Epilepsy surgery in Panama: Establishment of a successful hybrid program as a model for small middle-income countries.

OBJECTIVE: The majority of the 65 million people worldwide with epilepsy live in low- and middle-income countries. Many of these countries have inadequate resources to serve the large patient population affected by epilepsy. Panama is a middle-income country that currently has only 2 facilities that can provide basic epilepsy services and no epilepsy surgery services. To address this need, a group of Panamanian physicians partnered with U.S. epilepsy health care providers to test a hybrid epilepsy surgery program, combining resources and expertise. METHODS: From 2011 to 2017, a multidisciplinary team of neurologists, neurosurgeons, and an electroencephalography (EEG) technician from the United States traveled to Panama 6 times and, in collaboration with the local team, performed surgical procedures for intractable epilepsy at the national children's hospital. Resective surgeries were performed with intraoperative electrocorticography and/or implantation of subdural and depth electrodes and extra-operative monitoring. Cost was calculated using Panama government data. RESULTS: Twenty-seven children with intractable epilepsy were surgically treated. Fifteen children are seizure-free (Engle class I), 11 children are Engel II, and one child is Engel III. No major morbidity or mortality occurred, with only one postoperative infection. The average cost of treatment was calculated at $9850 per patient. SIGNIFICANCE: This program is a model for creating a multinational and multi-institutional collaboration to provide surgical epilepsy treatment in a middle-income country without an adequate infrastructure. To be successful, this collaboration needed to address medical, technical, and cultural challenges. This partnership helps to alleviate some of the present need for surgical epilepsy services while laying the groundwork for the development of a future local independent epilepsy surgery program.

Eastern equine encephalitis in Latin America.

BACKGROUND: The eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE) viruses are pathogens that infect humans and horses in the Americas. Outbreaks of neurologic disease in humans and horses were reported in Panama from May through early August 2010. METHODS: We performed antibody assays and tests to detect viral RNA and isolate the viruses in serum samples from hospitalized patients. Additional cases were identified with enhanced surveillance. RESULTS: A total of 19 patients were hospitalized for encephalitis. Among them, 7 had confirmed EEE, 3 had VEE, and 1 was infected with both viruses; 3 patients died, 1 of whom had confirmed VEE. The clinical findings for patients with EEE included brain lesions, seizures that evolved to status epilepticus, and neurologic sequelae. An additional 99 suspected or probable cases of alphavirus infection were detected during active surveillance. In total, 13 cases were confirmed as EEE, along with 11 cases of VEE and 1 case of dual infection. A total of 50 cases in horses were confirmed as EEE and 8 as VEE; mixed etiologic factors were associated with 11 cases in horses. Phylogenetic analyses of isolates from 2 cases of equine infection with the EEE virus and 1 case of human infection with the VEE virus indicated that the viruses were of enzootic lineages previously identified in Panama rather than new introductions. CONCLUSIONS: Cases of EEE in humans in Latin America may be the result of ecologic changes that increased human contact with enzootic transmission cycles, genetic changes in EEE viral strains that resulted in increased human virulence, or an altered host range. (Funded by the National Institutes of Health and the Secretaría Nacional de Ciencia, Tecnología e Innovación, Panama.).

Further evidence on the favorable role of the anomeric effect on the cleavage of HepDirect and cyclophosphamide prodrugs.

On the basis of previous conformational and configurational studies of 4-aryl-substituted cyclophosph(on)ates derived from d-xylofuranose derivatives, wherein it was proposed that the anomeric effect is involved in the spontaneous isomerization of the P atom and the C4 carbon, and consequently, this unusual behavior was associated with the cleavage of the HepDirect prodrugs. We synthesized an analogous series of 2-amino-2-oxo-1,3,2-dioxaphosphorinanes and performed a conformational and configurational analysis in solution and the solid state followed by an examination of their mutagenic activity. The results showed that the 2-amino-2-oxo-1,3,2-dioxaphosphorinanes with the largest mutagenic activity contain either a 4-methoxyphenyl or 4-fluorophenyl group at C4 carbon and presented a major chair conformation, which is prone to weaken the C4-O3 bond via the anomeric effect and facilitates the cleavage for the release of the biologically active metabolite.

Cerebrospinal fluid and plasma concentrations of proinflammatory mediators in human immunodeficiency virus-infected children.

BACKGROUND: The pathogenesis of HIV encephalopathy is poorly understood especially in children. Studies suggest that HIV replication and the release of proinflammatory mediators in the central nervous system contribute to the pathogenesis of HIV dementia in adults. METHODS: Cerebrospinal fluid (CSF) and plasma samples from 23 HIV-infected children were longitudinally analyzed at Weeks 0, 8, 16 and 48 for HIV RNA and concentrations of the following proinflammatory mediators: monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha, regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage-inflammatory protein (MIP)-1-alpha, MIP-1-beta and matrix metalloproteinase-9 (MMP-9). RESULTS: All 23 children had detectable concentrations of MCP-1 in the CSF at all time points evaluated. However, of the remaining of proinflammatory mediators measured in CSF at baseline, only a few children had detectable concentrations: tumor necrosis factor-alpha, n = 1; RANTES, n = 5; MMP-9, n = 9; MIP-1-alpha and MIP-1-beta, n = 0. A reduction from baseline to Week 48 was observed in CSF concentrations of MCP-1 and, among children with detectable values, MMP-9, which paralleled declines in CSF HIV RNA. CONCLUSION: These results suggest that MCP-1 and MMP-9 may be involved in the pathogenesis of central nervous system disease in HIV-infected children.

[Caspases: apoptosis inducing molecules]. / Caspasas: moléculas inductoras de apoptosis.

Caspases are key proteins for the transduction and ejection of the apoptotic signals induced by several stimuli. These proteins are present within the cell as inactive precursors that need a proteolytic cleavage in order to be active. There are two main caspases group, the initiators and executors. The formers are activated by autoproteolysis when translocated to specific cell compartments or trough the coupling of adapters and or activators. The executors caspases are activated by cleavage of an initiator caspase. These proteases are responsible then for the final cleavage of diverse substrates that mediate the morphologic changes during apoptosis. Among these there are signalization, DNA repairing, structure, transcription proteins, etc. Caspases represent a new paradigm in the signal transduction pathway, and are implicated in a large number of physiologic and pathologic processes. In a near future they could be useful pathologic markers and therapeutic targets.

Silymarin downregulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma.

Silymarin is a naturally available bioflavonoid and is a strong antioxidant with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated whether dietary supplementation of silymarin has any role in lipid components, lipid-metabolizing enzymes, free fatty acid profile, and expression of cyclooxygenase-2 (COX-2) in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in rats. NDEA-induced rats showed severe hyperlipidemia along with upregulated expression of COX-2 as revealed by western blotting and immunohistochemistry. Dietary silymarin supplementation attenuated this hyperlipidemia and downregulated the expression of COX-2. Thus we conclude that compounds like silymarin with potent hypolipidemic effect are strong candidates as chemopreventive agents for the treatment of liver cancer.

Effect of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance, and clinical manifestations of encephalopathy.

OBJECTIVES: This study evaluated the effect of treatment with abacavir/lamivudine/zidovudine versus lamivudine/zidovudine on cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA and clinical manifestations of HIV encephalopathy in children. STUDY DESIGN: HIV-infected children 7 months to 10 years of age (n = 23) were studied. CSF and plasma were obtained at baseline and weeks 8, 16, and 48. Genotype analysis of HIV was attempted at baseline and week 48. Neurologic evaluations were performed at baseline and weeks 16, 32, and 48. RESULTS: At baseline, 83% of children had >2.00 log(10) copies/mL HIV RNA in CSF, but only 10% had HIV RNA measurable at week 48. Among children in whom paired genotyping of HIV was possible, 8 of 11 had identical patterns in both CSF and plasma at baseline, whereas at week 48, only 1 of 9 children had similar patterns. Neurologic abnormalities were observed in 83% of children at baseline but only 35% of children at week 48 (P =.004), suggesting a benefit of treatment. CONCLUSIONS: Antiretroviral therapy was associated with a decline in CSF HIV RNA and an improvement in neurologic status. The development of genotypic mutations was different in CSF and plasma, suggesting discordant viral evolution. These results suggest that antiretroviral treatment in children should include agents with activity in the CNS.

Sida y discriminación: opiniones entre odontologos de Santo Domingo / AIDS and discrimination : facts between dentists in Santo Domingo

De agosto a septiembre de 1991, se realizó una encuesta epidemiológica transversal dirigida a 260 odontólogos de Santo Domingo, República Dominicana, para obtener sus opiniones sobre el SIDA y la discriminación de que son objeto los pacientes. Se obtuvo respuesta de 215 adontólogos, es decir, 82.7 por ciento. Los resultados de la encuesta señalan que 82.4 por ciento de los odontólogos interroga a sus pacientes sobre el SIDA, no encontrándose significación estadistica (p-NS) al compararlos según edad, sexo y especialidad. La mayoria (88.4 por ciento ) no solicita a sus pacientes la prueba del HIV. La encuesta reveló que solo 4.7 por ciento de los odontólogos ha atendido a pacientes seropositivos y/o con SIDA, y 64.7 por ciento los discrimina. Los homosexuales (70.2 por ciento ), las trabajadoras del sexo (55.0 por ciento ), los toxicómanos (52.1 por ciento ) y los hemofílicos (40.5 por ciento ) son los grupos de riesgo más discriminados, justificando esta actitud por temor a: "perder sus clientes" (78.1 por ciento ), a "contagiarse" (47.9 por ciento ), "contaminar sus instrumentos" (38.1 por ciento ) y "afectación de su imagen social" (20.5 por ciento ). Sin embargo, admiten que el codigo deontológico los obliga a brindar sus servicios, aunque 24.7 por ciento no reconoce esta obligación moral. Por último, según estos resultados, debe admitirse un claro reconocimiento de que el riesgo existe y que la preocupación entre los profesionales de la salud es justificada