadly cancer with intrinsic chemoresistance. Understanding this property will aid in therapy. Glucosylceramide synthase (GCS) is associated with resistance and poor outcome; little is known about glioblastomas. In glioblastoma cells, temozolomide and paclitaxel induce ceramide increase, which in turn promotes cytotoxicity. In drug-resistant cells, both drugs are unable to accumulate ceramide, increased expression and activity of GCS is present, and its inhibitors hinder resistance. Resistant cells exhibit cross-resistance, despite differing in marker expression, and cytotoxic mechanism. These findings suggest that GCS protects glioblastoma cells against autophagic and apoptotic death, and contributes to cell survival under chemotherapy.

In vivo 19F MR imaging and spectroscopy for the BNCT optimization.

The aim of this study was to evaluate in vivo the boron biodistribution and pharmacokinetics of 4-borono-2-fluorophenylalanine ((19)F-BPA) using (19)F MR Imaging ((19)F MRI) and Spectroscopy ((19)F MRS). The correlation between the results obtained by both techniques, (19)F MRI on rat brain and (19)F MRS on blood samples, showed the maximum (19)F-BPA uptake in C6 glioma model at 2.5h after infusion determining the optimal irradiation time. Moreover, the effect of L-DOPA as potential enhancer of (19)F-BPA tumour intake was assessed using (19)F MRI.

Alfa talasemia e hidrops fetal no inmune a propósito de un caso diagnosticado en la Unidad de Ultrasonografía del Hospital Clínico San Borja Arriarán / Non-immune hydrops fetalis and alfa thalassemia

We report the unique case of a patient of asiatic origin (chinese), who was evaluated, followed and treated at the Sonography Unit of the Maternity Ward, Clinical Hospital San Borja Arriarán (HCSBA), with the collaboration of the Fetal Medicine Unit, Clinical Hospital of the University of Chile. The patient presented a 30 weeks gestation, which at the moment of evaluation showed a fetus with noninmune Hydrops (mother RH(+), Du (-)). Perinatal evaluation discarded cardiopathy, aneuploidiesmarkers and other malformations accounting for this condition. Fetal ultrasonographic evaluation showed severe cardiac insufficiency, middle cerebral artery Doppler (MCA) suggestive of severe anemia and severe oligoamnios with normal kidneys. Dueto these fi ndings and to the asiatic origin of the patient, the ethiological possibilities of viral infection, B19 parvovirus or anemia of genetic origin such as alfa thalassemia were suggested. Cordocentesis shows hematocrite of 39 percent, discordant with the value estimated by MCA Doppler, which reduced the possibility of a viral origin. We sent a fetal blood sample for Hb electrophoresis. Given the critical hemodynamic conditions and having completed the profilaxis of the hyaline membrane, gestation is interrupted by cesarean section, getting a male NB weighing 2.400 gr, in poor condition, who dies at 10 hours from birth. Electrophoresis reported postcesarean section confirms the diagnosis.

Se reporta el caso inédito, de una paciente de origen asiático (China), evaluada, seguida y tratada en la Unidad de Ultrasonografía de la Maternidad del Hospital Clínico San Borja Arriarán (HCSBA), con la colaboración de la Unidad de Medicina Fetal del Hospital Clínico de la Universidad de Chile. La paciente cursaba un embarazo de 30 semanas al momento de ser evaluada en nuestra unidad donde se diagnosticó una gestación única con un feto que presentaba un hidrops no inmune (madre Rh(+), Du (-)). La evaluación perinatal descartó cardiopatía, marcadores de aneuploidía y otras malformaciones que explicaran dicha condición. La evaluación ultrasonográfica fetal mostraba insuficiencia cardiaca severa, Doppler de arteria cerebral media (ACM) sugerente de anemia severa, oligoamnios severo con riñones normales. Debido a estos hallazgos y al origen asiático de la paciente se plantea la posibilidad etiológica de una anemia por infección viral, (parvovirus B19), o una anemia de origen genético, como la alfa talasemia. La cordocentesis muestra un hematocrito de 39 por ciento, discordante con el valor estimado por Doppler de ACM, lo que alejaba la posibilidad de un origen viral y se envía muestra de sangre fetal para electroforesis de hemoglobina(Hb) fetales. Dada las condiciones hemodinámicas críticas y haber completado profilaxis de membrana hialina se interrumpe el embarazo mediante una cesárea obteniéndose un RN de sexo masculino de 2.400 g, hidrópico, en malas condiciones que fallece a las 10 horas de vida. La electroforesis de proteína de sangre fetal, informada post cesárea, confirma el diagnóstico de alfa talasemia.

Intracranial metastasis of testicular seminoma in an HIV-positive. Case report and review.

We present what appears to be the first case of an intracranial metastasis from testicular seminoma in an HIV-positive patient. The computed tomography and magnetic resonance imaging appearance of the lesion mimicked meningioma or lymphoma. A significant increase in the risk of testicular seminoma has been reported in AIDS patients. Whenever there is lymph-node involvement upon diagnosis of testicular seminoma, intracranial metastases may appear. After surgical removal of an intracranial metastasis from testicular seminoma, radiotherapy should be considered. Chemotherapy is to be included in the treatment of intracranial metastases from testicular seminoma with systemic involvement.

Estimación de los costos totales y parciales de diagnóstico: tratamiento quirúrgico y seguimiento de la hidatidosis hepática en el Hospital San Juan de Dios Santiago Chile 1990-1999 / Estimation of the total and partial costs of diagnosis, surgical treatment and follow up of the liver hydatidosis in the Hospital San Juan de Dios, Santiago, Chile 1990-1999

La hidatidosis hepática es la forma más frecuente de presentación del estado larval de la taenia Echinococcus granulosus en el hombre y nuestro medio no es la excepción. Esta forma de presentación de la hidatidosis es grave y conlleva una serie de problemas económicos tanto para el paciente como para los servicios de salud, ya que su resolución más frecuente es la quirúrgica. Los gastos económicos son los únicos que podemos establecer como costos de esta enfermedad, ya que la morbilidad y mortalidad, indicadores que han sido empleados hasta la fecha, tienen serias limitaciones por efecto de la subnotificación de casos operados en los hospitales. De acuerdo a estos antecedentes se decidió estudiar los gastos económicos de diagnóstico, procedimientos, fármacos y consultas producidos por las cirugías hidatídicas hepáticas realizadas en la década del 90 en el Hospital San Juan de Dios de Santiago, centro de referencia regional para estas intervenciones. Con este fin se estudiaron las fichas clínicas de 16 casos con el diagnóstico de Hidatidosis hepática operada, y cuyos registros estaban completos. Todos los antecedentes de consultas, exámenes, fármacos, tipos de cirugía, etcétera, fueron valorizados de acuerdo a los valores del sistema básico de salud en Chile, analizando posteriormente los valores por el método estadístico de mediana. Se lograron reunir 16 casos de entre 23 y 71 años, siendo en su mayoría pertenecientes al sector rural. Los pacientes estuvieron hospitalizados entre 6 y 71 días, con una mediana de 17 días. El costo mínimo de un caso alcanzó a $ 617.953 y el máximo a $ 3.147.373, con un costo total de $ 1.117.450, equivalente a USA $ 1.591. Este valor correspondió a la mediana del total de casos de hidatidosis hepática. Los costos de exámenes generales fueron los más altos seguidos por la TAC y los menores correspondieron a los exámenes bacteriológicos. De acuerdo a estos antecedentes la hidatidosis hepática en nuestro medio frecuentemente tienen un valor cercano a los 1.600 dólares en su tratamiento. De acuerdo a la prevalencia de la infección y la forma de presentación clínica más frecuente de ella, las autoridades de salud deberían incrementar los programas de prevención de la patología para evitar el costo económico en salud individual, familiar y social que ella produce

Estimación de los costos totales y parciales de diagnóstico, tratamiento quirúrgico y seguimiento de la hidatidosis pulmonar en el Hospital San Juan de Dios, Santiago, Chile, 1990-1999 / Estimation of the total and partial costs of diagnostic, surgical treatment and follow up of the lung hidatidosis in the hospital San Juan de Dios, Santiago, Chile, 1990-1999

La hidatidosis pulmonar es una patología que requiere generalmente de cirugía para su tratamiento y cuyo costo no ha sido establecido directamente sino que sólo a través de la mortalidad y morbilidad que produce. El presente estudio pretendió establecer los costos económicos que significa la hidatidosis pulmonar en cuanto a diagnóstico, tratamiento y seguimiento en 15 casos atendidos entre 1990 y 1999 en el Hospital San Juan de Dios. Para este propósito las fichas médicas fueron valorizadas de acuerdo a los aranceles FONASA, y los insumos mediante los valores de la Central de Abastecimiento del MINSAL. Los resultados mostraron que la hidatidosis pulmonar tiene una mediana de hospitalización de 22 días, con una mediana de 1 cirugía por paciente, el costo total por pacientee osciló entre US$942 y US$3.839, con una mediana de US$1.683. Al sumar las licencias médicas este costo sube a un total de US$1.848. Los mayores costos están dados por la cirugía propiamente tal, seguido por los exámenesimagenológicos, los cuales además de tener utilidad diagnóstico permiten al médico mejorar su abordaje quirúrgico. De acuerdo a los resultados, la hidatidosis sigue siendo una patología frecuente e importante, no tan solo por el impacto en la salud de las personas, sino también por la carga que implica la enfermedad para el paciente, la familia y los servicios de salud

Cerebellar mature teratoma in adulthood.

Mature teratoma of the posterior cranial fossa in adults is extremely rare. We report a particularly rare case of medio-lateral cerebellar mature teratoma that became symptomatic in a middle-aged man. The CT revealed the lesion of heterogeneous density with calcifications in the solid medial portion. Only the MRI could reliably define the borders of the cystic component extending into the left cerebellar lobe. Histologically the presence of fully matured representative tissues of the 3 germ layers ensured the diagnosis of mature teratoma. We suggest that the cyst formation from progressive latent hemorrhage and/or secretion from the gland cells of the tumor, may be responsible for the clinical decompensation even in adulthood.

Hipertrigliceridemia y terapia anti-retroviral en pacientes VIH: casos clínicos / Hypertrigliceridaemia and antiretroviral therapy in HIV patients: clinical cases

En los últimos años, la terapia anti-retroviral ha reducido significativamente la morbimortalidad en pacientes VIH (+). Esto ha permitido evidenciar la existencia de distintos efectos metabólicos adversos relacionados con ella. Uno de estos efectos es la hipertrigliceridemia, trastorno del metabolismo lipídico que es factor predisponente para el desarrollo de la pancreatitis aguda y de cardiopatía coronaria y que se asocia con mayor frecuencia con el uso de inhibidores de la proteasa. El manejo de estos paciente incluye la modificación de hábitos de vida y el uso de drogas hipoglicemiantes. Algunos autores consideran la modificación de la terapia antiretroviral como manejo alternativo. Se presentandos casos clínicos y una revisión del tema

Multiple intracranial lesions in head injury: clinical considerations, prognostic factors, management, and results in 95 patients.

BACKGROUND: The goal of this study was to identify clinical and radiological predictors of prognosis in patients with multiple post-traumatic intracranial lesions. METHODS: We reviewed 95 patients (75 male and 20 female) between the ages of 18 and 70 (average 38) admitted between 1993 and 2000 with multiple post-traumatic intracranial lesions. Intracranial pressure (ICP) monitoring was carried out in 67 patients (70%); 77 received intensive care unit (ICU) treatment. Since in all cases it was possible to identify a clearly predominant lesion, 3 groups of patients emerged from the data: the first with extradural hematoma (EDH), the second with a combination of homolateral subdural (SDH) and intracerebral hematoma (ICH), and the third with pure focal intracerebral hematoma (ICH). RESULTS: Twenty-seven patients were treated conservatively, 2 of whom died (7.4%); both had bilateral ICH and compression of the basal cisterns. Sixty-eight patients underwent one or more surgeries; 8 died (11.7%). In the group with EDH-predominant lesions (27 cases) all patients were operated (16 for multiple lesions); no one died. In the group with SDH+ICH-predominant lesions, 26 of 32 patients were operated (10 had multiple procedures); 6 died (18.7%), 3 were vegetative. In the group with ICH-predominant lesion, 15 of 36 patients were operated (7 bilaterally); 4 died (11%). Decompressive craniectomy proved to be a useful means to control ICP. Bilateral lobectomy is not recommended because of poor results. Immediate postoperative computed tomography (CT) scan proved to be mandatory to detect additional surgically treatable lesions (16 cases). Statistical analysis was performed by means of chi(2) analysis and multiple linear regression model. The multiple linear regression model was used to ascertain risk factors independently associated with the outcome. The type of lesion (presence of SDH+ICH predominant lesion), the worst recorded Glasgow Coma Scale (GCS) score, the presence of prolonged increased ICP, and the absence of pupillary reflexes were all statistically significant predictors of a bad outcome (dead or vegetative state). CONCLUSIONS: Multiple lesions have the same prognosis as the corresponding single lesions; therefore, their management should be guided by the predominant pathology.

Concomitant cisplatin/5-FU infusion and radiotherapy in advanced head and neck cancer: 8-year analysis of results.

BACKGROUND: The purpose of this study was to analyze long-term follow-up of a single institution's experience with a regimen of concomitant cisplatin/fluorouracil (5-FU) infusion and radiation given every other week. This analysis was stimulated by results of a randomized trial showing superiority for this regimen over induction cisplatin/5-FU chemotherapy followed by radiotherapy, especially in regional disease control. METHODS: All patients with stage III/IV disease who were referred by surgeons for nonoperative therapy and had a follow-up of at least 2 years were included. Concomitant chemoradiotherapy was administered days 1-5 of a 2-week treatment cycle, for a total of 7 cycles, with cisplatin 60 mg/m2 day 1, 5-FU 800 mg/m2 given over 24 hours days 1-5, and radiation 2 Gy days 1-5. RESULTS: Seventy-eight patients with stage III (n = 16) or IV (n = 62) were treated and followed for a median of 8 years. Six patients died during treatment, of aspiration pneumonia, sudden death, gastrointestinal bleeding, and stroke. When assessed 6 weeks after the end of treatment, 45 patients (63%) had no clinical evidence of disease, whereas 27 (37%) still had some persistent abnormality. However, 17 of these "partial responders" have not recurred. In all, 24 patients (31%) have recurred or progressed, 13 at the primary site, 5 after 3 years. None of 16 stage III and 24 (39%) of 62 stage IV patients ever progressed. Tongue and glottic larynx did best, with only 1 of 22 patients ever failing (none locally). Supraglottic and oral cavity cancers other than tongue had the worst failure rates. Nineteen patients (24%) died of other causes (DOC), tumor-free. Patients who DOC correlated strongly with T stage (p < .002) but not with N stage or with AJC stage. The 5-year progression-free survival was 60% (confidence interval [CI] = 49% to 72%), and overall survival was 43% (CI = 33% to 56%). CONCLUSIONS: Disease control for this advanced head and neck cancer population was excellent. This regimen was especially effective in advanced tongue and glottic cancers and all stage III disease sites. Advanced supraglottic and hypopharynx cancers are problematic. These, and especially T4 lesions, are associated with high DOC rates, possibly in part related to swallowing malfunction. Nevertheless, the long-term survival without surgical intervention was high with this regimen.

In vivo 31P spectroscopy study of treated and untreated recovery of rat partial brain ischemia.

Quantitative 31P NMR was used to follow the time variation of the hypometabolic response to hypoxic partial ischemia in an animal model. The purpose of the study was to establish the value of this repeated spectroscopy operating by means of a surface coil. It aimed at determining whether a therapeutic intervention could influence the transient changes occurring during the insult or early recovery. A pharmacological substance was thus used during a reversible forebrain ischemia, induced by a combination of vascular occlusion and mild hypoxia in two groups of rats. As an available and convenient example, L-carnitine was chosen. Statistical analysis of the experimental results revealed a significant difference of the Pi and PCr levels between treated and untreated animals.

Flow cytometric DNA analysis in prediction of intravesical recurrence from human bladder-cancer.

A series of 128 patients undergoing diagnostic and/or therapeutic transurethral resection for primary urothelial bladder carcinoma was prospectively studied in order to evaluate the relative importance of DNA-ploidy and S-phase fraction (SPF) by flow cytometry and of several clinicopathological features in predicting disease-free survival. Only frozen tissue was used. The mean follow-up was 22 months (range: 3-61 months). DNA-aneuploidy was present in 64% of the cases (82/128), while multiclonality was found in 29% of the DNA-aneuploid cases (24/82). In the univariate statistical analysis, high stage, DNA-aneuploidy (mono- and multiclonal patterns) and high SPF value (>11.6%) proved to be significantly related to the risk of intravesical recurrence, while a significant trend was present for histological grade. In the multivariate analysis only high SPF value (>11.6%) and DNA-aneuploidy were independently related to risk of relapse (RR of 2.39 and 2.40 respectively).

[Neurosurgical aspects of urologic metastases]. / Aspetti neurochirurgici delle metastasi urologiche.

Metastases in the central nervous system (C.N.S.) from urological tumors can be spinal or craniocerebral. The experience of 30 patients with spinal and craniocerebral metastases from urological tumors admitted to Neurosurgical Clinic of the University of Milan, is reported. They were 7.5% of the all number of metastases admitted at the Neurosurgical Department, during the same period. The brain metastases constitute 10% of brain metastases diagnosed in this period. Only patients with solitary (to CT scan and NMR) metastasis, and with a general prognosis that allow to an adequate and useful period of survival, are submitted to surgical treatment. 23 patients (76.6%) are surgical treated. The mean survival from the discovery of the C.N.S. metastases was 9 months (9.4 months among surgically treated patients and 7.8 months among those were not operated). Surgical mortality was 13%. Out of patients with survival until 5 months, patients submitted to surgical treatment showed a better quality of life. Our results allow us to affirm that in selected patients surgical removal of solitary metastases, could improve the quality of survival, but is not able to prolong substantially the period of survival.

Partial cerebral ischemia assessed by "in vivo" 31P NMR spectroscopy in rats.

31P NMR spectroscopy was used to assess the cerebral ischemia status in rats by measuring the relative levels of phosphate metabolites. Partial cerebral ischemia was induced in 49 rats by reversible occlusion of the carotid arteries. Rats were intubated and mechanically ventilated on a hypoxic gas mixture. Physiological parameters such as temperature and arterial pressure were strictly controlled during the experiments. 31P spectra were acquired at 7 T during basal observation, for 15-20 min after the induction of ischemia, and for 1 hr after reperfusion. Depletion and increase in PCr and Pi levels, respectively, were already observable in the collected spectra within few minutes after the onset of ischemia. No appreciable changes were found in the ATP levels.

Membrane lipids modifications in human gliomas of different degree of malignancy.

A great deal of experimental evidence shows that the growth of tumors is accompanied by significant changes at the expense of the cell surface. For the present paper, we set out to analyse the composition of membrane lipids (cholesterol, phospholipids, neutral and acidic glycosphingolipids, sulphatides) in human cerebral astrocytomas, which is a group of tumors that offer a valid model for the study of the various grades of cellular transformations in vivo. The results obtained in the present study permit us to draw a series of conclusions in relation to the malignancy grade of glial human tumors. In particular, an increase in the malignancy is accompanied by: 1) a reduction of the total lipids, a reduction that involves all the principal classes of lipids of the plasma membrane, for which it has been possible to demonstrate a correlation of an exponential nature, which is significant with the increasing of the histological grading; 2) a gradual accumulation, in the area of glycosphingolipids, of lattosylceramide and GD3, molecules that can constitute a valid marker of the malignancy grade; moreover, the glycolipid composition of astrocytomas of high degree differs from that of tumors of a low grade because of the presence of more complex glycolipids (trihexosylceramide and tetraosylceramide); 3) a gradual increase, in the area of phospholipids, of PC/PE and PC/SM ratios, indices of the microviscosity of the membrane. The data obtained suggest that the profound modifications of membrane lipids, which are gradually accompanied by a progressive increase in the malignancy of the tumor, can, on the one hand, be responsible for functional variations connected with neoplastic growth, and, on the other hand, constitute valuable biochemical parameters which are useful, together with histological studies, in the diagnosis of these tumors.

Study of cellular DNA content by flow cytometry in primary bladder carcinomas. Significance of monoclonal and multiclonal varieties of DNA aneuploidy.

A prospective study of cellular DNA content by flow cytometry was performed on a nonconsecutive series of 67 patients undergoing diagnostic and/or therapeutic transurethral resection for primary urothelial bladder carcinoma. DNA-aneuploidy was present in 82% of the cases (55/67), while multiclonality was found in 45% of the DNA-aneuploid cases (25/55). DNA-ploidy was much more strictly correlated with histological grading (p less than 0.005) than with papillary or non-papillary growth pattern (p less than 0.05) or T staging (p less than 0.05). Of 26 patients with a minimum follow-up of 24 months, 100% (6/6) of cases with DNA-diploid neoplasias showed no signs of disease relapse, versus 10% (2/20) of those with DNA-aneuploid neoplasias (p less than 0.001). Furthermore, tumoral progression occurred in 10 of 20 cases (50%) with aneuploid DNA content. In this latter group of 10 cases a multiclonal DNA-aneuploid pattern was found, with a significant difference (p less than 0.001).

Gastrointestinal manifestations of epidermolysis bullosa in children.

The medical and surgical management of the chronic and recurrent esophageal and anal lesions of recessive dystrophic epidermolysis bullosa pose challenging problems for the physician. Various therapeutic approaches are discussed, and the case histories of four problem patients are reviewed.

Modified crossed-ellipse radiofrequency coil for MRI.

New coil geometries obtained by computer simulations from the crossed-ellipse rf coil are reported. These geometries with elliptical transverse section improve the signal-to-noise ratio with respect to the classic ellipse and saddle coils. The increase of signal-to-noise ratio is mainly due to the reduction of coil losses and to the better B1 efficiency and distribution.