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Biomedical subjects

C Diaz

Publications and source records attributed to C Diaz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Impaired eosinophil recruitment to the cornea in P-selectin-deficient mice in Onchocerca volvulus keratitis (River blindness).

PURPOSE: A murine model of helminth-induced keratitis (river blindness) that is characterized by a biphasic recruitment of neutrophils (days 1-3) and eosinophils (days 3+) to the cornea has been developed. The purpose of this study was to determine the relative contribution of P- and E-selectin in recruitment of these inflammatory cells from limbal vessels to the corneal stroma. METHODS: P- and E-selectin gene knockout (-/-) mice were immunized with antigens extracted from the parasitic helminth Onchocerca volvulus. One week after the last immunization, parasite antigens were injected directly into the corneal stroma. Mice were killed on days 1 and 3 postchallenge, and eyes were immunostained with either anti-eosinophil major basic protein (MBP) or with anti-neutrophil Ab. The number of cells in the cornea was determined by direct counting. RESULTS: Recruitment of eosinophils to the cornea was significantly impaired in P-selectin(-/-) mice (63.9% fewer eosinophils on day 1 [P: = 0.0015], and 61% fewer on day 3 [P: < 0.0001]) compared with control C57BL/6 mice. In contrast, P-selectin deficiency had no effect on neutrophil recruitment to the cornea. There was no inhibition of eosinophil and neutrophil migration to the corneas of E-selectin(-/-) mice, indicating that there is no direct role for this adhesion molecule in helminth-induced keratitis. CONCLUSIONS: The present study demonstrates that P-selectin is an important mediator of eosinophil recruitment to the cornea. P-selectin interactions may therefore be potential targets for immunotherapy in eosinophil-mediated ocular inflammation.

Animals↗
PubMed1999

Obstetric and newborn outcomes in a cohort of HIV-infected pregnant women: a report of the women and infants transmission study.

OBJECTIVE: To determine obstetric and neonatal outcomes in a cohort of HIV-infected pregnant women and to assess whether HIV-related immunosuppression increases the risk of adverse outcomes of pregnancy. METHODS: Between 1989 and 1994, interview, physical examination, laboratory, and medical record data were prospectively collected from HIV-infected pregnant women and on their newborns. Factors associated with adverse pregnancy outcome and HIV disease status were correlated with pregnancy outcome using logistic regression analysis. RESULTS: 634 women delivered after 24 weeks of gestation. Preterm birth, low birth weight, and small-for-gestational-age neonates occurred in 20.5%, 18.9%, and 24.0% of pregnancies, respectively. Factors associated with low birth weight were CD4 percentage <14%, history of adverse pregnancy outcome, pediatric HIV infection, bleeding during pregnancy, and Trichomonas infection. Preterm birth was associated with CD4 percentage <14%, a history of adverse pregnancy outcome, and bleeding during pregnancy. Being small for gestational age was associated with maternal hard drug use during pregnancy, Trichomonas infection, history of adverse pregnancy outcome, and hypertension. CONCLUSIONS: Adverse pregnancy outcomes are common for HIV-infected women and are associated with low maternal CD4 percentage and pediatric HIV infection. Preterm birth, low birth weight, and small-for-gestational-age ranking, however, are also associated with previously recognized sociodemographic and obstetric factors that are not unique to HIV infection.

Adult↗
PubMed1999

Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams.

CONTEXT: With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus (HIV), an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs. OBJECTIVE: To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a randomized cohort of uninfected children. DESIGN: Prospective cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076, a perinatal zidovudine HIV prevention trial, and Protocol 219, a long-term observational protocol. SETTING: Pediatric research clinics in the United States. PATIENTS: Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28, 1997, in Protocol 219 (122 in the zidovudine group and 112 in the placebo group). MAIN OUTCOME MEASURES: Physical growth measurements, immunologic parameters, cognitive/developmental function, occurrence of neoplasms, and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinically indicated. Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age. RESULTS: Median age of children at time of last follow-up visit was 4.2 years (range, 3.2-5.6 years). There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets; weight, height, and head circumference z scores; and cognitive/developmental function. No deaths or malignancies occurred. Two children (both exposed to zidovudine) are being followed up for abnormal, unexplained ophthalmic findings. One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months; the child is clinically asymptomatic. CONCLUSIONS: No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years. Continued prospective evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission.

Anti-HIV Agents↗
PubMed1999

The role of gravity in the evolutionary emergence of multicellular complexity: microgravity effects on arthropod development and aging.

While experiments carried out in Space with isolated cells have shown that eucaryotic cells are able to sense and respond to the absence of gravity by modifying their reactions, experiments in which more complex processes have been investigated, such as Biological Systems undergoing development under Microgravity, have been surprisingly unaffected by the space environment. This can be considered a curious result since all organisms are evolutionarily adapted to the current level of the gravity force in our planet and should eventually change if this parameter will vary in a permanent manner. In fact, the small effects of the modifications in gravity on development in short term experiments may be equivalent to the difficulties in detecting the involvement of other basic physical processes such as diffusion-controled auto-organizative reactions in currently developing biological systems. An apparent exception to this lack of effect is experiments where brine shrimp dormant gastrulae directly exposed to the space environment accumulate developmental defects as a consequence of cosmic irradiation. In this article we discuss the idea that at a certain stage during the evolutionary emergence of multicellular organisms the cues laid by generic forces such as gravity were involved in the evolutionary organization of these primitive organisms. As evolution proceed, these early mechanisms may have been obscured and/or made redundant by the appearance of new internal, environment-independent biological regulatory mechanisms. On the other hand, behavioral responses that may be important, for example, in setting the life-spans of organisms may still be more readily susceptible to manipulation by external cues as experiments carried out by our group in Space and on the ground with Drosophila melanogaster indicate. Grant Numbers: ESP-1775.

Animals↗
PubMed1999

Phosphatidylserine externalization during differentiation-triggered apoptosis of erythroleukemic cells.

K562 erythroleukemia cells undergo apoptosis when induced to differentiate along the erythroid lineage with hemin. This event, characterized by DNA fragmentation, correlated with downregulation of the survival protein, BCL-xL, and decrease in mitochondrial transmembrane potential (deltapsi[m]) that ultimately resulted in cell death. Reorientation of phosphatidylserine (PS) from the cells inner-to-outer plasma membrane leaflet and inhibition of the aminophospholipid translocase was observed upon hemin-treatment. Constitutive expression of BCL-2 did not inhibit hemin-induced alterations in lipid asymmetry or decrease in deltapsi[m], and only moderately prevented DNA fragmentation. BCL-2, on the other hand, effectively inhibited actinomycin D-induced DNA fragmentation, the appearance of PS at the cells outer leaflet and the decrease in deltapsi[m]. The caspase inhibitor, z.VAD.fmk, blocked DNA fragmentation by both hemin and actinomycin D, but inhibited PS externalization only in the actinomycin D-treated cells. These results suggest that, unlike pharmacologically-induced apoptosis, PS externalization triggered by differentiation-induced apoptosis occurs by a mechanism that is associated with a decrease in deltapsi[m], but independent of BCL-2 and caspases.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Evaluation of human immunodeficiency virus (HIV) type 1 load, CD4 T cell level, and clinical class as time-fixed and time-varying markers of disease progression in HIV-1-infected children.

Human immunodeficiency virus (HIV) type 1 RNA load, CD4 T cell level, and Centers for Disease Control and Prevention (CDC) clinical class history were measured as potential correlates of a CDC class C diagnosis or death in 165 HIV-1-infected children followed from birth. These covariates were assessed at fixed "landmark" ages from 6 to 24 months and were also assessed as time-varying values. Virus load was associated with progression in all analyses, even after adjusting for immunologic and clinical status. This confirms its importance for monitoring pediatric disease progression. CD4 T cell level was associated with disease progression in time-varying but not in adjusted landmark analysis, suggesting that CD4 cells reflects immediate risk more than long-term risk. The distinction between clinical class B and lower classes is prognostic during the first 18 months of life; class C versus classes N/A/B becomes more important as the patient ages. Virologic, immunologic, and clinical status all provide information regarding disease progression risk.

Biomarkers↗
PubMed1999

Cutaneous granulomatous lesions in common variable immunodeficiency: complete resolution after intravenous immunoglobulins.

A 64-year-old man with common variable immunodeficiency developed a persistent papulonodular ulcerative eruption on the right leg. Histopathological examination disclosed a chronic inflammatory infiltrate with central necrosis and palisading granuloma. Repeated microbiological (bacteriological, mycological and mycobacteriological) studies failed to isolate any microorganism. After treatment with intravenous immunoglobulins, a progressive resolution of the skin lesions was observed with a complete clearing after 10 months. Clinicopathological features and therapeutic approaches of sterile granulomatous lesions associated with primary immunodeficiencies are reviewed.

Common Variable Immunodeficiency↗
PubMed1999

A randomized and controlled trial of the effect of treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock.

OBJECTIVE: To evaluate the effects of increased oxygen delivery on mortality and morbidity. DESIGN: Randomized, controlled trial. SETTING: Medical-surgical ICU of a tertiary care hospital. PATIENTS: Sixty-three patients classified according to predetermined criteria as having severe sepsis or septic shock. INTERVENTIONS: The patients were randomly assigned to one of two groups: the control group (n = 32) received conventional therapy with a normal targeted value of oxygen delivery, and the treatment group (n = 31) received therapy with a targeted oxygen delivery index (DO2I) value of > 600 mL/min/m2. The therapeutic approach to maintain BP, arterial saturation, hemoglobin concentration, and pulmonary artery occlusion pressure was similar in both groups. MEASUREMENTS AND MAIN RESULTS: The hemodynamic, oxygen transport, and gastric intramucosal pH measurements were recorded at the time of admission to the study and every 6 h for the next 96 h. The outcome measures were the rate of patient mortality and the number of organ dysfunctions occurring during the ICU stay. The study groups were similar with respect to demographics and admission hemodynamic variables, but the percentage of patients with positive blood cultures was significantly higher in the control group than in the treatment group, respectively: 34 vs 13% (p = 0.04). The average cardiac index was significantly higher in the treatment group than in the control group, respectively: 3.96 vs 3.05 L/min/m2 (p = 0.01). This factor did not significantly affect the DO2I. Nine of the 31 treatment group patients reached an average DO2I value of > 600 mL/min/m2. The rate of mortality in the control group patients up to the time of ICU discharge (66%) was similar to that seen in the treatment group (74%), respectively: 21 of 32 vs 23 of 31 (p = 0.46). The number of dysfunctional organs per patient was also similar in the control and treatment groups, respectively: 2.1+/-1.1 vs 2.6+/-1.2 (p = 0.12). CONCLUSION: Treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock does not reduce mortality or morbidity.

Aged↗
PubMed1999

Combination therapy with stavudine (d4T) plus didanosine (ddI) in children with human immunodeficiency virus infection. The Pediatric AIDS Clinical Trials Group 327 Team.

OBJECTIVES: To evaluate the safety, tolerance, and antiviral activity of combination therapy with stavudine (d4T) plus didanosine (ddI) in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: The study enrolled HIV-infected children who successfully completed Pediatric AIDS Clinical Trials Group (PACTG) protocol 240 (d4T versus zidovudine [ZDV] monotherapy) without disease progression or who had received ZDV monotherapy by prescription for at least the preceding 6 months. Children who had received d4T monotherapy in PACTG 240 were assigned to treatment with d4T plus ddI (arm 1). Children who had received ZDV monotherapy in PACTG 240 or by prescription were randomized in a double-blind manner to treatment with either d4T alone (arm 2) or d4T plus ddI (arm 3). Patients were followed for 48 weeks each. RESULTS: A total of 108 children were enrolled. The mean age was 5.0 years (range, 1. 6 to 11.5 years), with mean baseline plasma HIV RNA concentration and CD4(+) lymphocyte count of 4.6 log10 copies/mL (range, 2.6 to 5. 9 log10 copies/mL) and 819 cells/microL (range, 8 to 3431 cells/microL), respectively. Both d4T monotherapy and d4T plus ddI combination therapy were well-tolerated, with 96 (89%) patients completing 48 weeks of study treatment. Plasma HIV RNA concentrations showed larger average declines in arm 3 compared with arm 2 at study week 12 (0.49 vs 0.18 log10 copies/mL, respectively); these average declines were maintained through week 48 (0.51 vs 0.17 log10 copies/mL, respectively). Fewer than 8% of the patients in any of the treatment arms had plasma HIV RNA concentrations below the limit of quantification (200 copies/mL) at any time point. CONCLUSIONS: Combination therapy with d4T plus ddI is safe and well-tolerated in HIV-infected children, producing durable, but incomplete, suppression of virus replication. This combination of nucleoside antiretroviral agents may provide a valuable backbone to protease inhibitor-containing treatment regimens for HIV-infected children.

Anti-HIV Agents↗
PubMed1999

European and Latin-American countries associated in a networked database of outstanding guidelines in unusual clinical cases (ELCANO).

The aim of ELCANO, an EU-funded project, is to build a virtual multilingual multimedia library of unusual clinical cases related to gastroenterology. Based on a standardisation of the format to report and the representation of clinical information on WWW, the multilingual multimedia case has been developed and till now 350 cases have been included. User satisfaction and user acceptance of ELCANO are under evaluation.

Databases as Topic↗
PubMed1999

Telematics applications to support the role of the community pharmacists as self-medication advisors. TESEMED Consortium.

One of the applications developed within the EU-funded projects TESEMED and TESEMED-II is a program for the information and continuous training of community pharmacists, with the aim to empower them as advisors of the citizens about self-medication topics. Several programs are being developed on the basis of ad-hoc developed protocols about minor ailments (currently, cold and flu, haemorrhoids, constipation and cough). Each program includes three modules: a hypertextual version of the protocol, an interactive scheme of it, and an educational tool called Encounter Simulator, that trains the pharmacist about the protocol by means of simulated pharmacist-customer interactions. The testing of these applications with 84 community pharmacists offers positive results in terms of expectations, program characteristics and perceived usefulness.

Common Cold↗
PubMed1998

Safety of the maternal-infant zidovudine regimen utilized in the Pediatric AIDS Clinical Trial Group 076 Study.

OBJECTIVE: To determine the safety of the zidovudine (ZDV) regimen utilized in the Pediatric AIDS Clinical Trial Group (ACTG) 076 study. DESIGN: ACTG 076 was a randomized, double-blind, placebo-controlled trial which demonstrated that a ZDV regimen could prevent mother-to-child HIV-1 transmission. Infants were followed through 18 months of age and women were followed through 6 months postpartum. METHODS: Maternal complications, pregnancy outcomes, growth and development of the uninfected infants, and HIV-1 disease progression in the women were monitored prospectively. RESULTS: Maternal therapy was well tolerated. There was no serious pattern of adverse pregnancy outcomes associated with ZDV use. Amongst the ZDV-exposed infants, the only recognized toxicity was anemia within the first 6 weeks of life; the risk for anemia was not associated with premature delivery, duration of maternal treatment, degree of maternal immunosuppression, or maternal anemia. ZDV treatment was not associated with an increased incidence of newborn structural abnormalities. At 18 months of age, uninfected infants did not differ in growth parameters or immune function. No childhood neoplasias were reported in either group. In the women, at 6 months postpartum, there were no differences in clinical, immunologic, or virologic disease progression. CONCLUSION: There were no identified problems that would alter current recommendations for the routine use of ZDV for the prevention of mother-child HIV-1 transmission.

Anti-HIV Agents↗
PubMed1998

Disease progression in a cohort of infants with vertically acquired HIV infection observed from birth: the Women and Infants Transmission Study (WITS).

BACKGROUND: The Women and Infants Transmission Study is an ongoing prospective cohort study of HIV-infected pregnant women and their infants. We used the 1994 U.S. Centers for Disease Control and Prevention (CDC) classification system for HIV infection in children to describe HIV disease progression in 128 HIV-infected children, and examined maternal and infant characteristics associated with disease course. METHODS: The Kaplan-Meier method was used to calculate probabilities of entry into CDC clinical classes A, B, and C (mild, moderate, and severe HIV disease); CDC immunologic stages 2 and 3; and death. Relative risks of progression for selected predictor events were estimated using the Cox proportional hazards model. RESULTS: With a median 24 months of follow-up, the median ages at entry into clinical classes A, B and C were 5, 11, and 48 months, respectively. Increased risk of progression to class C was seen in infants who had: onset of class B events (p < .001); progression to immunologic stage 2 (p < .001) or 3 (p < .001); early culture positivity (in first 48 hours, p < .01; in first 7 days, p = .03); and early appearance (within the first 3 months of life) of lymphadenopathy, hepatomegaly, or splenomegaly (p < .001). CONCLUSIONS: Reaching specific clinical or immunologic stages were strong predictors of progression to AIDS or death. Early onset of clinical signs (onset of lymphadenopathy, hepatomegaly, or splenomegaly < or =3 months of age), and early culture positivity (within the first 48 hours or within the first week of life), defined the infant with highest risk of disease progression.

Cohort Studies↗
PubMed1998

Encephalopathy and progression of human immunodeficiency virus disease in a cohort of children with perinatally acquired human immunodeficiency virus infection. Women and Infants Transmission Study Group.

OBJECTIVE: To describe the incidence, predictors, and survival of children with human immunodeficiency virus (HIV) encephalopathy followed in the Women and Infants Transmission Study cohort. STUDY DESIGN: Retrospective review of clinical and immunologic staging of perinatally HIV-infected infants, based on the 1994 Centers for Disease Control and Prevention Classification System. RESULTS: Data were available for 128 HIV-infected children, with a median follow-up of 24 months. HIV encephalopathy was diagnosed in 27 (21%) of children. Median survival after diagnosis was 14 months. Of children with encephalopathy, 74% had at least moderate immunosuppression by the time of diagnosis. Encephalopathy represented the first acquired immunodeficiency syndrome-defining condition in 67%, and the only one in 26% of children. Hepatosplenomegaly or lymphadenopathy during the first 3 months of life was diagnosed in 63%, in contrast to 29% of those without encephalopathy (p value = 0.001). Cardiomyopathy was present in 30% of the children with encephalopathy versus 2% of those without encephalopathy. High viral load in infancy was associated with increased risk of encephalopathy but was not predictive of age at onset. CONCLUSIONS: Encephalopathy in children with HIV is common and is associated with high viral load, immunodeficiency, and shortened survival. Encephalopathy was more likely to develop in infants with early signs and symptoms of HIV, although age at onset could not be predicted.

AIDS Dementia Complex↗
PubMed1998

Outcome of chronic hepatitis B in Caucasian children during a 20-year observation period.

BACKGROUND/AIMS: Chronic hepatitis B virus infection can lead to cirrhosis and hepatocellular carcinoma, particularly in men over 40 years of age and in areas where childhood-onset infection is common. The sequence of events from paediatric infection to severe disease in adults is only partially known. The aim of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood during 20 years of follow-up. PATIENTS: One hundred and eighty-five consecutive, otherwise healthy, Caucasian children were enrolled in Padua (Italy) and in Madrid (Spain) between 1975 and 1985, and followed for an average period of 13 years; 168 were hepatitis B e antigen (HBeAg) positive and five had cirrhosis. RESULTS: Thirty patients received steroids or levamisole and 21 interferon, but treatment did not significantly influence HBeAg clearance. Overall, two (1.1%) children, with initial cirrhosis, developed hepatocellular carcinoma and the other three (1.6%) cirrhotic patients became asymptomatic carriers of infection after anti-HBe seroconversion and biochemical remission; 14 (7.5%) children maintained HBeAg positive hepatitis; 155 (83.8%) became asymptomatic carriers of infection after anti-HBe seroconversion and biochemical remission; six (3.2%) experienced reactivation of liver disease and viral replication after remission and five (2.7%) maintained biochemical features of liver damage after HBeAg clearance. Only 6% cleared hepatitis B surface antigen. CONCLUSIONS: Even considering the bias of treatment, the large majority of Caucasian children with chronic hepatitis B became asymptomatic carriers of infection with normal alanine amino-transferase during the first 20 years of observation. Cirrhosis is an early, rare complication, and a risk factor for hepatocellular carcinoma. A subgroup of patients who experienced reactivation or maintained liver damage after HBeAg clearance seems to be at greater risk for disease progression during adult life.

Adjuvants, Immunologic↗