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1.
Phys Rev Lett ; 130(5): 051802, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36800478

RESUMO

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.

2.
Phys Rev Lett ; 127(20): 201801, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34860065

RESUMO

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 and 810 km from the beam source, is analyzed using an exposure of 12.51×10^{20} protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of 121 of neutral-current candidates are observed at the far detector, compared to a prediction of 122±11(stat.)±15(syst.) assuming mixing only between three active flavors. No evidence for ν[over ¯]_{µ}→ν[over ¯]_{s} oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles θ_{24}<25° and θ_{34}<32° at the 90% C.L. for 0.05 eV^{2}≤Δm_{41}^{2}≤0.5 eV^{2}, the range of mass splittings that produces no significant oscillations at the near detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos.

4.
Phys Rev Lett ; 120(22): 221805, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29906174

RESUMO

We report on multinucleon effects in low momentum transfer (<0.8 GeV/c) antineutrino interactions on plastic (CH) scintillator. These data are from the 2010-2011 antineutrino phase of the MINERvA experiment at Fermilab. The hadronic energy spectrum of this inclusive sample is well described when a screening effect at a low energy transfer and a two-nucleon knockout process are added to a relativistic Fermi gas model of quasielastic, Δ resonance, and higher resonance processes. In this analysis, model elements introduced to describe previously published neutrino results have quantitatively similar benefits for this antineutrino sample. We present the results as a double-differential cross section to accelerate the investigation of alternate models for antineutrino scattering off nuclei.

5.
Phys Rev Lett ; 116(7): 071802, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26943528

RESUMO

Two different nuclear-medium effects are isolated using a low three-momentum transfer subsample of neutrino-carbon scattering data from the MINERvA neutrino experiment. The observed hadronic energy in charged-current ν_{µ} interactions is combined with muon kinematics to permit separation of the quasielastic and Δ(1232) resonance processes. First, we observe a small cross section at very low energy transfer that matches the expected screening effect of long-range nucleon correlations. Second, additions to the event rate in the kinematic region between the quasielastic and Δ resonance processes are needed to describe the data. The data in this kinematic region also have an enhanced population of multiproton final states. Contributions predicted for scattering from a nucleon pair have both properties; the model tested in this analysis is a significant improvement but does not fully describe the data. We present the results as a double-differential cross section to enable further investigation of nuclear models. Improved description of the effects of the nuclear environment are required by current and future neutrino oscillation experiments.

6.
J Exp Med ; 158(6): 2171-6, 1983 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-6315853

RESUMO

Human cytomegalovirus is shown to be a nonspecific polyclonal B cell activator. The B cell response is independent of virus replication and requires little, if any, T cell help.


Assuntos
Linfócitos B/imunologia , Citomegalovirus/imunologia , Humanos , Ativação Linfocitária
7.
Cochrane Database Syst Rev ; (2): CD003147, 2006 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-16625571

RESUMO

BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices provide constant back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect. OBJECTIVES: To determine the effectiveness and acceptability of PEP devices compared to other forms of physiotherapy as a means of improving mucus clearance and other outcomes in people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The electronic database CINAHL was also searched from 1982 to 2001. Most recent search of the Group's register: February 2006. SELECTION CRITERIA: Randomised controlled studies in which PEP was compared with any other form of physiotherapy in people with CF. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion and exclusion criteria to publications and assessed the quality of the included studies. MAIN RESULTS: Forty studies were identified and twenty-five studies involving 507 participants met the review inclusion criteria. Most included studies had low scores on a scale of study quality. Twenty of these studies involving 300 participants were cross-over in design. Data were not published in sufficient detail in most of these studies to perform meta-analysis.Forced expiratory volume in one second (FEV1) was the most frequently measured outcome. Single interventions or series of treatments continued for up to three months demonstrated no significant difference in effect between PEP and other methods of airway clearance on FEV1. Long-term studies had equivocal or conflicting results regarding the effect on FEV1. Participant preference was reported in nine studies. In all studies with an intervention period of at least one month, measures of participant preference were in favour of PEP. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high level evidence. AUTHORS' CONCLUSIONS: There was no clear evidence that PEP was a more or less effective intervention overall than other forms of physiotherapy. There was limited evidence that PEP was preferred by participants compared to other techniques, but this finding is from studies of low quality.


Assuntos
Fibrose Cística/terapia , Muco/metabolismo , Respiração com Pressão Positiva/métodos , Fibrose Cística/complicações , Volume Expiratório Forçado , Humanos , Depuração Mucociliar , Ensaios Clínicos Controlados Aleatórios como Assunto , Capacidade Vital
8.
Hypertension ; 4(6): 782-8, 1982.
Artigo em Inglês | MEDLINE | ID: mdl-7141604

RESUMO

Inflatable suits were constructed for lower body compression in pigs and dogs. The suit for pigs encompassed hindquarters and part of the abdomen, and the smaller suit for dogs compressed only the hindquarters, leaving free the abdominal cavity. In conscious, diazepam-pretreated pigs, the compression lasted 30 minutes; during that period the blood pressure increased 50/38 mm Hg over the baseline. In chloralose-anesthetized dogs, the compression was extended to 3 hours; the blood pressure increase was 44/53 mm Hg. Blood pressure fell to the baseline immediately after decompression in both animals. In both species the substantial blood pressure increase was due to an increase of vascular resistance; this did not induced the expected baroreceptor-mediated bradycardia. In dogs, the blood pressure increase was accompanied by a large increase of plasma norepinephrine (from 179 to 975 pg/ml). To test whether the increase of vascular resistance reflected the mechanical compression of the vessels under the suit, animals were pretreated with trimethaphan. In pigs the trimethaphan substantially decreased the vascular resistance and the blood pressure response. This indicated that a portion of the vasoconstriction occurred in areas outside the suit. Lower body compression is a new model to cause prolonged blood pressure elevation by noninvasive and nonpharmacologic means. The mechanism of the blood pressure elevation requires further investigation.


Assuntos
Hipertensão/etiologia , Pressão , Abdome , Animais , Cães , Feminino , Trajes Gravitacionais , Hemodinâmica , Membro Posterior , Hipertensão/sangue , Masculino , Norepinefrina/sangue , Suínos , Trimetafano/farmacologia , Resistência Vascular
9.
Cancer Epidemiol Biomarkers Prev ; 5(10): 795-800, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8896890

RESUMO

The purpose of this study was to examine in vivo the activity of cytochrome P450 (CYP) 2A6, an enzyme capable of activating carcinogens, including N-nitrosodimethylamine, in humans with the carcinogenic liver fluke infection, opisthorchiasis viverrini, before and after treatment with the antiparasitic agent, praziquantel. Coumarin hydroxylase activity of CYP 2A6 was assessed by administering a probe drug, coumarin, and measuring its metabolite, 7-hydroxycoumarin, in urines collected between 0-2 h and 2-4 h of 106 people with varying intensities of Opisthorchis viverrini infection. Five individuals who did not excrete any detectable 7-hydroxy coumarin (and have a genetic defect probably leading to an absence of catalytic activity of the CYP 2A6 protein) were excluded from analysis. Infected people excreted an average of 22.7 mumol of 7-hydroxycoumarin in the first 2 h after taking the drug, whereas the mean of the uninfected group was 19.4 mumol; this difference did not reach statistical significance (P = 0.10). However, a highly significant increase in CYP 2A6-related activity was observed in infected individuals who also had radiological evidence of biliary fibrosis (28.1 mumol) compared to those without (19.4 mumol; P = 0.01). Reassessments of coumarin hydroxylase activity of CYP 2A6 made 2 months after praziquantel treatment showed highly significant reductions in the amount of 7-hydroxycoumarin excreted among the infected groups but no difference in the uninfected group. These results suggest that expression of CYP 2A6 is induced among chronically infected people who also have fibrosis of the intrahepatic bile duct. As already demonstrated in an animal model and now observed in humans for the first time, this increase in CYP 2A6-related enzyme activity may represent an important mechanistic link between inflammatory products of chronic liver fluke infection (e.g., DNA alkylation damage from endogenously formed N-nitrosamines) and the high risk of cholangiocarcinoma faced by infected individuals.


Assuntos
Hidrocarboneto de Aril Hidroxilases , Colangiocarcinoma/etiologia , Sistema Enzimático do Citocromo P-450/metabolismo , Hepatopatias Parasitárias/enzimologia , Oxigenases de Função Mista/metabolismo , Opistorquíase/enzimologia , Análise de Variância , Animais , Antiplatelmínticos/uso terapêutico , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores/análise , Colangiocarcinoma/epidemiologia , Citocromo P-450 CYP2A6 , Citocromo P-450 CYP2E1/metabolismo , Feminino , Fibrose , Humanos , Hepatopatias Parasitárias/complicações , Hepatopatias Parasitárias/tratamento farmacológico , Hepatopatias Parasitárias/metabolismo , Masculino , Opistorquíase/complicações , Opistorquíase/tratamento farmacológico , Opistorquíase/metabolismo , Praziquantel/uso terapêutico , Fatores de Risco , Tailândia
10.
Neurology ; 58(5): 709-16, 2002 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-11889232

RESUMO

BACKGROUND: Autoantibodies have been implicated in the development of chronic focal encephalitis (CFE) or Rasmussen's disease, a progressive and intractable form of epilepsy characterized by uncontrollable unilateral focal seizures, brain atrophy, and inflammation. OBJECTIVE: To investigate the origin and characteristics of the B cell population that trigger or sustain brain inflammation in patients with CFE. METHODS: The authors used immunoglobulin (Ig) complementary determining region 3 (CDR3)-size spectratyping and DNA sequencing to examine the rearranged IgG heavy chain (IgGH) transcript repertoire in resected brain samples from four patients with CFE. They also performed Western blotting on human and rat brain homogenates and immunostaining on a human neuronal cell line to test the reactivity of sera from patients with CFE. RESULTS: The authors observed substantial perturbations from the normal, unstimulated repertoire of immunoglobulin genes. Sequencing of randomly selected clones confirmed the restricted profile and provided evidence for somatic mutation patterns characteristic of antigen-specific stimulation. They also observed IgGVH-CDR3 sequence diversity among patients. When sera were assayed from patients with CFE for specificity against rat and human brain homogenates, heterogeneous reactivity patterns were detected among patients. Immunostaining of postmitotic human neuronal cells demonstrated reactivity of some patients' sera against neural antigens. CONCLUSIONS: These findings support an important role for clonally expanded B lymphocytes in some forms of epilepsy, but also indicate a wide spectrum of reactivity characteristic of antigenic heterogeneity.


Assuntos
Linfócitos B/imunologia , Encéfalo/imunologia , Regiões Determinantes de Complementaridade/genética , Encefalite/imunologia , Rearranjo Gênico do Linfócito B , Imunoglobulina G/genética , Animais , Linfócitos B/fisiologia , Encéfalo/patologia , Regiões Determinantes de Complementaridade/metabolismo , Encefalite/fisiopatologia , Feminino , Genes de Imunoglobulinas , Humanos , Imunoglobulina G/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley
11.
AIDS Res Hum Retroviruses ; 16(3): 183-90, 2000 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-10710206

RESUMO

The immunologic and virologic efficacy and safety of interferon a (IFN-alpha) administered in combination with zidovudine (ZDV) and zalcitabine (ddC) was evaluated in HIV-infected subjects with CD4+ cell counts between 300 and 500 cells/ml and no more than 14 weeks of prior antiretroviral therapy. A total of 256 subjects enrolled in an open-label, randomized controlled trial. Subjects were randomized equally into treatment groups. All subjects received ZDV and ddC, while half also receive IFN-alpha (3 MU subcutaneously every 24 hr). At 48 weeks the median average area under the curve minus baseline (AAUCMB) for plasma HIV-1 RNA for the two-drug group was -0.68 versus -0.75 log10 copies/ml for the IFN-alpha group (p = 0.046). Mean HIV-1 RNA changes from baseline to 48 weeks for these groups were -0.65 and -1.12 log10 copies/ml, respectively (p = 0.010). The median AAUCMB for CD4+ cell count for the two-drug group was 28 versus -1 cells/mm3 for the IFN-alpha group (p = 0.011). Neutropenia, anemia, and drug intolerance were more common in the IFN-alpha group. This study demonstrates that IFN-alpha inhibits HIV-1 replication but attenuates the CD4+ cell response to dual therapy with ZDV and ddC.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Interferon-alfa/uso terapêutico , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Resistência Microbiana a Medicamentos , Feminino , Proteína do Núcleo p24 do HIV/sangue , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue
12.
Int J Parasitol ; 21(6): 719-21, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1757200

RESUMO

B10 mice were immunized with an Opisthorchis viverrini somatic extract and then their responses were analyzed. The antigenic fractions of the extract were separated by SDS-polyacrylamide gel electrophoresis, electroblotted to nitrocellulose membranes and solubilized for use in lymphocyte culture. Antibody specificity was also visualized by immunoblotting using immunized mouse sera. The Mr of the main immunogenic fractions for T cells ranged from 28 to 46 kDa, whereas those recognized by antibodies were 45, 52, 56, 59, 65, 69, 75 and 81 kDa. The results indicate a striking difference in the antigenic recognition pattern of T and B cells which may be important for selecting antigen molecules for immunological studies of this trematode infection in man.


Assuntos
Antígenos de Helmintos/imunologia , Linfócitos B/imunologia , Opisthorchis/imunologia , Linfócitos T/imunologia , Animais , Anticorpos Anti-Helmínticos/análise , Imunização , Ativação Linfocitária , Camundongos
13.
Int J Parasitol ; 24(6): 833-43, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7982745

RESUMO

Infection with the liver fluke, Opisthorchis viverrini, remains a major public health problem in Northeast Thailand, where approximately one-third of the population is infected. The northeast region is largely populated by Laos-descendent Thais who enjoy eating raw fish, which harbour the infective stage of the fluke. The parasite has maintained its presence in the population despite the widespread use of praziquantel and dissemination of health education material throughout the region by vigorous government-sponsored programs in recent years. The most severe consequence of liver fluke infection is cholangiocarcinoma, i.e. cancer of the bile duct epithelium. Although mortality due to the parasites alone appears to be uncommon, cholangiocarcinoma arising as a result of infection is one of the leading causes of death in the region. This paper reviews the pathogenesis of infection and the geographic, hospital-based and community studies which demonstrate the close relationship between infection and cancer. In addition, data from the Cancer Registry of Khon Kaen, Northeast Thailand and population-based studies using ultrasonography to visualize early tumours which illuminate the very high frequency of the cancer among heavily infected individuals and communities are discussed. Finally, the paper will close with a brief commentary on the prospects for control of the parasite and its likely impact on the frequency of cancer given the current epidemiological situation of liver fluke infection.


Assuntos
Neoplasias dos Ductos Biliares/epidemiologia , Hepatopatias Parasitárias/epidemiologia , Opistorquíase/epidemiologia , Animais , Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/mortalidade , Cyprinidae/parasitologia , Geografia , Humanos , Incidência , Hepatopatias Parasitárias/mortalidade , Morbidade , Opistorquíase/complicações , Opistorquíase/mortalidade , Sistema de Registros , Tailândia/epidemiologia
14.
Am J Trop Med Hyg ; 52(6): 521-4, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7611558

RESUMO

A monoclonal antibody-based enzyme-linked immunosorbent assay (MAb-ELISA) was evaluated for its potential in the diagnosis of opisthorchiasis in an area endemic for Opisthorchis viverrini infection. The method, based on the detection of the 89-kD O. viverrini metabolic antigen in the feces (coproantigen), was previously estimated to be sensitive enough to detect antigen excreted by a single mature fluke. In the present study, fecal specimens from 207 apparently healthy villagers in northeastern Thailand were analyzed in a double-blind test for the presence of O. viverrini eggs by microscopic examination and for antigen by MAb-ELISA. The microscopic examination was carefully done to minimize false-positive results due to eggs of Lecithodendriid trematodes. The specimens were divided into six groups based on the number of eggs per gram of feces, namely, egg negative, 1-500, 501-1,500, 1,501-3,000, 3,001-6,000, and more than 6,000. The results showed that the ELISA is sufficiently sensitive and specific for the diagnosis of O. viverrini infection. The slightly higher rate of coproantigen positive by the ELISA compared with microscopic examination may reflect lower specificity of the ELISA or its higher sensitivity over microscopic examination in detecting light infections. Different lines of evidence presented here support the latter explanation.


Assuntos
Anticorpos Monoclonais , Antígenos de Helmintos/análise , Fezes/parasitologia , Opistorquíase/diagnóstico , Opisthorchis/imunologia , Análise de Variância , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Helmintos/imunologia , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Humanos , Contagem de Ovos de Parasitas , Sensibilidade e Especificidade
15.
Am J Trop Med Hyg ; 55(3): 295-301, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8842118

RESUMO

The liver fluke, Opisthorchis viverrini, is both highly prevalent and closely associated with cholangio-carcinoma in northeast Thailand. This study measured associations between intensity of liver fluke infection and nonmalignant hepatobiliary disease diagnosed by ultrasonography among 1, 807 largely asymptomatic adult residents drawn from endemic communities. Abnormalities significantly associated with intensity of infection included gallbladder enlargerment in all dimensions, presence of sludge, irregular gallbladder wall, liver enlargement, and enhanced portal vein radicle echoes. While gallbladder enlargement was not sex-specific, the prevalence odds of the other abnormalities were 2-3 times higher among males compared with females. Those recently treated with the anthelmintic praziquantel had higher odds of these abnormalities compared with others with the same infection status who were untreated. The low prevalence of gallstones suggests that this impairment of gallbladder structure and function does not frequently stimulate gallstone formation. However, gallbladder disturbances, together with chronic inflammation and fibrosis of the bile ducts, which are visualized as enhanced portal vein radicle echoes, may contribute to the strikingly enhanced susceptibility to cholangiocarcinoma among people, especially males, with heavy liver fluke infection.


Assuntos
Neoplasias dos Ductos Biliares/etiologia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/etiologia , Opistorquíase/complicações , Adulto , Colelitíase , Estudos Transversais , Fezes/parasitologia , Feminino , Vesícula Biliar/patologia , Humanos , Fígado/patologia , Masculino , Opistorquíase/tratamento farmacológico , Praziquantel/uso terapêutico
16.
FEMS Microbiol Lett ; 50(1-2): 15-9, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2525505

RESUMO

The Escherichia coli entE gene encodes a polypeptide necessary in the latter stages of biosynthesis of the siderophore enterobactin. The entE gene and adjacent DNA were sequenced. The predicted EntE polypeptide consists of 536 amino acids and has a Mr of 58,299 and a net charge of -7.33. Genetic evidence combined with this and previous sequencing data indicate that the genes entCEB(G)A are transcribed as unit from a promoter upstream of entC.


Assuntos
Enterobactina/genética , Escherichia coli/genética , Genes Bacterianos , Serina/análogos & derivados , Sequência de Aminoácidos , Sequência de Bases , Enterobactina/análise , Dados de Sequência Molecular
17.
Clin Ther ; 18(3): 411-28, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8829017

RESUMO

A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with the angiotensin II receptor antagonist losartan, alone or with hydrochlorothiazide (HCTZ), and the dihydropyridine calcium channel blocker nifedipine gastrointestinal therapeutic system (GITS) in patients whose sitting diastolic blood pressure measurements were between 95 and 115 mm Hg, inclusive, while receiving placebo. Patients were randomized to receive either losartan or nifedipine GITS in a double-masked, double-dummy fashion. A 4-week placebo washout period established baseline untreated blood pressure measurements and was followed by a 12-week active treatment period. Patients receiving losartan (n = 110) were initially given 50 mg once a day (QD) and could be titrated to losartan/HCTZ 50 mg/12.5 mg QD after 4 weeks followed by losartan/HCTZ 50 mg/25 mg QD after 8 weeks, as necessary. Patients in the nifedipine GITS group (n = 113) received 30 mg QD, which could titrated to 60 mg QD after 4 weeks followed by 90 mg QD after 8 weeks. Medication was titrated upward as necessary to achieve a sitting trough diastolic blood pressure < 90 mm Hg. Efficacy, tolerability, and quality-of-life scores were assessed after 12 weeks of each therapy. Trough sitting diastolic blood pressure reductions after 4, 8, and 12 weeks of therapy were clinically comparable: losartan, -8.9, -11.6, and -12.7 mm Hg, respectively, and nifedipine GITS, -9.3, -11.0, and -11.1 mm Hg, respectively, with the mean reduction in sitting diastolic blood pressure at 12 weeks in the losartan group 1.6 mm Hg lower (95% confidence interval, 3.4 mm Hg lower to 0.3 mm Hg Higher) than the mean reduction in sitting diastolic blood pressure in the nifedipine GITS group. Similarly, reductions in systolic blood pressure between the two treatment groups were comparable at all time points. The percentage of patients reaching the goal trough sitting diastolic blood pressure was comparable for the two treatment groups, with 74% of patients in the losartan regimen and 68% of patients in the nifedipine GITS regimen reaching the goal. Of patients reporting adverse events in the two groups (75 patients receiving losartan and 69 receiving nifedipine GITS), there was significantly more edema in the nifedipine GITS group (15% vs 4%; P = 0.005). Fourteen (12%) patients in the nifedipine GITS group were withdrawn due to an adverse event (eight of these were for edema). Six patients (5%) in the losartan group were withdrawn due to an adverse event (none of these patients had edema). There were significant differences in the patient-reported quality-of-life symptom bother inventory with respect to edema, with nifedipine GITS therapy causing significantly more bother due to edema in patients, regardless of whether that symptom was present at baseline (27% vs 9%; P = 0.0004). No statistically significant differences for bother due to the other symptoms in the inventory were noted. Of note, while the incidence of patient-reported symptom bother due to edema in the nifedipine GITS group was 27%, the incidence of physician-reported drug-related edema was 12%. This difference points to the need for improved physician-patient communication regarding adverse effects and their impact of patients' quality of life. In conclusion, a regimen of losartan, when compared with a regimen of nifedipine GITS, provides comparable efficacy, and with respect to edema, superior tolerability, less bother to patients, and fewer therapy dropouts.


Assuntos
Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Nifedipino/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Tetrazóis/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Diuréticos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hidroclorotiazida/efeitos adversos , Hipertensão/complicações , Imidazóis/efeitos adversos , Losartan , Masculino , Pessoa de Meia-Idade , Nifedipino/efeitos adversos , Qualidade de Vida , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Tetrazóis/efeitos adversos
18.
Clin Ther ; 18(4): 608-25, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8879890

RESUMO

A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with treatment regimens including the angiotensin II receptor antagonist losartan, with hydrochlorothiazide (HCTZ) added as needed, with regimens including the dihydropyridine calcium channel blocker amlodipine with HCTZ added as needed. The trial included patients whose sitting diastolic blood pressure (SiDBP) measurements were between 95 and 114 mm Hg, inclusive, at placebo baseline. Patients were randomized to receive either losartan or amlodipine in a double-masked, double-dummy fashion. A 4-week placebo washout period was followed by a 12-week active treatment period. Patients in the losartan arm (n = 97) were initially given 50 mg of oral (PO) losartan once a day (QD); the medication could be titrated to 50-mg losartan/ 12.5-mg HCTZ PO QD after 4 weeks, followed by 50-mg losartan plus 25-mg HCTZ PO QD after 8 weeks as necessary. Patients in the amlodipine group (n = 93) received 5-mg amlodipine PO QD, which could be titrated to 10 mg PO QD after 4 weeks, followed by 10 mg plus 25-mg HCTZ PO QD after 8 weeks. Medication was titrated upward as necessary to achieve trough SiDBP < 90 mm Hg. Efficacy, tolerability, and quality-of-life scores were assessed after 12 weeks of therapy with each regimen. Trough SiDBP reductions after 4, 8, and 12 weeks of therapy were clinically comparable (losartan group: 7.3, 10.4, and 11.1 mm Hg, respectively; amlodipine group: 7.9, 11.2, and 11.8 mm Hg, respectively). Similar reductions in systolic blood pressure were also seen for both treatment groups. The percentage of patients reaching goal SiDBP (defined as trough SiDBP < 90 mm Hg or SiDBP > or = 90 mm Hg with a > or = 10 mm Hg drop from placebo baseline) was comparable for the two groups, with 68% of patients in the losartan group and 71% of patients in the amlodipine group reaching goal. Significantly more patients in the amlodipine group had drug-related adverse experiences (27% vs 13%). In particular, drug-related edema was more common in patients receiving the amlodipine regimen than in those receiving the losartan regimen (11% vs 1%). Patients in the amlodipine arm reported significantly more bother due to edema, regardless of whether edema was present at baseline, than did patients in the losartan arm (12% vs 2%), although overall quality of life was not different in the two treatment groups. This study demonstrates that a regimen of losartan with HCTZ added as needed, when compared with a regimen of amlodipine with HCTZ added as needed, provides comparable efficacy and superior tolerability and less bother to patients with respect to edema.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Qualidade de Vida , Tetrazóis/uso terapêutico , Adulto , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Tolerância a Medicamentos , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/efeitos adversos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Losartan , Masculino , Pessoa de Meia-Idade , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversos
19.
Exp Biol Med (Maywood) ; 226(7): 686-91, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11444105

RESUMO

Endothelial cells (EC) that form the inner lining of blood vessels remain quiescent in the normal adult vasculature except during angiogenesis and reendothelialization, which result in EC proliferation and migration. EC placed in culture at subconfluent density also undergo cell multiplication and movement. This report demonstrates that whereas in confluent EC in a compact monolayer, the EC-EC adhesion molecule platelet-endothelial cell adhesion molecule-1 (PECAM-1) is strongly expressed at cell borders, little or no PECAM-1 immunostaining is detected in sparse or migrating cultured EC. Consistent with this observation, steady-state PECAM-1 mRNA expression was much lower in subconfluent EC than in confluent EC. The absence of PECAM-1 expression in sparse EC appeared not to be linked to ability to proliferate, since PECAM-1 expression remained low even in the presence of nitric oxide (NO) or mitomycin C, agents that inhibit EC growth. However, another growth-inhibitory agent, TGF-beta 1, did not alter PECAM-1 staining. Based on these observations, it is hypothesized that cell-associated mechanical forces underlying cell tensegrity regulate PECAM-1 expression.


Assuntos
Divisão Celular , Movimento Celular , Endotélio Vascular/química , Endotélio Vascular/citologia , Regulação da Expressão Gênica , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Northern Blotting , Comunicação Celular , Células Cultivadas , Humanos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , RNA Mensageiro/análise , Veias Umbilicais
20.
Trans R Soc Trop Med Hyg ; 80(5): 774-92, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3603617

RESUMO

The study design of a project to investigate the epidemiology, population dynamics and control of intestinal nematode infections in fishing village communities in Southern India is described. The paper focuses on Ascaris lumbricoides infection and describes changes in prevalence and intensity (worm burdens) with host age, the aggregated frequency distributions of parasite numbers per person, a density-dependent relationship between parasite fecundity and worm burden and rates of reinfection following chemotherapeutic treatment. The age-intensity of infection profile is convex in form, where maximum worm burdens are attained in children in the age range five to nine years. On the basis of juvenile to adult worm ratioos, the life expectancy of Ascaris in man is estimated to be of the order of one year. Rates of reacquisition of worms after chemotherapy are shown to be dependent on host age. Wormy individuals with heavy infections are shown to be predisposed to this state such that they reacquire heavier than average worm burdens following treatment.


Assuntos
Ascaríase/prevenção & controle , Enteropatias Parasitárias/prevenção & controle , Pamoato de Pirantel/uso terapêutico , Pirantel/análogos & derivados , Adolescente , Adulto , Fatores Etários , Idoso , Ascaríase/epidemiologia , Ascaríase/parasitologia , Ascaris/isolamento & purificação , Criança , Pré-Escolar , Fezes/parasitologia , Feminino , Humanos , Índia , Lactente , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/parasitologia , Masculino , Pessoa de Meia-Idade , Contagem de Ovos de Parasitas , Recidiva
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