RESUMEN
BACKGROUND: Workers exposed to sewage may have an increased risk of infection by Helicobacter pylori and hepatitis E virus (HEV). OBJECTIVES: To assess the incidence of clinical hepatitis E and peptic ulcers and the seroconversion rate of antibodies to H pylori and HEV in workers with and without sewage exposure. METHODS: 332 workers exposed to sewage and a control group of 446 municipal manual workers (61% participation rate) entered a prospective cohort study with clinical examination and determination of antibodies to H pylori and HEV (immunoglobulins G and A or G and M, respectively). Survival curves were examined with log rank tests and Cox regressions. Travelling to endemic areas, socioeconomic level, age, country of childhood, number of siblings, and personal protective equipment were considered as the main confounding factors. RESULTS: Incidence of clinical hepatitis E was not increased in sewage workers. One peptic ulcer and three eradications were recorded in sewage workers compared with no peptic ulcers and 12 eradications in control workers. Incidence rates of approximately 0.01, 0.10, and 0.15 seroconversion/person-year for hepatitis E, H pylori IgG and H pylori IgA, respectively, were found in both exposed and non-exposed workers. Survival curves did not show an increased risk in sewage workers and no association with any exposure indicator was found. Sensitivity analyses did not alter these results. CONCLUSIONS: Sewage does not appear to be a source of occupational infection by H pylori or HEV in trained sewage workers with personal protective equipment working in a region with good sanitation.
Asunto(s)
Infecciones por Helicobacter/epidemiología , Helicobacter pylori , Hepatitis E/epidemiología , Enfermedades Profesionales/epidemiología , Úlcera Péptica/epidemiología , Aguas del Alcantarillado/efectos adversos , Adolescente , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Métodos Epidemiológicos , Femenino , Infecciones por Helicobacter/etiología , Infecciones por Helicobacter/transmisión , Helicobacter pylori/inmunología , Anticuerpos Antihepatitis/sangre , Hepatitis E/transmisión , Virus de la Hepatitis E/inmunología , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional/análisis , Equipos de Seguridad/estadística & datos numéricos , Suiza/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Workers exposed to sewage may have an increased risk of infection by Helicobacter pylori and hepatitis E virus (HEV). AIMS: To assess the prevalence of clinical hepatitis E (HE) and peptic ulcer disease as well as the seroprevalence of antibodies to H pylori and HEV in workers with and without sewage exposure and to look for symptoms due to exposure to endotoxin. METHODS: In the first year of a prospective cohort study 349 sewage exposed workers and 429 municipal manual workers (participation: 61%) underwent a complete medical examination. Travelling to endemic areas, socioeconomic level, age, country in which childhood was spent, and number of siblings were considered as the main confounding factors. RESULTS: Peptic ulcer disease and clinical HE did not occur more often in workers exposed to sewage. Prevalence of antibodies to HEV was 3.3% and overall prevalence of IgG antibodies to H pylori was 42% with large differences between subgroups. Logistic regression did not show an increased risk of seropositivity or antibodies to parietal cells in sewage exposed workers, but disentangling the effect of exposure from that of confounders was extremely difficult. No increase of symptoms due to exposure to endotoxin was found in sewage workers, with the exception of diarrhoea. CONCLUSIONS: No clear increased risk of infection by H pylori or by HEV in workers exposed to sewage was found in this cross-sectional study, but these results need to be confirmed by follow up.
Asunto(s)
Helicobacter pylori/inmunología , Virus de la Hepatitis E/inmunología , Hepatitis E/epidemiología , Enfermedades Profesionales/epidemiología , Úlcera Péptica/epidemiología , Aguas del Alcantarillado/efectos adversos , Adulto , Anticuerpos Antibacterianos/sangre , Femenino , Anticuerpos Antihepatitis/sangre , Hepatitis E/sangre , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/sangre , Exposición Profesional , Células Parietales Gástricas/inmunología , Úlcera Péptica/sangre , Prevalencia , Estudios Prospectivos , Estudios Seroepidemiológicos , Suiza/epidemiologíaRESUMEN
Hepatitis E virus (HEV) is found in waste water which represents a route of infection. However, the risk for sewage workers is unknown. Thus, we aimed at determining the prevalence of anti-HEV antibodies in sewage workers from the Canton of Zurich. The anti-HEV antibodies evaluated in 288 subjects with exposure to sewage and 306 controls, a total of 594 subjects. Overall, twenty-two (3.7%) subjects had anti-HEV, the seroprevalence was similar in those exposed and controls. The most important risk factor, travelling in endemic areas, was lacking in two workers, who both were exposed to sewage. A follow up study in the population will soon give further evidence on the incidence rate.
Asunto(s)
Anticuerpos Antihepatitis/sangre , Virus de la Hepatitis E/inmunología , Hepatitis E/transmisión , Enfermedades Profesionales/etiología , Aguas del Alcantarillado/virología , Hepatitis E/epidemiología , Hepatitis E/inmunología , Humanos , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/inmunología , Factores de Riesgo , Estudios Seroepidemiológicos , SuizaRESUMEN
Monitoring of viral RNA has become indispensable for the management of HIV-1 infection, but is expensive. This study investigated whether a highly improved test for p24 antigen could serve as an alternative. Thirty-four patients enrolled during 1997 into two treatment studies were tested prospectively for viral RNA by the Roche HIV-1 Monitor and for p24 antigen using signal-amplification-boosted ELISA of heat-denatured plasma. P24 antigen was detectable in 75.8% of 178 samples and HIV RNA in 73.9% of 138 samples. The half-life of p24 antigen in the first phase of effective treatment was 1.6 +/-.4 days (RNA, 1.7 +/-.8). An apparent second, slower decay phase had a half-life of 42 +/- 16 days. Treatment failure occurred in 14 patients. Secondary treatment failures with RNA rebounds from undetectable levels to < or = 10(3) copies/ml in two patients with an undetectable viral load and 10(3) HIV RNA copies/ml, respectively, at baseline were not detected by p24 antigen but carried a low risk for secondary resistance mutations. The other 12 failures were on average detected 29 days earlier by p24 antigen than by RNA (P =.0204), owing to slightly more frequent testing for p24 than for RNA (2.7 vs. 2.4 tests). Average costs for p24 antigen testing up to a failure were only 20.5% of those for RNA (P <.0001). These results indicate that heat-denatured, amplification-boosted p24 antigen measurement can be used as a simple and inexpensive alternative to HIV RNA testing for monitoring treatment.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Ensayo de Inmunoadsorción Enzimática/métodos , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , ARN Viral/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática/economía , Infecciones por VIH/sangre , Infecciones por VIH/virología , Semivida , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Juego de Reactivos para Diagnóstico/economía , Resultado del Tratamiento , Carga ViralRESUMEN
It has been hypothesized that immunoactivation may contribute to brain damage and affect outcome after traumatic brain injury (TBI). In order to determine the role of inflammation after TBI, we studied the interrelationship of the immune mediators sICAM-1 and IL-6 with the levels of S-100beta and neuronal specific enolase (NSE), both recognized markers of brain damage. In addition, the extent and type of cerebral injury and the neurological outcome were related to these measured markers of injury. An evident elevation of S-100beta (range of means: 2.7-81.4 ng/mL) and NSE (range of means: 2.0-81.3 ng/mL) was observed in CSF of all 13 patients during the first 3 posttraumatic days and decreased over 2 weeks. In parallel, the production of sICAM-1 (range of means: 0.7-11.9 ng/mL) and IL-6 (range of means: 0.1-8.2 ng/mL) was also markedly enhanced in CSF. The CSF means of S-100beta and NSE per patient correlated with IL-6 (r = 0.60, p < 0.05; and r = 0.64, p < 0.05, respectively), whereas the corresponding means in serum showed a significant correlation only between NSE and IL-6 (r = 0.56, p < 0.05). Maximal CSF values of NSE and sICAM-1 correlated with each other (r = 0.57, p < 0.05). The contusion sizes assessed on the CT scans correlated with the means of S-100beta (r = 0.63, p < 0.05) and NSE (r = 0.71, p < 0.05) in CSF and with the mean of S-100beta in serum, although not statistically significant (r = 0.52, p = 0.06), but not with serum NSE. Interestingly, linear regression analysis demonstrated that means of S-100beta in CSF (r = 0.78, p = 0.002) and serum (r = 0.82, p < 0.001) correlated with the GOS. These results indicate that the elevation of these parameters in CSF depends on the extent of injury and that S-100beta may be a predictor of outcome after TBI, whereas NSE reflects better the inflammatory response.
Asunto(s)
Lesiones Encefálicas/enzimología , Lesiones Encefálicas/patología , Encéfalo/patología , Neuronas/patología , Fosfopiruvato Hidratasa/sangre , Fosfopiruvato Hidratasa/líquido cefalorraquídeo , Proteínas S100/sangre , Proteínas S100/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Lesiones Encefálicas/sangre , Lesiones Encefálicas/líquido cefalorraquídeo , Intervalos de Confianza , Humanos , Inflamación/sangre , Inflamación/líquido cefalorraquídeo , Inflamación/enzimología , Molécula 1 de Adhesión Intercelular/sangre , Molécula 1 de Adhesión Intercelular/líquido cefalorraquídeo , Interleucina-6/sangre , Interleucina-6/líquido cefalorraquídeo , Modelos Lineales , Persona de Mediana Edad , Factores de Crecimiento Nervioso , Evaluación de Resultado en la Atención de Salud/métodos , Subunidad beta de la Proteína de Unión al Calcio S100 , Estadísticas no ParamétricasRESUMEN
Controlling the extent of inflammatory responses following brain injury may be beneficial since posttraumatic intracranial inflammation has been associated with adverse outcome. In order to elucidate the potential role of anti-inflammatory mediators, the production of interleukin-10 (IL-10) was monitored in paired cerebrospinal fluid (CSF) and serum of 28 patients with severe traumatic brain injury (TBI) and compared to control samples. The pattern of IL-10 was analyzed with respect to the patterns of IL-6, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in both fluids during a time period of up to 22 days. In parallel, the function/dysfunction of the blood-brain barrier (BBB) was monitored using the CSF-/serum-albumin quotient (Q(A)) and compared to intrathecal cytokine levels. Mean IL-10 concentration in CSF was elevated in 26 out of 28 TBI patients (range: 1.3-41.7 pg/ml) compared to controls (cut-off: 1.06 pg/ml), whereas only seven patients had elevated mean IL-10 concentration in serum (range: 5.4-23 pg/ml; cut-off: 5.14 pg/ml). The time course of IL-10 was similar in both fluids, showing a peak during the first days and a second, lower rise in the second week. Intrathecal IL-10 synthesis is hypothesized since CSF-IL-10 levels exceeded serum-IL-10 levels in most of the patients, IL-10-index (CSF/serum-IL-10/QA) was elevated in 23 individuals, and elevation of CSF-IL-10 showed to be independent from severe BBB dysfunction. Neither CSF nor serum IL-10 values correlated with the dysfunction of the BBB. IL-10, IL-6 and TGF-beta1 showed similar patterns in CSF over time, whereas rises of TNF-alpha corresponded to declines of IL-10 levels. Our results suggest that IL-10 is predominantly induced intrathecally after severe TBI where it may downregulate inflammatory events following traumatic brain damage.
Asunto(s)
Barrera Hematoencefálica , Lesiones Encefálicas/inmunología , Interleucina-10/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Factor de Crecimiento Transformador beta/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Lesiones Encefálicas/metabolismo , Femenino , Humanos , Interleucina-10/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Factor de Crecimiento Transformador beta/sangre , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Interleukin-6 (IL-6) and its soluble receptor (sIL-6-R) were measured in cerebrospinal fluid (CSF) and serum of 11 severely head injured patients for up to 3 weeks following trauma. IL-6 increased immediately after injury displaying much higher concentrations in CSF than in serum (n = 11). Differently, median levels of sIL-6-R remained in the normal ranges being 10 times higher in serum than in CSF. However, increased amounts over control levels were found in CSF (n = 7) and intrathecal release of sIL-6-R was also suggested (n = 7). Although no correlation with the extent of cerebral lesion or with clinical outcome was evident, elevation of sIL-6-R in CSF supports a pivotal role for IL-6/sIL-6-R complex in the injured brain.
Asunto(s)
Lesiones Encefálicas/sangre , Lesiones Encefálicas/líquido cefalorraquídeo , Interleucina-6/sangre , Interleucina-6/líquido cefalorraquídeo , Receptores de Interleucina-6/sangre , Receptores de Interleucina-6/metabolismo , Adulto , Líquido Cefalorraquídeo/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , SolubilidadRESUMEN
Human immunodeficiency virus infection is characterized by a progressive decline in the number of peripheral blood CD4(+) T lymphocytes, which finally leads to AIDS. This T-cell decline correlates with the degree of in vitro-induced lymphocyte apoptosis. However, such a correlation has not yet been described in feline AIDS, caused by feline immunodeficiency virus (FIV) infection. We therefore investigated the intensity of in vitro-induced apoptosis in peripheral blood lymphocytes from cats experimentally infected with a Swiss isolate of FIV for 1 year and for 6 years and from a number of long-term FIV-infected cats which were coinfected with feline leukemia virus. Purified peripheral blood lymphocytes were either cultured overnight under nonstimulating conditions or stimulated with phytohemagglutinin and interleukin-2 for 60 h. Under stimulating conditions, the isolates from the infected cats showed significantly higher relative counts of apoptotic cells than did those from noninfected controls (1-year-infected cats, P = 0.01; 6-year-infected cats, P = 0.006). The frequency of in vitro-induced apoptosis was inversely correlated with the CD4(+) cell count (P = 0. 002), bright CD8(+) cell count (P = 0.009), and CD4/CD8 ratio (P = 0. 01) and directly correlated with the percentage of bright major histocompatibility complex class II-positive peripheral blood lymphocytes (P = 0.004). However, we found no correlation between in vitro-induced apoptosis and the viral load in serum samples. Coinfection with feline leukemia virus enhanced the degree of in vitro-induced apoptosis compared with that in FIV monoinfected cats. We concluded that the degree of in vitro-induced apoptosis was closely related to FIV-mediated T-cell depletion and lymphocyte activation and could be used as an additional marker for disease progression in FIV infection.
Asunto(s)
Apoptosis , Síndrome de Inmunodeficiencia Adquirida del Felino/etiología , Síndrome de Inmunodeficiencia Adquirida del Felino/patología , Virus de la Inmunodeficiencia Felina/patogenicidad , Infecciones por Lentivirus/etiología , Infecciones por Lentivirus/patología , Linfocitos/patología , Animales , Biomarcadores , Relación CD4-CD8 , Gatos , Síndrome de Inmunodeficiencia Adquirida del Felino/inmunología , Femenino , Productos del Gen gag/análisis , Humanos , Virus de la Inmunodeficiencia Felina/inmunología , Técnicas In Vitro , Infecciones por Lentivirus/inmunología , Activación de Linfocitos , Linfocitos/inmunología , Linfocitos/virología , Masculino , Linfocitos T/inmunología , Linfocitos T/patología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
An overwhelming intracranial inflammatory response occurs as a consequence of severe head trauma, leading to cerebral edema and secondary brain injury. Cytokines are important mediators of post-traumatic cerebral inflammation. In the present study, levels of interleukin-12 (IL-12), a pro-inflammatory cytokine which activates cellular immune response mechanisms, were measured by ELISA in 140 matched serum and ventricular cerebrospinal fluid (CSF) samples from ten patients with severe traumatic brain injury. The mean IL-12 CSF levels were significantly elevated in all patients in the course of 14 days after trauma, compared to CSF samples from 15 control patients. Assessment of the IL-12 CSF/serum ratio and of the blood-brain barrier function, using the CSF/serum albumin ratio, suggest that elevated IL-12 CSF levels might be in part derived from intracerebral cytokine synthesis.
Asunto(s)
Lesiones Encefálicas/líquido cefalorraquídeo , Interleucina-12/líquido cefalorraquídeo , Adolescente , Adulto , Barrera Hematoencefálica/fisiología , Encéfalo/metabolismo , Lesiones Encefálicas/sangre , Femenino , Traumatismos Cerrados de la Cabeza/sangre , Traumatismos Cerrados de la Cabeza/líquido cefalorraquídeo , Humanos , Interleucina-12/biosíntesis , Interleucina-12/sangre , Masculino , Persona de Mediana EdadRESUMEN
The fetal liver is the main hematopoietic organ during intrauterine life. Morphometrical studies were performed on liver sections to detect changes occurring with intrauterine growth retardation and preeclampsia. Compared with the controls (n = 10), fetuses from preeclamptic mothers showed a severe reduction of erythroid cells by 60% on average (n = 18). Closer examination revealed that the erythroid cells at early stages of differentiation were more affected (80% reduction) than at later stages (55%). Seven out of 18 fetuses from preeclamptic mothers did not show growth retardation but exhibited severely reduced hepatic erythropoiesis. We suggest that the prime factor for impaired red blood cell production is preeclampsia itself rather than intrauterine growth retardation. Regulation of erythropoiesis in utero might depend on the interaction of many hematopoietic growth factors, and preeclampsia might alter the balance. To test this notion, we quantitated erythropoietin in fetal blood and various cytokines in the amniotic fluid. An elevation of erythropoietin and interleukin (IL)-3 levels was seen in babies born under the conditions of preeclampsia, whereas the concentrations of granulocyte/macrophage-colony-stimulating factor (CSF), granulocyte-CSF, and IL-1 beta were reduced, and the levels of IL-6 and IL-8 remained constant. With preeclampsia, a discrepancy between elevation of erythrocyte numbers in peripheral blood and depression of hematopoiesis at the main production site, the fetal liver, is seen. Concomitantly, there is elevation of some but reduction of other hematopoietic cytokines. We envision that during the course of preeclampsia quantitation of hematopoietic growth factors might allow to predict the deterioration of in utero life conditions.
Asunto(s)
Eritropoyesis , Feto/patología , Hígado/patología , Preeclampsia/patología , Líquido Amniótico/metabolismo , Estudios de Casos y Controles , Citocinas/metabolismo , Eritropoyesis/fisiología , Eritropoyetina/sangre , Femenino , Sangre Fetal/metabolismo , Retardo del Crecimiento Fetal/etiología , Retardo del Crecimiento Fetal/patología , Retardo del Crecimiento Fetal/fisiopatología , Feto/fisiopatología , Factores de Crecimiento de Célula Hematopoyética/metabolismo , Humanos , Hígado/fisiopatología , Intercambio Materno-Fetal , Preeclampsia/complicaciones , Preeclampsia/fisiopatología , EmbarazoRESUMEN
In an adjuvant clinical trial for high-risk patients with malignant melanoma by using recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha 2b (rIFN-alpha 2b), we monitored the development of antibodies against rIFN-alpha and various immunoparameters as biologic markers for IFN activity in vivo. Thirty-one patients (22 men, nine women) with high-risk malignant melanoma received eight 6-week cycles of rIL-2 and rIFN-alpha. Serum samples of all patients were screened for the presence of antibodies against IFN-alpha by a solid enzyme immunoassay (EIA). Specimens testing positive in the EIA were assessed for their ability to neutralize the antiviral effects of IFN-alpha in vitro in an antibody-neutralizing bioassay (ANB). Furthermore, serum levels of neopterin, beta 2-microglobulin, soluble IL-2 receptor (sIL-2R), anticardiolipin and antithyroglobulin were evaluated. Of 31 patients, 11 (36%) developed binding antibodies; three (27%) of them had antibodies with neutralizing capacities (range, 350-28,000 INU/ml). Of male patients, 8 (36%) of 22 versus 1 (11%) of nine female patients developed antibodies. Statistical analysis (unpaired t test) revealed that all patients with antibody titers showed significant (p < 0.04) lower serum levels of beta 2-microglobulin and reproducible decreases in sIL-2R levels, whereby those with neutralizing antibodies showed significantly (p < 0.0001) lower values than did those with binding antibodies. Elevations of anticardiolipin (17 of 31) and antithyroglobulin (one of 31) were not correlated to the presence of IFN antibodies. Our results show the in vivo significance of antibodies against rIFN-alpha, especially of those with neutralizing capacities. Monitoring of antibody formation as well as immunoparameters like beta 2-microglobulin in clinical trials can contribute to identifying patients who, if necessary, might benefit from alternative IFN treatment, for instance, by using natural IFNs.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Anticuerpos/efectos adversos , Inmunoterapia Activa , Interferón-alfa/inmunología , Interferón-alfa/uso terapéutico , Melanoma/inmunología , Neoplasias Cutáneas/inmunología , Adyuvantes Inmunológicos/efectos adversos , Adulto , Anciano , Formación de Anticuerpos , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interleucina-2/efectos adversos , Interleucina-2/uso terapéutico , Masculino , Melanoma/terapia , Persona de Mediana Edad , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Neoplasias Cutáneas/terapiaRESUMEN
There is strong evidence that the immune response to Borrelia burgdorferi (Bb) contributes to the pathogenesis of Lyme disease. Bb are transmitted by ticks to the skin, which is particularly rich in dendritic cells (DC). The initial reaction of these APCs may already set the course to immune pathogenesis. To study the role of DC, biopsies from human skin were incubated with Bb and investigated in toto with electron microscopy. In addition, DC freshly isolated from dermis (DDC) and epidermis (Langerhans cells) were compared with blood-derived DC (BDC). In situ, Bb were found in the dermal layer of the skin only, occasionally cleared by DDC. Isolated DDC and BDC, but not Langerhans cells, readily engulfed Bb preferentially using coiling phagocytosis. Internalized Bb were located free in the cytosol and inside of phagolysosomes of DDC and BDC. Intravesicular Bb Ags were colocalized with MHC class II molecules. In addition, live Bb induced IL-12 production in BDC. Bb-pulsed BDC activated naive and primed autologous Bb-specific T cells, as measured by detection of granulocyte-macrophage CSF gene transcription and proliferative response, respectively. These data indicate that human DC phagocytose, process, and present Bb Ags. The way in which DC may influence the immune response in Lyme disease, however, remains to be evaluated.
Asunto(s)
Presentación de Antígeno , Antígenos Bacterianos/inmunología , Grupo Borrelia Burgdorferi/inmunología , Células Dendríticas/inmunología , Células de Langerhans/inmunología , Fagocitosis , Piel/inmunología , Secuencia de Bases , Células Sanguíneas , Grupo Borrelia Burgdorferi/aislamiento & purificación , Células Dendríticas/microbiología , Epidermis/inmunología , Regulación de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Humanos , Interleucina-12/biosíntesis , Interleucina-12/genética , Enfermedad de Lyme/microbiología , Lisosomas/microbiología , Microscopía Fluorescente , Microscopía Inmunoelectrónica , Datos de Secuencia Molecular , Subgrupos de Linfocitos T/inmunologíaRESUMEN
In a prospective randomized trial in patients undergoing major abdominal surgery, the impact of a new enteral formula supplemented with arginine, omega-3 fatty acids, and nucleotides (A, n = 14) on immunological parameters was compared with a standard enteral formula (B, n = 14) and a low calorie/low fat intravenous solution (C, n = 13). Four days postoperatively, a statistically significant decrease in total leukocyte count (A, 9.0 +/- 2.9; B, 8.0 +/- 2.4; C, 11.1 +/- 3.5 x 10(6) cells/mL; A versus C, B versus C; p < 0.05), higher percentage of lymphocytes (A, 14.3 +/- 4.9; C, 8.2 +/- 6.1; p < 0.05), and decreased median CRP levels (A, 80.4 [69.9]; B, 70 [74]; C, 88.5 [142] in mg/L; A versus C, p < 0.05; B versus C; p < 0.05) were observed in the enteral nutrition groups. The expression of activated surface antigen HLA-DR was diminished on CD14+ cells over 4 d (A, 58.2 [39.2]; B, 52.2 [36.2]; C, 76.6 [25.2] in %; A versus C, p < 0.05; B versus C, p < 0.05) and 8-10 d (A, 37.9 [31.4]; C, 58.5 [37.6]; p < 0.05) postoperatively. Significantly enhanced median phagocytic activity of CD14+ monocytes and granulocytes was observed in group C 8-10 days postoperatively (A, 83.3 [11.8]; B, 71.6 [34.1]; C, 87.4 [10.8]; A versus B, B versus C, p < 0.05; and A, 75.7 [10.0]; B, 69.0 [37.8]; C, 80.0 [10.1] in %, B versus C, p < 0.05, respectively). Postoperative hospital and intensive care unit stay was similar among the three groups; however, infectious complications were less frequent in group A (A versus C, p = 0.15). Thus, a modified enteral nutritional support and supplementation may influence the immune competence toward a more efficient defense response.
Asunto(s)
Arginina/administración & dosificación , Nutrición Enteral , Ácidos Grasos Omega-3/administración & dosificación , Inmunidad , Nucleótidos/administración & dosificación , Procedimientos Quirúrgicos Operativos , Anciano , Complemento C4/metabolismo , Ingestión de Energía , Grasas/administración & dosificación , Femenino , Humanos , Inmunoglobulinas/sangre , Infecciones , Interleucinas/metabolismo , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Concentrations of five cytokines, GM-CSF, G-CSF, IL-1, IL-6 and IL-8, were determined within five compartments under four different conditions: at the time of a Caesarean section performed between 25 and 38 weeks' gestational age in normal pregnancy without uterine contraction (n = 12), in normal pregnancy with labour already established (n = 8), in pregnancy complicated by amniotic infection (n = 11), or under the conditions of preeclampsia with fetal intrauterine dystrophy (n = 13), cytokine concentrations were determined in fetal arterial and venous blood, in amniotic fluid, and in retroplacentally obtained maternal blood and peripheral maternal blood. With dystrophy, the concentrations of GM-CSF, G-CSF and IL-1 were about 20-50% lower (P < 0.01) in the amniotic fluid, and IL-6 and IL-8 were elevated in maternal peripheral blood (P < 0.01) but not within maternal retroplacental blood. Thus, preeclampsia/intrauterine dystrophy is characterized by reduction of some cytokines within the amniotic fluid compartment and concomitant reactive augmentations of other cytokines within the maternal and fetal organism. With amniotic fluid infection, concentrations of G-CSF, IL-6 and IL-8 were elevated in all compartments (P < 0.001) but GM-CSF and IL-1 showed a significant rise only within amniotic fluid and retroplacental maternal blood (P < 0.001), a rise that was apparently not transmitted to peripheral maternal or fetal blood. Care was taken to exclude the presence of uterine contractions in the group of controls, because this condition by itself causes severe elevation of cytokine concentrations, which are pronounced within amniotic fluid.
Asunto(s)
Citocinas/análisis , Complicaciones del Embarazo/metabolismo , Embarazo/metabolismo , Líquido Amniótico/metabolismo , Corioamnionitis/metabolismo , Citocinas/sangre , Femenino , Sangre Fetal/metabolismo , Retardo del Crecimiento Fetal/metabolismo , Factor Estimulante de Colonias de Granulocitos/análisis , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Humanos , Interleucina-1/análisis , Interleucina-6/análisis , Interleucina-8/análisis , Trabajo de Parto/metabolismo , Placenta/irrigación sanguínea , Preeclampsia/metabolismoRESUMEN
The activation by concanavalin A Con A of human peripheral blood lymphocytes (PBLs) in the presence of monocytes as accessory cells was investigated in cultures exposed to microgravity conditions in Spacelab. Activation of T cells was measured as incorporation of [3H]thymidine into DNA, secretion of interleukin-2 (IL-2), and interferon-gamma, and expression of IL-2 receptors. Whereas, as discovered in earlier experiments, the activation of resuspended T cells is strongly inhibited, activation of cells attached to microcarrier beads is more than doubled in microgravity. The results suggest that the depression of the activation in resuspended cells may be attributed to a malfunction of monocytes acting as accessory cells. In fact, although the ultrastructure of resuspended monocytes is not altered in microgravity, the secretion of IL-1 is strongly inhibited. Our data suggest that (1) IL-2 is produced independently of IL-1, (2) IL-1 production is triggered only when monocytes (and lymphocytes?) adhere to microcarriers, (3) the expression of IL-2 receptors depends on IL-1, and (4) provided sufficient IL-1 is available, activation is enhanced in microgravity. Finally, cultures of resuspended PBLs and monocytes in microgravity constitute a complete and natural system in which monocytes are not operational. This may be useful for studies of the role of accessory cells and cell-cell interactions in T lymphocyte activation.
Asunto(s)
Transducción de Señal , Linfocitos T/citología , Ingravidez , Medicina Aeroespacial , Comunicación Celular/fisiología , Células Cultivadas , Concanavalina A/farmacología , ADN/metabolismo , Glucosa/metabolismo , Humanos , Interferón gamma/metabolismo , Interleucina-1/metabolismo , Interleucina-2/metabolismo , Activación de Linfocitos , Masculino , Microscopía Electrónica , Monocitos/citología , Monocitos/metabolismo , Monocitos/fisiología , Receptores de Interleucina-2/metabolismo , Linfocitos T/metabolismo , Linfocitos T/fisiología , Timidina/metabolismo , Tritio , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: The tremendous progress in imaging techniques over the past few years has not resulted in an earlier diagnosis of pancreatic cancer (PC). The search for a noninvasive diagnostic tool, capable of early diagnosis, led to the development of a series of tumor markers. This article discusses the evaluation of the latest one--CA 242--and its comparison with established markers such as CA 19.9, CA 50, and carcinoembryonic antigen (CEA). METHODS: The markers were tested in preoperative serum samples collected from 300 patients and 30 healthy controls between April 1986 and May 1991. There were 68 patients with ductal carcinoma of the pancreas, 24 with other pancreatic tumors, 57 with acute pancreatitis, 29 with chronic pancreatitis (CP), 90 with benign disease of the upper gastrointestinal tract, and 32 with malignant disease. The test for CA 242 consisted of a DELFIA research kit (WALLAC OY, Turku, Finland) with a cutoff level of 20 U/ml. The other markers were tested with commercially available kits. RESULTS: Sensitivities for PC in this population, with other malignant neoplasms accounting for 16% of the group, were 66.2%, 70.6%, and 70.6% for CA 242, CA 19.9, and CA 50, respectively (90% specificity level). The best results were achieved with the combination of CA 242 and CA 50, reaching a sensitivity of 75.0%. The differential diagnosis between PC and CP could be made with a sensitivity of 64.7%, 79.4%, and 77.9%, respectively, for the three markers. CONCLUSIONS: The authors conclude that, on its own, CA 242 does not improve the sensitivities reached with CA 19.9 and CA 50, but the combination does achieve both a higher sensitivity and specificity.
Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores/sangre , Biomarcadores de Tumor/sangre , Neoplasias Pancreáticas/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Diagnóstico Diferencial , Estudios de Evaluación como Asunto , Femenino , Humanos , Neoplasias Hepáticas/secundario , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Pancreatitis/sangre , Pancreatitis/diagnóstico , Neoplasias Peritoneales/secundario , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
Tumor necrosis factor alpha (TNF alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA) and by cell culture bioassay in supernatants of lipopolysaccharide-stimulated feline monocyte cultures and in cat serum samples. There was a good correlation between the results obtained by the two methods. From the fact that TNF alpha was neutralized quantitatively by antibodies to human TNF alpha in feline monocyte supernatants and in feline sera, it was concluded that feline TNF alpha immunologically cross-reacts with human TNF alpha and that the human TNF alpha ELISA can be used to quantitate feline TNF alpha. During the first 6 months after experimental feline immunodeficiency virus (FIV) infection no differences in serum TNF alpha values were observed between infected and non-infected cats. TNF alpha levels increased significantly after primary vaccination with a feline leukemia virus (FeLV) vaccine in FIV infected cats over those in the non-infected controls. During secondary immune response TNF alpha levels rose transiently for a period of a few days in both the FIV positive and the FIV negative cats. After FeLV challenge, TNF alpha levels increased in all animals challenged with virulent FeLV for a period of 3 weeks. This period corresponded to the time necessary to develop persistent FeLV viremia in the control cats. It was concluded from these experiments that in the asymptomatic phase of FIV infection no increased levels of TNF alpha are present, similar to the situation in asymptomatic HIV infected humans. Activation of monocytes/macrophages in FIV infected cats by stimuli such as vaccination or FeLV challenge readily leads to increased levels of TNF alpha.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida del Felino/inmunología , Virus de la Inmunodeficiencia Felina/inmunología , Virus de la Leucemia Felina/inmunología , Leucemia Experimental/inmunología , Proteínas Oncogénicas de Retroviridae/inmunología , Factor de Necrosis Tumoral alfa/análisis , Vacunas Virales/inmunología , Animales , Gatos , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Leucemia Experimental/complicaciones , Activación de Macrófagos/inmunología , Masculino , Monocitos/inmunología , Proteínas Oncogénicas de Retroviridae/administración & dosificación , Organismos Libres de Patógenos Específicos , Vacunas Virales/administración & dosificaciónRESUMEN
Potential risk factors for the development of hepatocellular carcinoma were analysed in 40 Caucasian patients with this malignancy. A higher proportion (14 of 40; 35%) had evidence of hepatitis C virus (HCV) infection than had evidence of either hepatitis B virus (HBV) carriage (17.5%) or alcohol abuse (30%). In all 14 patients whose sera were reactive by HCV ELISA (Ortho second generation test), the presence of antibodies to HCV were confirmed by recombinant immunoblot assay (Ortho RIBA-2). Furthermore, two independent laboratories detected HCV-RNA in 10 of the 14 (71%) anti-HCV positive sera. Two additional sera were shown to contain HCV-RNA when reanalysed by a modified PCR using oligonucleotide primers designed to amplify a shorter fragment of the 5' noncoding region of the genome. Seven of the anti-HCV positive patients also had evidence of prior HBV infection and 2 admitted to alcohol abuse. HCV infection was the only identifiable risk factor in 6 patients. These data confirm the association between HCV infection and hepatocellular carcinoma and suggest that persistent viral replication accompanies tumour development in the majority of patients whose serum contains anti-HCV.
Asunto(s)
Carcinoma Hepatocelular/complicaciones , Hepatitis C/complicaciones , Neoplasias Hepáticas/complicaciones , Viremia/complicaciones , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/microbiología , Femenino , Hepacivirus/inmunología , Hepacivirus/aislamiento & purificación , Hepacivirus/fisiología , Anticuerpos Antihepatitis/sangre , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/microbiología , Masculino , Persona de Mediana Edad , ARN Viral/aislamiento & purificación , Replicación Viral , Población BlancaRESUMEN
From November 1989 to April 1990 we analyzed prospectively the prevalence of anti-hepatitis C virus antibodies and the possible mode of infection in 90 outpatients with repeatedly elevated alanine-aminotransferase levels. The clinical and serological course of these patients was evaluated after 1, 3 and 6 months. Initially, 24 patients (26.6%) were positive for anti-HCV antibodies, but subsequently only 14 of these patients (15.5%) were positive in the follow-up tests. 9 patients (10%) showed no antibodies against HCV in control evaluations and one patient dropped out of the investigation. The 9 patients with a negative result in the control tests had median relative anti-HCV concentrations of 2.0 (range 1.2-4.1) in contrast to 5.5 (range 1.6-256.5) in the 14 patients with a confirmed anti-HCV test (p less than 0.001). None of those 9 patients had received blood transfusions, 7 had consumed drugs intravenously and only 2 had no specific risk for HCV infection. The consistently anti-HCV positive patients had median alanine-aminotransferase levels between 115 and 200 U/l, whereas the levels in initially anti-HCV positive and subsequently negative patients ranged from 75-90 U/l. The initial prevalence of anti-HCV antibodies in 26.6% of our patients is related to the high rate of either false positive results or sero-conversion in 38% of this group. We recommend cautious interpretation of anti-HCV test results with relative anti-HCV concentrations less than or equal to 2 in equivocal clinical situations.
Asunto(s)
Hepacivirus/inmunología , Anticuerpos Antihepatitis/aislamiento & purificación , Adulto , Alanina Transaminasa/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis C/enzimología , Hepatitis C/transmisión , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Reacción a la TransfusiónRESUMEN
Between 1987 and 1988 592 serum samples were analyzed in order to determine the prevalence of cytomegalovirus (CMV), hepatitis-B and HIV-1 antibodies among healthy blood donors and different risk groups in the region of Zurich, Switzerland. Samples from 100 healthy blood donors, 100 hospital patients, 100 renal transplant recipients, 142 iv drug addicts and 150 homosexuals were analyzed. Among 111 (74%) of the 150 homosexuals studied, antibodies against CMV were identified. On the other hand, only a third of the remaining probands proved to be anti-CMV positive (26-37%). All the groups aged between 20 and 39 years showed an increase in anti-CMV frequency with advancing age. Among the 47 homosexuals aged between 20 and 29 years, 30 (64%) were already anti-CMV positive. The relevance of CMV as a sexually transmissible disease is discussed.