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Biomedical subjects

Julio Sotelo

Publications and source records attributed to Julio Sotelo.

At least 19 recordsLinked to original sources
PubMed2006

Western and Asian features of multiple sclerosis in Mexican Mestizos.

OBJECTIVES: The objective of this study was to compare the clinical expression of MS in Mexican Mestizos with that of patients of European or Asian descent; as well as to compare the annual frequency of new cases with that observed in the previous decades. PATIENTS AND METHODS: All patients with diagnosis of definite MS seen at the National Institute of Neurology and Neurosurgery of Mexico from January 1993 to December 2003 were studied (n=312). Sociodemographic and clinical characteristics were compared with reports of patients from either Western or Asian origin; the long-term disability score was analyzed according to gender, age of onset of MS and the initial symptom. RESULTS: The clinical expression of MS in Mexican Mestizos shares some characteristics with both, Asian and Western forms of MS indicating that the genetic composition of Mexican Mestizos participates in the clinical expression of the disease. Also, at the prevalence date, the mean age of patients and the duration of the disease were lower in our patients than in MS patients from endemic countries suggesting a true increasing incidence in recent times, rather than only improved case ascertainment. CONCLUSIONS: Clinical expression of MS in Mexican Mestizos shows the coexistence of some features common in European and in Asian cases.

Adult↗
PubMed2006

Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Malignant cell clones resistant to chemotherapy and radiotherapy frequently lead to treatment failure in patients with glioblastoma multiforme. Preliminary studies suggest that adding chloroquine to conventional therapy may improve treatment outcomes. OBJECTIVE: To examine the effect of adding chloroquine to conventional therapy for glioblastoma multiforme. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: National Institute of Neurology and Neurosurgery of Mexico. PATIENTS: 30 patients with surgically confirmed glioblastoma confined to 1 cerebral hemisphere, with a Karnofsky performance score greater than 70, no comorbid disease, and age younger than 60 years. INTERVENTIONS: Oral chloroquine at 150 mg/d for 12 months beginning on postoperative day 5 or placebo. All patients received conventional chemotherapy and radiotherapy. MEASUREMENTS: Primary outcome was survival after surgery; surviving patients were followed up to October 2005. Periodic evaluation using the Karnofsky scale and imaging studies, as well as hematologic tests and ophthalmologic examinations, was done in all patients. RESULTS: Median survival after surgery was 24 months for chloroquine-treated patients and 11 months for controls. At the end of the observation period, 6 patients treated with chloroquine had survived 59, 45, 30, 27, 27, and 20 months, respectively; 3 patients from the control group had survived 32, 25, and 22 months, respectively. Although not statistically significantly different, the rate of death with time was approximately half as large in patients receiving chloroquine as in patients receiving placebo (hazard ratio, 0.52 [95% CI, 0.21 to 1.26]; P = 0.139). LIMITATIONS: The observed advantage of chloroquine may be due to chance; differences in pretreatment characteristics and conventional treatment regimens could not be adjusted for because of the small sample size. CONCLUSIONS: Chloroquine may improve mid-term survival when given in addition to conventional therapy for glioblastoma multiforme. These results suggest that larger, more definitive studies of chloroquine as adjuvant therapy for glioblastoma are warranted.

Adult↗
PubMed2006

Clinico-pathological and immunohistochemical characteristics associated to recurrence/regrowth of craniopharyngiomas.

BACKGROUND: Craniopharyngioma is a rare, benign epithelial brain tumor of the suprasellar region with a high rate of recurrence. Clinical and histopathological features that might be predictors of recurrence/regrowth have not been clearly delineated. METHODS: We compared recurrence/regrowth of the tumors with the clinico-pathological characteristics, vascular density, cell proliferation index, and immunohistochemical profile (cytokeratins, epithelial membrane antigen [EMA], carcinoembrionary antigen [CEA], and laminin) of 47 patients with craniopharyngioma followed for more than 5 years. RESULTS: Tumors were adamantinomatous in 42 cases (89%) and papillary squamous in 5 cases (11%). Immunoreactivity for cytokeratin 8/18/19 was positive in 64%; cytokeratin 5 in 42%; laminin 8 in 62%; and CEA in 21%. The cell proliferation index and vascular density were greater in adamantinomatous than in papillary tumors (22+/-6 versus 17+/-3, p=0.05; and 21+/-3 versus 17+/-3, p=0.037, respectively); they were neither related to recurrence nor to regrowth. No significant differences were found between adamantinomatous and papillary tumors regarding the presence of cytokeratin, laminin, CEA or glial fibrillary acidic protein (GFAP). Recurrence rate at 5 years was 59%. No relation was found between recurrence and adjuvant radiotherapy (AR). Residual tumor after surgery, whorl-like arrays (p=0.04) and immunoreactivity for p53 (p=0.022) were significantly related to recurrence/regrowth. CONCLUSIONS: Residual tumor after surgery, immunoreactivity to p53 and presence of whorl-like arrays are associated to recurrence/regrowth of craniopharyngioma.

Adult↗
PubMed2005

Ventriculoperitoneal shunt of continuous flow vs valvular shunt for treatment of hydrocephalus in adults.

BACKGROUND: Shunting for hydrocephalus is the neurosurgical procedure most frequently associated with long-term complications. We developed an alternative to valvular shunts based on a simple shunt procedure whose functioning depends on a peritoneal catheter with a highly precise cross-sectional internal diameter of 0.51 mm. Preliminary studies have shown that the shunt of continuous flow (SCF) is superior to valvular shunts for the treatment of hydrocephalus in adults. Here, we show the long-term performance of the SCF in adult patients with hydrocephalus secondary to a comprehensive variety of neurological disorders. METHODS: In a 5-year period, ventriculoperitoneal shunting was performed on 307 patients with hydrocephalus; 114 of them were treated with the SCF and 193 controls were treated with a conventional valvular shunt. Patients were followed from 1 to 5 years after surgery; endpoint observation was considered at surgical reintervention because of shunt failure. RESULTS: At the end of the observation period (44 +/- 17 months), the failure rate of the shunting device was 14% for the SCF and 46% for controls (P < .0002). Shunt endurance was 88% in patients with SCF and 60% in controls. Along the study, signs of overdrainage developed in 40% of patients treated with valvular shunt, but they were not observed in patients with SCF. CONCLUSIONS: The design of the SCF was calculated according to the mean rates of cerebrospinal fluid production; it takes simultaneous advantage of the intraventricular pressure and the siphon effect and complies with the principle of uninterrupted flow, maintaining a fair equilibrium that prevents under- and overdrainage. The SCF is a simple, inexpensive, and effective treatment for hydrocephalus in adults.

Adolescent↗
PubMed2005

Prolonged exposure to lead lowers the threshold of pentylenetetrazole-induced seizures in rats.

PURPOSE: The aim of this work was to study the effects of prolonged exposure to lead on the threshold of experimental seizures induced by pentylenetetrazole (PTZ). METHODS: The 120 Wistar male rats were allocated randomly into four groups; (A) controls, and lead-treatment groups (B, C, and D) that received lead acetate in the drinking water for a period of 30 days at concentrations of 250, 500, and 1,000 ppm, respectively. After exposure, a trial of PTZ-induced seizures was conducted in all groups, and blood contents of lead were determined by atomic absorption spectrophotometry. RESULTS: Blood lead contents increased in a dose-dependent manner. Time elapsed to develop the first myoclonic jerk and the tonic-clonic seizure was less in all lead-exposed groups than in controls. This effect was greater in the groups administered 500 and 1,000 ppm of lead. The required doses of PTZ to induce myoclonic jerks and tonic-clonic seizures were lower in lead-exposed rats than in controls. CONCLUSIONS: We found a reduction in the threshold for seizures in rats whose blood contents of lead were similar to those of humans from some areas of urban centers with high levels of air pollution.

Air Pollutants↗
PubMed2005

Cas IIgly induces apoptosis in glioma C6 cells in vitro and in vivo through caspase-dependent and caspase-independent mechanisms.

In this work, we investigated the effects of Casiopeina II-gly (Cas IIgly)--a new copper compound exhibiting antineoplastic activity--on glioma C6 cells under both in vitro and in vivo conditions, as an approach to identify potential therapeutic agents against malignant glioma. The exposure of C6 cells to Cas IIgly significantly inhibited cell proliferation, increased reactive oxygen species (ROS) formation, and induced apoptosis in a dose-dependent manner. In cultured C6 cells, Cas IIgly caused mitochondrio-nuclear translocation of apoptosis induction factor (AIF) and endonuclease G at all concentrations tested; in contrast, fragmentation of nucleosomal DNA, cytochrome c release, and caspase-3 activation were observed at high concentrations. Administration of N-acetyl-L-cystein, an antioxidant, resulted in significant inhibition of AIF translocation, nucleosomal DNA fragmentation, and caspase-3 activation induced by Cas IIgly. These results suggest that caspase-dependent and caspase-independent pathways both participate in apoptotic events elicited by Cas IIgly. ROS formation induced by Cas IIgly might also be involved in the mitochondrio-nuclear translocation of AIF and apoptosis. In addition, treatment of glioma C6-positive rats with Cas IIgly reduced tumor volume and mitotic and cell proliferation indexes, and increased apoptotic index. Our findings support the use of Cas IIgly for the treatment of malignant gliomas.

Acetylcysteine↗
PubMed2004

Coexpression of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor cMET predict recurrence of meningiomas.

Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the cMET tyrosine kinase participate in cancer invasion, angiogenesis and metastasis in a wide variety of neoplastic cells. Meningioma is a bening tumour, however, it has a high rate of recurrence after surgery; the most important factor to predict relapse is the extent of surgical resection, several other potentially predictive factors have been studied with poor results. We examined by immunohistochemistry the expression of HGF/SF and its cMET receptor in a group of patients with benign meningioma with or without recurrence (n = 17 and n = 25, respectively), after a minimal follow-up of least 6 years. Expression and coexpression of HGF/SF and cMET were compared with cell proliferation index, vascular density and clinical outcome. Coexpression of HGF/SF and cMET in meningiomas had a significant association with cell proliferation index and with recurrence (P < 0.037). Determination of HGF and cMET coexpression in meningiomas could be used as a predictor of recurrence.

Adult↗
PubMed2004

Brief presence of varicella-zoster vral DNA in mononuclear cells during relapses of multiple sclerosis.

BACKGROUND: A possible viral cause for multiple sclerosis (MS) has long been suspected. A progressive increase in MS has been reported in Mexico during the past 20 years; a conspicuous antecedent of varicella infection during childhood has been the most relevant finding in the medical history of patients with MS. OBJECTIVE: To investigate the possible participation of varicella-zoster virus (VZV) in the etiopathogenesis of MS. DESIGN, SETTING, AND PATIENTS: We searched, by polymerase chain reaction (PCR), for VZV DNA in peripheral mononuclear cells of 82 patients with relapsing-remitting MS. Additionally, genes gD from herpes simplex viruses 1 and 2 were sought by PCR, as well as IgG and IgM serum antibodies to VZV. RESULTS: Viral DNA from the genes open reading frame (ORF)31, ORF62, ORF63, and ORF67 of VZV was found in mononuclear cells from 13 (87%) of 15 patients with MS who were tested during acute relapse. All patients who were tested during remission (n = 67) were negative for the DNA, including patients who were initially positive and were tested again after 2 months of remission. All control patients with a comprehensive variety of neurologic diseases (n = 100) and healthy controls (n = 20) also tested negative. All subjects were negative for herpes simplex viruses 1 and 2 DNA, and no differences were found in serum antibodies to VZV. CONCLUSIONS: The finding of genes of VZV in peripheral mononuclear cells, restricted to a brief period during clinical relapse of MS, suggests either its participation in the etiopathogenesis of MS or an epiphenomenon of viral activation simultaneous with the relapse of MS.

Adolescent↗
PubMed2004

Interstitial quinacrine activates a distinctive immune response effective for tumor immunotherapy.

BACKGROUND: Interstitial immunotherapy consists of the local injection of immune cells or molecules with cytotoxic properties to destroy neoplastic cells. Intratumor injection of quinacrine induces intense recruitment of activated immune cells that leads to necrosis and elimination of experimental malignant neoplasms; this effect seems to be mediated by immune molecules. METHODS: We measured the tissue content of activated immune cells and various cytokines at different times during the first 8 days after a single interstitial injection of 150 mg quinacrine in rats. RESULTS: A large cell infiltrate by macrophages, CD4(+), CD8(+), and natural killer cells was evident a few hours after quinacrine injection. In comparison with controls, tissue contents of 4 cytokines had a marked increase: macrophage chemoattractant protein-1 increased 115-fold; interleukin-6, 9-fold; RANTES (regulated on activation, normal T cell expressed and secreted), 13-fold; and macrophage inflammatory protein-2, 10-fold. Other cytokines, like interleukins 1beta, 2, 4, 10, interferon-gamma, tumor necrosis factor-alpha, complement 3, and C reactive protein did not increase significantly, indicating that the endogenous local response to quinacrine follows a singular pathway of immune activation. CONCLUSIONS: Interstitial quinacrine is a strong activator of innate immunity and is not mediated by the usual mechanisms of immune recognition. It constitutes an original approach for regional immunotherapy of neoplasms that is not mediated solely by induction of local, cytotoxic chemical necrosis.

Animals↗
PubMed2004

Angiotensin II, cell proliferation and angiogenesis regulator: biologic and therapeutic implications in cancer.

Angiotensin II (ANG II) is the main effector peptide in the renin-angiotensin system. It is generated by the activation of Angiotensin I through the Angiotensin II Converter Enzyme (ACE II). ANG II has multiple physiologic effects that regulate vascular tone, hormone secretion, tissue growth and neural activity. It has systemic (endocrine) and local (paracrine and autocrine) effects, favoring cell growth and differentiation through four types of receptors from which types 1 and 2 (AT(1) and AT(2)) are the most important. Stimulation of AT(1) leads to the activation of intracellular pathways that finally lead to vasoconstriction, inflammation and proliferation. The AT(2) receptor is mainly expressed in fetal tissue and scantly in the cardiovascular system under different circumstances. Its effects are opposite to those of the AT(1). The stimulation of AT(1) activates second messengers that lead to a rapid production of diacylglycerol and 1-4-5-inositol triphosphate, as well as to the activation of C protein. Several reports indicate that ANG II can induce neovascularization in experimental systems due to the expression of different growth factors such as angiopoietin 2, vascular endothelial factor, and its receptor, fibroblast growth factor, platelet derived growth factor, transforming growth factor beta and epidermal growth factor. Other mechanisms associated with ANG II induced angiogenesis are nitric oxide synthase and metalloproteinase expression, as well as inflammation induction. Angiogenesis is a fundamental process to tissue repair and development, and it participates in several pathologic processes. In addition, the AT(1) receptor is expressed in many malignant neoplasms and its blockade through ECA II inhibitors and ANG II antagonists has shown antineoplastic activity as well as angiogenesis inhibition in tumoral experimental models. This review discusses the mechanisms by which ANG II participates in neoplastic and non-neoplastic tissue angiogenesis and its possible therapeutic implications.

Angiotensin II↗
PubMed2004

Continuous-flow shunt for treatment of hydrocephalus due to lesions of the posterior fossa.

OBJECT: Management of hydrocephalus caused by expansive lesions of the posterior fossa is complicated by two main drawbacks of shunt devices: sudden decompression and overdrainage. The ventriculoperitoneal (VP) continuous-flow (CF) shunt is characterized by a peritoneal catheter with an internal diameter of 0.51 mm that promotes continuous drainage of cerebrospinal fluid (CSF) at its production rate. The authors have previously demonstrated in adult patients with hydrocephalus that sudden decompression and overdrainage are absent when this shunt is used; here they report the findings of a prospective study in which the goal was to test the performance of this shunt in patients with severe hydrocephalus due to lesions of the posterior fossa. METHODS: During a 5-year period, 103 patients with severe hydrocephalus caused by lesions of the posterior fossa were treated by placement of a VP shunt. In 53 of these patients (control group) a shunt and valve system was surgically implanted and in 50 patients a CF shunt was implanted. All patients were followed up for a minimum of 2 years after surgery. Shunt revision or change was necessary in 21 patients (40%) with conventional shunts and in four patients (8%) with the CF shunt (p < 0.003). Signs of overdrainage were observed in 18 patients (34%) in the control group, four of whom had ascending transtentorial herniation; this complication was not seen in patients with the CF shunt. CONCLUSIONS: The CF shunt had a low rate of dysfunction and an absence of complications caused by overdrainage, which were frequently associated with the control shunts. The hydrodynamic properties of the CF shunt make it effective, even in severe cases of hydrocephalus caused by lesions of the posterior fossa.

Adolescent↗
PubMed2003

Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine.

OBJECT: Therapy of malignant tumors is frequently curtailed by the emergence of chemoresistant cell clones. Experimentally, the authors have demonstrated that chemotherapy for glioma in rats is markedly improved by the administration of the antimutagenic quinacrine. They studied the effects of chloroquine, an antimutagenic with an optimal pharmacological profile for human use, as adjuvant for the treatment of patients with glioblastoma multiforme (GBM). METHODS: In a prospective controlled randomized trial, 18 patients with GBM underwent standard treatment with surgery, chemotherapy, and radiotherapy; nine received an additional 150-mg dose of chloroquine daily starting 1 day after surgery and continued through the observation period. Nine matched patients were included as controls. Neuroimaging studies and clinical response were periodically compared. The follow-up period ranged from 24 to 50 months. Survival time was defined as the main outcome measure. Survival was significantly longer in chloroquine-treated patients than in controls (33 +/- 5 and 11 +/- 2 months, respectively [p < 0.0002]). At the end of the observation period, four patients (46%) treated with chloroquine were alive, two had evidence of tumor remission after 2 years; in another two, tumor recurrence developed after 2 and 4 years of remission, respectively. No control patient survived more than 22 months after surgery. CONCLUSIONS: Chronic administration of chloroquine greatly enhanced the response of GBM to antineoplastic treatment. Because the cytotoxicity of chloroquine on malignant cells is negligible, these favorable results appear mediated by its strong antimutagenic effect that precludes the appearance of resistant clones during radiotherapy and chemotherapy.

Adolescent↗