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Biomedical subjects

F Moraga

Publications and source records attributed to F Moraga.

At least 19 recordsLinked to original sources

Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa-HBV-IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa-IPV/Hib and hepatitis B vaccines administered in two simultaneous injections to infants at 2, 4 and 6 months of age.

An open, randomised, multicentre trial was performed to compare the reactogenicity and safety profile of the administration of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio (DTPa-HBV-IPV) vaccine administered in one injection mixed with Haemophilus influenzae type b (Hib) conjugate vaccine (Group 1) with that of a pentavalent DTPa-IPV vaccine mixed with a Hib vaccine (DTPa-IPV/Hib), simultaneously administered with HBV (Group 2) in two injections in opposite thighs, as a primary vaccination course, to healthy infants at 2, 4 and 6 months of age. A total of 235 completed the study, 120 from Group 1 and 115 from Group 2. Blood samples (pre-vaccination and 1 month after the third dose) were obtained from a subset of infants (Group 1: 40; Group 2: 31) to assess the immune response to vaccination. Local and general solicited symptoms were recorded by parents on diary cards. Seven hundred and five diary cards (Group 1: 360; Group 2: 345) were collected. The clinically relevant and most commonly reported local reaction was pain (infant cried when the limb was moved) in 2.5% (Group 1) and 1.2% (Group 2) of diary cards. Fever was more frequently reported in Group 1 (21% of diary cards) than in Group 2 (12% of diary cards). However only 3 and 2% of doses in Groups 1 and 2, respectively, were responsible for a rectal temperature between 38.6 and 39.5 degrees C and only one case (Group 2) had > or =39.5 degrees C. Other clinically relevant general symptoms were rarely recorded: irritability (2-2.8%), loss of appetite (0.3-0.6%) and drowsiness (0.3-0.3%). All subjects included in the immunogenicity analysis had seroprotective titres to diphtheria, tetanus, polio virus types 1 and 3, Hib. Almost all subjects were seroprotected for anti-polio type 2 and hepatitis B (with the exception of 1 subject in Group 1 for each antigen). The vaccines response rates to pertussis antigens were over 97 and 90% in Groups 1 and 2, respectively. This study shows that, from a clinical perspective, the DTPa-HBV-IPV/Hib vaccine given in a single injection has a similar reactogenicity and safety profile to that of two licensed vaccines (DTPa-IPV/Hib, HBV) given in two simultaneous injections to infants at 2, 4 and 6 months of age. This is a valuable advantage, since in some countries, such as Spain and the UK, an additional injection (for the administration of meningococcal C conjugate vaccine) has been recently included in the infants' vaccination calendars.

Antibodies, Bacterial↗

Epidemiology and economic impact of varicella in immunocompetent children in Spain. A nation-wide study.

The epidemiology and burden of varicella was assessed through the prospective study of 683 children under 15 years, by 58 primary care paediatricians working on seven autonomous communities of Spain. The mean age was 4.5+/-2.7 years, and 566 (83%) were secondary cases. There were 111 complications in 101 children (14.8%), skin superinfection being the most frequent (8.9%), followed by respiratory tract (4.5%) and eye (2.2%) infections. The mean number of visits to the paediatric clinic was 1.42 (95% C.I. 1.37-1.47), and 5.6% of the children were attended in the emergency department of a hospital previously. All children had at least one prescription, being antihistamines and antipyretics the most prescribed. Thirteen percent received systemic antibiotics and 11% acyclovir. Children were mainly cared by grandparents, and parents were off work for a mean of 0.97 days (1.61 if children under 5 years attended day-care facilities; 0.51 if they did not). Costs derived from medical attention totalled 32.5, and social indirect costs were 63.77.

Adolescent↗

Lemierre syndrome in a previously healthy young girl.

UNLABELLED: Lemierre syndrome is a severe postanginal sepsis complicated by internal jugular thrombophlebitis. We report on a 14 y-old girl affected by high fever, shivering chills, headache, severe lateral neck pain, left ocular proptosis and general malaise. Magnetic resonance imaging of the head and neck showed right internal jugular vein and sigmoid sinus thrombosis. Fusobacterium sp. was identified in the blood culture. CONCLUSION: Our report is a reminder that Lemierre syndrome still exists and remains potentially life threatening. A high index of suspicion is necessary to prompt diagnosis and treatment.

Adolescent↗

Effects of noninhibitory alpha-1-antitrypsin on primary human monocyte activation in vitro.

A major function of alpha-1-antitrypsin (AAT) is the inhibition of overexpressed serine proteinases during inflammation. However, it is also known that the biological activity of AAT is affected by chemical modifications, including oxidation of the reactive-site methionine, polymerization, and cleavage by unspecific proteases, all of which will result in AAT inactivation and/or degradation. All inactive forms of AAT can be detected in tissues and fluids recovered from inflammatory sites. To test for a possible link between the inflammation-generated, noninhibitory, cleaved form of AAT and cellular processes associated with inflammation, we studied the effects of this form at varying concentrations on human monocytes in culture. We found that cleaved AAT at concentrations ranging between 1 and 10 microM in monocyte cultures over 24 h induces elevation in monocyte chemoattractant protein-1 (MCP-1) and pro-inflammatory cytokines such as TNFalpha and IL-6 and also increases production of interstitial collagenase (MMP-1) and gelatinase B (MMP-9), members of two different classes of matrix metalloproteinase. Moreover, monocytes stimulated with higher doses of cleaved AAT show an increase in cellular oxygen consumption by about 30%, while native AAT under the same experimental conditions inhibits oxygen consumption by about 50%. These results indicate that the cleaved form of AAT may play a role in monocyte recruitment and pro-inflammatory activation during inflammatory processes, and also suggest that changes in structure occurring upon AAT cleavage could alter its functional properties with potential pathological consequences.

Cells, Cultured↗

C-terminal fragment of alpha1-antitrypsin activates human monocytes to a pro-inflammatory state through interactions with the CD36 scavenger receptor and LDL receptor.

Monocyte scavenger receptor, CD36 has been implicated in the pathogenesis of atherosclerosis as a major oxidised LDL receptor mediating lipid accumulation and foam cell formation. Previously, we found that treatment of monocyte cultures with the carboxyl terminal fragment of alpha1-antitrypsin (C-36) increases lipid binding and uptake, induces LDL receptor mRNA and CD36 receptor protein expression, and also significantly increases production of pro-inflammatory molecules. To assess the role of the CD36 receptor in proatherogenic monocyte activation by the C-36 fragment, we tested whether specific anti-CD36 receptor antibodies would block the effects of C-36 on monocyte activation. We find that pre-incubation of cells with anti-LDL and anti-CD36 receptor antibodies (10 microg/ml) blocks binding of 125I-C-36 by about 50%. Similarly, cells pre-incubated with oxidised LDL or native LDL at concentrations from 2.5 to 10 microg/ml showed a loss of 125I-C-36 binding (up to 49 and 57%) and uptake (up to 47 and 59.8%), respectively. In parallel experiments, monocytes were first incubated for 1 or 6 h with anti-CD36 antibodies (10 microg/ml) prior to adding C-36 peptide. Anti-CD36 antibodies suppressed C-36-induced production of gelatinase B, monocyte chemoattractant protein-1, interleukin-6 and cellular oxygen consumption to control levels, whereas levels of TNFalpha were unaffected. In contrast, saturation of LDL receptors with excess of anti-LDL (20 microg/ml) significantly inhibited C-36 induced TNFalpha levels. Results indicate that the C-36 peptide binds to both LDL and CD36 scavenger receptors which involves selective upregulation of pro-inflammatory molecules and activation of the respiratory burst in human monocytes. This also supports important roles for CD36 and LDL receptors in atherogenesis and suggests that blockade of CD36 receptor can be protective in pro-inflammatory activation of human monocytes.

Arteriosclerosis↗

[Acute mountain sickness at 3500 and 4250 m. A study of symptom, incidence and severity].

BACKGROUND: Acute Mountain Sickness (AMS) refers to signs and symptoms associated with hypobaric hypoxia. Its reported incidence is highly variable. AIM: To determine the incidence of AMS symptoms and severity at 3,500 and 4,250 m above sea level. SUBJECTS AND METHODS: A population of 362 soldiers without former exposure to altitude was studied. AMS symptoms, were assessed by an extensively used standard questionnaire (Lake Louise), applied 36-72 hours after exposure to high altitude. RESULTS: A group of 200 recruits ascended to Putre (3,500 m) and a second group (162) ascended to Alto Pacollo (4,250 m). The incidence of AMS was 28% and 60% respectively (p < 0.05). Headaches and sleeping difficulties were the most frequent symptoms at both altitudes. Furthermore, severe digestive problems and dizziness were described in a high proportion of individuals at both 3,500 and 4,250 m. CONCLUSIONS: The prevalence of AMS in this study is similar to that reported elsewhere at equivalent altitudes.

Acute Disease↗

Activation of primary human monocytes by the oxidized form of alpha1-antitrypsin.

The oxidation of methionine residues in many proteins, including the serine proteinase inhibitor alpha1-antitrypsin (AAT), can result in functional inactivation. In this study we investigated the pro-inflammatory properties of oxidized AAT (oxAAT), specifically its ability to activate human monocytes in culture. Monocytes stimulated with oxAAT at concentrations up to 0.2 mg/ml for 24 h showed significant elevation in monocyte chemoattractant protein-1, cytokine interleukin-6, and tumor necrosis factor-alpha expression and increased NADPH oxidase activity. Monocytes activated with oxAAT showed surprising effects on lipid metabolism. Expression of low density lipoprotein (LDL) receptors increased by up to 76% compared with controls but was not accompanied by any changes in (125)I-labeled LDL binding and, paradoxically, decreased LDL uptake, degradation, and intracellular cholesterol synthesis. oxAAT also down-regulated the scavenger receptor CD36, which takes up and is up-regulated by oxidized LDL and is down-regulated by cholesterol efflux. As a by-product of oxidative events accompanying inflammation, oxAAT has multiple effects on cytokine expression, generation of reactive oxygen species, and on intracellular lipid metabolism. The up-regulation of monocyte-derived reactive oxygen by oxAAT could potentially result in self-amplification of AAT oxidation and, thereby, the other effects deriving from it. This implies that there are as yet unidentified regulatory processes that control this cycle.

CD36 Antigens↗

The carboxyl-terminal fragment of alpha1-antitrypsin is present in atherosclerotic plaques and regulates inflammatory transcription factors in primary human monocytes.

alpha1-Antitrypsin (AAT) serine proteinase inhibitor is found in most biological fluids, diffuses into most tissues, and is an important factor in controlling tissue damage by proteases in inflammatory diseases such as atherosclerosis. We have previously reported that the C-terminal fragment (C-36) generated during the cleavage of AAT by proteinases forms amyloid fibrils which have biological effects unrelated to precursor functions. Here we show that the C-36 fragment is present in atherosclerotic plaques, particularly within the fibrous cap at the base of the lipid core. We also found that human monocyte stimulation with C-36 fibrils led to a strong activation of both peroxisome proliferator-activated receptors alpha and gamma (PPARalpha and PPARgamma) at 1, 2, and 18 h of cell culture. A parallel increase in the intracellular lipid accumulation was also observed. Furthermore, stimulation of monocytes with C-36 for 18 h led to activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) activation. These data for the first time demonstrate the peptide of AAT as a component of atherosclerotic plaques and as a novel activator of PPARalpha, PPARgamma, NF-kappaB, and AP-1 in cultured monocytes. Taken together, the effects of the peptide represent a new mechanism of monocyte activation that may be of importance not only in atherogenesis, but also in other inflammatory processes.

Arteriosclerosis↗

[Microorganisms isolated in cases of pertussis-like syndrome].

OBJECTIVE: To describe the etiologic study of the pertussis-like syndrome, not only as far as Bordetella genus is concerned but also regarding the causative role of other microorganisms for a 11-year period (1988-1998). METHODS: In all specimens from patients suffering from pertussis-like cough the presence of Bordetella spp., other bacteria, viruses, and mycoplasma was investigated. The analysed data included microbiological findings and epidemiologic issues (age, sex, hospital admission area, yearly distribution and seasonal period). RESULTS: A total of 1,063 specimens were investigated, most of them nasopharyngeal aspirates (910), corresponding to 905 patients; a positive culture was obtained form 56.9 of these patients. B. pertussis was isolated from 10.5% of patients. As for other bacteria, Haemophilus influenzae and Streptococcus pneumoniae were also isolated, in 16.9% and 15.8% of occasions, respectively. The respiratory syncitial virus was isolated from 10.7% of patients and other viruses in 9.4%. Among mycoplasma, Ureaplasma urealyticum predominated, with a recovery rate of 2.9%. The male/female ratio was 495/410; the ages of 67.2% of patients ranged from 0 to 6 months; a total of 689 (76.1%) required hospital admission. The recovery of B. pertussis and adenoviruses predominated during spring and summer months. In contrast, H. influenzae, S. pneumoniae and respiratory syncitial virus were recovered more frequently during winter months. CONCLUSIONS: Most patients with pertussis-like syndrome are children aged less than 6 months. The recovery percentages of B. pertussis and respiratory syncitial virus are identical and therefore we think that the investigation of their presence in this syndrome is fully warranted as well as the search for other microorganisms, since clinical symptoms are commonly non-specific among infants.

Age Distribution↗

Non-Hodgkin's lymphoma after liver transplantation: response to chemotherapy.

An increased incidence of lymphoproliferative disorders in immunosuppressed organ transplant recipients has long been recognised. Lymphoproliferative disorders occur in 2% of orthotopic liver transplant patients. Different therapies have been used, but the optimal treatment remains unknown. Relatively little information is available on experience with cytotoxic chemotherapy. Three children who developed Burkitt-like, non-Hodgkin's lymphomas after liver transplantation are described. The disease failed to regress after initial management, which included a reduction in immunosuppression. With cytotoxic chemotherapy all three achieved complete remission, which continued 36+, 35+, and 16+ months after diagnosis. Results suggest that in selected cases chemotherapy can be safe in late-onset lymphomas appearing after solid organ transplantation.

Burkitt Lymphoma↗

Fetal and maternal blood oxygen affinity: a comparative study in llamas and sheep.

We compared blood oxygen affinity (P50) and hemoglobin concentration among fetal and maternal llamas and sheep, as respective examples of species native to high and low altitudes. P50, hemoglobin concentration and blood oxygen content were determined at sea level in 16 pregnant llamas, 6 pregnant sheep and their respective fetuses. P50 was similar in fetal llamas and sheep, but maternal llamas had higher blood oxygen affinity than maternal sheep. As a consequence, the P50 difference between mother and fetus was less in llamas than in sheep. Fetal llamas had higher hemoglobin concentrations than fetal sheep. In contrast, the maternal hemoglobin concentrations were similar. The blood oxygen content was higher in fetal and maternal llamas than in fetal and maternal sheep. We conclude that the llama, a species native to the altiplano, has a higher blood oxygen content than the sheep, as determined in the fetus by a high hemoglobin concentration and in the mother by a low P50.

Animals↗

Late recurrent metastasis in Wilms' tumour.

Recurrence of Wilms' tumour after 5 years of disease-free survival is rare. We present the case of a 26-year-old man who had been diagnosed of Wilms' tumour at the age of 6 years treated by surgery, chemotherapy, and radiotherapy and who remained disease free for 8 years, after which lung metastases were detected. Second complete remission was attained with surgery and chemotherapy and 20 years after initial diagnosis he again presented with lung metastases, similarly achieving complete remission with surgery and second-line chemotherapy. The clinical and biological aspects of late metastasis in this neoplasm are discussed.

Adult↗

[A little known entity: aggressive fibromatosis].

Aggressive fibromatosis is an unfrequent and little known entity, which in spite of being a histologically benign tumoration with scarce mitosis and without metastasis at distance, frequently presents with a high degree of local malignancy that can cause serious functional and aesthetical disturbance for the patient and even lead to death if infiltration of vital organs is presented, above all in cases of abdominal or maxillo-facial mass localization. The authors present their experience with 17 cases of aggressive fibromatosis observed in our centre: four of abdominal localization, six in extremities, five in the maxillo-facial mass, one in the torax and one in the lumbo-sacral region. Histological diagnosis, either by puncture or biopsy, is complemented by studies of extension of the tumour based on ecography and TAC. All cases were treated according to the classical criteria of ample resection of the lesion, always when practicable, except in one infant case and in the torax, in which only a biopsy was effected. Of the 15 cases resected, nine cases had local relapses, six of which remained free of disease with a second operation, another two required a third operation and the remaining case needed five interventions. In six children chemotherapy was applied with vincristina, cyclophosphamide and adriamicina. A follow up was carried out in 14 patients, one of which died and the remaining 13 are free of disease. In spite of the fact that progestagene receptors were not evidenced in two of our cases, one presented complete remission of the tumor after treatment with medroxyprogesterone. In this case the coincidence of Gardner's syndrome arises in the family history.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

[Embryonal fatty tumors. Lipoblastoma-lipoblastomatosis].

The authors present four cases. The first case is a diaphragmatic-mediastinal, the second one is a cervical-mediastinal one, the third case has a buttock, the last one is a case of hip-thigh. Their ages are one, eight and three years old and the fourth case is seven days old. They appear in axilla, neck, thoracic wall and fat prevertebral tissue, in below three year old children. Despite their benignity, the tumors grow very fast. The complete extirpation is fundamental to avoid relapses, which are presented approximately in a 15 for 100 of the cases. Mutilations are not necessary, since it is a benign tumor. Finally, the authors amply review the literature. They differentiate the concepts of lipoma, hibernoma and lipoblastoma.

Buttocks↗

[Diagnostic clinical and immunologic characteristics of infection by the human immunodeficiency virus in infants].

Acquired immunodeficiency syndrome (AIDS) in infants has different clinical and immunological characteristics from adult AIDS because of immunological immaturity of the fetus and newborn when infection is produced. Differential diagnosis with primary immunodeficiency diseases, mainly with severe combined immunodeficiency and hypogammaglobulinemia is often difficult, but clinical, epidemiological and immunological data aid in establishing diagnosis. Repeated bacterial infections and abnormal antibody production are common in such children and gammaglobulin therapy is indicated to prevent them and avoid continuous immunological stimulation that viral replication and disease progression.

Acquired Immunodeficiency Syndrome↗

[Primary hyperlipoproteinemia in childhood (author's transl)].

Type V hyperlipoproteinemia is an unusual entity in children. Only 6 cases have been described so far to our knowledge. Authors present a 9 year old male that came for diagnosis of a hepatosplenomegaly. There was no evidence of abdominal pain, xanthomas or pancreatitis. Secondary disorders such as uncontrolled insulinopenic diabetes mellitus, glycogen storage disease, administration of estrogen compounds, nephrotic syndrome or uremia, and dysglobulinemias were excluded. His father presented the same lipoprotein pattern suggesting a dominant mode of inheritance. The administration of heparin showed a good response of serum proteinlipase.

Bone Marrow↗