RESUMEN

PURPOSE: Radiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications. METHODS: To investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018. RESULTS: During RCT, 77 (41%, 95% CI 34-49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = < 0.001), and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88), respectively. CONCLUSIONS: Reductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy.

Asunto(s)

Quimioradioterapia/efectos adversos , Neoplasias de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Anciano , Carboplatino/efectos adversos , Carboplatino/uso terapéutico , Quimioradioterapia/métodos , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Dermatitis/etiología , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/estadística & datos numéricos , Leucopenia/etiología , Persona de Mediana Edad , Supervivencia sin Progresión , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estomatitis Aftosa/etiología , Resultado del Tratamiento , Xerostomía/etiología

Asunto(s)

Médula Ósea/patología , Inclusiones Eritrocíticas , Cuerpos de Inclusión/ultraestructura , Síndromes Mielodisplásicos/patología , Neutrófilos/ultraestructura , Humanos , Leucopenia/etiología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Neutropenia/etiología

RESUMEN

OBJECTIVE: Bilirubin is considered an important antioxidant, anti-inflammatory factor and immunomodulator. The current investigation aimed to explore the association between bilirubin and white blood cell (WBC) count in a large Chinese cohort. METHODS: A total of 61091 participants (29259 males, 31832 females) were recruited from a Chinese tertiary hospital. Data were sorted by sex, and the association between bilirubin and WBC count was analyzed after dividing bilirubin levels into quartiles. RESULTS: Most parameters (including age, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, total bilirubin, blood urea nitrogen, creatinine, uric acid, triglycerides and WBC count) were significantly higher in men than in women. Bilirubin displayed significant negative relationships with most other measured variables. Linear logistic regression analysis further indicated their negative relationships. Females showed a significantly higher frequency of leucopenia than males. Significant associations of leucopenia with high bilirubin quartiles were shown in binary logistic regression models for both sexes, with a much closer association in men than in women. For instance, for men with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.600-times higher than that of men with values in quartile 1. For women with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.135-times higher than that of women with values in quartile 1. CONCLUSION: Bilirubin is negatively related to WBC count. Significant associations exist between leucopenia and high bilirubin quartiles, and these associations are more obvious in men than in women.

Asunto(s)

Bilirrubina/sangre , Recuento de Leucocitos , Adulto , Factores de Edad , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Femenino , Humanos , Incidencia , Leucopenia/epidemiología , Leucopenia/etiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valores de Referencia , Factores de Riesgo , Factores Sexuales

RESUMEN

OBJECTIVE: Bilirubin is considered an important antioxidant, anti-inflammatory factor and immunomodulator. The current investigation aimed to explore the association between bilirubin and white blood cell (WBC) count in a large Chinese cohort. METHODS: A total of 61091 participants (29259 males, 31832 females) were recruited from a Chinese tertiary hospital. Data were sorted by sex, and the association between bilirubin and WBC count was analyzed after dividing bilirubin levels into quartiles. RESULTS: Most parameters (including age, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, total bilirubin, blood urea nitrogen, creatinine, uric acid, triglycerides and WBC count) were significantly higher in men than in women. Bilirubin displayed significant negative relationships with most other measured variables. Linear logistic regression analysis further indicated their negative relationships. Females showed a significantly higher frequency of leucopenia than males. Significant associations of leucopenia with high bilirubin quartiles were shown in binary logistic regression models for both sexes, with a much closer association in men than in women. For instance, for men with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.600-times higher than that of men with values in quartile 1. For women with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.135-times higher than that of women with values in quartile 1. CONCLUSION: Bilirubin is negatively related to WBC count. Significant associations exist between leucopenia and high bilirubin quartiles, and these associations are more obvious in men than in women.

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Bilirrubina/sangre , Recuento de Leucocitos , Valores de Referencia , Índice de Masa Corporal , Modelos Logísticos , China/epidemiología , Factores Sexuales , Incidencia , Estudios Transversales , Factores de Riesgo , Factores de Edad , Leucopenia/etiología , Leucopenia/epidemiología

RESUMEN

Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1-4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1-4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3-5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.

Asunto(s)

Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Fiebre/epidemiología , Fiebre/etiología , Gripe Humana/epidemiología , Enfermedad Aguda , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Enfermedad Crónica/epidemiología , Femenino , Cefalea/etiología , Humanos , Lactante , Recién Nacido , Leucopenia/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Puerto Rico/epidemiología , Distribución por Sexo , Trombocitopenia/etiología , Adulto Joven

RESUMEN

Experimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). This study aimed to investigate leucocyte behaviour in bone marrow and blood after BD in rats. BD was induced using intracranial balloon catheter inflation. Sham-operated (SH) rats were trepanned only. Thereafter bone marrow cells were harvested every six hours from the femoral cavity and used for total and differential counts. They were analysed further by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression and apoptosis/necrosis [annexin V/propidium iodide (PI) protocol]. BD rats exhibited a reduction in bone marrow cells due to a reduction in lymphocytes (40%) and segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH rats (CD3, P = 0.1; CD4, P = 0.4; CD3/CD4, P = 0.4; CD5, P = 0.4, CD3/CD5, P = 0.2; CD8, P = 0.8). Expression of L-selectin and beta2 -integrins on granulocytes did not differ (CD11a, P = 0.9; CD11b/c, P = 0.7; CD62L, P = 0.1). There were no differences in the percentage of apoptosis and necrosis (Annexin V, P = 0.73; PI, P = 0.21; Annexin V/PI, P = 0.29). In conclusion, data presented suggest that the downregulation of the bone marrow is triggered by brain death itself, and it is not related to changes in lymphocyte subsets, granulocyte adhesion molecules expression or apoptosis and necrosis.

Asunto(s)

Células de la Médula Ósea/patología , Muerte Encefálica/patología , Animales , Apoptosis , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Muerte Encefálica/inmunología , Muerte Encefálica/metabolismo , Moléculas de Adhesión Celular/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Granulocitos/metabolismo , Hemodinámica/fisiología , Recuento de Leucocitos , Leucopenia/etiología , Subgrupos Linfocitarios/inmunología , Masculino , Necrosis , Ratas Wistar

RESUMEN

Histoplasmosis is common among persons living with human immunodeficiency virus/acquired immune deficiency syndrome (PLWHA) in Latin America, but its diagnosis is difficult and often nonspecific. We conducted prospective screening for histoplasmosis among PLWHA with signs or symptoms suggesting progressive disseminated histoplasmosis (PDH) and hospitalized in Hospital La María in Medellín, Colombia. The study's aim was to obtain a clinical and laboratory profile of PLWHA with PDH. During 3 years (May 2008 to August 2011), we identified 89 PLWHA hospitalized with symptoms suggestive of PDH, of whom 45 (51%) had histoplasmosis. We observed tuberculosis (TB) coinfection in a large proportion of patients with PDH (35%), so all analyses were performed adjusting for this coinfection and, alternatively, excluding histoplasmosis patients with TB. Results showed that the patients with PDH were more likely to have Karnofsky score ≤ 30 (prevalence ratio [PR] = 1.98, 95% confidence interval [CI] = 0.97-4.06), liver compromised with hepatomegaly and/or splenomegaly (PR = 1.77, CI = 1.03-3.06) and elevation in serum of alanine aminotransferase and aspartate aminotransferase to values > 40 mU/mL (PR = 2.06, CI = 1.09-3.88 and PR = 1.53, CI = 0.99-2.35, respectively). Using multiple correspondence analyses, we identified in patients with PDH a profile characterized by the presence of constitutional symptoms, namely weight loss and Karnofsky classification ≤ 30, gastrointestinal manifestations with alteration of liver enzymes and hepatosplenomegaly and/or splenomegaly, skin lesions, and hematological alterations. Study of the profiles is no substitute for laboratory diagnostics, but identifying clinical and laboratory indicators of PLWHA with PDH should allow development of strategies for reducing the time to diagnosis and thus mortality caused by Histoplasma capsulatum.

Asunto(s)

Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Coinfección/sangre , Infecciones por VIH/sangre , Histoplasmosis/sangre , Tuberculosis/sangre , Dolor Abdominal/etiología , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Coinfección/complicaciones , Coinfección/fisiopatología , Colombia , Tos/etiología , Diarrea/etiología , Disnea/etiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/fisiopatología , Cefalea/etiología , Hepatomegalia/etiología , Histoplasmosis/complicaciones , Histoplasmosis/fisiopatología , Humanos , Estado de Ejecución de Karnofsky , Leucopenia/etiología , Linfadenopatía/etiología , Masculino , Náusea/etiología , Úlcera Cutánea/etiología , Esplenomegalia/etiología , Trombocitopenia/etiología , Tuberculosis/complicaciones , Tuberculosis/fisiopatología , Vómitos/etiología , Pérdida de Peso

RESUMEN

OBJECTIVE: We previously reported a case series of acute pancreatitis (AP) and macrophage activation syndrome (MAS) in childhood (cSLE) patients; however, there are no data regarding the comparison of AP and MAS in large populations of cSLE and adult SLE (aSLE). METHODS: A study included 362 cSLE and 1830 aSLE patients. MAS was diagnosed according to preliminary diagnostic guidelines and AP according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Demographic data, clinical features, SLEDAI-2K, SLICC/ACR-DI, and treatment were assessed. RESULTS: Age in MAS patients was significantly lower compared with those without this complication [15 (8.8-55) vs. 33.5 (10.2-45.7) years, p = 0.007]. The frequencies of fever (94% vs. 37%, p = 0.001), leucopenia (82% vs. 19%, p = 0.0001), thrombocytopenia (65% vs. 19%, p = 0.013), hypertriglyceridemia (87% vs. 42%, p = 0.037), and hyperferritinemia (93% vs. 37%, p = 0.011) were also more frequently observed in AP patients with MAS compared in AP patients without MAS. Fever and hyperferritinemia concomitantly were more frequent in the former group (86% vs. 12%, p = 0.0015). Higher and significant frequency of AP in cSLE compared to aSLE patients [12/362 (3.3%) vs. 20/1830 (1.1%), p = 0.003], with similar AP duration [22 (6-60) vs. 15 (4-90) days, p = 0.534]. MAS (85% vs. 30%, p = 0.003) and death by MAS complication (31% vs. 0%, p = 0.017) were significantly higher in children compared with aSLE. CONCLUSIONS: This study provides novel data demonstrating that MAS occur in the majority of cSLE with AP with a higher mortality compared to aSLE. In addition, we identified in AP patients, a cluster of MAS clinical and laboratorial parameters more associated with this complication.

Asunto(s)

Lupus Eritematoso Sistémico/fisiopatología , Síndrome de Activación Macrofágica/fisiopatología , Pancreatitis/fisiopatología , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Niño , Femenino , Ferritinas/sangre , Fiebre/etiología , Humanos , Hipertrigliceridemia/etiología , Leucopenia/etiología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/etiología , Masculino , Persona de Mediana Edad , Pancreatitis/sangre , Pancreatitis/complicaciones , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trombocitopenia/etiología , Adulto Joven

RESUMEN

The risks related to dengue virus infection during pregnancy have been increasingly better described over the past 10 years. The possibility of maternal-fetal transmission is now recognized, but the diagnosis is still too late because of a wide range of clinical signs that the infected newborn child can present. From December 2009 to October 2010, Guadeloupe Island underwent an exceptional dengue epidemic. During this epidemic, at least four cases of vertical virus transmission were biologically proved. The purpose of this article is to describe the clinical aspects of these cases, some of which have rarely been described in this pathology. Of the four cases, one showed fetal growth restriction, one neonatal cholestasia, one twin pregnancy, and what seems to be the first case of hemophagocytic syndrome associated with a newborn child infected by this virus. Although the proportion of vertical transmission proved is low, compared with the number of adults affected during an epidemic, some severe cases urge us to be increasingly watchful with this emergent arbovirus, especially because its real incidence is still unknown.

Asunto(s)

Dengue/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Colestasis/etiología , Dengue/diagnóstico , Femenino , Retardo del Crecimiento Fetal/etiología , Guadalupe , Humanos , Hiperbilirrubinemia Neonatal/etiología , Recién Nacido , Leucopenia/etiología , Linfohistiocitosis Hemofagocítica/etiología , Masculino , Embarazo , Embarazo Gemelar , Tiempo de Protrombina , Trombocitopenia/etiología

RESUMEN

Rickettsia felis es el agente etiológico de la fiebre manchada transmitida por pulgas, cuyo principal vector y reservorio es Ctenocephalides felis . Típicamente, la enfermedad se presenta como fiebre aguda asociada a cefalea, astenia, exantema máculo-papular generalizado y, en algunos casos, con escara de inoculación. En los últimos años, R. felis ha venido adquiriendo un papel importante en la etiología del síndrome febril agudo, calificándola como una enfermedad emergente y subdiagnosticada. La inmunofluorescencia indirecta es actualmente el método diagnóstico de referencia. Sin embargo, esta técnica presenta limitaciones relacionadas con la reacción cruzada que existe entre las diferentes especies del género Rickettsia . En el presente reporte se describe el caso de un paciente de 16 años con síndrome febril agudo secundario a infección probable por R. felis .

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Rickettsia felis is the etiologic agent of flea-borne spotted fever, with Ctenocephalides felis as its main vector and reservoir. Typically, the disease presents as acute fever associated with headache, asthenia, generalized maculo-papular rash, and in some cases, an inoculation eschar. In recent years, R. felis has acquired an important role in the etiology of the acute febrile syndrome; it is indeed an emerging infectious disease, albeit underdiagnosed. Indirect immunofluorescence assay (IFA) is currently the reference diagnostic method. However, this technique has limitations related to the cross reactivity among different species of rickettsiae. Herein, we describe a case of a 16 year-old patient with an acute febrile syndrome secondary to probable infection with R. felis.

Asunto(s)

Adolescente , Animales , Gatos , Perros , Humanos , Masculino , Ctenocephalides/microbiología , Infecciones por Rickettsia/diagnóstico , Rickettsia felis/aislamiento & purificación , Anticuerpos Antibacterianos/sangre , Diagnóstico Diferencial , Dengue/diagnóstico , Exposición a Riesgos Ambientales , Caballos , Inmunoglobulina G/sangre , Leucopenia/etiología , Infecciones por Rickettsia/sangre , Infecciones por Rickettsia/transmisión , Rickettsia felis/inmunología , Trombocitopenia/etiología

RESUMEN

As a cutaneous variant of lupus erythematosus, discoid lupus erythematosus (DLE) is thought to have a good prognosis; however, the involvement of internal organs with a transition to systemic disease may occur. The progression from DLE to systemic lupus erythematosus has been reported in up to 28% of patients. This progression to systemic disease has been associated with a benign course. Herein, we report the case of a 31-year-old woman with a 10-year history of discoid lupus, now presenting with dyspnea and pleuritic chest pain of 1 month's duration. A significant drop in hemoglobin and hematocrit levels was observed in association with leukopenia, lymphopenia, a positive ANA, and hypocomplementemia. Chest radiography and computed tomography revealed bilateral infiltrates. An open lung biopsy confirmed the presence of intra-alveolar hemorrhage. Based on the results of the tests and analyses detailed herein, a diagnosis of pulmonary hemorrhage secondary to systemic lupus erythematosus was made. To our knowledge, pulmonary hemorrhage as the initial manifestation of the systemic involvement of discoid lupus has not been reported before.

Asunto(s)

Hemorragia/etiología , Enfermedades Pulmonares/etiología , Lupus Eritematoso Discoide/complicaciones , Adulto , Antibacterianos/uso terapéutico , Biopsia , Bronconeumonía/diagnóstico , Errores Diagnósticos , Progresión de la Enfermedad , Disnea/etiología , Femenino , Hemorragia/sangre , Hemorragia/diagnóstico por imagen , Hemorragia/patología , Humanos , Hidroxicloroquina/uso terapéutico , Leucopenia/etiología , Enfermedades Pulmonares/sangre , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/patología , Lupus Eritematoso Sistémico/complicaciones , Prednisona/uso terapéutico , Radiografía , Cirugía Torácica Asistida por Video

RESUMEN

Rickettsia felis is the etiologic agent of flea-borne spotted fever, with Ctenocephalides felis as its main vector and reservoir. Typically, the disease presents as acute fever associated with headache, asthenia, generalized maculo-papular rash, and in some cases, an inoculation eschar. In recent years, R. felis has acquired an important role in the etiology of the acute febrile syndrome; it is indeed an emerging infectious disease, albeit underdiagnosed. Indirect immunofluorescence assay (IFA) is currently the reference diagnostic method. However, this technique has limitations related to the cross reactivity among different species of rickettsiae. Herein, we describe a case of a 16 year-old patient with an acute febrile syndrome secondary to probable infection with R. felis.

Asunto(s)

Ctenocephalides/microbiología , Infecciones por Rickettsia/diagnóstico , Rickettsia felis/aislamiento & purificación , Adolescente , Animales , Anticuerpos Antibacterianos/sangre , Gatos , Dengue/diagnóstico , Diagnóstico Diferencial , Perros , Exposición a Riesgos Ambientales , Caballos , Humanos , Inmunoglobulina G/sangre , Leucopenia/etiología , Masculino , Infecciones por Rickettsia/sangre , Infecciones por Rickettsia/transmisión , Rickettsia felis/inmunología , Trombocitopenia/etiología

RESUMEN

OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of Pselectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30%, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70% reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals. CONCLUSION: The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage.

Asunto(s)

Muerte Encefálica/fisiopatología , Corticosterona/sangre , Hemodinámica/fisiología , Mediadores de Inflamación/sangre , Circulación Esplácnica/fisiología , Animales , Modelos Animales de Enfermedad , Molécula 1 de Adhesión Intercelular/fisiología , Leucopenia/sangre , Leucopenia/etiología , Masculino , Microcirculación/fisiología , Microscopía Fluorescente , Selectina-P/fisiología , Distribución Aleatoria , Ratas , Ratas Wistar

RESUMEN

OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of Pselectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30 percent, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70 percent reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals. CONCLUSION: The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage.

Asunto(s)

Animales , Masculino , Ratas , Muerte Encefálica/fisiopatología , Corticosterona/sangre , Hemodinámica/fisiología , Mediadores de Inflamación/sangre , Circulación Esplácnica/fisiología , Modelos Animales de Enfermedad , Molécula 1 de Adhesión Intercelular/fisiología , Leucopenia/sangre , Leucopenia/etiología , Microscopía Fluorescente , Microcirculación/fisiología , Selectina-P/fisiología , Distribución Aleatoria , Ratas Wistar

RESUMEN

OBJECTIVE: Protein-energy malnutrition (PEM) is an important public health problem affecting millions of people worldwide. Hematopoietic tissue requires a high nutrient supply, and a reduction in leukocytes, especially lymphocytes, suggests that some nutritional deficiencies might be altering bone marrow function and decreasing its ability to produce lymphocytes. In this study, we evaluated the effect that PEM has on lymphocyte subtypes and the cell cycle of CD5(+) cells. METHODS: Swiss mice were subjected to PEM using a low-protein diet containing 4% protein. When the experimental group had lost about 20% of their original body weight, we collected blood and bone marrow cells and evaluated the hemogram, the myelogram, bone marrow lymphoid markers using flow cytometry, and the cell cycle in CD5(+) bone marrow. RESULTS: Malnourished animals presented anemia, reticulocytopenia, and leukopenia with lymphopenia. The bone marrow was hypocellular, and flow cytometric analyses of bone marrow cells showed cells that were CD45(+) (91.2%), CD2(+) (84.9%), CD5(+) (37.3%), CD3(+) (23.5%), CD19(+) (43.3%), CD22(+) (34.7%), CD19(+)/CD2(+) (51.2%), CD19(+)/CD3(+) (24.0%), CD19(+)/CD5(+) (13.2%), CD22(+)/CD2(+) (40.1%), CD22(+)/CD3(+) (30.3%), and CD22(+)/CD5(+) (1.1%) in malnourished animals and CD45(+) (97.5%), CD2(+) (42.9%), CD5(+) (91.5%), CD3(+) (92.0%), CD19(+) (52.0%), CD22(+) (75.6%), CD19(+)/CD2(+) (62.0%), CD19(+)/CD3(+) (55.4%), CD19(+)/CD5(+) (6.7%), CD22(+)/CD2(+) (70.3%), CD22(+)/CD3(+) (55.9%), and CD22(+)/CD5(+) (8.4%) in control animals. Malnourished animals also presented more CD5(+) cells in the G0 phase of cell cycle development. CONCLUSION: Malnourished animals presented bone marrow hypoplasia, maturation interruption, prominent lymphopenia with depletion in the lymphoid lineage, and changes in cellular development. We suggest that these changes are some of the primary causes of lymphopenia in cases of PEM and partly explain the increase in susceptibility to infections found in malnourished individuals.

Asunto(s)

Anemia/etiología , Células de la Médula Ósea/inmunología , Subgrupos Linfocitarios/metabolismo , Linfopenia/etiología , Desnutrición Proteico-Calórica/inmunología , Animales , Antígenos CD , Células de la Médula Ósea/citología , Ciclo Celular , Dieta con Restricción de Proteínas , Modelos Animales de Enfermedad , Citometría de Flujo , Leucocitos/metabolismo , Leucopenia/etiología , Linfocitos/metabolismo , Ratones , Desnutrición Proteico-Calórica/complicaciones , Reticulocitos/metabolismo

RESUMEN

In order to determine the relationship between hematological parameters, parasitaemia and malaria episodes, we evaluated 59 individuals of both sexes, infected with Plasmodium vivax and 30 controls from Sucre state. Blood samples were obtained by venous puncture and from the earlobe at day of diagnosis, 8 and 30 days post-diagnosis. We carried out hematological analysis, microscopic and molecular (PCR) diagnosis and the parasitaemia was calculated. There were significant differences by sex for hemoglobin, erythrocytes and hematocrit (p < 0.01 in all three analysis). These values in males, decreased by day 8 with respect to day 0 (p < 0.001; p = 0.006 y p = 0.025, respectively). In females, significant differences were only seen in hemoglobin and hematocrit between controls and patients (p < 0.001). The average number of leucocytes at the day of diagnosis was within the reference values, but slightly lower compared to the controls and the samples during and after the treatment. The average proportion of eosinophils was higher than normal for both, controls and patients, during and after the treatment. Thrombocytopenia was observed at diagnosis, but a week after, the values increased significantly (p < 0.001). There was an inverse relationship between parasitaemia and platelet count and a direct relationship between the first and hemoglobin at day 0, as well as with the difference in platelet counts between day 0 and day 8 (p = 0.044 and p = 0.014, respectively). This difference was the only parameter related to the number of malaria episodes (p = 0.040). Thrombocytopenia showed to be an indicator of acute malaria.

Asunto(s)

Antimaláricos/uso terapéutico , Malaria Vivax/sangre , Parasitemia/sangre , Adolescente , Adulto , Anciano , Recuento de Células Sanguíneas , Estudios de Casos y Controles , Niño , Preescolar , Eosinofilia/etiología , Índices de Eritrocitos , Femenino , Hematócrito , Hemoglobinas/análisis , Humanos , Leucocitosis/etiología , Leucopenia/etiología , Malaria Vivax/complicaciones , Malaria Vivax/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Parasitemia/tratamiento farmacológico , Trombocitopenia/etiología , Adulto Joven

Asunto(s)

Anticuerpos Antinucleares/inmunología , Inmunoglobulinas/sangre , Síndrome de Sjögren/diagnóstico , Anemia/etiología , Biomarcadores/sangre , Globulinas/análisis , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Leucopenia/etiología , Síndrome de Sjögren/sangre , Síndrome de Sjögren/inmunología , Trombocitopenia/etiología

RESUMEN

Malnutrition modifies resistance to infection by impairing a number of physiological processes including hematopoesis and the immune response. In this study, we examined the production of Interleukin-4 (IL-4) and IL-10 in response to lipopolysaccharide (LPS) and also evaluated the cellularity of the blood, bone marrow, and spleen in a mouse model of protein-energy malnutrition. Two-month-old male Swiss mice were subjected to protein-energy malnutrition (PEM) with a low-protein diet (4%) as compared to the control diet (20%). When the experimental group lost approximately 20% of their original body weight, the animals from both groups received 1.25 microg of LPS intravenously. The cells in the blood, bone marrow, and spleen were counted, and circulating levels of IL-4 and IL-10 were evaluated in animals stimulated with LPS. Cells from the spleen, bone marrow, and peritoneal cavity of non-inoculated animals were collected for culture to evaluate the production of IL-4 and IL-10 after stimulating these cells with 1.25 microg of LPS in vitro. Malnourished animals presented leucopenia and a severe reduction in bone marrow, spleen, and peritoneal cavity cellularity before and after stimulus with LPS. The circulating levels of IL-10 were increased in malnourished animals inoculated with LPS when compared to control animals, although the levels of IL-4 did not differ. In cells cultured with LPS, we observed high levels of IL-10 in the bone marrow cells of malnourished animals. These findings suggest that malnourished mice present a deficient immune response to LPS. These alterations may be partly responsible for the immunodeficiency observed in these malnourished mice.

Asunto(s)

Interleucina-10/metabolismo , Interleucina-4/metabolismo , Lipopolisacáridos/farmacología , Desnutrición Proteico-Calórica/inmunología , Anemia/etiología , Animales , Recuento de Células Sanguíneas , Células Sanguíneas/inmunología , Células Sanguíneas/metabolismo , Proteínas Sanguíneas/metabolismo , Peso Corporal/efectos de los fármacos , Células de la Médula Ósea/efectos de los fármacos , Células Cultivadas , Dieta con Restricción de Proteínas , Modelos Animales de Enfermedad , Leucopenia/etiología , Macrófagos/metabolismo , Masculino , Ratones , Peritoneo/efectos de los fármacos , Peritoneo/patología , Desnutrición Proteico-Calórica/complicaciones , Albúmina Sérica/metabolismo , Bazo/citología , Bazo/efectos de los fármacos

RESUMEN

Protein-energy malnutrition (PEM) modifies resistance to infection, impairing a number of physiological processes, including hematopoiesis. In this study, we examined a few aspects of the inflammatory response to LPS in a model of PEM. We evaluated the cellularity of the blood, bone marrow and spleen, as well as phagocytic, fungicidal and spreading activity, the production in vivo and in vitro of TNF-alpha, IL-1alpha and IL-6, and the expression of CD14 and TLR-4/MD-2 receptors in macrophages. Two-month-old male Swiss mice were submitted to PEM with a low-protein diet containing 4% protein as compared to 20% protein in the control diet. When the experimental group had attained about 20% loss of their original body weight, they were used in the experiments. Malnourished animals presented anemia, leucopenia and severe reduction in bone marrow, spleen and peritoneal cavity cellularity. The production of TNF-alpha, IL-1alpha and IL-6 stimulated in vivo with LPS and the production of IL-6 in bone marrow cells cultured with LPS and the production of TNF-alpha in bone marrow, spleen and peritoneal cells cultured with LPS were significantly lower in malnourished animals. The expression of CD14 and TLR-4/MD-2 receptors was found to be significantly lower in macrophages of malnourished animals. These findings suggest that malnourished animals present a deficient response to LPS. The lower expression of the CD14 and TLR-4/MD-2 receptors may be partly responsible for the immunodeficiency observed in the malnourished mice. These data lead us to infer that the nutritional state interferes with the activation of macrophages and with the capacity to mount an immune response.

Asunto(s)

Receptores de Lipopolisacáridos/biosíntesis , Lipopolisacáridos/farmacología , Antígeno 96 de los Linfocitos/biosíntesis , Macrófagos Peritoneales/metabolismo , Desnutrición Proteico-Calórica/metabolismo , Receptor Toll-Like 4/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis , Anemia/etiología , Anemia/inmunología , Anemia/metabolismo , Anemia/patología , Animales , Peso Corporal/inmunología , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Síndromes de Inmunodeficiencia/etiología , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/metabolismo , Síndromes de Inmunodeficiencia/patología , Interleucina-1alfa/biosíntesis , Interleucina-1alfa/inmunología , Interleucina-6/biosíntesis , Interleucina-6/inmunología , Leucopenia/etiología , Leucopenia/inmunología , Leucopenia/metabolismo , Leucopenia/patología , Receptores de Lipopolisacáridos/inmunología , Antígeno 96 de los Linfocitos/inmunología , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/patología , Masculino , Ratones , Desnutrición Proteico-Calórica/complicaciones , Desnutrición Proteico-Calórica/inmunología , Desnutrición Proteico-Calórica/patología , Bazo/inmunología , Bazo/metabolismo , Bazo/patología , Receptor Toll-Like 4/inmunología

RESUMEN

We have examined the role of inflammatory cells, ischemia and serum complement on the development of acute experimental amoebic liver abscess in hamsters (AEALAH). In hamsters made leukopenic by whole body radiation (800 rad) and daily intraperitoneal glycogen injections, the absence of inflammatory cells and liver tissue damage surrounding the parasites resulted in their rapid (24 h) disappearance from the liver, which showed no lesions. Focal liver ischemia, always present in control AEALAH with inflammation and tissue destruction, was reproduced in radiated hamsters by injection of amoebae mixed with Superdex microspheres, but again in the absence of inflammation, amoebae caused no liver damage and disappeared in 24 h. In hamsters made hypocomplementemic by injection of purified cobra venom factor (CVF), amoebae caused AEALA indistinguishable from controls, but in leukopenic + hypocomplementemic hamsters, amoebae were unable to produce lesions and disappeared from the liver in 48 h. We conclude that inflammation and tissue damage are required for the survival of amoebae in AEALAH and for the progression of the experimental disease.

Asunto(s)

Proteínas del Sistema Complemento/inmunología , Entamoeba histolytica/fisiología , Hepatitis/patología , Isquemia/patología , Absceso Hepático Amebiano , Hígado/patología , Enfermedad Aguda , Animales , Proteínas Inactivadoras de Complemento/farmacología , Modelos Animales de Enfermedad , Venenos Elapídicos/farmacología , Entamoeba histolytica/efectos de la radiación , Femenino , Cobayas , Hepatitis/inmunología , Hepatitis/parasitología , Isquemia/inmunología , Isquemia/parasitología , Leucocitos/efectos de la radiación , Leucopenia/etiología , Hígado/inmunología , Hígado/parasitología , Absceso Hepático Amebiano/inmunología , Absceso Hepático Amebiano/parasitología , Absceso Hepático Amebiano/patología , Masculino , Traumatismos Experimentales por Radiación