RESUMEN
Knockout mice lacking the adenosine A(2A) receptor are less sensitive to nociceptive stimuli, and this may be due to the presence of pronociceptive A(2A) receptors on sensory nerves. In support of this hypothesis, we have recently shown that in A(2A) receptor knockout mice there are marked reductions in the changes of two markers of spinal cord neuronal activity, [(3)H]MK801 binding to NMDA receptors and uptake of [(14)C]-2-deoxyglucose, in response to formalin injection. We now report that following a more prolonged inflammatory stimulus, consisting of intraplantar injections of PGE(2) and paw pressure, there was in contrast an increase in [(3)H]MK801 binding and [(14)C]-2-deoxyglucose uptake in the spinal cords of the A(2A) receptor knockout mice which was much greater than in the wild-type mice. This increase suggests that when there is a pronounced inflammatory component to the stimulus, loss of inhibitory A(2A) receptors on inflammatory cells outweighs the loss of pronociceptive A(2A) receptors on peripheral nerves so that overall there is an increase in nociceptive signalling. This implies that although A(2A) antagonists have antinociceptive effects they may have only limited use as analgesics in chronic inflammatory pain.
Asunto(s)
Dolor/metabolismo , Receptor de Adenosina A2A/metabolismo , Médula Espinal/metabolismo , Animales , Antimetabolitos/farmacología , Autorradiografía , Desoxiglucosa/farmacología , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Inflamación/metabolismo , Ratones , Ratones NoqueadosRESUMEN
Mice lacking the adenosine A(2A) receptor are less sensitive to nociceptive stimuli, and A(2A) receptor antagonists have antinociceptive effects. We have previously shown a marked reduction in the behavioural responses to formalin injection in A(2A) receptor knockout mice. This may be due to the presence of pronociceptive A(2A) receptors on sensory nerves, and if so spinal cords from A(2A) receptor knockout mice may have altered neurochemical responses to a nociceptive stimulus. We tested this hypothesis by studying two parameters known to change with spinal cord activity, NMDA glutamate receptor binding and [(14)C]-2-deoxyglucose uptake, following intraplantar formalin injection in wild-type and A(2A) receptor knockout mice. In naïve untreated A(2A) knockout mice [(14)C]-2-deoxyglucose uptake in all regions of the spinal cord was significantly lower compared to the wild-type, similar to the reduced NMDA receptor binding that we have previously observed. Following formalin treatment, there was an decrease in [(3)H]-MK801 binding to NMDA receptors and an increase in [(14)C]-2-deoxyglucose uptake in the spinal cords of wild-type mice, and these changes were significantly reduced in the A(2A) knockout mice. In addition to altered behavioural responses, there are therefore corresponding reductions in spinal cord neurochemical changes induced by formalin in mice lacking adenosine A(2A) receptors. These observations support the hypothesis that activation of A(2A) receptors enhances nociceptive input into the spinal cord and suggests a possible role for A(2A) antagonists as analgesics.
Asunto(s)
Glucosa/metabolismo , Dolor/metabolismo , Receptor de Adenosina A2A/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Médula Espinal/metabolismo , Animales , Desoxiglucosa/metabolismo , Maleato de Dizocilpina/metabolismo , Eliminación de Gen , Masculino , Ratones , Ratones Noqueados , Dimensión del Dolor , Ensayo de Unión Radioligante , Receptor de Adenosina A2A/genéticaRESUMEN
OBJECTIVE: Three-dimensional (3D) ultrasound is gaining popularity in prenatal diagnosis. While there are no studies regarding the safety of 3D ultrasound, it is now widely performed in non-medical facilities, for non-diagnostic purposes. The present study was aimed at comparing the acoustic output, as expressed by thermal index (TI) and mechanical index (MI), of conventional two-dimensional (2D) and 3D/4D ultrasound during pregnancy. METHODS: A prospective, observational study was conducted, using three different commercially available machines (iU22, Philips Medical Systems; Prosound Alfa-10, Aloka; and Voluson 730 Expert, General Electric). Patients undergoing additional 3D/4D ultrasound examinations were recruited from those scheduled for fetal anatomy and follow-up exams. Fetuses with anomalies were excluded from the analysis. Data were collected regarding duration of the exam, and each MI and TI during 2D and 3D/4D ultrasound exams. RESULTS: A total of 40 ultrasound examinations were evaluated. Mean gestational age was 31.1 +/- 5.8 weeks, and mean duration of the exam was 20.1 +/- 9.9 min. Mean TIs during the 3D (0.27 +/- 0.1) and 4D examinations (0.24 +/- 0.1) were comparable with the TI during B-mode scanning (0.28 +/- 0.1, P = 0.343). The MIs during the 3D volume acquisitions were significantly lower than those in the 2D B-mode ultrasound studies (0.89 +/- 0.2 vs. 1.12 +/- 0.1, P = 0.018). The 3D volume acquisitions added 2.0 +/- 1.8 min of actual ultrasound scanning time (i.e. not including data processing and manipulation, or 3D displays, which are all post-processing steps). The 4D added 2.2 +/- 1.2 min. CONCLUSIONS: Acoustic exposure levels during 3D/4D ultrasound examination, as expressed by TI, are comparable with those of 2D B-mode ultrasound. However, it is very difficult to evaluate the additional scanning time needed to choose an adequate scanning plane and to acquire a diagnostic 3D volume.
Asunto(s)
Ruido , Obstetricia/métodos , Ultrasonografía Prenatal/normas , Adolescente , Adulto , Análisis de Varianza , Femenino , Edad Gestacional , Humanos , Embarazo , Estudios Prospectivos , Valores de Referencia , Método Simple Ciego , Tiempo , Ultrasonografía Prenatal/efectos adversos , Ultrasonografía Prenatal/métodosRESUMEN
This paper reports the success of outreach efforts to immunize adults at high risk of acquiring hepatitis B virus (HBV) infection. Local health department testers recruited clients when they sought anonymous HIV testing. Interested clients were serologically tested for HBV infection. Susceptibles were offered a free hepatitis B vaccine. Of 189 clients who were tested, 161 (86%) were susceptible to HBV infection and 140 (74%) were men who have sex with men (MSM). Of the susceptibles, 82 (51%) started the hepatitis B vaccine series. Sixty-five (80%) received three doses of hepatitis B vaccine and an additional 10 (12%) received two doses. Completing the hepatitis B vaccine series was associated with being a MSM (odds ratio [OR] 8.8, confidence interval [CI] 1.5-56.0) and with not being an injection drug user (IDU) (OR 0.2, CI 0.02-1.0). One way to provide hepatitis B vaccine to MSM is to attach an immunization program to a successful anonymous HIV testing program. The feasibility of implementing such programs would increase if public vaccine policymakers made more federally purchased hepatitis B vaccine available for adults.
Asunto(s)
Vacunas contra Hepatitis B/uso terapéutico , Hepatitis B/prevención & control , Homosexualidad Masculina , Programas de Inmunización , Adolescente , Adulto , Anciano , Femenino , Humanos , Programas de Inmunización/normas , Masculino , Persona de Mediana Edad , Conducta SexualRESUMEN
OBJECTIVE: Intrauterine growth restriction in an ovine model occurs after exposure to environmental heat stress for 80 days beginning at 35 days' gestation. Our objective was to determine whether intrauterine growth restriction is reversible on removal of the heat stress after only 55 days of exposure; that is, does a brief exposure at a critical point of development suffice? STUDY DESIGN: Five pregnant ewes were exposed to heat stress beginning at 35 days' gestation and were removed after 55 days of exposure. Five ewes in a control group were studied as contemporaneous controls and added to data from 37 ewes in a control group previously studied. Serial fetal biometric ultrasonographic measurements (biparietal diameter, abdominal circumference, femur length, and tibia length) were obtained beginning at 50 days' gestation. Growth curves were calculated for each parameter, and comparisons were made between fetuses in the group exposed to heat stress for 55 days and 42 fetuses in the control group and 4 fetuses from a previous study that were exposed to heat for 80 days. Regression lines, 95% confidence intervals, and slopes were determined for each study group. RESULTS: Both the 55-day and the 80-day heat exposure groups showed a significant reduction in fetal and placental weights compared with the control group. Animals in the 80-day group had significantly lower fetal and placental weights than the animals in the 55-day group (P <.05). Indexes of somatic growth (abdominal circumference, femur length, and tibia length) for the control group were significantly greater than those of either the 55-day group or the 80-day group (P <.001). Asymmetric growth restriction was evident in both heat groups by a biparietal diameter/abdominal circumference ratio that was significantly higher than in the control group (P <.004 for the 55-day group and P <.001 for the 80-day group). The slopes for somatic parameters (abdominal circumference, femur length, and tibia length) versus time became significantly different between the control and 55-day groups at 77, 101, and 80 days' gestation, respectively. The 55-day group had abdominal circumference and femur length measurements that were significantly greater than those in the 80-day group. CONCLUSION: The fetuses in the 55-day and 80-day groups reflect a pattern of asymmetric intrauterine growth restriction. Our findings suggest that the initial insult affecting fetal and placental growth occurs early in gestation, but removal of fetuses after only 55 days of exposure significantly reduces the degree of fetal growth restriction compared with that found in those fetuses exposed for 80 days.
Asunto(s)
Retardo del Crecimiento Fetal/etiología , Calor , Insuficiencia Placentaria/etiología , Abdomen/diagnóstico por imagen , Abdomen/embriología , Animales , Antropometría , Peso Corporal , Desarrollo Embrionario y Fetal , Femenino , Fémur/diagnóstico por imagen , Fémur/embriología , Edad Gestacional , Tamaño de los Órganos , Hueso Parietal/diagnóstico por imagen , Hueso Parietal/embriología , Placenta/patología , Embarazo , Ovinos , Tibia/diagnóstico por imagen , Tibia/embriología , Factores de Tiempo , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: The aim of the study was to compare the diagnostic utility of the Gram stain, the amniotic fluid glucose level, and the ratio of amniotic fluid glucose level to serum glucose level in detecting intra-amniotic infection. STUDY DESIGN: We conducted a prospective study of 127 patients with preterm labor and 26 patients with preterm premature rupture of the membranes (153 total). All patients underwent amniocentesis to diagnose intra-amniotic infection. The diagnostic criterion for intra-amniotic infection was a positive amniotic fluid culture result. RESULTS: The Gram stain is 80% sensitive and 91% specific when a positive is considered the presence of white blood cells or bacteria. Amniotic fluid glucose level and the ratio of amniotic fluid glucose level to serum glucose level are significantly lower when amniotic fluid culture results are positive, but as diagnostic tests they are inferior to the Gram stain. Logistic regression models that combine predictors yield superior accuracy with respect to individual tests. The most accurate combination was amniotic fluid glucose level and Gram stain with white blood cells or bacteria. Although the number of patients with preterm premature rupture of the membranes was small in this study (n = 26), analysis of our data suggests that the diagnostic performance levels of these tests were similar when used in patients with preterm labor and intact membranes and in patients with premature rupture of the membranes. CONCLUSIONS: The amniotic fluid glucose level and the ratio of amniotic fluid to serum glucose level have equivalent diagnostic utility and are inferior to the Gram stain. The combination of Gram stain with amniotic fluid glucose level is superior to any individual test.
Asunto(s)
Amnios/microbiología , Líquido Amniótico/química , Infecciones Bacterianas/diagnóstico , Glucemia/análisis , Violeta de Genciana/normas , Glucosa/análisis , Fenazinas/normas , Adulto , Líquido Amniótico/microbiología , Estudios de Evaluación como Asunto , Femenino , Rotura Prematura de Membranas Fetales/microbiología , Humanos , Trabajo de Parto Prematuro/microbiología , Embarazo , Estudios Prospectivos , Factores de TiempoRESUMEN
OBJECTIVE: With an ovine model in which growth restriction was induced by exposure to heat stress, our aims were as follows: (1) to describe the normal gestational age-related changes in Doppler velocimetry in the ovine fetal aorta and umbilical artery and (2) to compare Doppler velocimetry between heat-stressed and non-heat-stressed fetuses. STUDY DESIGN: Five ewes were exposed to heat stress for 55 days beginning at 35 days' gestation. Five ewes were not exposed and served as controls. Aortic and umbilical artery pulsed Doppler velocimetry was obtained, including the systolic/diastolic ratio, pulsatility index, and resistance index. Data were obtained between 50 and 120 days' gestation. Linear regression analysis was used to analyze gestational age-related changes in velocimetry. Comparison of mean index values between heat-stressed and non-heat-stressed fetuses were made with analysis of variance. RESULTS: Heat-stressed fetuses demonstrated significantly higher systolic/diastolic ratios and pulsatility index values for both umbilical artery (p < 0.025; p < 0.033) and aorta (p < 0.017; p < 0.022) compared with controls. The umbilical artery and aortic resistance index values were not different between groups (p < 0.079; p < 0.28). The slopes for each of the Doppler index values were negative in both normal and heat-stressed fetuses. Umbilical artery and aortic end-diastolic flows remained absent through the first 70 days of gestation in both groups. CONCLUSION: Doppler velocimetry index values decrease with increasing gestational age, reflecting decreased placental bed vascular resistance. The higher Doppler index values seen in the heat-stressed group are consistent with increased placental vascular resistance. The normal absence of diastolic flow until 70 days' gestation is similar to the pattern described in humans.
Asunto(s)
Modelos Animales de Enfermedad , Retardo del Crecimiento Fetal/diagnóstico , Flujometría por Láser-Doppler , Insuficiencia Placentaria/diagnóstico , Diagnóstico Prenatal/métodos , Animales , Aorta/fisiología , Femenino , Retardo del Crecimiento Fetal/etiología , Retardo del Crecimiento Fetal/fisiopatología , Edad Gestacional , Insuficiencia Placentaria/complicaciones , Embarazo , Flujo Pulsátil , Ovinos , Estadísticas no Paramétricas , Ultrasonografía Doppler , Arterias Umbilicales/fisiologíaRESUMEN
Pregnancies in women on dialysis and in women who have had renal transplant are no longer uncommon. Optimal obstetric outcomes require a multidisciplinary team approach, patient counseling, and clinicians who are knowledgeable and experienced in taking care of these patients. Counseling should begin before pregnancy, and all reproductive age women on dialysis and who have undergone renal transplant should receive family planning counseling. Preconceptional counseling should be provided to those patients who desire pregnancy. If the patient presents in early pregnancy, she should be informed about the maternal and fetal risks associated with her pregnancy. Prenatal care must include intensive surveillance for hypertension, preeclampsia, preterm labor, intrauterine growth restriction, anemia, infection, and renal allograft rejection. Aggressive treatment of complications is mandatory. There are limitations to our current knowledge about pregnancies in these patients. It is important for clinicians who provide care for these patients to be aware of these limitations when making obstetric management decisions. Cesarean section should be reserved for usual obstetric indications. Breast-feeding is not advised in patients taking cyclosporin or azathioprine. Transplant patients have unique gynecologic needs, so they should be encouraged to pursue follow-up gynecologic care after the pregnancy.