RESUMEN
INTRODUCTION: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. METHODS: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. RESULTS: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. CONCLUSION: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.
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Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Errores Innatos del Metabolismo/diagnóstico , Tamizaje Neonatal/métodos , Diagnóstico Precoz , Femenino , Hong Kong , Humanos , Recién Nacido , Masculino , Errores Innatos del Metabolismo/terapia , Proyectos Piloto , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
The purpose of this study was to determine the reliability of the data acquisition and modeling process of laser and white light scanners by evaluating the reproducibility of digitized simulated crowns with different convergences. A secondary purpose was to analyze the influence of die preparation by testing this hypothesis with a set of dies without ditching compared with a set with well-defined margins. Ditching or trimming the die defines the position of the margin and acts as a guide to gingival contour when the restoration is being waxed. Two light scanners (a white light optical scanner [Steinbichler Gmbh, Neubeuern, Germany] and red laser light scanner [TurboDent System, Taichung, Taiwan]) were evaluated. Two sets of simulated crowns were fabricated as cone frustrum models with a total occlusal convergence (TOC) of 0°, 5°, 10°, 15°, 20°, and 25° and a 9-mm base and 3-mm height using a precision milling machine and computer-aided design/computer-aided manufacturing (CAD/CAM) technique. One set of the dies was ditched immediately below the finish line to enhance marginal definition. Each die was optically digitized five times directly with the two different measuring systems. The area of each triangle in the scan that is occlusal to the margin line was calculated and summed to produce the final surface area measurement provided. The digitizing error was compared with the computed surface area of the original master die sets and compared with a paired t-test (df=4; 95% CI). There was no difference in accuracy of the untrimmed dies between the two systems evaluated. We also did not find any difference in the 0° (p=0.12) and 5° degree (p=0.21) groups among the ditched dies. However, when the TOC exceeded 5°, there was a significant difference between the two groups, with the laser groups having a smaller error percentage. Three-dimensional light scanning was not affected by the convergence angle except in the 0°-5° range. Trimming the dies greatly affected the accuracy of scanning.
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Diseño Asistido por Computadora/normas , Diseño de Prótesis Dental/normas , Modelos Dentales/normas , Corona del Diente/anatomía & histología , Preparación Protodóncica del Diente/normas , Diseño Asistido por Computadora/instrumentación , Humanos , Imagenología Tridimensional/normas , Rayos Láser , Luz , Reconocimiento de Normas Patrones Automatizadas , Reproducibilidad de los Resultados , Programas Informáticos , Acero Inoxidable/química , Propiedades de Superficie , Preparación Protodóncica del Diente/clasificación , Interfaz Usuario-ComputadorRESUMEN
Tyrosine hydroxylase deficiency is a rare neurotransmitter disorder affecting the rate-limiting step in catecholamine biosynthesis. There are about 40 cases reported worldwide. Here, we report the biochemical and molecular findings of eight unrelated Chinese patients with tyrosine hydroxylase deficiency. We have identified eight novel mutations with 5 missense, 2 nonsense and 1 splicing mutations in the TH gene, namely p.R153X, p.R169X, p.G294R, p.G315S, p.A385V, p.I394T, p.G408R, and c.1163+5G>C. The mutations of the TH gene in Chinese are heterogeneous.
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Pueblo Asiatico/genética , Hipotonía Muscular/genética , Tirosina 3-Monooxigenasa/deficiencia , Edad de Inicio , Niño , Preescolar , Distonía/genética , Femenino , Galactorrea/genética , Ácido Homovanílico/metabolismo , Hong Kong , Humanos , Lactante , Masculino , Mutación , Tirosina 3-Monooxigenasa/genéticaRESUMEN
OBJECTIVE: To estimate the incidence and document the clinical characteristics of Williams-Beuren syndrome in the Hong Kong Chinese population. DESIGN: Cytogenetic analysis and retrospective study. SETTING: Clinical Genetic Service, Department of Health, Hong Kong. PATIENTS: Forty-one Chinese patients with Williams-Beuren syndrome. MAIN OUTCOME MEASURES: From 1 January 1995 to 30 June 2002, fluorescence in situ hybridisation was used to confirm diagnoses in 41 cases of Williams-Beuren syndrome by detecting chromosome 7q microdeletion. Case records were reviewed, the incidence of the condition in the local population was estimated, and the main clinical characteristics were determined. RESULTS: The minimal incidence of Williams-Beuren syndrome in this locality was estimated to be approximately 1 per 23500 live births. Common dysmorphic facial features included periorbital fullness (83%), full lips (80%), a long philtrum (51%), a flat nasal bridge (41%), and abnormal teeth (37%). No patients had a stellate iris. The majority (82%) had at least one documented cardiac anomaly; among these patients, peripheral pulmonary stenosis was diagnosed in 61% and supravalvular aortic stenosis in 45%. Nearly all (93%) of the study group exhibited developmental delay. CONCLUSION: As in the West, patients with Williams-Beuren syndrome in the Hong Kong Chinese population display craniofacial dysmorphism, cardiovascular anomalies, and mental deficiency. Supravalvular aortic stenosis-the cardiac defect most commonly associated with Williams-Beuren syndrome in western countries-is less common than peripheral pulmonary stenosis in this region. Studies involving periodic cardiovascular evaluation are needed to confirm if this difference is significant.
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Síndrome de Williams/epidemiología , Adolescente , Estenosis Aórtica Supravalvular/epidemiología , Estenosis Aórtica Supravalvular/genética , Niño , Preescolar , Aberraciones Cromosómicas , Anomalías Craneofaciales/epidemiología , Anomalías Craneofaciales/genética , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/genética , Familia , Femenino , Pruebas Genéticas , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/genética , Hong Kong/epidemiología , Humanos , Hipercalcemia/epidemiología , Hipercalcemia/genética , Incidencia , Lactante , Recién Nacido , Masculino , Estenosis de la Válvula Pulmonar/epidemiología , Estenosis de la Válvula Pulmonar/genética , Estudios Retrospectivos , Síndrome de Williams/genéticaRESUMEN
A novel coronavirus-associated communicable respiratory disease, severe acute respiratory syndrome (SARS), spread worldwide after an outbreak in Guangdong Province of the People's Republic of China in November 2002. Since late February 2003, there has been an epidemic in Hong Kong involving both adult and pediatric patients. The clinical course, intensive care, and outcome of adolescent twin sisters with SARS are described. Adolescents infected with SARS may develop severe illness as adults, and close monitoring for disease progression in terms of both clinical and radiologic deterioration is warranted.
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Enfermedades en Gemelos , Síndrome Respiratorio Agudo Grave/fisiopatología , Adolescente , Femenino , Humanos , Pulmón/diagnóstico por imagen , Radiografía , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/aislamiento & purificación , Síndrome Respiratorio Agudo Grave/diagnóstico por imagenRESUMEN
Radioimmunotherapy with anti-CD20 monoclonal antibodies is a promising new treatment approach for patients with relapsed B-cell lymphomas. However, the majority of patients treated with conventional radiolabeled anti-CD20 antibodies eventually have a relapse because the low tumor-to-blood and tumor-to-normal organ ratios of absorbed radioactivity limit the dose that can be safely administered without hematopoietic stem cell support. This study assessed the ability of a streptavidin-biotin "pretargeting" approach to improve the biodistribution of radioactivity in mice bearing Ramos lymphoma xenografts. A pretargeted streptavidin-conjugated anti-CD20 1F5 antibody was infused, followed 24 hours later by a biotinylated N-acetylgalactosamine-containing "clearing agent" and finally 3 hours later by (111)In-labeled DOTA-biotin. Tumor-to-blood ratios were 3:1 or more with pretargeting, compared with 0.5:1 or less with conventional (111)In-1F5. Tumor-to-normal organ ratios of absorbed radioactivity up to 56:1 were observed with pretargeting, but were 6:1 or less with conventional (111)In-1F5. Therapy experiments demonstrated that 400 microCi (14.8 MBq) or more of conventional (90)Y-1F5 was required to obtain major tumor responses, but this dose was associated with lethal toxicity in 100% of mice. In marked contrast, up to 800 microCi (29.6 MBq) (90)Y-DOTA-biotin could be safely administered by the pretargeting approach with only minor toxicity, and 89% of the mice were cured. These data suggest that anti-CD20 pretargeting shows great promise for improving current therapeutic options for B-cell lymphomas and warrants further preclinical and clinical testing.
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Antígenos CD20/inmunología , Radioisótopos de Yodo/uso terapéutico , Linfoma de Células B/radioterapia , Radioinmunoterapia/métodos , Animales , Anticuerpos Monoclonales/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Radioisótopos de Yodo/farmacocinética , Ratones , Ratones Desnudos , Tasa de Supervivencia , Distribución Tisular , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
Gastric infection with Helicobacter pylori results in chronic active gastritis and in some individuals is associated with complications such as peptic ulceration and gastric cancers. A balance between bacterial factors and host responses may determine disease outcome. The mouse-adapted H. pylori strain SS1 has been utilized as a model to study disease pathogenesis. Although chronic gastritis is observed in this murine model of H. pylori infection, other complications of disease seen in the human host (such as peptic ulceration) are not identified. The objectives of this study were to characterize virulence factors of the mouse-adapted H. pylori strain SS1 and determine host responses to infection. Vacuolating cytotoxin activity of H. pylori strain SS1 was determined after incubation of HEp-2 cells with culture supernatant for 24 hr. Polymerase chain reaction was performed to detect the presence of the cagA and cagE genes. Chemokine responses from human gastric epithelial cells infected with H. pylori SS1 were assessed by measurement of the concentration of interleukin-8 in cell-free supernatants. C57BL/6 and gld mice were infected with strain SS1 or sham-infected. Eight weeks following infection, gastric tissues were obtained for histological analysis and surface hydrophobicity was measured by axisymmetric drop-shape analysis. H. pylori strain SS1 was cytotoxin negative, cagA positive, and cagE positive, but induced only a modest interleukin-8 response (684 +/- 140 pg/ml) from AGS gastric epithelial cells in comparison to a clinical isolate (4170 +/- 410 pg/ml, P < 0.0005). Increased inflammation was observed in the stomachs of H. pylori strain SS1-infected animals compared to uninfected controls. Gastritis was not associated with any disease complications. Despite mucosal inflammation, infected mice did not demonstrate alterations in gastric surface hydrophobicity (42.2 degrees +/- 2.2 degrees and 41.4 degrees +/- 3.2 degrees for C57BL/6 and gld, respectively) compared to uninfected mice (43.2 degrees +/- 2.3 degrees and 39.5 degrees +/- 1.6 degrees, respectively). In conclusion, murine infection with H. pylori SS1, which contains putative bacterial virulence factors, results in gastric inflammation. However, the mucosal changes are not associated with alterations in surface hydrophobicity. Therefore, the mouse model of infection with H. pylori, strain SS1 may not serve as an entirely appropriate model to study host factors associated with disease complications.
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Antígenos Bacterianos , Modelos Animales de Enfermedad , Gastritis/microbiología , Infecciones por Helicobacter/inmunología , Helicobacter pylori , Animales , Proteínas Bacterianas/inmunología , Toxinas Bacterianas/inmunología , Citotoxicidad Inmunológica , Femenino , Mucosa Gástrica/inmunología , Gastritis/inmunología , Helicobacter pylori/clasificación , Helicobacter pylori/genética , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Humanos , Ratones , Ratones Endogámicos C57BL , Especificidad de la Especie , VirulenciaRESUMEN
A method for quantifying an intramolecularly linked all-d-amino acid peptide, NR58-3.14.3, in rat serum by LC-MS using selected ion monitoring with inclusion of a diastereomer as internal standard was developed. The reproducible quantitation of multiply charged compounds by LC-MS using single ion or selective reaction monitoring is often a challenge as the intensity ratio of the ions in a series of different charge states can vary. Good precision was obtained in the selected ion monitoring mode by integrating the summed ion currents of the singly, doubly, and triply charged molecular ions. Since stable isotope analogs are costly and integration of residual unlabeled material can be of concern, a diastereomer of NR58-3.14.3, NR58-3.14.5, was used as internal standard. The diastereomers were indistinguishable by electrospray MS, but fully separated by reversed-phase LC. Consequently, interference due to isotopic impurities or coelution was not encountered. The calibration plot was linear throughout a concentration range of 0.2 to 200.0 microg/ml (r(2) = 0.9996). Intraday precision of the standards analyzed was less than 12% RSD over the calibration range and the accuracy within +/-11% RE. Serum pharmacokinetics were in good agreement with the pharmacokinetic profiles of small, ionic, and polar molecules.
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Quimiocina CCL2/análogos & derivados , Péptidos Cíclicos/sangre , Animales , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Líquida de Alta Presión/normas , Femenino , Espectrometría de Masas/métodos , Espectrometría de Masas/normas , Péptidos Cíclicos/farmacocinética , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , EstereoisomerismoRESUMEN
Cataplexy, a symptom of narcolepsy, is a loss of muscle tone usually triggered by sudden, emotionally significant stimuli. We now report that locus coeruleus neurons cease discharge throughout cataplexy periods in canine narcoleptics. Locus coeruleus discharge rates during cataplexy were as low as or lower than those seen during rapid-eye-movement sleep. Prazosin, an alpha1 antagonist, and physostigmine, a cholinesterase inhibitor, both of which precipitate cataplexy, decreased locus coeruleus discharge rate. Our results are consistent with the hypothesis that locus coeruleus activity contributes to the maintenance of muscle tone in waking, and that reduction in locus coeruleus discharge plays a role in the loss of muscle tone in cataplexy and rapid-eye-movement sleep. Our results also show that the complete cessation of locus coeruleus activity is not sufficient to trigger rapid-eye-movement sleep in narcoleptics.
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Cataplejía/fisiopatología , Locus Coeruleus/fisiopatología , Neuronas/fisiología , Antagonistas Adrenérgicos alfa/farmacología , Animales , Inhibidores de la Colinesterasa/farmacología , Perros , Electrofisiología , Locus Coeruleus/efectos de los fármacos , Locus Coeruleus/patología , Locus Coeruleus/fisiología , Neuronas/efectos de los fármacos , Fisostigmina/farmacología , Prazosina/farmacología , Sueño REM/fisiologíaRESUMEN
OBJECTIVE: To investigate the relationship between oxygen transport patterns and outcome in patients with sepsis syndrome or septic shock managed according to two different treatment regimens. DESIGN: Retrospective study of a subgroup of patients with sepsis syndrome or septic shock taken from a randomized, prospective, controlled trial. SETTING: General intensive care units in a teaching and a district general hospital. PATIENTS: Seventy-eight patients classified according to predetermined criteria as having sepsis syndrome or septic shock were drawn retrospectively from a larger study group of 109 consecutive patients considered to be at risk for developing multiple organ failure. INTERVENTIONS: All patients received volume expansion to an optimal pulmonary artery occlusion pressure. If the therapeutic goals (cardiac index of > 4.5 L/min/m2, oxygen delivery [DO2] of > 600 mL/min/m2, and oxygen consumption [VO2] of > 170 mL/min/m2) were not achieved with fluids alone, patients were randomized to either a control group or a treatment group. In the treatment group, dobutamine (5 to 200 micrograms/kg/min) was administered to increase cardiac index and DO2 until all three goals were simultaneously achieved. In the control group, dobutamine was administered only if the cardiac index was < 2.8 L/min/m2. In both groups, norepinephrine was infused to maintain mean arterial pressure at 80 mm Hg. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, oxygen transport, and lactate measurements were made at the time of admission to the study, at the time of optimal volume administration, at 1, 2, 4, 8, 12, 16, 20, and 24 hrs, then every 6 hrs for the next 24 hrs, and at least every 8 hrs thereafter. The time at which all therapeutic goals were first achieved simultaneously or the time of maximal DO2 was identified and termed "tmax." Survivors from both the control and treatment groups significantly (p < .001) increased cardiac index and DO2 in response to maximal resuscitation, and despite an associated decrease in oxygen extraction (p < .01), there was a significant (p < .01) increase in VO2. In nonsurvivors from both groups, despite significant increases in cardiac index (p < .05) and DO2 (p < .01) at tmax, oxygen extraction decreased (p < .01) and VO2 remained unchanged. DO2 and VO2 were significantly lower (p < .05) at tmax in nonsurvivors than in survivors from both groups. Persistently high lactate concentrations were characteristic of nonsurvivors. CONCLUSIONS: Survivors of sepsis syndrome or septic shock are characterized by an ability to increase both DO2 and VO2. In contrast, nonsurvivors typically have reduced cardiac reserve, they fail to increase VO2 following resuscitation, and when delivery is enhanced with aggressive inotropic support, oxygen extraction falls. These patterns of response were similar in both treatment and control groups, although the magnitude of the changes was exaggerated in the treatment group. These observations may help to explain the findings by some investigators that treatment aimed at achieving survivor values of cardiac index, DO2, and VO2 fails to improve outcome when instituted following admission to intensive care.
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Oxígeno/metabolismo , Choque Séptico/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/metabolismo , Agonistas alfa-Adrenérgicos/administración & dosificación , Transporte Biológico , Cardiotónicos/administración & dosificación , Dobutamina/administración & dosificación , Hemodinámica , Humanos , Norepinefrina/administración & dosificación , Estudios Retrospectivos , Choque Séptico/fisiopatología , Choque Séptico/terapia , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: Elevation of systemic oxygen delivery and consumption has been associated with an improved outcome in critically ill patients. We conducted a randomized trial to determine whether boosting oxygen delivery by infusing the inotropic agent dobutamine would improve the outcome in a diverse group of such patients. METHODS: On the basis of previously published recommendations, we established the following goals: a cardiac index above 4.5 liters per minute per square meter of body-surface area, oxygen delivery above 600 ml per minute per square meter, and oxygen consumption above 170 ml per minute per square meter. If these goals were not achieved with volume expansion alone, patients were randomly assigned to a treatment or control group. The treatment group received intravenous dobutamine (5 to 200 micrograms per kilogram of body weight per minute) until all three goals had been achieved. Dobutamine was administered to the control group only if the cardiac index was below 2.8 liters per minute per square meter. RESULTS: A total of 109 patients were studied. In nine patients the therapeutic goals were achieved with volume expansion alone; all nine patients survived to leave the hospital. Fifty patients were randomly assigned to the treatment group, and 50 to the control group. During treatment, there were no differences between the two groups in mean arterial pressure or oxygen consumption, despite a significantly higher cardiac index and level of oxygen delivery in the treatment group (P < 0.05). Although the predicted risk of death during hospitalization was 34 percent for both groups, the in-hospital mortality was lower in the control group (34 percent) than in the treatment group (54 percent) (P = 0.04; 95 percent confidence interval, 0.9 to 39.1 percent). CONCLUSIONS: The use of dobutamine to boost the cardiac index and systemic oxygen delivery failed to improve the outcome in this heterogeneous group of critically ill patients. Contrary to what might have been expected, our results suggest that in some cases aggressive efforts to increase oxygen consumption may have been detrimental.
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Enfermedad Crítica/terapia , Consumo de Oxígeno , Terapia por Inhalación de Oxígeno , Adulto , Anciano , Anciano de 80 o más Años , Gasto Cardíaco , Intervalos de Confianza , Enfermedad Crítica/mortalidad , Dobutamina/efectos adversos , Dobutamina/uso terapéutico , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Norepinefrina/uso terapéutico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
STUDY OBJECTIVE: To evaluate the response to therapy aimed at achieving supranormal cardiac and oxygen transport variables (cardiac index [CI] > 4.5 L/min/m2, oxygen delivery [DO2] > 600 ml/min/m2, and oxygen consumption [VO2] > 170 ml/min/m2) in a heterogenous group of critically ill patients and to assess its relationship to outcome. DESIGN: Patients were divided retrospectively into two groups. Group 1 (n = 15) achieved supranormal values for CI, DO2 and VO2 simultaneously during the first 24 h. Group 2 (n = 17) failed to achieve these goals simultaneously at any time point. SETTING: General intensive care units in a teaching and a district general hospital. PATIENTS: Thirty-two patients at risk of developing multiple organ failure were studied prospectively. INTERVENTIONS: Patients received volume expansion and then, if necessary, dobutamine (5 to 200 micrograms/kg/min) to increase CI and DO2 until all three goals were achieved simultaneously. RESULTS: In group 2, target VO2 could never be reached despite the fact that 11 (65 percent) patients achieved target CI and DO2 simultaneously. In this group, lactate levels did not fall and 16 patients died. In contrast, in group 1, attainment of all goals was associated with a significant reduction (p < 0.05) in blood lactate levels, and all but one of these patients survived. The persistently raised lactate levels in group 2 were associated with significantly higher venous oxygen saturation (SvO2) and lower oxygen extraction ratio (OER); in these patients, SvO2 rose and OER fell in response to increases in DO2. CONCLUSION: These results suggest that failure to increase VO2 was related predominantly to an inability of the tissues to extract or utilize oxygen rather than a failure to increase DO2. These findings support the hypothesis that in order to survive a critical illness, patients must achieve a high level of VO2. An inability to do so is reflected in persistently elevated blood lactate levels and an extremely poor prognosis.
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Cuidados Críticos/métodos , Consumo de Oxígeno , Oxígeno/sangre , Adulto , Anciano , Distribución de Chi-Cuadrado , Terapia Combinada , Cuidados Críticos/estadística & datos numéricos , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/epidemiología , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/terapia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Choque Séptico/sangre , Choque Séptico/epidemiología , Choque Séptico/fisiopatología , Choque Séptico/terapia , Resultado del TratamientoAsunto(s)
Cateterismo Venoso Central/veterinaria , Dilatación Gástrica/veterinaria , Cobayas , Vólvulo Gástrico/veterinaria , Animales , Cateterismo Venoso Central/efectos adversos , Femenino , Dilatación Gástrica/etiología , Embarazo , Enfermedades de los Roedores/etiología , Vólvulo Gástrico/etiologíaRESUMEN
CGS 13080, imidazo[1,5-a]pyridine-5-hexanoic acid, was evaluated for perinatal and postnatal effects in third trimester pregnant guinea pigs and their offspring. The compound was administered via 48 hour continuous intravenous infusion to a group of pregnant guinea pigs (n = 16) at a dose of 3 mg/kg/hr starting on gestational day 52 (via chronically implanted indwelling jugular venous cannulas). A saline control group (n = 12) received equivalent volumes of normal saline 0.5 ml/kg/hr throughout the dosing period. A third group (surgery-sham, n = 16) was subjected to cannulation but not infused. A gross examination of each dam and piglets was conducted at necropsy on day 5 of lactation. The neonatal brains and all gross lesions (maternal and neonatal) were removed and fixed for histopathological examination. Compound-related clinical signs were noted in dams during the dosing phase of gestation. Six guinea pigs developed cephalic lymphatic swelling during the infusion. This observation may be correlated to the reported redistribution of fluid volume to the thorax of guinea pigs given intravenous injections of CGS 13080. There were no compound-induced effects on labor, delivery, or any of the examined reproductive parameters. There were no compound-related clinical signs, or effects on survival, body weight and developmental parameters in the F1 generation. Histopathological examination of the brains and other organs did not reveal any compound-related abnormalities. Based on these results, it was concluded that CGS 13080 did not elicit adverse perinatal and postnatal effects in guinea pigs.
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Imidazoles/administración & dosificación , Trabajo de Parto/efectos de los fármacos , Lactancia/efectos de los fármacos , Preñez/efectos de los fármacos , Piridinas/administración & dosificación , Tromboxano-A Sintasa/antagonistas & inhibidores , Animales , Peso al Nacer/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/embriología , Esquema de Medicación , Ingestión de Alimentos/efectos de los fármacos , Femenino , Cobayas , Infusiones Intravenosas , Riñón/efectos de los fármacos , Riñón/embriología , Hígado/efectos de los fármacos , Hígado/embriología , Pulmón/efectos de los fármacos , Pulmón/embriología , EmbarazoRESUMEN
The relationship between survival and cardiac responsiveness to therapy aimed at achieving supranormal values for cardiac index, oxygen delivery and oxygen consumption (cardiac index (CI) > 4.5 l/min/m2, oxygen delivery (DO2) > 600 ml/min/m2, and oxygen consumption (VO2) > 170 ml/min/m2), has been investigated in a heterogeneous group of critically ill patients. Thirty-two patients were prospectively studied and divided into survivors and non-survivors. Cardiac reserve was assessed by determining changes in CI, left ventricular stroke work index (LVSWI) and cardiac power output (CPO) in response to optimal fluid administration and inotropic stimulation with dobutamine. On admission LVSWI and CPO were significantly higher in survivors (P < 0.05), despite no significant differences in pulmonary artery occlusion pressure (PAOP). In response to fluid CI, CPO and LVSWI increased significantly in survivors (P < 0.01), but not in non-survivors. Following optimal fluid administration, survivors achieved significantly higher values for CI, LVSWI (P < 0.01), and CPO (P < 0.001) than non-survivors. At maximum resuscitation all three variables were significantly higher in survivors than in non-survivors (P < 0.001). The dose of dobutamine administered to non-survivors (median (range) 100 (5-200)) was significantly greater (P < 0.001) than that given to the survivors (median (range) 10 (0-25)). The dose of dobutamine was limited by complications in 12 of the non-survivors. These observations suggest that cardiac reserve is an important determinant of outcome following critical illness. In unresponsive patients attempts to achieve supranormal oxygen delivery and consumption with massive inotropic support may not only be ineffective but frequently precipitates tachydysrhythmias and myocardial ischaemia.
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Cuidados Críticos/métodos , Corazón/fisiopatología , Consumo de Oxígeno/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Gasto Cardíaco/fisiología , Dobutamina/uso terapéutico , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Oxígeno/sangre , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
The syndrome of symmetrical peripheral gangrene is characterised by distal ischaemic damage in two or more extremities, without large vessel obstruction. Four patients with bilateral pedal ischaemia are described and their haemodynamic profiles presented. In all four cases the syndrome developed in association with noradrenaline administration, sepsis and DIC, despite a high cardiac output and a low calculated systemic vascular resistance index. Early treatment with epoprostenol was instituted in the final case and was successful.
Asunto(s)
Enfermedades del Pie/inducido químicamente , Gangrena/inducido químicamente , Norepinefrina/efectos adversos , Adulto , Anciano , Gasto Cardíaco , Coagulación Intravascular Diseminada/complicaciones , Epoprostenol/uso terapéutico , Femenino , Enfermedades del Pie/tratamiento farmacológico , Enfermedades del Pie/fisiopatología , Gangrena/tratamiento farmacológico , Gangrena/fisiopatología , Humanos , Infecciones/complicaciones , Masculino , Norepinefrina/administración & dosificación , Choque/complicaciones , Choque/tratamiento farmacológico , Resistencia VascularRESUMEN
Ninety-two consecutive adult patients admitted with acute life-threatening complications of haematological malignancy were studied to determine long term outcome. The quality of life was evaluated in seven long term survivors who are currently alive more than 1 year after hospital discharge using three validated methods: the Nottingham Health Profile, the Hospital Anxiety and Depression Scale and the Perceived Quality of Life Scale. Patients were also asked whether they had returned to work, whether their daily activities were limited and whether they would be willing to undergo intensive care again under the same circumstances. The in-hospital mortality rate was 77%. Median duration of long term survival was 23 months (range 6 weeks to 8 years). Long term survival did not appear to be related to either the aetiology or the severity of the acute illness, but seemed to be determined solely by the nature and progress of the underlying malignancy. The quality of life of six of the seven long term survivors is good, while that of the other is acceptable. None of the patients reported any increased limitation of their daily activities, five had returned to full time employment and all seven stated that they would be willing to undergo intensive care again under the same circumstances.
Asunto(s)
Cuidados Críticos , Leucemia/psicología , Linfoma/psicología , Calidad de Vida , Adulto , Anciano , Ansiedad/etiología , Cuidados Críticos/psicología , Depresión/etiología , Femenino , Estudios de Seguimiento , Humanos , Leucemia/complicaciones , Leucemia/mortalidad , Linfoma/complicaciones , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Dithioate DNA was synthesized and used for various biochemical studies. Results from these studies indicate that dithioate DNA is a potent inhibitor of HIV Reverse Transcriptase, activates endogenous RNase H in HeLa cell nuclear extracts, and is a useful probe for studying protein-DNA interactions.