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1.
Nat Mater ; 18(9): 948-954, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31086324

RESUMO

In multi-orbital materials, superconductivity can exhibit several coupled condensates. In this context, quantum confinement in two-dimensional superconducting oxide interfaces offers new degrees of freedom to engineer the band structure and selectively control the occupancy of 3d orbitals by electrostatic doping. Here, we use resonant microwave transport to extract the superfluid stiffness of the (110)-oriented LaAlO3/SrTiO3 interface in the entire phase diagram. We provide evidence of a transition from single-condensate to two-condensate superconductivity driven by continuous and reversible electrostatic doping, which we relate to the Lifshitz transition between 3d bands based on numerical simulations of the quantum well. We find that the superconducting gap is suppressed while the second band is populated, challenging Bardeen-Cooper-Schrieffer theory. We ascribe this behaviour to the existence of superconducting order parameters with opposite signs in the two condensates due to repulsive coupling. Our findings offer an innovative perspective on the possibility to tune and control multiple-orbital physics in superconducting interfaces.

2.
Nat Commun ; 9(1): 407, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29379023

RESUMO

In LaAlO3/SrTiO3 heterostructures, a gate tunable superconducting electron gas is confined in a quantum well at the interface between two insulating oxides. Remarkably, the gas coexists with both magnetism and strong Rashba spin-orbit coupling. However, both the origin of superconductivity and the nature of the transition to the normal state over the whole doping range remain elusive. Here we use resonant microwave transport to extract the superfluid stiffness and the superconducting gap energy of the LaAlO3/SrTiO3 interface as a function of carrier density. We show that the superconducting phase diagram of this system is controlled by the competition between electron pairing and phase coherence. The analysis of the superfluid density reveals that only a very small fraction of the electrons condenses into the superconducting state. We propose that this corresponds to the weak filling of high-energy dxz/dyz bands in the quantum well, more apt to host superconductivity.

3.
Sci Rep ; 5: 12751, 2015 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-26244916

RESUMO

The recent development in the fabrication of artificial oxide heterostructures opens new avenues in the field of quantum materials by enabling the manipulation of the charge, spin and orbital degrees of freedom. In this context, the discovery of two-dimensional electron gases (2-DEGs) at LaAlO3/SrTiO3 interfaces, which exhibit both superconductivity and strong Rashba spin-orbit coupling (SOC), represents a major breakthrough. Here, we report on the realisation of a field-effect LaAlO3/SrTiO3 device, whose physical properties, including superconductivity and SOC, can be tuned over a wide range by a top-gate voltage. We derive a phase diagram, which emphasises a field-effect-induced superconductor-to-insulator quantum phase transition. Magneto-transport measurements show that the Rashba coupling constant increases linearly with the interfacial electric field. Our results pave the way for the realisation of mesoscopic devices, where these two properties can be manipulated on a local scale by means of top-gates.

4.
Microbes Infect ; 3(9): 739-45, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11489422

RESUMO

An increasing number of clinical cases of Hantavirus infections have been reported from various regions in Asia, Europe and North America. Hantaviruses (family Bunyaviridae, genus Hantavirus) are enveloped and possess a single-stranded trisegmented RNA genome of negative polarity. Rodents or insectivores are natural hosts of hantaviruses and transmit the virus to humans chiefly by aerosolisation. These viruses are the causative agents of haemorrhagic fever with renal and pulmonary syndromes. In the northeast of France, Puumala hantavirus causes, every year, more than 150 mild forms of haemorrhagic fever with a renal syndrome known as nephropathia epidemica. Serological tests may lack sensitivity for diagnosing early stages of infection and virus isolation is limited because it grows poorly in cell culture. Since reverse transcription (RT)-PCR amplification is an efficient method for detecting viral genomes in patient specimens, we developed an assay using a Taqman probe and compared it with the classical RT-PCR amplification. To achieve this goal, a Puumala strain was grown in Vero E6 cells and RNA extracted from the culture supernatant. We found that the semi-nested RT-PCR detected a minimal amount of 300 TCID(50) mL(-1), while the Taqman PCR allowed detection of less than 10 TCID(50) mL(-1 )and provided a quantitative analysis.


Assuntos
Orthohantavírus/genética , Orthohantavírus/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taq Polimerase/metabolismo , Animais , Sequência de Bases , Chlorocebus aethiops , Orthohantavírus/fisiologia , Infecções por Hantavirus/virologia , Dados de Sequência Molecular , RNA Viral/análise , RNA Viral/isolamento & purificação , Sensibilidade e Especificidade , Células Vero
5.
Biochimie ; 77(7-8): 651-60, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8589075

RESUMO

The NADPH oxidase of phagocytic cells is a multimeric enzyme complex activated during phagocytosis. It catalyzes the production of the superoxide anion, precursor of many toxic oxygen metabolites involved in the defense against microorganisms. The enzyme becomes active after assembly on a membrane bound flavocytochrome b of cytosolic factors p47 phox, p67 phox and p40 phox and of low molecular mass GTP binding proteins. This paper reviews recent results concerning the role of two small G proteins, Rac and Rap 1A in oxidase activation. Native prenylated small G proteins are either in the form of a complex in which the GDP bound G protein is associated with a guanine nucleotide dissociation inhibitor, GDI, or in an active GTP bound form able to trigger the activity of its effector. Rac and Rho share a common GDI. As chemotaxis, under Rho control, and oxidase activation, under Rac control, show mutually exclusive signalling pathways, we propose a model where the GDI would switch from one pathway to the other by sequestering either Rac or Rho.


Assuntos
Proteínas de Ligação ao GTP/fisiologia , NADH NADPH Oxirredutases/sangue , Neutrófilos/enzimologia , Animais , Ativação Enzimática , Humanos , Peso Molecular , NADPH Oxidases , Fagócitos/enzimologia , Explosão Respiratória , Superóxidos/sangue
6.
Antiviral Res ; 61(2): 111-7, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14670584

RESUMO

Chikungunya virus (CHIKV) and Semliki Forest virus (SFV) were used in our laboratory to screen active antiviral compounds against viruses of the Alphavirus genus. Antiviral activity was estimated by the reduction of the cytopathic effect of each alphavirus on infected Vero cells and by virus titer reduction. Cytotoxicity was evaluated by determining the inhibition of Trypan blue exclusion in confluent cell cultures and by the evaluation of the inhibitory effect on cell growth. With CHIKV and SFV, the selectivity indices of human recombinant interferon-alpha and iota-carrageenan were much higher than that of ribavirin, which has been previously investigated for its inhibitory effect on alphavirus infections. Compared to ribavirin, 6-azauridine was more effective against CHIKV and showed a similar antiviral activity against SFV. IFN-alpha2b, glycyrrhizin, 6-azauridine, and ribavirin caused a concentration-dependent reduction in the virus yield with CHIKV and SFV. Moreover, the combination of IFN-alpha2b and ribavirin had a subsynergistic antiviral effect on these two alphaviruses and should be evaluated for the treatment of these infections.


Assuntos
Antivirais/administração & dosagem , Vírus Chikungunya/efeitos dos fármacos , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Vírus da Floresta de Semliki/efeitos dos fármacos , Animais , Azauridina/administração & dosagem , Vírus Chikungunya/fisiologia , Chlorocebus aethiops , Efeito Citopatogênico Viral/efeitos dos fármacos , Sinergismo Farmacológico , Ácido Glicirrízico/administração & dosagem , Técnicas In Vitro , Interferon alfa-2 , Proteínas Recombinantes , Vírus da Floresta de Semliki/fisiologia , Células Vero , Replicação Viral/efeitos dos fármacos
7.
Antiviral Res ; 28(1): 69-80, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8585761

RESUMO

Human recombinant interferon-alpha (IFN-alpha) was assayed for its antiviral effect on hepatitis A virus (HAV) replication in the human hepatoma cell line PLC/PRF/5. IFN-alpha resulted in concentration-dependent reduction of HAV antigen expression and HAV replication. IFN-alpha had a prophylactic effect, but was still effective when it was added after the infection, even at the end of the first replication cycle. An important increase in 2',5'-oligoadenylate synthetase activity in the IFN-treated human liver cells was observed. The antiviral effect of IFN-alpha could be attributed to the induction of this enzyme. Moreover we have shown that IFN-alpha and glycyrrhizin were synergistic in their antiviral actions against HAV. IFN-alpha emerged, from the present study, as a promising candidate for chemotherapy of severe forms of hepatitis A.


Assuntos
Antivirais/farmacologia , Hepatovirus/efeitos dos fármacos , Interferon-alfa/farmacologia , 2',5'-Oligoadenilato Sintetase/metabolismo , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacologia , Ácido Glicirrízico , Antígenos de Hepatite/análise , Hepatovirus/imunologia , Hepatovirus/fisiologia , Humanos , Proteínas Recombinantes de Fusão/farmacologia , Fatores de Tempo , Células Tumorais Cultivadas , Replicação Viral/efeitos dos fármacos
8.
Antiviral Res ; 23(1): 63-76, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8141593

RESUMO

Glycyrrhizin (GL) achieved a concentration-dependent inhibition of the replication of hepatitis A virus (HAV) in PLC/PRF/5 cells. GL has been shown to inhibit an early stage of the HAV replication. GL was not virucidal and had no measurable effect on the adsorption of [3H]uridine-labelled virions to cells. GL inhibited HAV penetration of the plasma membrane as measured by the amount of infective virus no longer neutralizable by specific antibody over time.


Assuntos
Antivirais/farmacologia , Ácido Glicirretínico/análogos & derivados , Hepatovirus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Antígenos Virais/efeitos dos fármacos , Antígenos Virais/metabolismo , Carcinoma Hepatocelular , Ácido Glicirretínico/farmacologia , Ácido Glicirrízico , Antígenos da Hepatite A , Hepatovirus/imunologia , Hepatovirus/patogenicidade , Hepatovirus/fisiologia , Fatores de Tempo , Células Tumorais Cultivadas
9.
J Biotechnol ; 69(2-3): 183-90, 1999 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-10361725

RESUMO

A recombinant Fab that recognizes a neutralizing epitope located in the (296-400) region of protein E of dengue virus was obtained from cloned hybridoma cells secreting the mouse monoclonal antibody (mAb) 4E11. The Fd and light chain antibody genes were amplified by polymerase chain reaction, cloned into the phagemid vector pMad, expressed in bacteria to produce Fab fragments and sequenced. The mAb 4E11, in particular its light chain complementary-determining regions, shared homologies with two other anti-viral mAbs. The affinity of the parental mAb and the cloned Fab to the MalE-E(296-400) fusion protein were shown to be of the same magnitude, i.e. nanomolar. Fab 4E11 neutralization capacity was found between 8 and 4-times or less lower than that of mAb 4E11, depending on serotypes, thus the Fab could have a smaller antiviral activity than the mAb in vitro.


Assuntos
Anticorpos Antivirais/imunologia , Vírus da Dengue/imunologia , Fragmentos Fab das Imunoglobulinas/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/isolamento & purificação , Afinidade de Anticorpos , Antígenos Virais/imunologia , Clonagem Molecular , Ensaio de Imunoadsorção Enzimática , Epitopos , Hibridomas , Fragmentos Fab das Imunoglobulinas/genética , Fragmentos Fab das Imunoglobulinas/isolamento & purificação , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Leves de Imunoglobulina/genética , Camundongos , Dados de Sequência Molecular , Testes de Neutralização , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Análise de Sequência de DNA , Ensaio de Placa Viral
10.
IEEE Trans Med Imaging ; 9(1): 5-10, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-18222745

RESUMO

An automated process for the detection of the left ventricular end diastolic contour is defined. The extraction of a pure left ventricular behavior, obtained by the application of the Gram-Schmidt orthogonalization process on a set of vectors representing the three main typical behaviors present in the scintigraphic sequence, yields the synthesis of a new factorial image particularly matched for the extraction of the left ventricular region of interest (ROI). An edge following technique with conditional dilation applied simultaneously on the two binary images resulting from processing the new left ventricular factorial and the average images with a Laplacian operator gives a robust method for the detection of the left ventricular ROI.

11.
Med Hypotheses ; 58(4): 291-2, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12027522

RESUMO

Several recent epidemiological studies have shown that vaccinations against biological warfare using pertussis as an adjuvant were associated with the Gulf war syndrome. If such epidemiological findings are confirmed, we propose that the use of pertussis as an adjuvant could trigger neurodegeneration through induction of interleukin-1beta secretion in the brain. In turn, neuronal lesions may be sustained by stress or neurotoxic chemical combinations. Particular susceptibility for IL-1beta secretion and potential distant neuronal damage could provide an explanation for the diversity of the symptoms observed on veterans.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Síndrome do Golfo Pérsico/etiologia , Vacina contra Coqueluche/efeitos adversos , Vacinação/efeitos adversos , Adulto , Barreira Hematoencefálica , Encéfalo/metabolismo , Encéfalo/patologia , Ativação Enzimática , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Interleucina-1/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Biológicos , Degeneração Neural/etiologia , Degeneração Neural/patologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/patologia
12.
Med Hypotheses ; 31(1): 35-8, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2138242

RESUMO

Many data suggest that patients with Down's syndrome (DS) suffer from digestive malabsorption. A fecal test of absorption (search for undigested meat fibers following the ingestion of a measured diet) was conducted in 4 patients with DS. The results point to malabsorption in these patients and support the hypothesis of malabsorption in DS. The etiology of probable malabsorption in DS is discussed. Data are presented suggesting that chronic malnutrition caused by malabsorption could be the cause of the neuropathologic signs of Alzheimer's disease occurring at or slightly before the fourth decade in all patients with DS.


Assuntos
Síndrome de Down/fisiopatologia , Absorção Intestinal/fisiologia , Adulto , Doença de Alzheimer/etiologia , Doença de Alzheimer/fisiopatologia , Síndrome de Down/complicações , Feminino , Humanos , Síndromes de Malabsorção/etiologia , Síndromes de Malabsorção/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Distúrbios Nutricionais/etiologia , Distúrbios Nutricionais/fisiopatologia
13.
Bull Soc Pathol Exot ; 89(3): 204-8, 1996.
Artigo em Francês | MEDLINE | ID: mdl-8998416

RESUMO

After the outbreaks of cholera, dysenteriae, meningitidis of which the rwandese refugees have been the victims in August and September 1994 in the camps of the Goma's area (Zaïre), the medical teams were confronted with a great number of fevers of unknown origin. In order to explore the possible etiologies, we have conducted a cases/controls study (n = 96). Clinically, the cases occur more frequently than controls headache (p < 0.001), splenomegaly (p = 0.02) and neutropeny (p < 0.001) Serologically, it has been constated non significantly difference between cases and controls, but prevalence of HIV-1 infections (19 and 6%) and arbovirus (23 and 10%) infections are very high. Arbovirosis could explain, partially or associated with HIV and tuberculosis, the presence of these fevers undeterminated more than malaria or typhus epidemic.


Assuntos
Febre de Causa Desconhecida/epidemiologia , Refugiados , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Infecções por Arbovirus/complicações , República Democrática do Congo , Feminino , Febre de Causa Desconhecida/etiologia , Humanos , Masculino , Ruanda/etnologia , Tuberculose/complicações
14.
Bull Soc Pathol Exot ; 83(5): 611-20, 1990.
Artigo em Francês | MEDLINE | ID: mdl-2085907

RESUMO

During and after the Rift Valley Fever epidemic in southern mauritania, we conducted epidemiological inquiries in order to determine epidemic and epizootic areas. The epidemic area was divided into two different zones. The first was located along the right bank of the Senegal River, around the town of Rosso. The second was located near the town of Kaedi. This epidemic area was included within the epizootic area, which stretched to the south, between Rosso and Saint-Louis. Several ecological changes had occurred in the recent past including erection of dams on the Senegal River for irrigation, and heavier rainfall than during previous years.


Assuntos
Surtos de Doenças , Febre do Vale de Rift/epidemiologia , Animais , Água Doce , Humanos , Mauritânia/epidemiologia , Estações do Ano , Viagem
15.
Bull Soc Pathol Exot ; 83(5): 621-7, 1990.
Artigo em Francês | MEDLINE | ID: mdl-2085908

RESUMO

Randomized epidemiological studies conducted inside the Rift Valley fever epidemic area permitted an estimate of the different epidemiological rates. For the town of Rosso, the total number of infected persons was estimated at 9,320, the total number of symptomatic diseases at 1,013 and the number of deaths at 47. The minimal number of deaths for the area which had access to the hospital was 232. The immunity rate in the town was 34.89% after the epidemic. The ELISA test was used to test human and animal IgG and IgM antibodies. Human samples were collected using the "confetti" technique. After the epizootic the incidence was 36.9% and the immunity was 70.06% for animals sampled in the town.


Assuntos
Surtos de Doenças , Febre do Vale de Rift/epidemiologia , Animais , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Incidência , Mauritânia/epidemiologia , População , Febre do Vale de Rift/mortalidade , Vírus da Febre do Vale do Rift/imunologia
16.
Presse Med ; 31(1 Pt 1): 3-9, 2002 Jan 12.
Artigo em Francês | MEDLINE | ID: mdl-11826584

RESUMO

SPARSE DATA: The Gulf war syndrome remains a little know entity since its first appearance 10 years ago. The objective of our work was to synthesize the data published on the subject in the scientific literature. We analysed the results of American and English epidemiological surveys, from which it was difficult to distinguish the existence of a univocal syndrome. IMPRECISE DEFINITION: It is difficult to give a clear clinical definition of the syndrome, the signs of which fluctuate depending on the studies. Chronic fatigue is frequently associated with the Gulf war syndrome, although some studies have described electrophysiological neurological lesions. NUMEROUS HYPOTHESES: The role of stress, vaccinations and their adjuvants, exposition to neurotoxic substances and weak uranium have been incriminated. We propose that multiple factors be integrated in the research for the genesis of this atypic syndrome.


Assuntos
Síndrome do Golfo Pérsico , Animais , Inglaterra , Síndrome de Fadiga Crônica/diagnóstico , Humanos , Doenças do Sistema Nervoso/diagnóstico , Síndrome do Golfo Pérsico/diagnóstico , Síndrome do Golfo Pérsico/epidemiologia , Síndrome do Golfo Pérsico/etiologia , Estresse Fisiológico/complicações , Estados Unidos
17.
Med Trop (Mars) ; 57(3 Suppl): 28-36, 1997.
Artigo em Francês | MEDLINE | ID: mdl-9513176

RESUMO

Arboviruses occur throughout the world in plants and animals: reptiles, birds and mammals including man. These relatively recent RNA-containing viruses have great evolutionary potential and are a major cause of epidemics. Arboviruses exhibit a dual life cycle involving continual transmission to and from the vertebrate host and arthropod vector which ingests or inoculates the agent during blood meals. Agents belong to many different viral families and represent an important source of emerging diseases. Because of the mode of transmission is vectorial, spread can enhanced by man-made changes in the ecosystem. This risk is often underestimated. The population explosion provides a great opportunity for the progression of these arboviruses.


Assuntos
Infecções por Arbovirus/transmissão , Arbovírus/fisiologia , Culicidae/virologia , Zoonoses/transmissão , Animais , Infecções por Arbovirus/epidemiologia , Infecções por Arbovirus/fisiopatologia , Infecções por Arbovirus/veterinária , Infecções por Arbovirus/virologia , Arbovírus/classificação , Arbovírus/genética , Arbovírus/crescimento & desenvolvimento , Aves/virologia , Infecções por Bunyaviridae/transmissão , Culicidae/classificação , Surtos de Doenças , Ecossistema , Microbiologia Ambiental , Infecções por Flavivirus/transmissão , Humanos , Insetos Vetores/virologia , Mamíferos/virologia , Plantas/virologia , Crescimento Demográfico , RNA Viral/análise , RNA Viral/genética , Répteis/virologia , Fatores de Risco , Carrapatos/virologia , Infecções por Togaviridae/transmissão , Zoonoses/virologia
18.
Allerg Immunol (Paris) ; 27(8): 300-6, 1995 Oct.
Artigo em Francês | MEDLINE | ID: mdl-8851038

RESUMO

In this multicenter parallel group randomized trial 254 teenagers, aged 12-15, suffering from perennial allergic rhinitis were investigated. Four evaluations (D-10, D0, D15, D30) were performed according to the following design: a 10-day run-in period (D-10, D0) to determine/establish the patient eligibility and to perform an allergologic checkup. The decision to include the patient was made at D0 according to selection criteria. a 30-day treatment period (D0 to D30). The patient received either cetirizine 10 mg once a day or placebo given in a double blind way according to randomization. Efficacy was assessed at each visit with a nasal symptom score (sneezing, rhinorrhea, obstruction, pruritus) and an ocular symptom score (watery eyes, conjunctival pruritus, red eyes). In addition, an objective evaluation was performed by means of anterior rhinoscopy. Global evaluations by the investigator and the patient on visual analog scales were assessed. Side effects were recorded. At baseline there was no significant difference between the two groups. At day 15 and day 30, all symptoms, subjective as well as objective, were significantly improved in the cetirizine group. Tolerance was good with no significant difference between cetirizine and placebo.


Assuntos
Cetirizina/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Adolescente , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Humanos , Masculino , Fatores de Tempo
19.
Allerg Immunol (Paris) ; 28(1): 19-24, 1996 Jan.
Artigo em Francês | MEDLINE | ID: mdl-8882207

RESUMO

875 adolescents of both sexes, aged between 12 and 15 years, who had presented with a perennial allergic rhinitis, were included in an open study that was conducted by pediatricians and allergologists on the efficacy of ZYRTEC (CETIRIZINE). There were four evaluations in the study, at Day-10, D 0, D15 and D30 and it was conducted according to the following plan: A first period (D-10 to D 0) to establish the eligibility of the subjects to be tested, and to establish the clinical allergic history, before definitive inclusion at D 0. A second period, of therapy, of 30 days, during which the subjects took a 10 mg tablet of ZYRTEC as a daily dose. Efficacy was evaluated at each visit by scores of intensity of major symptoms (sneezing, nasal discharge, nasal obstruction, nasal pruritus) and secondary symptoms (ocular score ... ) of rhinitis, as well as anterior rhinoscopy. The patients made an auto-evaluation of symptoms at different times. Analysis of the different parameters showed a real efficacy of ZYRTEC, for 30 days of treatment, in young patients. Furthermore, the tolerance of the product is excellent. This study has shown an overall improvement in the symptoms of perennial allergic rhinitis in patients who were treated with ZYRTEC in conditions similar to those of usual medical practice by pediatricians and allergologists.


Assuntos
Cetirizina/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Adolescente , Feminino , Humanos , Masculino
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