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BACKGROUND & AIMS: In the Asia-Pacific region, perinatal transmission of the hepatitis B virus (HBV) is the primary cause of chronic hepatitis B infection. Despite the use of HBIG and HBV vaccination, HBV perinatal transmission (PT) occurs in 10-30% of infants born to highly viremic mothers. We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers. METHODS: Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0×10(7) copies/ml mothers received telbivudine 600 mg/day from week 20 to 32 of gestation (n=135) or served as untreated controls (n=94). All infants in both arms received 200 IU of HBIg within 12 h postpartum and recombinant HBV vaccine of 20 µg at 0, 1, and 6 months. HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate. All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. RESULTS: Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen (HBeAg) levels and normalization of elevated ALT levels before delivery. A striking decline of HBV DNA levels started from treatment onset to week 4, and sustained in a low level since week 12. Forty-four (33%) of the 135 telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia (DNA<500 copies/ml) at delivery. Seven months after delivery, the incidence of perinatal transmission was lower in the infants that completed follow-up born to the telbivudine-treated mothers than to the controls (0% vs. 8%; p=0.002). HBV DNA levels were only detectable in HBsAg+infants. No significant differences in anti-HBs levels were observed during postnatal follow-up. No serious adverse events were noted in the telbivudine-treated mothers or their infants. CONCLUSIONS: Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission. Telbivudine was well-tolerated with no safety concerns in the telbivudine-treated mothers or their infants on short term follow up. These data support the use of telbivudine in this special population.
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Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Nucleósidos/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Pirimidinonas/uso terapéutico , Adulto , Antivirales/efectos adversos , Antivirales/uso terapéutico , ADN Viral/sangre , Femenino , Anticuerpos contra la Hepatitis B/administración & dosificación , Antígenos de Superficie de la Hepatitis B/sangre , Vacunas contra Hepatitis B/administración & dosificación , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/prevención & control , Hepatitis B Crónica/transmisión , Humanos , Lactante , Recién Nacido , Masculino , Nucleósidos/efectos adversos , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Pirimidinonas/efectos adversos , Telbivudina , Timidina/análogos & derivados , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The use of hypertonic crystalloid solutions, including sodium chloride and bicarbonate, for treating severe sepsis has been much debated in previous investigations. We have investigated the effects of three crystalloid solutions on fluid resuscitation in severe sepsis patients with hypotension. METHODS: Ninety-four severe sepsis patients with hypotension were randomly assigned to three groups. The patients received the following injections within 15 min at initial treatment: Ns group (n = 32), 5 ml/kg normal saline; Hs group (n = 30), with 5 ml/kg 3.5% sodium chloride; and Sb group (n = 32), 5 ml/kg 5% sodium bicarbonate. Cardiac output (CO), systolic blood pressure, mean arterial pressure (MAP), body temperature, heart rate, respiratory rate and blood gases were measured. RESULTS: There were no differences among the three groups in CO, MAP, heart rate or respiratory rate during the 120 min trial or the 8 hour follow-up, and no significant differences in observed mortality rate after 28 days. However, improvement of MAP and CO started earlier in the Sb group than in the Ns and Hs groups. Sodium bicarbonate increased the base excess but did not alter blood pH, lactic acid or [HCO3]- values; and neither 3.5% hypertonic saline nor 5% sodium bicarbonate altered the Na+, K+, Ca2+ or Cl- levels. CONCLUSION: All three crystalloid solutions may be used for initial volume loading in severe sepsis, and sodium bicarbonate confers a limited benefit on humans with severe sepsis. TRIAL REGISTRATION: ISRCTN36748319.
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Pruebas de Función Cardíaca , Corazón/fisiología , Hipotensión/tratamiento farmacológico , Soluciones Isotónicas/uso terapéutico , Sepsis/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis Químico de la Sangre , Análisis de los Gases de la Sangre , Presión Sanguínea/efectos de los fármacos , Temperatura Corporal/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Niño , Preescolar , Soluciones Cristaloides , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Soluciones Isotónicas/administración & dosificación , Masculino , Persona de Mediana Edad , Ventilación Pulmonar/efectos de los fármacos , Sepsis/mortalidadRESUMEN
BACKGROUND: Our previous study has established a macaque model with early-phase endotoxic shock. The present study further investigated myocardial and blood vessel injury in Macaques by examining the subsequent expression of ACP, selectins, iNOS, and cTnI in response to LPS treatment. METHODS: In an experiment with anaesthetised, instrumental macaques, eleven animals were randomised into: an En group (n=6), receiving a dose of 2.8 mg kg(-1) lipopolysaccharides (LPS) by i.v.; and a Co group (n=5), injected with normal saline of 1 ml kg(-1). Cytochemistry of acid phosphatase (ACPase) in heart was performed by electron microscope at 120 min following endotoxin injection. Three immunochemical stains, namely, L-selectin, P-selectin and iNOS protein in heart, were studied. In addition, cardiac troponin I (cTnI), L-selectin and P-selectin in plasma were detected. RESULTS: In the early phase of endotoxic shock, LPS caused myocardial lysosome damage. The data of immunochemical staining showed the thrombus formation in vessels and the increase of iNOS, L-Selectin and P-Selectin expression in heart, but LPS challenge did not change L-selectin, P-selectin and cTnI in plasma. CONCLUSION: The increase of iNOS, L-selectin and P-selectin protein expression following endotoxin administration may have caused vessel injury and myocardial damage in macaques.
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Selectina L/metabolismo , Miocardio/metabolismo , Miocardio/patología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Selectina-P/metabolismo , Choque Séptico/complicaciones , Animales , Modelos Animales de Enfermedad , Escherichia coli , Femenino , Lipopolisacáridos , Macaca , Masculino , Choque Séptico/metabolismo , Choque Séptico/patología , Troponina I/sangreRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha 2a (PEG-IFN alpha-2a) in treating patients with chronic hepatitis B. METHOD: Seventy-two patients with chronic hepatitis B were assigned to a PEG-IFN alpha-2a (experimental) group (n=42) and an interferon alpha (control) group (n=30) randomly. Each patient in the experimental group received 180 microg PEG-IFN alpha-2a every week. Each patient in the control group received 500 MU interferon alpha every day. All the patients were treated for 48 weeks, and then were followed for another 48 weeks with no treatment. RESULTS: At the end of the 12th week, the rate of HBeAg negative cases was 30% in the PEG-IFN alpha-2a group, which was much higher than in the control group (x2 = 4.162, P < 0.05). The values of HBeAg and the log value of HBV DNA in the PEG-IFN alpha-2a group were much lower than the values before the treatment (t = 2.689, t = 4.080, P <0.01), but there was no difference between before and after treatment in the control group ( t = 1.229, t = 1.009, P > 0.05). At the end of the 24th week, the rate of HBeAg negative cases in the PEG-IFN alpha-2a group was much higher than that in the control group (x2=6.190, P < 0.05). The value of HBeAg and the log value of HBV DNA in the PEG-IFN alpha-2a group were much lower than in the control group (t=2.215, t=2.122, P < 0.05). At the end of the 48th week, besides the reduction mentioned above, the rate of cases with HBeAg/antiHBe seroconversion and normalization of ALT and complete responsiveness in the PEG-IFN alpha-2a group were all much higher than those in the control group (x2=5.771, x2=5.617, x2=5.308, P < 0.05). At the end of 48 weeks with no treatment, all the parameters mentioned above in the PEG-IFN alpha-2a group were much better than those in the control group and they remained so, but they were different in the control group (x2=11.943, t=3.439, t=6.111, x2=9.930, x2=9.522, x2=7.920, P < 0.01). Nine patients in the PEG-IFN alpha-2a group had liver biopsies before their treatment and also at the end of their treatment. The expressions of HBsAg and HBcAg were decreased at the end of the treatment. The rate of expression of HBsAg in the liver tissues before the treatment was 88.9% but only 22.2% at the end of the treatment (x2=8.001, P < 0.01). The rate of expression of HBcAg in the livers before treatment was 66.7% but only 33.3% at the end of the treatment. Before and at the end of the PEG-IFN alpha-2a treatment, there were no significant changes in the degrees of inflammation and fibrosis and the quantity of collagen in the liver tissues. Three patients in the PEG-IFN alpha-2a group (10%) were HbsAg negative. Two of them were found so at the end of 32 weeks with treatment and one patient was found at the end of 24 weeks with no treatment, but there were no HBsAg negative patients in the control group. The adverse reactions that occurred in the PEG-IFN alpha-2a and in the control groups were similar. CONCLUSION: PEG-IFN alpha-2a was effective in inhibiting HBV replication. The effect of PEG-IFN alpha-2a was lasting. PEG-IFN alpha-2a was well tolerated during our treatment.
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Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Adolescente , Adulto , Femenino , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Adulto JovenRESUMEN
OBJECTIVE: Our recent study demonstrated that sodium bicarbonate improved cardiac function in macaque models with early-phase endotoxic shock. In the present study, we investigated further the ryanodine receptor/calcium release-channel (RyR) and calcium pump after fluid resuscitation of macaques with early-phase endotoxic shock. METHODS: Twenty-four anaesthetised macaques were assigned to four groups. Nineteen animals were given an intravenous dose of 2.8 mgkg(-1) lipopolysaccharide (LPS). Sixty minutes after the LPS challenge, the animals were given (i) 5 mLkg(-1) normal saline (Ns group, n = 6), (ii) 5 mLkg(-1) of 5% sodium bicarbonate (Sb group, n = 6) or (iii) 5 mLkg(-1) of 3.5% hypertonic sodium chloride (Hs group, n = 7). The control group (Co group, n = 5) received 1 mLkg(-1) normal saline and then with 5 mLkg(-1) normal saline 60 min later. RESULTS: Endotoxin produced a reduction of the density of RyR but did not alter the affinity of RyR. Compared with normal saline, sodium bicarbonate or hypertonic saline induced a restoration of density of RyR but did not influence the affinity of RyR and the calcium pump. CONCLUSION: Up-regulation of RyR performance in myocardium following administration of sodium bicarbonate contributes to the improvement of cardiac function in macaques in the early phase of endotoxic shock.
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ATPasas Transportadoras de Calcio/efectos de los fármacos , Resucitación/métodos , Canal Liberador de Calcio Receptor de Rianodina/efectos de los fármacos , Solución Salina Hipertónica/farmacología , Choque Séptico/metabolismo , Bicarbonato de Sodio/farmacología , Animales , ATPasas Transportadoras de Calcio/metabolismo , Modelos Animales de Enfermedad , Escherichia coli , Femenino , Fluidoterapia , Lipopolisacáridos/administración & dosificación , Macaca , Masculino , Miocardio/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Solución Salina Hipertónica/uso terapéutico , Choque Séptico/etiología , Choque Séptico/terapia , Bicarbonato de Sodio/uso terapéutico , Regulación hacia ArribaRESUMEN
These studies established a macaque model of early-phase endotoxic shock, and investigated the resuscitation effects of three different solutions. Twenty-four macaques were assigned to four groups. Nineteen animals were given an intravenous dose of 2.8 mg/kg lipopolysaccharide (LPS). At 60 min after LPS challenge, the animals were given (i) 5 mL/kg normal saline (Ns group, n=6), (ii) 5% of 5 mL/kg sodium bicarbonate (Sb group, n=6), (iii) hypertonic 3.5% sodium chloride of 5 mL/kg (Hs group, n=7). The control group (Co group, n=5) was first injected with 1 mL/kg Ns and with 5 mL/kg Ns 60 min later. Haemodynamic parameters and blood gases were measured during the experiment, and myocardial morphology was examined on termination of the experiment. Administration of LPS caused hypotension and decreases of the left ventricular work index (LVWI). In the Sb group, mean arterial pressure, cardiac index, systemic vascular resistance index, LVWI and right ventricular work index were significantly higher than those of the Ns group. Pathological changes of myocardium were identified in all of the LPS groups. The studies suggest that macaques are suitable models for studying endotoxic shock and potential fluid therapies.