[Children's and adolescents' perception of their quality of life in cases of attention deficit hyperactivity disorder with and without pharmacological treatment and in controls]. / Percepcion de niños y adolescentes sobre la calidad de vida en casos de trastorno por deficit de atencion/hiperactividad con y sin tratamiento farmacologico y en controles.

INTRODUCTION: Health-related quality of life perceived by children and teenagers is important to assess the effects of therapeutic intervention. AIM: To analyze quality of life, comparing cases of attention deficit hyperactivity disorder (ADHD) treated with methylphenidate, untreated cases and controls. SUBJECTS AND METHODS: Sampling of 228 participants between 8 and 14 years-old. Consecutive sampling in ADHD according to DSM-IV criteria (ADHD Rating Scales IV) and random sampling of matched controls by sex and age. Evaluation of quality of life using KIDSCREEN-52 (children version). ANOVA with Bonferroni correction was used. RESULTS: There is a moderate significant correlation between greater intensity of ADHD symptoms and worse quality of life, except in the dimension of physical well-being. Cases of untreated ADHD have significantly worse quality of life than controls on psychic well-being, mood, autonomy school environment and social acceptance. Cases of treated ADHD present similar results, except in the school environment and psychological well-being. The cases of ADHD treated only differ significantly from ADHD not treated in having a better school environment. CONCLUSIONS: The cases of ADHD present dimensions of KIDSCREEN-52 with worse quality of life than controls and the cases of ADHD treated with methylphenidate only differ significantly from those not treated in presenting better results in the school environment.

TITLE: Percepcion de niños y adolescentes sobre la calidad de vida en casos de trastorno por deficit de atencion/hiperactividad con y sin tratamiento farmacologico y en controles.Introduccion. La calidad de vida relacionada con la salud percibida por niños y adolescentes es un factor importante para valorar los efectos de una intervencion terapeutica. Objetivo. Analizar la calidad de vida comparando casos con trastorno por deficit de atencion/hiperactividad (TDAH) tratados farmacologicamente con metilfenidato, casos no tratados y controles. Sujetos y metodos. Muestra de 228 participantes de 8-14 años. Muestreo consecutivo de casos de TDAH segun los criterios del Manual diagnostico y estadistico de los trastornos mentales, cuarta edicion, y muestreo aleatorio de controles emparejados por sexo, edad y zona sociodemografica. Evaluacion de la calidad de vida mediante el KIDSCREEN-52 (version niños y adolescentes). Para responder al objetivo se utilizo ANOVA con correccion de Bonferroni. Resultados. Observamos una correlacion significativa moderada entre mayor intensidad de sintomas de TDAH y peor calidad de vida, excepto en el bienestar fisico. Los casos de TDAH no tratados tienen significativamente peor calidad de vida que los controles en bienestar psiquico, autonomia, estado de animo, entorno escolar y aceptacion social. Los casos de TDAH tratados observan similares resultados excepto en el entorno escolar y el bienestar psiquico, que no presentan diferencias significativas con los controles. Los casos de TDAH tratados por comparacion con los de TDAH no tratados solo presentan significativamente mejor calidad de vida en el entorno escolar. Conclusion. Los casos de TDAH presentan dimensiones del KIDSCREEN-52 con peor calidad de vida que los controles y los casos de TDAH tratados con metilfenidato solo se diferencian significativamente de los no tratados porque presentan mejores resultados en el entorno escolar.

[Approach to quality objectives in incidents of patients in peritoneal dialysis]. / Cumplimiento de objetivos de calidad y evolución de los pacientes incidentes en diálisis peritoneal.

INTRODUCTION: In 2007 the Scientific Quality-technical and Improvement of Quality in Peritoneal Dialysis was edited. It includes several quality indicators. As far as we know, only some groups of work had evaluated these indicators, with inconclusive results. AIM: To study the evolution and impact of guidelines in Peritoneal Dialysis. METHODS: Prospective cohort study of each incident of patients in Peritoneal Dialysis, in a regional public health care system (2003-2006). We prospectively collected baseline clinical and analytical data, technical efficacy, cardiovascular risk, events and deaths, hospital admissions and also prescription data was collected every 6 months. RESULTS: Over a period of 3 years, 490 patients (53.58 years of age; 61.6% males.) Causes of ERC: glomerular 25.5%, diabetes 16%, vascular 12.4%, and interstitial 13.3%. 26.48% were on the list for transplant. Dialysis efficacy: Of the first available results, the residual renal function was 6.37 ml/min, achieving 67.6% of all the objectives K/DOQI. 38.6% remained within the range during the entire first year. Anaemia: 79.3% received erythropoietic stimulating agents and maintained an average Hb of 12.1 g/dl. The percentage of patients in the range (Hb: 11-13 g/dl) improved after a year (58.4% vs 56.3% keeping in the range during this time of 25.6%). Evolution: it has been estimated that per patient-year the risk of: 1) mortality is 0.06 IC 95% [0.04-0.08]; 2) admissions 0.65 [0.58-0.72]; 3) peritoneal infections 0.5 [0.44-0.56]. CONCLUSION: Diabetes Mellitus patients had a higher cardiovascular risk and prevalence of events. The degrees of control during the follow-up in many topics of peritoneal dialysis improve each year; however they are far from the recommended guidelines, especially if they are evaluated throughout the whole study.

Efectos de la infección aguda y crónica por Trypanosoma cruzi en la gestación de los ratones / Effects of acute and chronic Trypanosoma cruzi infection in pregnant mice

Pathogens may impair reproduction in association or not with congenital infections. We have investigated the effect of acute infection with Trypanosoma cruzi, the protozoan agent of Chagas disease, on reproduction of female mice. In the acute, parasitemic, phase of the infection, female mice were totally unable to reproduce. Most of them (80%) were infertiles and did not develop any gestation. In the few gravid infected mice, implantation numbers were as in uninfected control mice. However, their fetuses presented a weight meanly reduced by 40% as compared to those of uninfected females, and all of them died during the gestation or whithin 48 h after birth. Such massive mortality did not result from congenital infection, which did not occur. The infertility and the fetal mortality occuring early in gestation (resorptions) were significantly correlated with a high maternal parasitemia, whereas later fetal mortality was associated with the presence of intracellular parasites in the utero-placental unit. The decidua was particularly receptive to T. cruzi multiplication, since this tissue harboured 125 fold more amastigotes than the maternal heart or other placental tissues. In addition, placentas of dead fetuses presented histopathological lesions (inflammatory infiltrates, fibrine deposits and ischemic necrosis). Such harmfull effects of acute infection were not observed when female mice were in the chronic phase of the infection, since these reproduce normally. Their fetuses only suffered from moderate and reversible growth retardation. These results indicate that, following the maternal parasite burden, T. cruzi infection may induce very deleterious effects on gestation.

Cultivo de condrocitos / Chondrocyte culture

El cultivo de condrocitos para uso en humanos forma parte de una técnica quirúrgica encaminada hacia la regeneración de cartílago articular cuyos resultados aún son preliminares y debatidos. En el presente artículo mostramos la forma de cultivar condrocitos detallando la técnica en sí misma, así como otro tipo de requerimientos legales que el proceso de cultivo debe cumplir para que dichas células sean aptas para su uso en pacientes. También exponemos los resultados clínicos obtenidos con la aplicación de la técnica denominada implante de condrocitos autólogos en nuestro hospital empleando, últimamente, células cultivadas en nuestro propio laboratorio. (AU)

Modulation induced by estradiol in the acute phase of Trypanosoma cruzi infection in mice.

We investigated the effect of 17beta-estradiol on mice resistant to infection by Trypanosoma cruzi. Infected Balb/C, C3H and C57BL/6 female mice had a longer survival time than males, C57BL/6 showing the highest difference (50% cumulative mortality in females versus 100% in males). This lineage was treated with estradiol (from 0.05 microg to 500 microg/mouse) 1 day before infection. Treatment with 50 microg or 500 microg estradiol/ mouse increased mortality and parasitaemia. Low doses had no effect or tended to reduce both parameters. Given that estradiol presented no in vitro effect on trypomastigotes or epimastigotes, the involvement of a direct hormonal effect on the parasite is improbable. Alterations in the humoral T. cruzi-specific response were also discarded, since the kinetics and concentration of anti-T. cruzi IgG were not affected by the treatment. Females infected during an estradiol-descending phase (meta-oestrus) survived longer than those infected during other phases of the oestrous cycle. We confirmed that estradiol interferes with T. cruzi infection.

Percutaneous colonoscopic cecostomy for management of chronic constipation in children.

BACKGROUND: Chronic constipation and encopresis are common problems in children with spina bifida and anorectal anomalies. Commonly used therapies include complicated bowel regimens and antegrade continence enemas delivered via surgically placed appendicostomies and radiologically placed cecostomies. METHODS: A technique is described for percutaneous placement of cecostomies for the delivery of continence enemas or venting. RESULTS: Percutaneous cecostomies were placed in 12 patients. Improvement in bowel management occurred in all patients. CONCLUSIONS: Percutaneous endoscopic cecostomy is a safe and effective method for the treatment of intractable constipation.

Prolonged duration of response to infliximab in early but not late pediatric Crohn's disease.

OBJECTIVES: Tumor necrosis factor-alpha plays a central role in chronic intestinal inflammation of Crohn's disease. Targeting this cytokine with the chimeric monoclonal antibody infliximab has emerged as an effective form of therapy in adult Crohn's disease patients. We sought to determine whether infliximab treatment would benefit pediatric patients with medically refractory Crohn's disease. We also assessed the duration of response, comparing children with early disease to children with long-standing (late) Crohn's disease. METHODS: Fifteen consecutive children (mean age 12.8 +/- 3.2 yr) with medically refractory Crohn's disease were enrolled in a prospective, open-label trial of a single, 5-mg/kg infliximab intravenous infusion. Medically refractory disease was defined as an inability to taper steroids, lack of response to immunomodulator therapy over 4 months, and active disease as measured by the Pediatric Crohn's Disease Activity Index (PCDAI). Primary endpoints included measurements of disease activity (PCDAI), steroid use, and duration of clinical response. RESULTS: In all, 14/15 children (94%) improved after infliximab infusion, with a significant decrease of both PCDAI and daily steroid use by 4 wk. Ten patients (67%) achieved complete remission by 10 wk. Among the 14 patients who responded, three of six children (50%) with early disease maintained clinical response through the 12-month trial period, compared to none of eight children with late disease. There were no serious complications associated with the use of infliximab in any of the patients. CONCLUSIONS: Infliximab is safe and effective in the short-term treatment of medically refractory pediatric Crohn's disease. More importantly, there is a remarkably prolonged duration of response after infliximab therapy in children with early compared to late Crohn's disease.

Deficient iNOS in inflammatory bowel disease intestinal microvascular endothelial cells results in increased leukocyte adhesion.

Microvascular endothelial cells play a key role in inflammation by undergoing activation and recruiting circulating immune cells into tissues and foci of inflammation, an early and rate-limiting step in the inflammatory process. We have previously [Binion et al., Gastroenterology112:1898-1907, 1997] shown that human intestinal microvascular endothelial cells (HIMEC) isolated from surgically resected inflammatory bowel disease (IBD) patient tissue demonstrate significantly increased leukocyte binding in vitro compared to normal HIMEC. Our studies [Binion et al., Am. J. Physiol.275 (Gastrointest. Liver Physiol. 38):G592-G603, 1998] have also demonstrated that nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) normally plays a key role in downregulating HIMEC activation and leukocyte adhesion. Using primary cultures of HIMEC derived from normal and IBD patient tissues, we sought to determine whether alterations in iNOS-derived NO production underlies leukocyte hyperadhesion in IBD. Both nonselective (N(G)-monomethyl-L-arginine) and specific (N-Iminoethyl-L-lysine) inhibitors of iNOS significantly increased leukocyte binding by normal HIMEC activated with cytokines and lipopolysaccharide (LPS), but had no effect on leukocyte adhesion by similarly activated IBD HIMEC. When compared to normal HIMEC, IBD endothelial cells had significantly decreased levels of iNOS mRNA, protein, and NO production following activation. Addition of exogenous NO by co-culture with normal HIMEC or by pharmacologic delivery with the long-acting NO donor detaNONOate restored a normal leukocyte binding pattern in the IBD HIMEC. These data suggest that loss of iNOS expression is a feature of chronically inflamed microvascular endothelial cells, which leads to enhanced leukocyte binding, potentially contributing to chronic, destructive inflammation in IBD.

[Evaluation of a transcutaneous bilirubinometer]. / Evaluación de un instrumento de medición de la bilirrubina transcutánea.

OBJECTIVE: Transcutaneous bilirubinometers are useful in screening and monitoring neonatal hyperbilirubinemia. These instruments reduce the number of blood samples needed, but their validity has been questioned. The aim of this study was to evaluate the accuracy and reliability of a classic transcutaneous bilirubinometer. METHOD: Descriptive observational cross-sectional study of a sam-ple of 117 simultaneous measurements of transcutaneous and serum bilirubin in 82 jaundiced newborn infants. We analyzed the agreement between repeat measurements and measurements in different sites. We developed predictive models of serum bilirubin and analyzed their validity. RESULTS: All points of measurement displayed excellent agreement between repeat measures (intraclass correlation co-efficient higher than 0.92). Forehead measurements had a linear correlation coefficient of 0.75; in the sternum II-near correlation coefficient varied according to the absence or presence of phototherapy (0.86 and 0.54 respectively). The error intervals in which predictions of se-rum bilirubin were found were #+ 2 mg/dl for low values and #+ 4 mg/dl for high values (#> 15 mg/dl). CONCLUSIONS: Reliability of the transcutaneous bilirubinometer evaluated was high, but the substantial degree of error in se-rum bilirubin make its accuracy questionable, especially in patients with high levels.

Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status.

BACKGROUND AND METHODS: Kashin-Beck disease is a degenerative osteoarticular disorder that is endemic to certain areas of Tibet, where selenium deficiency is also endemic. Because selenium is involved in thyroid hormone metabolism, we studied the relation among the serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects 5 to 15 years of age in 12 villages around Lhasa, Tibet, including 1 control village in which no subject had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. RESULTS: Among the 575 subjects, 280 (49 percent) had Kashin-Beck disease, 267 (46 percent) had goiter, and 7 (1 percent) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66 percent had a urinary iodine concentration of less than 2 microg per deciliter (157 nmol per liter; normal, 5 to 25 microg per deciliter [394 to 1968 nmol per liter]). The mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects (1.2 vs. 1.8 microg per deciliter [94 vs. 142 nmol per liter], P<0.001) and hypothyroidism was more frequent (23 percent vs. 4 percent, P=0.01). Severe selenium deficiency was documented in all villages; 38 percent of subjects had serum concentrations of less than 5 ng per milliliter (64 nmol per liter; normal, 60 to 105 ng per milliliter [762 to 1334 nmol per liter]). When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not. CONCLUSIONS: In areas where severe selenium deficiency is endemic, iodine deficiency is a risk factor for Kashin-Beck disease.

PIP: Selenium is involved in thyroid hormone metabolism. Kashin-Beck disease is a degenerative osteoarticular disorder endemic to certain areas of Tibet, where selenium deficiency is also endemic. Findings are reported from an investigation of the relationship among serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects aged 5-15 years in 12 villages around Lhasa, Tibet, including 1 control village in which no one had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. 280 (49%) subjects had Kashin-Beck disease, 267 (46%) had goiter, and 7 (1%) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66% had a urinary iodine concentration of less than 2 mcg/dl. Mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects and hypothyroidism was more frequent. Severe selenium deficiency was documented in all villages, with 38% of subjects having serum concentrations of less than 5 ng/ml. When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not.

Maternal Trypanosoma cruzi-specific antibodies and worsening of acute infection in mouse offspring.

The role of antibodies in the previously demonstrated harmful effect of Trypanosoma cruzi-infected mothers on progeny infection was studied by injecting either serum from chronically infected animals or purified T. cruzi-specific antibodies into uninfected mice during gestation and lactation periods. It was verified that injected antibodies were transferred to offspring. Pregnant or lactating animals exhibited lower circulating antibody levels than nonpregnant or pregnant but nonlactating mice, respectively, suggesting that such antibody transfer occurred in both fetuses and suckling offspring. When infected two months after birth, offspring of mice treated with chronic serum or purified antibodies displayed significantly higher parasitemia than offspring from mothers receiving control serum or immunoglobulins unrelated to T. cruzi. These results indicate that soluble factors contained in sera of infected mice, and particularly antibodies, when transferred from mothers to their young, are able to worsen T. cruzi acquired infection in the offspring.

High circulating levels of fibronectin and antibodies against its RGD adhesion site during mouse Trypanosoma cruzi infection: relation to survival.

The levels of fibronectin (FN), a multifunctional glycoprotein known to mediate in vitro Trypanosoma cruzi-host cell adhesion, were measured in the plasma of T. cruzi-infected BALB/c mice. The infection induced a long-lasting increase of fibronectin levels during the acute parasitemic phase of the disease. Immunoblotting analysis showed the occurrence of lower-molecular-size FN fragments in the plasma of acutely infected animals, suggesting an infection-related FN degradation. FN levels were found to be significantly lower in dying mice harboring higher parasitemias than in surviving animals. A weak level of natural IgM against the RGD adhesion site of FN was detected before and during the first 3 weeks of infection. The level was significantly higher in surviving mice. From the fourth week postinfection, a significant increase in the levels of anti-RGD antibodies coincided with a decrease of circulating FN. These antibodies were mainly of the IgM, IgG1, and IgG2a isotypes. Taken together, these data suggest that both FN and anti-FN antibodies may contribute to the outcome of T. cruzi infection in mice.

High tumor necrosis factor alpha (TNF-alpha) production in Trypanosoma cruzi-infected pregnant mice and increased TNF-alpha gene transcription in their offspring.

Since tumor necrosis factor alpha (TNF-alpha) is known to be involved in the feto-maternal relationship, this cytokine was studied in Trypanosoma cruzi-infected pregnant BALB/c mice and their fetuses and offspring. Pregnant chronically infected mice displayed significantly higher levels of circulating TNF-alpha than animals either only infected or only pregnant. TNF-alpha was undetectable in sera of uninfected and nonpregnant mice as well as in breast milk obtained from infected and uninfected animals. Fetuses from infected mice exhibited significantly more cells containing TNF-alpha mRNA in their thymus than fetuses from uninfected mothers. When infected 2 months after birth, offspring born to infected and uninfected mothers displayed similar amounts of circulating TNF-alpha during chronic infection, whereas this cytokine was only weakly detectable during the acute phase of the disease. An intravenous injection of lipopolysaccharide during acute infection strongly increased the production of TNF-alpha in offspring born to infected mothers to levels higher than those in progeny from uninfected mice. These results suggest that TNF-alpha is an important cytokine in the feto-maternal relationship during T. cruzi infection and that fetuses and offspring of infected mothers are primed to produce elevated levels of TNF-alpha.

[Pre-transplantation evaluation with echo-Doppler of the receptor's vascular risk factors]. / Evaluación pretrasplante mediante eco-Doppler de los factores de riesgo vascular del receptor.

A total of 51 potential recipients of a renal transplant (RT) have been evaluated with an Eco-Doppler study of the posterior femoral, popliteal and posterior tibial corteries. Acceleration (AC), mean rate (MR), maximum systolic rate (MXSR) and minimal diastolic rate (MNDR), as well as pulsatility (PI) and resistance index (RI) were measured. Arterial high blood pressure (HBP), smoking, time in haemodialysis (HD) and cholesterol and triglycerides levels, were evaluated as vascular risk factors. RI and PI were maximal, and MXSR, MR and AC minimal at the popliteal artery level. Smoking (number of cigarettes/day) (R = 0.77), systolic blood pressure (BP) (R = 0.43), time of HBP evolution (R = 0.044), cholesterol level (R = 0.43) and time in HD (R = 0.35) correlate with Eco-Doppler parameters. Fifteen of these 51 patients underwent transplantation, and increased RR and PR with decreased MR and MXSR were seen post-RT in the ipsilateral popliteal and posterior tibial arteries. Eco-Doppler is a useful technique to evaluate the vascular risk of potential RT recipients.

Trypanosoma cruzi infection in mice induces a polyisotypic hypergammaglobulinaemia and parasite-specific response involving high IgG2a concentrations and highly avid IgG1 antibodies.

Trypanosoma cruzi infection in BALB/c mice induced a reversible polyisotypic hypergammaglobulinaemia, with particularly high levels of IgG2a, IgM and IgE. Hypergammaglobulinaemia started during the acute phase of infection and persisted during chronic disease until 11-13 weeks post-infection (w.p.i.), when immunoglobulin levels, with the exception of IgE, returned near normal values. Parasite-specific antibodies counted for 14 to 23% of gammaglobulinaemia, in acute and chronic infection respectively. The titres of IgM antibodies rose from two w.p.i. IgA, IgE and IgG subclass antibodies built up gradually over the time of parasite clearance (i.e., between three and six w.p.i.). All antibody isotypes, including IgM reached significant and stable titres throughout chronic infection. IgG2a, IgG1 and IgM antibodies had constantly higher titres than the other antibody isotypes. The dominance of IgG2a antibodies was due to their high plasma concentrations, around 70% of all antibodies available in the chronic infection. IgG1 had the highest functional avidity, whereas its concentration corresponded to only 10% of the whole antibody fraction. These results indicate that T. cruzi infection in mice induces a polyisotypic humoral immune response, dominated by some antibody isotypes, with major differences in concentrations and functional avidities. This could be of crucial importance in determining the outcome of infection.

Modulation of T-cell responsiveness during Trypanosoma cruzi infection: analysis in different lymphoid compartments.

Spleen and lymph node cells of Trypanosoma cruzi-infected mice were studied for mitogen-induced responsiveness in terms of proliferation and lymphokine production (IL-2, IFN-gamma). Splenocyte (SP) as well as lymph node cell (LN) proliferation and IL-2 production were depressed during the acute phase of the infection. Proliferative capacity of LN cells recovered completely and that of SP partially during the chronic phase. In contrast to these suppressive effects, the mitogen-induced IFN-gamma response was enhanced. In vitro co-incubation of normal SP or LN cells with trypomastigotes resulted in a reduced mitogen-induced cell proliferation and IL-2 secretion, similar to those seen with cells taken from infected mice. In contrast, trypomastigotes exerted a stimulatory activity on the mitogen-induced IFN-gamma response of both SP and LN cells. Addition of lymph node cells from T. cruzi-infected mice (LN-I) to lymph node cells of control mice (LN-C) suppressed strongly the mitogen-induced responsiveness of such cocultures. A marginal level of suppression was recorded in cocultures of spleen cells from infected mice (SP-I) and control spleen cells (SP-C). The potent suppressive cells within LN-I populations were identified as macrophage-like and such cells were absent in SP-C and peritoneal exudate cells from T. cruzi infected animals.

An Fc gamma RII-, Fc gamma RIII-specific monoclonal antibody (2.4G2) decreases acute Trypanosoma cruzi infection in mice.

In order to study the role of Fc gamma Rs in Trypanosoma cruzi infection in mice, the 2.4G2 monoclonal antibody (MAb), specific to the extracellular domains of Fc gamma RII and Fc gamma RIII, was injected intraperitoneally into mice. Flow cytometry studies of uninfected mice showed that 2.4G2 MAb bound to peritoneal and lymph node cells, respectively, on days 2 and 6 after injection. Repeating 2.4G2 injections every 3 to 4 days decreased the availability of Fc gamma Rs on peritoneal, lymph node, and spleen cells. Injections of 2.4G2 MAb into T. cruzi-infected mice, at days -1, 3, 7, 11, 16, 20, and 24 relative to infection, reduced mortality in comparison with that in infected animals injected with an unrelated MAb (50 versus 93.3% mortality; P < 0.01). Parasitemia in 2.4G2-treated mice was significantly (three times) lower than in control animals on days 21 and 24 postinfection (P < 0.05), before parasite-specific antibodies were detectable at significant levels. Immunoglobulin and T. cruzi-specific antibody levels were similar in all groups of mice. These results indicate that repeated injections of 2.4G2 MAb administered to acutely infected mice reduce the in vivo infection level, suggesting that Fc gamma Rs play a role in the early host invasion by T. cruzi parasites.

Trypanosoma cruzi infection in mice enhances the membrane expression of low-affinity Fc receptors for IgG and the release of their soluble forms.

The membrane expression of low-affinity Fc receptors for IgG (Fc gamma RII/III) on cells and the number of Fc gamma RII/III(+) cells were studied by flow cytometry, using the 2.4G2 MoAb, in mice infected by Trypanosoma cruzi. Cells from spleen, mesenteric lymph nodes and peritoneum were collected on days 10, 20, 30 and 40 post infection (p.i.). The in vivo serum level of soluble Fc gamma RII/III, as well as its in vitro release by cells from infected mice were studied. Parasitaemia and IgG1, IgG2a and IgG2b T. cruzi-specific antibody titres were also recorded. Both the expression of Fc gamma R on cell membrane and the absolute number of Fc gamma R(+) cells increased in spleen and in mesenteric lymph nodes, but not in peritoneum. The modifications in spleen occurred in the early and late parasitaemic phase of infection, i.e., before and after detection of T. cruzi-specific antibodies (from day 10 to 40 p.i.). In mesenteric lymph nodes, the variations were observed only in the early acute infection, when antibodies were not yet detectable at significant levels (on days 10 and 20 p.i.). Higher levels of soluble Fc gamma R were detected in sera and in culture supernatants of spleen and lymph node cells from day 20 to 40 p.i. These results show that T. cruzi infection in mice upregulates the expression and the release of Fc gamma RII/III, in the acute phase of infection, before as well as after the rise of antibody response.

Direct identification of Trypanosoma cruzi natural clones in vectors and mammalian hosts by polymerase chain reaction amplification.

The polymerase chain reaction was used to amplify the highly variable region of the kinetoplast minicircle of Trypanosoma cruzi directly in biological samples (feces of infected Triatomine bugs, blood samples of experimentally infected mice, and artificially infected human blood samples). Hybridization of the amplified DNAs with reference stocks representing different genotypes (natural clones) enabled us to characterize the stocks infecting the biological samples under study. The main interest of this new approach is the diagnosis of T. cruzi infection and simultaneous direct identification of the different natural clones circulating in vectors and mammalian blood without isolation of the stocks. The suitability of this technique for epidemiologic studies is also discussed.

Chagas' disease: decreased resistance to Trypanosoma cruzi acquired infection in offspring of infected mice.

The course of Trypanosoma cruzi infection was studied in an experimental model, using the offspring of mice that were chronically infected with T. cruzi. When infected two months after birth, a higher mortality rate in heavily parasitized mice occurred in these offspring than in controls born to uninfected mothers. The harmful maternal influence reached a maximum when offspring were exposed both to prenatal (placental) and postnatal (lactating) influences. It was a reversible phenomenon that led to a T. cruzi-specific failure of the offspring to control the acute phase of the infection. Such features are suggestive of a maternally-induced impairment of the immune response of the offspring.