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Biomedical subjects

G Portillo

Publications and source records attributed to G Portillo.

8 recordsLinked to original sources

Interactive image-guided surgical resection of intracranial arteriovenous malformations.

Surgical excision is the only treatment method that immediately prevents increased morbidity or mortality as a result of hemorrhage from arteriovenous malformations (AVMs). For those lesions located deep within the cerebral hemispheres or near eloquent areas, conventional surgical resection may be associated with an unacceptable degree of morbidity and mortality. Herein we report our experience in the resection of these lesions using interactive image guidance. There were five women and five men in the patient group. Their age ranged from 16 to 73 years (mean = 41). Clinical presentation included hemorrhage (n = 7), headaches (n = 2), and seizures (n = 1). All lesions were classified using the Spetzler-Martin grading system as follows: grade I (n = 4), grade II (n = 5), and grade III (n = 1). The locations of the lesions were supratentorial (9) and infratentorial (1). Surgical planning was carried out using the Neurological Surgery Planning System software developed at Wayne State University. An infrared-based system was used to locate and define the lesion intraoperatively. For those lesions located near or within eloquent areas, an awake craniotomy with functional mapping was carried out. Clinical follow-up ranged from 3 to 62 months (mean = 34). Complete surgical excision was achieved in all patients, which was demonstrated postoperatively by digital substraction angiography. The preoperative neurological status remained unchanged in seven patients and improved in three. There was no associated morbidity and mortality with this technique. Image-guided surgical resection of arteriovenous malformations represents a valuable technique, especially in small deep-seated lesions and in those near eloquent areas.

Adolescent↗

Permanent I-125 brain stem implants in children.

Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gyx4 fractions. After 4-6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7-9 months from diagnosis) and four patients remain alive (5-38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.

Brachytherapy↗

Hepatitis B virus (HBV)-specific cytotoxic T-cell response in humans: production of target cells by stable expression of HBV-encoded proteins in immortalized human B-cell lines.

To analyze the hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response during acute and chronic viral hepatitis, target cells that express HBV-encoded antigens in the context of the appropriate HLA restriction element must be available for each subject studied. Since HBV is not infectious for human cells in vitro, such target cells must be produced by DNA-mediated gene transfer into cultured human primary cells or cell lines. For this purpose, we have developed a panel of Epstein-Barr virus-based episomal expression vectors containing each of the HBV open reading frames under the transcriptional control of the simian virus 40 early promoter. Transfection of Epstein-Barr virus-immortalized B-cell lines with this panel of recombinants consistently leads to stable expression of the HBV envelope, nucleocapsid, and polymerase proteins. The HBV X gene product is transiently expressed following transfection, but stable expression of this protein cannot be maintained on a long-term basis. To assess the suitability of this system for the identification of HBV-specific CTL in humans, a panel of EBO-HBV transfectants of defined HLA haplotype was used to monitor the HBV-specific CTL response in a patient with acute viral hepatitis type B. Transfectants that stably express the HBV nucleocapsid (core) antigen were found to serve as excellent targets for the detection of HLA class I-restricted CTL that recognize endogenously synthesized HBV core antigen in this patient; they were also successfully used to stimulate the specific expansion of these CTL in vitro.

B-Lymphocytes↗

Effect of cytokines on HLA-DR and IL-1 production by a monocytic tumour, THP-1.

The monocytic tumour, THP-1, expresses many of the properties of monocytes, both by cell surface staining and its capacity to produce monokines. It was used as a source of homogenous monocytic cells as a model to determine whether a variety of highly purified or recombinant cytokines could induce HLA-DR expression and the production of interleukin-1 (IL-1). Interferon-gamma (IFN-gamma) alone induced HLA-DR. Tumour necrosis factor (TNF), lymphotoxin (LT) and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone were able to induce IL-1 but not HLA-DR. When IFN-gamma was combined with TNF, induction of HLA-DR and IL-1 was enhanced in a synergistic manner. These effects were detectable at a pretranslational level as synergistic effects were observed on DR alpha mRNA and IL-1 beta mRNA levels. The results demonstrate the specificity of IFN-gamma as the inductive stimulus for HLA-DR expression by THP-1 cells. As IFN-gamma and TNF are products of activated T cells, the synergistic role for these molecules in macrophage activation is discussed.

Biological Factors↗

Phase III clinical trials with praziquantel in S. japonicum infections in the Philippines.

Following successful Phase II clinical studies with praziquantel (2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino [2,1-a]isoquinolin-4-one, EMBAY 8440, Biltricide), expanded field trials of Phase III were conducted in Mindoro Oriental, Leyte and Davao Norte, to reassess efficacy, safety and acceptability of the drug on a larger scale. A total of 6,134 cases were treated with the best tolerated and effective dose of 60 mg/kg bwt which for practical purposes was given in 2 instead of 3 divided doses as applied in the earlier trials. Two aliquots of one stool from each individual were examined quantitatively by a modification of the thick smear method one week before, six and twelve months after treatment. Although 67.8% were noted to have drug-related side effects, most were mild to moderate, with only 1.2% considered as severe. Severe reactions consisted mainly of colicky abdominal pain, occurring about 1 h after drug intake, usually accompanied by fever, sweating, urge to defecate, and occasionally by discharge of bloody stool. These reactions, however, required only symptomatic treatment with antispasmodics and antipyretics. Stool follow-up 6 months after treatment showed 89.2% of EPG (eggs per gram of faeces) negativity, with an overall egg reduction of 91.1%. Twelve months after treatment, practically the same results were obtained with 87.5% still negative cases and an egg reduction of 90.5%. This study confirms safety and efficacy of the drug as well as its acceptability when given on a community wide scale.

Adolescent↗