Toll-like receptors 2, 4, and 9 modulate promoting effect of COPD-like airway inflammation on K-ras-driven lung cancer through activation of the MyD88/NF-ĸB pathway in the airway epithelium.

Introduction: Toll-like receptors (TLRs) are an extensive group of proteins involved in host defense processes that express themselves upon the increased production of endogenous damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) due to the constant contact that airway epithelium may have with pathogenic foreign antigens. We have previously shown that COPD-like airway inflammation induced by exposure to an aerosolized lysate of nontypeable Haemophilus influenzae (NTHi) promotes tumorigenesis in a K-ras mutant mouse model of lung cancer, CCSPCre/LSL-K-rasG12D (CC-LR) mouse. Methods: In the present study, we have dissected the role of TLRs in this process by knocking out TLR2, 4, and 9 and analyzing how these deletions affect the promoting effect of COPD-like airway inflammation on K-ras-driven lung adenocarcinoma. Results: We found that knockout of TLR 2, 4, or 9 results in a lower tumor burden, reduced angiogenesis, and tumor cell proliferation, accompanied by increased tumor cell apoptosis and reprogramming of the tumor microenvironment to one that is antitumorigenic. Additionally, knocking out of downstream signaling pathways, MyD88/NF-κB in the airway epithelial cells further recapitulated this initial finding. Discussion: Our study expands the current knowledge of the roles that TLR signaling plays in lung cancer, which we hope, can pave the way for more reliable and efficacious prevention and treatment modalities for lung cancer.

Targeting IL-1ß as an immunopreventive and therapeutic modality for K-ras-mutant lung cancer.

K-ras-mutant lung adenocarcinoma (KM-LUAD) is associated with abysmal prognosis and is tightly linked to tumor-promoting inflammation. A human mAb, canakinumab, targeting the proinflammatory cytokine IL-1ß, significantly decreased the risk of lung cancer in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study. Interestingly, we found high levels of IL-1ß in the lungs of mice with K-rasG12D-mutant tumors (CC-LR mice). Here, we blocked IL-1ß using an anti-IL-1ß mAb in cohorts of 6- or 14-week-old CC-LR mice to explore its preventive and therapeutic effect, respectively. IL-1ß blockade significantly reduced lung tumor burden, which was associated with reprogramming of the lung microenvironment toward an antitumor phenotype characterized by increased infiltration of cytotoxic CD8+ T cells (with high IFN-γ and granzyme B expression but low programmed cell death 1 [PD-1] expression) while suppressing neutrophils and polymorphonuclear (PMN) myeloid-derived suppressor cells. When querying the Cancer Genome Atlas data set, we found positive correlations between IL1B expression and infiltration of immunosuppressive PMNs and expression of their chemoattractant, CXCL1, and PDCD1 expressions in patients with KM-LUAD. Our data provide evidence that IL-1ß blockade may be a preventive strategy for high-risk individuals and an alternative therapeutic approach in combination with currently available treatments for KM-LUAD.

Lung Cancer Murine Models and Methodology for Immunopreventive Study.

Lung cancer is the second most common cancers in the world and remains as the cancer with the highest incidence of death (Siegel et al. CA Cancer J Clin 71(1):7-33, 2021). K-RAS mutation is one of the most common mutations in non-small-cell lung cancer (NSCLC), encompassing 15-30% of lung adenocarcinomas (Cancer Genome Atlas Research Network. Nature 511:543-550, 2014). In this chapter, we describe various murine models with the goal of studying the role of inflammation in development and promotion of lung cancer. Immunomodulatory strategies are described in detail as well as the protocols that follow the intervention for harvesting various tissue and fluids for immune-profiling.

Cytotype and genotype predict mortality and recruitment in Colorado quaking aspen (Populus tremuloides).

Species responses to climate change depend on environment, genetics, and interactions among these factors. Intraspecific cytotype (ploidy level) variation is a common type of genetic variation in many species. However, the importance of intraspecific cytotype variation in determining demography across environments is poorly known. We studied quaking aspen (Populus tremuloides), which occurs in diploid and triploid cytotypes. This widespread tree species is experiencing contractions in its western range, which could potentially be linked to cytotype-dependent drought tolerance. We found that interactions between cytotype and environment drive mortality and recruitment across 503 plots in Colorado. Triploids were more vulnerable to mortality relative to diploids and had reduced recruitment on more drought-prone and disturbed plots relative to diploids. Furthermore, there was substantial genotype-dependent variation in demography. Thus, cytotype and genotype variation are associated with decline in this foundation species. Future assessment of demographic responses to climate change will benefit from knowledge of how genetic and environmental mosaics interact to determine species' ecophysiology and demography.

The effects of health insurance on the choice of medical procedures: Evidence from heart attacks and childbirths.

This paper investigates the effect of health insurance on the use of alternative procedures to treat a given medical condition. In particular, we estimate the effect of health insurance on the use of bypass surgery after a heart attack and on the use of a C-section after a normal pregnancy. These procedures are the most expensive, compared to the alternatives. Theoretically, the demand for some procedures like bypass surgery is likely to be inelastic. In this situation, health insurance should have no effect on the use of the procedure. For other procedures such as C-section, demand may be more elastic, especially after a normal pregnancy without complications. We use a nationally representative dataset of inpatient hospital admissions from the United States and control for individual and hospital characteristics. The results from our empirical analysis support our predictions. For patients admitted to a hospital because of a heart attack, being uninsured has no effect on the probability of bypass surgery. However, for patients admitted for childbirth, the uninsured have a substantially lower probability of a C-section delivery.

The Effect of Shelter-in-Place Orders on Social Distancing and the Spread of the COVID-19 Pandemic: A Study of Texas.

Objectives: We study how the state-wide shelter-in-place order affected social distancing and the number of cases and deaths in Texas. Methods: We use daily data at the county level. The COVID-19 cases and fatalities data are from the New York Times. Social distancing measures are from SafeGraph. Both data are retrieved from the Unfolded Studio website. The county-level COVID-related policy responses are from the National Association of Counties. We use an event-study design and regression analysis to estimate the effect of the state-wide shelter-in-place order on social distancing and the number of cases and deaths. Results: We find that the growth rate of cases and deaths is significantly lower during the policy period when the percentage of the population that stays at home is highest. The crucial question is whether the policy has a causal impact on the sheltering percentages. The fact that some counties in Texas adopted local restrictive policies well before the state-wide policy helps us address this question. We do not find evidence that this top-down restrictive policy increased the percentage of the population that exercised social distancing. Discussion: Shelter-in-place policies are more effective at the local level and should go along with efforts to inform and update the public about the potential consequences of the disease and its current state in their localities.

Interplay between estrogen and Stat3/NF-κB-driven immunomodulation in lung cancer.

K-ras mutant lung adenocarcinoma (LUAD) is the most common type of lung cancer, displays abysmal prognosis and is tightly linked to tumor-promoting inflammation, which is increasingly recognized as a target for therapeutic intervention. We have recently shown a gender-specific role for epithelial Stat3 signaling in the pathogenesis of K-ras mutant LUAD. The absence of epithelial Stat3 in male K-ras mutant mice (LR/Stat3Δ/Δ mice) promoted tumorigenesis and induced a nuclear factor-kappaB (NF-κB)-driven pro-tumor immune response while reducing tumorigenesis and enhancing anti-tumor immunity in female counterparts. In the present study, we manipulated estrogen and NF-κB signaling to study the mechanisms underlying this intriguing gender-disparity. In LR/Stat3Δ/Δ females, estrogen deprivation by bilateral oophorectomy resulted in higher tumor burden, an induction of NF-κB-driven immunosuppressive response, and reduced anti-tumor cytotoxicity, whereas estrogen replacement reversed these changes. On the other hand, exogenous estrogen in males successfully inhibited tumorigenesis, attenuated NF-κB-driven immunosuppression and boosted anti-tumor immunity. Mechanistically, genetic targeting of epithelial NF-κB activity resulted in reduced tumorigenesis and enhanced the anti-tumor immune response in LR/Stat3Δ/Δ males, but not females. Our data suggest that estrogen exerts a context-specific anti-tumor effect through inhibiting NF-κB-driven tumor-promoting inflammation and provide insights into developing novel personalized therapeutic strategies for K-ras mutant LUAD.

Enfermedad de Moyamoya: Cefalea crónica y demencia progresiva asociadas a infartos cerebrales múltiples / Moyamoya disease: Chronic headache and progressive dementia associated with multiple brain strokes

Se reporta el caso de un paciente de 32 años de edad que desde los 17 y hasta la actualidad, ha experimentado cefaleas constrictivas de minutos de duración, desencadenadas por actividad o esfuerzos físicos. En los últimos siete años ha presentado progresiva declinación cognitiva y cambios acentuados de personalidad con creciente dependencia para el desarrollo de actividades elementales. A los 27 años desarrolló hemiplejía izquierda total con recuperación completa en dos semanas. Muestra asimismo episodios de estado confusional severo y conducta infantil. Los exámenes de laboratorio descartaron cardiopatía, ateroesclerosis y enfermedades autoinmunes sistémicas en el paciente. Estudios neuroimagenológicos del cerebro (TAC, Angio - TEM y RM cerebralcontrastada) pusieron en evidencia seis infartos cerebrales, en estadios subagudos y crónicos, severa estenosis de las arterias cerebrales anteriores y presencia de un microaneurisma en el segmento M de la arteria cerebral media izquierda. Una limitación del presente reporte es la ausencia de estudios con angiografía digital, debida a dificultades económicas. En conclusión, el caso corresponde a un paciente con cefalea crónica asociada a demencia progresiva, en el que estudios de neuroimágenes y pruebas neuropsicológicas sustentan el diagnóstico de deterioro cognitivo asociado a la enfermedad de Moyamoya.

The case of a 32 years old male patient who since age 17 has experienced constrictive headaches of several minutes duration, triggered by physical effort is reported. For the last seven years there, he has presented a progressive cognitive decline cognitive, and marked personality changes, having become extremely dependent even for conducting elemental activities. At the age of 27, he experienced total left hemiplegia from which he completely recovered in two weeks. He also shows severe confusional states and child-like behavior. Laboratory tests ruled out heart disease, atherosclerosis and systemic autoimmune diseases. Brain neuroimaging tests (CT, Angio - TEM and contrasted cerebral MRI) revealed the occurrence of six cerebral infarcts, in subacute and chronic stages, severe stenosis of the anterior cerebral arteries, and presence of microaneurysm in the M segment of the left middle brain artery. A limitation of this report is the absence of a study with digital angiography, due to economic difficulties. In short, the case of a patient with chronic headache associated with progressive dementia is presented, with neuroimaging and neuropsychological tests that support the diagnosis of of cognitive impairment associated with Moyamoya disease.

Xantomatosis cerebrotendinosa: Reporte de un caso en el Perú: Evaluación clínica integral y estudios de neuroimágenes / Cerebrotendinous Xanthomatosis: Report of a case in Peru: Comprehensive clinical evaluation and neuroimaging studies

Se presenta el caso de una paciente de 73 años de edad que, a los 30 años aproximadamente, comenzó a quejarse de dolor al caminar, localizando la molestia a nivel de las regiones aquilianas, con subsecuente aumento de volumen; al paso del tiempo, estas molestias la obligaron a efectuar consulta médica. Los análisis de laboratorio mostraron severa dislipidemia mixta. Al lado de información de significativa declinación cognitiva, provista por familiares (vgr., (i.e., olvidos frecuentes, desorientación, atención disminuida, concentración pobre), hubo evidencia de ánimo fluctuante, labilidad emocional, crisis ansiosas evolucionando hacia ataques de pánico. El test minicognitivo de Folstein, mostró severo estado demencial y en el examen neurológico se constataron ataxia cerebelosa y signos de piramidalismo parcial. El examen oftalmológico puso en evidencia xantelasmas, cataratas y un denso arco senil. El estudio del cerebro con resonancia magnética (RM) mostró el daño encefálico y signos sugestivos de depósitos del colastenol en el SNC. La presencia de xantomas , los hallazgos oftalmológicos, la demencia definidamente progresiva y la ataxia cerebelosa fueron hallazgos clínicos que permitieron establecer el diagnóstico de xantomatosis cerebrotendinosa.

The case of a 73 years-old woman that, since approximately the age of 30 years started to complain of pain when walking, is presented. The symptom was mainly located in the acchillean regions which, as time advanced, showed gradual volume increase and, finally, forced her to seek medical evaluation. Accompanying relatives reported a several years’ history of gradually increasing cognitive difficulties (i.e., forgetfulness, disorientation, poor attention and concentration), fluctuating mood (from periods of good humor switching to sudden episodes of sadness and crying spells), emotional lability and anxiety crises evolving into brief panic attacks. The Mini-cognitive Fenton Test confirmed severe dementia and the neurological evaluation showed cerebellar ataxia and partial pyramidalism. The ophthalmological examination revealed xanthelasmas, cataracts and dense arcus senilis. Xanthomas were detected in the Achillean tendons of both lower extremities. Auxiliary laboratory and densitometric tests demonstrated mixed dyslipidemia and dorsal-lumbar osteoporosis, respectively, and magnetic resonance imaging of the brain (RMC) confirmed SNC damage and suggested deposits of cholestenol, thus confirming the diagnosis of Cerebroitendinous Xanthomatosis.

Understanding the Complexity of the Tumor Microenvironment in K-ras Mutant Lung Cancer: Finding an Alternative Path to Prevention and Treatment.

Kirsten rat sarcoma viral oncogene (K-ras) is a well-documented, frequently mutated gene in lung cancer. Since K-ras regulates numerous signaling pathways related to cell survival and proliferation, mutations in this gene are powerful drivers of tumorigenesis and confer prodigious survival advantages to developing tumors. These malignant cells dramatically alter their local tissue environment and in the process recruit a powerful ally: inflammation. Inflammation in the context of the tumor microenvironment can be described as either antitumor or protumor (i.e., aiding or restricting tumor progression, respectively). Many current treatments, like immune checkpoint blockade, seek to augment antitumor inflammation by alleviating inhibitory signaling in cytotoxic T cells; however, a burgeoning area of research is now focusing on ways to modulate and mitigate protumor inflammation. Here, we summarize the interplay of tumor-promoting inflammation and K-ras mutant lung cancer pathogenesis by exploring the cytokines, signaling pathways, and immune cells that mediate this process.

COPD-Type lung inflammation promotes K-ras mutant lung cancer through epithelial HIF-1α mediated tumor angiogenesis and proliferation.

Chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, is an independent risk factor for lung cancer. Lung tissues obtained from human smokers with COPD and lung cancer demonstrate hypoxia and up-regulated hypoxia inducible factor-1 (HIF-1). HIF-1 activation is the central mechanism for controlling the cellular response to hypoxia during inflammation and tumor development. These facts suggest a link between COPD-related airway inflammation, HIF-1, and lung cancer. We have previously established a mouse model of COPD-like airway inflammation that promotes lung cancer in a K-ras mutant mouse model (CC-LR). Here we show that tumors in the CC-LR model have significantly elevated levels of HIF-1α and HIF-1 activity. To determine the tumor-promoting functions of HIF-1 in CC-LR mice, the gene Hif1a which encodes HIF-1α and is required for HIF-1 activity, was disrupted in the lung epithelium of CC-LR animals. Airway epithelial specific HIF-1α deficient mice demonstrated significant reductions in lung surface tumor numbers, tumor angiogenesis, and tumor cell proliferation in the absence or presence of COPD-like airway inflammation. In addition, when CC-LR mice were bred with transgenic animals that overexpress a constitutively active mutant form of human HIF-1α in the airway epithelium, both COPD- and adenocarcinoma-like phenotypes were observed. HIF-1α overexpressing CC-LR mice had significant emphysema, and they also showed potentiated tumorigenesis, angiogenesis, and cell proliferation accompanied by an invasive metastatic phenotype. Our gain and loss of function studies support a key role for HIF-1α in the promotion of lung cancer by COPD-like inflammation.

The health conditions and the health care consumption of the uninsured.

This paper investigates the difference in the health conditions and the health care consumption of uninsured individuals as compared to individuals with private insurance, using a nationally representative data set of inpatient hospital admissions from the US. In line with the previous literature, our results indicate that uninsured individuals are, on average, in worse health conditions. However, if we compare individuals within the same diagnosis category, the uninsured are actually healthier, with a lower number of chronic conditions and a lower risk of mortality. This indicates that the uninsured are admitted to the hospital only for more serious conditions. In addition, our results show that uninsured individuals consume less health care. In particular, conditional on being admitted to a hospital and controlling for health conditions, the uninsured have lower total charges, fewer procedures, and a higher mortality rate.

[Risk factors for nosocomial infection in a level III Neonatal Intensive Care Unit]. / Factores de riesgo asociados a infección nosocomial (IN) en una Unidad de Cuidados Intensivos Neonatales (UCIN) de tercer nivel.

INTRODUCTION: Nosocomial infections are a major and a frequent problem in neonatal intensive care units and increase morbidity, mortality, and costs. The objective of this study was to identify the risk factors associated with nosocomial infections in a neonatal intensive care unit. METHODS: Nested case control study. Records from patients were registered: gestational age, sex, birth weight, central venous catheter and other devices, congenital malformations, surgeries, mechanical ventilation, steroid use, H2 blockers, length of stay in neonatal intensive care unit, type of infection, and etiological agent. RESULTS: We studied 188 cases with nosocomial infections and 192 controls without nosocomial infections. The most frequent infection was sepsis (34.8%) and coagulase negative Staphylococcus was the principal etiological agent (37.2%). The risk factors associated with nosocomial infection were central venous catheter (OR: 7.3; 95% CI: 2.3-22.8), duration of neonatal intensive care unit stay>14 days (OR: 3.4; 95% CI: 1.7-6.7), H2 blockers (OR: 2.3; 95% CI: 1.2-4.2), number of surgeries≥2 (OR: 3; 95% CI: 1.1-7.9) and mechanical ventilation>7 days (OR: 2.1; 95% CI: 1.1-4.2). CONCLUSIONS: Some risk factors associated to nosocomial infections in this study are similar to those found previously, with the exception of the number of surgeries that was not reported in previous studies.

Sonoran propolis: chemical composition and antiproliferative activity on cancer cell lines.

In this study, we have analyzed the chemical composition and antiproliferative activity of propolis from three different arid and semiarid regions of Sonora, Mexico. We identified and quantitated the main chemical constituents of propolis by HPLC-MS. The most abundant constituents of propolis were pinocembrin, pinobanksin 3-acetate, and chrysin. Sonoran propolis had a strong antiproliferative activity on both murine and human cancer cell lines in a concentration-dependent manner. The propolis constituents CAPE, galangin, xanthomicrol and chrysin showed significant antiproliferative activity on most of the cancer cells tested. DNA harvested from cancer cell cultures treated with Sonoran propolis exhibited a ladder of internucleosomal DNA cleavage characteristic of apoptosis. In summary, we have identified and quantitated the main constituents of Sonoran propolis. These propolis samples possess a strong antiproliferative activity on cancer cell lines.

Síndrome de Parry Romberg / Parry Romberg Syndrome

El síndrome de Parry Romberg es una entidad clínica que se caracteriza por una hemiatrofia facial progresiva que produce alteraciones estéticas, funcionales, psíquicas, sociales y en ocasiones de evolución fatal. Presentamos dos casos, el primero inicialmente diagnosticado con esclerodermia lineal a los 8 años de edad. La segunda inicial enfermedad a los 2 años con placa alopécica en región frontal. Los pacientes progresan a síndrome de Parry Romberg en dos años. En ambos se encontró hemiatrofia facial izquierda, epilepsia, hemiatrofia cerebral ipsilateral y en el segundo caso uveíttis, IgM y cultivo positivo para Borrelia sp. Los pacientes fallecieron por status epiléptico. La teoría de la alteración de la primera etapa de la embriogénesis podría explicar el compromiso de tejidos derivados de diferentes capas embrionarias, sin embargo se propone a la Borrelia como desencadenante para la rápida progresión de la enfermedad.

Parry Romberg syndrome is a clinical entity characterized by progressive facial hemiatrophy with aesthetic, functional sy chic an’, social alterations of occasional fatal outcome. We present two cases; the first was diagnosed of lineal scleroderma at 8 years old and the second with alopecic plaque in frontal region at 2 years old. They progressed to Parry Romberg syndrome in two years. In both we found left facial hemiatrophy, epilepsy, ipsilateral cerebral hemiatrophy; uveitis, IgM and positive culture of Borrelia in the second case.The patients died with epileptics status. The theory of alteration of first stage of embryogenesis may explain the compromise of tissues derived from different embryologic cap, nevertheless some propose infection with Borrelia as accelerator of the progression of the disease.

[Wilson'S disease: dominant neuropsychiatric form. Case presentation and its physiopathologic interpretation based upon magnetic resonance of the encephalon]. / Enfermedad de Wilson: Forma Neuropsiquiátrica dominante presentación de un caso y su interpretación fisiopatológica basada en resonancia magnética del encéfalo.

This is a presentation of a clinical case of Wilson s disease. The patient is a 26 year old woman who began to evidence psychological symptoms, which were later accompanied by neurological manifestations such as asymmetrical hand tremor, parkinsonism, dystonia and later on, dysphagia and mutism. The ophthalmological examination found a Kayser Fleischer ring in Descemet s membrane. There was disturbance of copper metabolism documented with reduction of serum ceruloplasmin and increase of the urinary excretion of copper. Cirrhosis was demonstrated through laparoscopy and liver biopsy. The brain magnetic resonance showed frontotemporal atrophy and a degenerative process at the basal ganglia, cerebellum and brain stem. This information could suggest probable neuropsychiatric physiopathology. The stenosis and intense cervical dysphagia, associated with the crycopharyngeal membrane, has not been mentioned previously.

Tuberculosis del sistema nervioso. Observaciones sobre 1360 pacientes estudiados en tres centros asistenciales de Lima / nervous system tuberculosis. Observations on 1360 patients studied at three asistential centers in Lima

Objetivo: Relacionar la prevalencia de tuberculosis, durante catorce años consecutivos (1984-1997) con los casos de neurotuberculosis registrados durante dicho lapso, especificando las características clínicas de estos últimos. Método: Se recogió información en el Ministerio de Salud (MS), el Hospital Nacional Dos de Mayo (HN2M), el Instituto Nacional de Salud del Niño (INSN) y el Instituto Nacional de Enfermedades Neoplásicas (INEN). Luego se analizaron las historias clínicas de 1360 casos de neurotuberculosis, examinados personalmente por los autores, durante los 14 años, siguiendo los criterios de la Organización Mundial de la Salud (OMS). Resultados: Se comprobó incremento progresivo de la tuberculosis durante el período de observación. La tuberculosis del sistema nervioso reveló sintomatología proteiforme y muchos casos atípicos. Sin embargo, pudo dividirse en tres grupos principales: meningoencefalitis tuberculosa (1124 pacientes, 439 adultos y 685 niños); tuberculosis espinal con comprensión radicular o medular (98 enfermos, 62 adultos y 36 niños); y tuberculomas (138 pacientes, 81 adultos y 57 niños). Conclusiones: El aumento de la prevalencia de tuberculosis se debe probablemente a recidivas por abandono o interrupción del tratamiento, agravación de los problemas sociales de la población y aparición de la epidemia de infección por el virus de la inmunodeficiencia humana (VIH). La elevada mortalidad y morbilidad de los pacientes con tuberculosis del sistema nervioso posiblemente obedece a que el paciente llega al médico en fase avanzada de la enfermedad y a la aparición de cepas farmacorresistentes de m. tuberculosis.

Diagnóstico de la investigación biomédica en el Perú comunicación preliminar / Diagnostic of the biomedical research in Peru

El presente es un estudio evaluativo de los principales aspectos del desarrollo científico y tecnológico biomédico en el Perú y en el marco del desarrollo global del país, así como latinoamericano y mundial. Se comentan los modelos de salud empleados para llegar a las desigualdades económico-sociales e inequidades existentes. Se analiza la asociación positiva entre el organismo rector de ciencia y tecnología, el sector salud y la Organización Panamericana de la Salud, para promover la realización de proyectos prioritarios en el Perú, con evaluaciones por pares y decisión a nivel nacional. El artículo incide en aspectos de producción científica y bibliográficos, así como de recursos humanos e inversión en ciencia y tecnología; así mismo, plantea un análisis de fortalezas, debilidades y probables escenarios futuros. Se señala la necesidad de reforzar la información y comunicación a niveles de excelencia y la construcción de una nueva cultura en investigación biomédica. Se destaca la importancia de implantar un sistema de acreditación institucional progresivo, recursos humanos con el perfil requerido, producción científica con stándares adecuados y mayor agresividad en la utilización de la cooperación externa.

Complicaiones neurológicas en el tratamiento de las adicciones y de las psicosis / Neurological complications in the treatment of the addiction and psychotic disorders

Se describen seis casos de complicaciones neurológicas observadas durante el tratamiento de la fármacodependencia y algunas reacciones psicóticas. Las observaciones corresponden a un síndrome neuroléptico persistente inducido por dosis considerables de fenotiazinas y butirofenonas en un paciente tratado con inmovilización farmacológica por dependencia al alcohol y a la cocaína. La segunda observación correspode a un enfermo esquizofrénico, quien desarrolló un síndrome neuroléptico maligno. Precipitado por fenotiazinas y butirofenonas. El caso tres consistió en muerte súbita durante un tratamiento con narcosis prolongada por clorpromazina, prometacina y haloperidol, la cuarta observación correspondía a parkinsonismo crónico y disquinesia tardía por clorpromazina y carbonato de litio. El quinto caso consistió en acatisia y distonía de las manos precipitada por butirofenonas y flufenazina. La última observación correspondió a oculogiria aguda, amnesia y rigidez generalizada consecutiva al uso de clorpromazina, fluoxetina y benzodiazepinas. Se discuten los mecanismos de producción de los síndromes descritos y los métodos asequibles para evitar estas graves complicaciones, cuando se usan fármacos que si bien son de gran utilidad en los transtornos psicóticos, son ineficaces en el tratamiento de las fármacodependencias.

Adicción cocainica, inmunodeficiencia y abcesos cerebrales / Cocaine adiction, inmunodeficiency and brain abscess

Se han estudiado tres pacientes adictos a la cocaína que desarrollaron abscesos cerebrales. El primero tuvo un absceso de localización hemisférica, el segundo paciente presentó abscesos múltiples en el cerebelo y la protuberancia, finalmente, el último desarrolló múltiples abscesos de diferente tamaño y localizaciones. Los tres casos mostraban signos de inmunodeficiencia probablemente celular y humoral. Se presentan las observaciones clínicas detalladas, se discute la asociación de la adicción cocaínica y su repercusión en la inmunidad de los pacientes, predisponiéndoles a numerosas infecciones.