RESUMEN
Helicases are promising antiviral drug targets because their enzymatic activities are essential for viral genome replication, transcription, and translation. Numerous potent inhibitors of helicases encoded by herpes simplex virus, severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, West Nile virus, and human papillomavirus have been recently reported in the scientific literature. Some inhibitors have also been shown to decrease viral replication in cell culture and animal models. This review discusses recent progress in understanding the structure and function of viral helicases to help clarify how these potential antiviral compounds function and to facilitate the design of better inhibitors. The above helicases and all related viral proteins are classified here based on their evolutionary and functional similarities, and the key mechanistic features of each group are noted. All helicases share a common motor function fueled by ATP hydrolysis, but differ in exactly how the motor moves the protein and its cargo on a nucleic acid chain. The helicase inhibitors discussed here influence rates of helicase-catalyzed DNA (or RNA) unwinding by preventing ATP hydrolysis, nucleic acid binding, nucleic acid release, or by disrupting the interaction of a helicase with a required cofactor.
Asunto(s)
Antivirales/farmacología , ADN Helicasas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , ARN Helicasas/antagonistas & inhibidores , ADN Helicasas/química , ADN Helicasas/fisiología , ADN Primasa/antagonistas & inhibidores , Papillomaviridae/efectos de los fármacos , Papillomaviridae/enzimología , ARN Helicasas/química , ARN Helicasas/fisiología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/enzimología , Serina Endopeptidasas , Simplexvirus/efectos de los fármacos , Simplexvirus/enzimología , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas Virales/antagonistas & inhibidoresRESUMEN
It is shown that calcium increases the in vitro transfection potency of plasmid DNA-cationic liposome complexes from 3- to 20-fold. The effect is Ca(2+) specific as other cations, such as Mg(2+) and Na(+), do not give rise to enhanced transfection and the effect can be inhibited by the presence of EGTA. It is shown that Ca(2+) increases cellular uptake of the DNA-lipid complexes, indicating that increased transfection potency arises from increased intracellular delivery of both cationic lipid and plasmid DNA in the presence of Ca(2+). In particular, it is shown that the levels of intact intracellular plasmid DNA are significantly enhanced when Ca(2+) is present. The generality of the Ca(2+) effect for enhancing complex-mediated transfection is demonstrated for a number of different cell lines and different cationic lipid formulations. It is concluded that addition of Ca(2+) represents a simple and useful protocol for enhancing in vitro transfection properties of plasmid DNA-cationic lipid complexes.
Asunto(s)
Calcio , Liposomas , Plásmidos , Transfección/métodos , Animales , Radioisótopos de Carbono , Línea Celular , Chlorocebus aethiops , Cricetinae , Citomegalovirus/genética , Portadores de Fármacos , Ácido Egtácico/farmacología , Proteínas Fluorescentes Verdes , Humanos , Proteínas Luminiscentes/análisis , Proteínas Luminiscentes/genética , Fosfatidiletanolaminas/farmacocinética , Plásmidos/administración & dosificación , Plásmidos/efectos de los fármacos , Regiones Promotoras Genéticas , Compuestos de Amonio Cuaternario/farmacocinética , Células Tumorales CultivadasRESUMEN
Previous work has shown that plasmid DNA can be encapsulated in small 'stabilized plasmid-lipid particles' (SPLP) composed of 1, 2-dioleyl-3-phosphatidylethanolamine (DOPE), the cationic lipid N, N-dioleyl-N,N-dimethylammonium chloride (DODAC) and poly(ethylene glycol) (PEG) conjugated ceramides (PEG-Cer), employing a detergent dialysis procedure. These SPLP have potential as vectors for in vivo gene therapy. This study is aimed at characterizing the influence of the cationic lipid and PEG-Cer species on SPLP formation and in vitro transfection properties. It is shown that the transfection potency of SPLP is sensitive to the cationic lipid species employed, the size of the PEG polymer incorporated in the PEG-ceramide and the length of the acyl chain contained in the ceramide anchor. With regard to the influence of cationic lipid, the transfection levels achieved were highest for SPLP containing N-[2, 3-(dioleyloxy)propyl]-N,N-dimethyl-N-cyanomethylammonium chloride (DODMA-AN) and lowest for SPLP containing 3-beta-[N-(N', N'-dimethylaminoethyl)carbamoyl]-cholesterol (DC-CHOL), according to the series DODMA-AN>N-[2,3-(dioleyloxy)propyl]-N,N, N-trimethylammonium chloride (DOTMA)>DODAC>N,N-distearyl-N, N-dimethylammonium chloride (DSDAC)>DC-CHOL. Incorporation of short (PEG(750)) PEG polymers in the PEG-ceramide components resulted in modest improvements in transfection levels over PEG(2000) and PEG(5000) polymers, however variation of the length of the acyl chain contained in the hydrophobic ceramide anchor from octanoyl (PEG-CerC(8)) to myristoyl (PEG-CerC(14)) to arachidoyl (PEG-CerC(20)) had the most dramatic effects. Transfection levels achieved for SPLP containing PEG-CerC(8) were substantially larger than observed for SPLP containing PEG-CerC(14) or PEG-CerC(20), consistent with a requirement for the PEG-ceramide to dissociate from the SPLP surface for maximum transfection potency. It is also shown that the ability of SPLP to be accumulated into cells is a dominant factor influencing transfection potency, and that the transfection potency of SPLP that are accumulated is at least equivalent to that of cationic lipid-plasmid DNA complexes.
Asunto(s)
Lípidos/química , Plásmidos/química , Transfección/métodos , Línea Celular , Detergentes , Liposomas , Tamaño de la Partícula , Plásmidos/metabolismo , Polietilenglicoles , PolímerosRESUMEN
In eight subjects anesthetized with moderate to high doses of inhalation anesthetics (isoflurane or desflurane) during normocapnia, the onset of electrical silence in EEG was associated with a sudden reduction of blood flow velocity monitored from the middle cerebral artery. The magnitude of this reduction was 38 +/- 11% (mean +/- SD; range 24-44%). The change in EEG always preceded the change in flow velocity by 5-7 s. These observations suggest that some flow-metabolism coupling mechanism is preserved during inhalation anesthesia in humans.
Asunto(s)
Anestesia por Inhalación , Circulación Cerebrovascular , Electroencefalografía , Adolescente , Adulto , Anestésicos por Inhalación , Velocidad del Flujo Sanguíneo , Desflurano , Humanos , Isoflurano/análogos & derivadosRESUMEN
We previously reported that the N-methyl-D-aspartate receptor antagonists dizocilpine maleate and ketamine improved the neurological severity score (NSS) after head trauma in rats. Other investigators have reported increased calcium and decreased magnesium following head trauma in untreated rats. The present study was designed to determine whether ketamine influences the concentrations of calcium and magnesium in brain tissue following head trauma. Eighty-six male Sprague-Dawley rats (180 +/- 15 g) were divided into eight groups. Groups A (no head injury) and C (head injury) received no treatment. Groups B (no head injury) and D-H (head injury) received ketamine. In groups D, E, and F, ketamine, 180 mg/kg i.p., was given 1, 2, and 4 h after head trauma, respectively. In groups G and H, ketamine, 120 and 60 mg/kg, respectively, was given 1 h after head trauma. After we killed the rats at 48 h, cortical slices were taken to measure tissue calcium and magnesium content by the inductively coupled plasma atomic emission spectroscopy method. In the contused hemispheres, calcium increased and magnesium decreased (p < 0.0001). Among the head-injured groups, the increase in brain tissue calcium was smaller in groups receiving 60 mg/kg of ketamine at 1 h or 180 mg/kg of ketamine at 1, 2, or 4 h than in the group not receiving ketamine. The decrease in brain tissue magnesium was smaller in the groups receiving 180 mg/kg of ketamine at 1 and 2 h than in the group not receiving ketamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Lesiones Encefálicas/metabolismo , Encéfalo/metabolismo , Calcio/metabolismo , Ketamina/farmacología , Magnesio/metabolismo , Animales , Encéfalo/efectos de los fármacos , Corteza Cerebral/metabolismo , Ketamina/administración & dosificación , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The brain is rich in creatine kinase-BB isoenzyme activity (CK-BB), which is not normally present in cerebrospinal fluid (CSF). Results of previous studies have shown that CK-BB can be detected in the CSF of patients with aneurysmal subarachnoid hemorrhage (SAH), but whether CK-BB levels correlate with patients' neurologic outcomes is unknown. OBJECTIVE: To evaluate the relationship between CSF CK-BB level and outcome after SAH. DESIGN: Prospective observational cohort. SETTING: University-affiliated tertiary care center. PATIENTS: Convenience sample of 30 patients seen for cerebral aneurysm clipping. INTERVENTIONS: We sampled and assayed CSF for CK isoenzymes a median of 3 days after SAH in 27 patients, and at the time of unruptured aneurysm clipping in 3 patients. MAIN OUTCOME MEASURES: Without knowledge of CK results, we assigned the Glasgow Outcome Scale score early (approximately 1 week) and late (approximately 2 months) after surgery. RESULTS: Higher CSF CK-BB levels were associated with higher Hunt and Hess grades at hospital admission (Spearman rank correlation, p = 0.69; P<.001), lower Glasgow Coma Scale scores at hospital admission (p = -0.72; P<.001), and worse early outcomes on the Glasgow Outcome Scale (p = -0.64; P<.001). For patients with a favorable early outcome (Glasgow Outcome Scale score, 3-5), all CK-BB levels were less than 40 U/L. With a cutoff value of 40 U/L, CK-BB had a sensitivity of 70% and a specificity of 100% for predicting unfavorable early outcome (Glasgow Outcome Scale score, 1-2). Having a CK-BB level greater than 40 U/L increased the chance of an unfavorable early outcome, from 33% (previous probability) to 100%, whereas a CK-BB level of 40 U/L or less decreased it to 13%. Similar findings were obtained when considering late outcomes. CONCLUSION: The level of CSF CK-BB may help predict neurologic outcome after SAH.
Asunto(s)
Creatina Quinasa/líquido cefalorraquídeo , Hemorragia Subaracnoidea/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Escala de Coma de Glasgow , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/cirugía , Isoenzimas , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Hemorragia Subaracnoidea/etiología , Factores de Tiempo , Resultado del Tratamiento , Ventriculostomía/métodosRESUMEN
OBJECTIVE: An assessment of the thrombotic, infectious, and technical complications of continuous jugular bulb catheter monitoring in the intensive care unit (ICU) was made. METHODS: Over a 1-year period, 44 patients suffering from traumatic brain injury, subarachnoid hemorrhage, or stroke received jugular bulb catheter monitoring in the ICU. They were followed for catheter insertion complications and the development of bacteremia. In 20 patients chosen randomly, an ultrasonographic evaluation was performed after removal of the catheter for an assessment of internal jugular vein thrombosis. RESULTS: Of the 44 patients, 1 became bacteremic; the source was identified as a thoracostomy site. Among the complications related to the 44 catheter insertions, there were 2 instances of carotid artery puncture (4.5%), 1 misplaced catheter (thoracic placement), and 1 clinically insignificant hematoma. Of the 20 patients investigated with ultrasonography, 8 (40%) had nonobstructive, subclinical internal jugular vein thrombi after jugular bulb catheter monitoring (95% confidence interval, 19-61%). The median monitoring duration was 3 days (range, 1-6 d). No clinical factor was identified to be associated with thrombus formation. CONCLUSION: We conclude the following: 1) the risk of bacteremia related to the jugular bulb catheter was negligible; 2) complications related to catheter insertion were rare and clinically insignificant; and 3) the incidence of subclinical internal jugular vein thrombosis after jugular bulb catheter monitoring is considerable. Although it is worthy to note this complication, no patient with a thrombus became symptomatic in the present series. The risk-benefit assessment of this monitoring technique must include consideration of subclinical thrombosis.
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Bacteriemia/etiología , Lesiones Encefálicas/terapia , Catéteres de Permanencia , Trastornos Cerebrovasculares/terapia , Venas Yugulares , Monitoreo Fisiológico/instrumentación , Hemorragia Subaracnoidea/terapia , Trombosis/etiología , Adolescente , Adulto , Anciano , Falla de Equipo , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Riesgo , Ultrasonografía Doppler en ColorRESUMEN
OBJECTIVE: To address the accuracy of a bedside jugular bulb oxygen saturation (SjO2) catheter monitor (Baxter-Edwards, Santa Ana, CA) versus in vitro co-oximetry measurements in the intensive care unit (ICU). METHODS: By prospective protocol, we compared blood gas measurements with simultaneously recorded continuous bedside oximetric monitor values for 31 ICU patients with traumatic brain injury undergoing jugular bulb catheter monitoring. For suboptimal fiberoptic light signal quality indices, the catheter was repositioned, flushed, or both before drawing the sample for in vitro measurement. Laboratory and bedside monitor data were examined for association using the chi2 and paired t tests and a linear regression model. RESULTS: We assessed 195 samples (median, 5 per patient; range, 1-14) who were monitored an average of 3.4 (range, 1-6) days. The in vivo monitor (range, 32-94%) and in vitro co-oximetry (range, 38-93%) values had acceptable correlation (y = 0.94x + 4.4, r2 = 0.80). For bedside monitor detection of jugular bulb desaturation (SjO2 < 50% for 10 min), the kappa statistic was 0.35, the sensitivity was 45 to 50%, and the specificity was 98 to 100%. CONCLUSION: Continuous ICU SjO2 monitoring correlates significantly with in vitro values, but less so than previously described during intracranial surgery. Although sensitivity of the bedside monitor to detect confirmed desaturations remains an issue, the high specificity indicates that it is less of a concern that patients may be misdiagnosed as having desaturations resulting in unnecessary interventions. Nonetheless, suspected jugular bulb desaturation should be verified before taking therapeutic actions.
Asunto(s)
Lesiones Encefálicas/sangre , Unidades de Cuidados Intensivos , Venas Yugulares/metabolismo , Monitoreo Fisiológico/métodos , Oximetría/normas , Oxígeno/sangre , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Sensibilidad y EspecificidadRESUMEN
Somatosensory evoked potentials (SEP) were recorded during and immediately following temporary middle cerebral artery (MCA) occlusion to determine whether they can be used to predict ischemic lesions to the somatosensory cortex (SI). Twenty-one cynomolgus female monkeys were subjected to four different MCA occlusion durations (15-60 min) during hypotension (45-50 mm Hg mean arterial blood pressure). The amplitude and central conduction time (CCT) of the median nerve SEP were recorded preceding, during, and following occlusion. Two groups were established based on the development of SI ischemic lesions: animals developing SI lesions formed the SI-lesion group (n = 9), and animals without ischemic lesions or with lesions outside the SI cortex formed the SI-spared group (n = 12). Changes in the SEP during and following MCA occlusion under conditions of hypotension were similar to those reported by others. The SEP disappeared in all animals within 15 min of occlusion and reappeared 5 min following reperfusion. Several differences were observed between the SI-lesion and SI-spared groups. The SI-lesion group had a more rapid decrease in SEP amplitude during the first 5 min of occlusion and had smaller SEP amplitudes and longer CCTs during reperfusion. These results suggest that changes in SEP amplitude and latency during and immediately following temporary MCA occlusion predict development of SI ischemic lesions.
Asunto(s)
Isquemia Encefálica/fisiopatología , Infarto Cerebral/fisiopatología , Potenciales Evocados Somatosensoriales , Animales , Electroencefalografía , Femenino , Hipotensión/fisiopatología , Macaca fascicularis , Factores de TiempoRESUMEN
To examine the relationship between serum glucose and the outcome of patients suffering from head injury, the authors retrospectively reviewed the clinical course of 169 patients admitted for treatment to Harborview Medical Center (a regional trauma center). All patients underwent craniotomy for evacuation of intracranial hematoma and/or placement of a subarachnoid bolt for intracranial pressure monitoring under general anesthesia. Patients with a Glasgow Coma Scale (GCS) score of 8 or less had significantly higher serum glucose levels than patients with GCS scores of 12 to 15 (mean +/- standard error of the mean 192 +/- 7 mg/dl vs. 130 +/- 8 mg/dl or 10.7 +/- 0.4 mmol/liter vs. 7.2 +/- 0.4 mmol/liter) (p less than 0.0001). Patients who subsequently remained in a vegetative state or died had significantly higher glucose levels both on admission and postoperatively than patients who had good outcome or moderate disability (217 +/- 12 mg/dl vs. 167 +/- 6 mg/dl or 12.1 +/- 0.7 mmol/liter vs. 9.3 +/- 0.3 mmol/liter on admission, and 240 +/- 16 mg/dl vs. 156 +/- 5 mg/dl or 13.3 +/- 0.9 mmol/liter vs. 8.9 +/- 0.3 mmol/liter postoperatively) (p less than 0.0001). Among the more severely injured patients (GCS score less than or equal to 8), a serum glucose level greater than 200 mg/dl (11.1 mmol/liter) postoperatively is associated with a significantly worse outcome (p less than 0.01). The authors conclude that severely head-injured patients frequently develop hyperglycemia and the elevated serum glucose level may aggravate ischemic insults and worsen the neurological outcome in such patients.
Asunto(s)
Lesiones Encefálicas/complicaciones , Escala de Coma de Glasgow , Hiperglucemia/etiología , Adulto , Glucemia/metabolismo , Encefalopatías/etiología , Lesiones Encefálicas/cirugía , Isquemia Encefálica/complicaciones , Coma , Femenino , Humanos , Hiperglucemia/complicaciones , Masculino , Estudios RetrospectivosRESUMEN
Jugular bulb oxygen monitoring can be used to estimate the adequacy of cerebral blood flow to support cerebral metabolism after severe head injury. In the present study, the authors studied the cerebral arteriovenous oxygen difference (AVDO[2]) before and after treatment in 32 head-injured patients (Glasgow Coma Scale scores < or = 8) to examine the relationships among AVDO and cerebral perfusion pressure (CPP), delayed cerebral infarction, and outcome. Fifteen patients (Group A) underwent craniotomy for hematoma evacuation and 17 (Group B) received mannitol for sustained intracranial hypertension (intracranial pressure > 20 mm Hg, > 10 minutes). Radiographic evidence of delayed cerebral infarction was observed in 14 patients. Overall, 17 patients died or were severely disabled. Cerebral AVDO(2) was elevated before craniotomy or mannitol administration; the mean AVDO(2) for all patients before treatment was 8.6 +/- 1.8 vol%. Following craniotomy or mannitol administration, the AVDO(2) decreased in 27 patients and increased in five patients (mean AVDO(2) 6.2 +/- 2.1 vol% in all patients; 6 +/- 1.9 vol% in Group A; and 6.4 +/- 2.4 vol% in Group B). The mean CPP was 75 +/- 9.8 mm Hg and no relationship with AVDO(2) was demonstrated. Before treatment, the AVDO(2) was not associated with delayed cerebral infarction or outcome. By contrast, a limited improvement in elevated AVDO(2) after craniotomy or mannitol administration was significantly associated with delayed cerebral infarction (Group A: p < 0.001; Group B: p < 0.01). Similarly, a limited improvement in elevated AVDO(2) after treatment was significantly associated with an unfavorable outcome (Group A: p < 0.01; Group B: p < 0.001). In conclusion, these findings strongly indicate that, despite adequate cerebral perfusion, limited improvement in elevated cerebral AVDO(2) after treatment consisting of either craniotomy or mannitol administration may be used to help predict delayed cerebral infarction and poor outcome after traumatic brain injury.
Asunto(s)
Arterias Cerebrales , Infarto Cerebral/etiología , Venas Cerebrales , Traumatismos Craneocerebrales/complicaciones , Traumatismos Craneocerebrales/terapia , Craneotomía , Manitol/uso terapéutico , Oxígeno/sangre , Adulto , Anciano , Infarto Cerebral/diagnóstico por imagen , Traumatismos Craneocerebrales/fisiopatología , Femenino , Predicción , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Anesthetic agents are often administered in the presence of ethyl alcohol, both in research and in the clinical setting. The authors tested the hypothesis that anesthetic agents may affect cerebrovascular responses to ethanol. A closed cranial window preparation in the rat was used to compare the response of pial arterioles to topically applied ethanol (0.01% to 1% vol/vol) in the presence of alpha-chloralose/urethane (50 and 600 mg/kg, respectively) or halothane (0.5% to 1%) anesthesia. Heart rate, mean arterial blood pressure, and blood gas levels were maintained stable and within the physiological range throughout each experiment. Ethanol induced significant vasoconstriction in alpha-chloralose/urethane-anesthetized animals (multivariate analysis of variance (MANOVA), p = 0.039); conversely, ethanol induced significant vasodilation of the pial arterioles in halothane-anesthetized animals (MANOVA, p = 0.017). These responses were significantly different from one another (MANOVA, p = 0.001). Thus, the choice of anesthetic agent alters the cerebrovascular response to ethanol, and care should be taken to ascertain the influence of anesthesia in both research and clinical settings.
Asunto(s)
Anestésicos/farmacología , Etanol/farmacología , Piamadre/irrigación sanguínea , Anestésicos por Inhalación/farmacología , Anestésicos Intravenosos/farmacología , Animales , Arteriolas/efectos de los fármacos , Arteriolas/fisiología , Cloralosa/farmacología , Interacciones Farmacológicas , Halotano/farmacología , Masculino , Análisis Multivariante , Ratas , Ratas Sprague-Dawley , Uretano/farmacología , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
The purpose of this study was to determine whether patients with minor head injury experience impairments in cerebral autoregulation. Twenty-nine patients with minor head injuries defined by Glasgow Coma Scale (GCS) scores of 13 to 15 underwent testing of dynamic cerebral autoregulation within 48 hours of their injury using continuous transcranial Doppler velocity recordings and blood pressure recordings. Twenty-nine age-matched normal volunteers underwent autoregulation testing in the same manner to establish comparison values. The function of the autoregulatory response was assessed by the cerebral blood flow velocity response to induced rapid brief changes in arterial blood pressure and measured as the autoregulation index (ARI). Eight (28%) of the 29 patients with minor head injury demonstrated poorly functioning or absent cerebral autoregulation versus none of the controls, and this difference was highly significant (p = 0.008). A significant correlation between lower blood pressure and worse autoregulation was found by regression analysis in head-injured patients (r = 0.6, p < 0.001); however, lower blood pressure did not account for the autoregulatory impairment in all patients. Within this group of head-injured patients there was no correlation between ARI and initial GCS or 1-month Glasgow Outcome Scale scores. This study indicates that a significant number of patients with minor head injury may have impaired cerebral autoregulation and may be at increased risk for secondary ischemic neuronal damage.
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Lesiones Encefálicas/fisiopatología , Circulación Cerebrovascular , Homeostasis , Adolescente , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Conmoción Encefálica/diagnóstico por imagen , Conmoción Encefálica/fisiopatología , Lesiones Encefálicas/diagnóstico por imagen , Isquemia Encefálica/etiología , Estudios de Casos y Controles , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/fisiopatología , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/fisiopatología , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Análisis de Regresión , Factores de Riesgo , Fracturas Craneales/diagnóstico por imagen , Fracturas Craneales/fisiopatología , Ultrasonografía Doppler Transcraneal , Resistencia VascularRESUMEN
OBJECT: The authors sought to determine whether 3,3-bis (3-fluorophenyl) propylamine (NPS 846), a novel noncompetitive N-methyl-D-aspartate receptor antagonist, alters outcome after closed head trauma in rats. METHODS: The experimental variables were: presence or absence of closed head trauma, treatment with NPS 846 or no treatment, and time at which the rats were killed (24 or 48 hours). The NPS 846 (1 mg/kg) was administered intraperitoneally at 1 and 3 hours after closed head trauma or sham operation. Outcome measures were the neurological severity score (NSS), ischemic tissue volume, hemorrhagic necrosis volume, and specific gravity, water content, and concentrations of calcium, sodium, potassium, and magnesium in brain tissue. The following closed head trauma-induced changes in the injured hemisphere (expressed as the mean +/- the standard deviation) were reversed by NPS 846: decreased specific gravity of 1.035 +/- 0.006 at 24 hours was increased to 1.042 +/- 0.004; the decreased potassium level of 0.583 +/- 0.231 mg/L at 48 hours and at 24 hours was increased to 2.442 +/- 0.860 mg/L; the increased water content of 84.7 +/- 2.6% at 24 hours was decreased to 79.8 +/- 2%; the increased calcium level of 0.592 +/- 0.210 mg/L at 24 hours was decreased to 0.048 +/- 0.029 mg/L; and the increased sodium level of 2.035 +/- 0.649 mg/L was decreased to 0.631 +/- 0.102 mg/L. Administration of NPS 846 also lowered the NSS (improved neurological status) at 48 hours (7 +/- 3) and caused no significant changes in ischemic tissue or hemorrhagic necrosis volumes in the injured hemisphere at 24 or 48 hours. CONCLUSIONS: In this model of closed head trauma, NPS 846 improved neurological outcome, delayed the onset of brain edema, and improved brain tissue ion homeostasis.
Asunto(s)
Fluorobencenos/uso terapéutico , Traumatismos Cerrados de la Cabeza/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Propilaminas/uso terapéutico , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Animales , Agua Corporal/química , Encéfalo/metabolismo , Encéfalo/patología , Edema Encefálico/metabolismo , Edema Encefálico/patología , Edema Encefálico/prevención & control , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Isquemia Encefálica/prevención & control , Calcio/análisis , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patología , Hemorragia Cerebral/prevención & control , Fluorobencenos/administración & dosificación , Traumatismos Cerrados de la Cabeza/metabolismo , Traumatismos Cerrados de la Cabeza/patología , Homeostasis , Inyecciones Intraperitoneales , Puntaje de Gravedad del Traumatismo , Magnesio/análisis , Necrosis , Fármacos Neuroprotectores/administración & dosificación , Potasio/análisis , Propilaminas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Sodio/análisis , Gravedad Específica , Factores de Tiempo , Resultado del TratamientoRESUMEN
Vaginal agenesis is a rare anomaly that may result from a variety of different underlying diagnoses. The most important aspects of the surgical management of this condition are: correct diagnosis of both the underlying abnormality and its anatomy, documentation of any associated renal or skeletal anomalies, and proper psychological preparation of the young woman for any anticipated corrective surgery. Over the years, there have been many different techniques devised in an attempt to provide these women with a functioning vagina that approximates normal anatomy. The purpose of this article is to review the surgical options for the management of this anomaly.
Asunto(s)
Procedimientos de Cirugía Plástica , Vagina/anomalías , Vagina/cirugía , Colon Sigmoide/trasplante , Dilatación , Femenino , Humanos , Laparoscopía , Resultado del Tratamiento , Vulva/cirugíaRESUMEN
The existence of numerous techniques for the creation of pneumoperitoneum at laparoscopy indicates that none have been proven totally efficacious or complication free. These methods include the standard technique of insufflation after insertion of the Veress needle via the umbilicus or less commonly via the transfundal or transforniceal routes, open laparoscopy involving dissection through the linea alba and opening of the peritoneum under direct vision, and direct trocar insertion as well as variations on these techniques. After reviewing the methods available and surveying the existing data concerning the rates of failure and complications, we conclude that no single technique can claim to be overwhelmingly superior, and that laparoscopists should, therefore, acquaint themselves with at least two of these techniques. Finally, we recommend a large-scale combined survey by the colleges of obstetricians and gynecologists and surgeons on rates of failure and complications of the varied approaches of abdominal entry for laparoscopy.
Asunto(s)
Neumoperitoneo Artificial/métodos , Humanos , Laparoscopía , Agujas , Neumoperitoneo Artificial/efectos adversos , PuncionesRESUMEN
Mature cystic teratomas (MCT), commonly called dermoid cysts, are the most common benign germ cell tumors of the ovary in women of reproductive age. Future fertility is of major concern among these women; therefore, the surgical management must focus on preserving ovarian tissue and minimizing adhesion formation. Patients requiring surgery should be appropriately counseled about the risks and benefits of laparoscopy and laparotomy, the risks of intraoperative MCT spillage and adhesion formation. In addition, the risks of recurrence and malignant transformation should be discussed. The parents of children with MCTs have the same concerns as older women and a similar discussion should take place. The goal of this article is to review these issues and provide the physician with the information to counsel their patients preoperatively.
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Laparoscopía , Laparotomía , Neoplasias Ováricas/cirugía , Teratoma/cirugía , Animales , Femenino , Humanos , Complicaciones Intraoperatorias , Complicaciones Posoperatorias , Recurrencia , Adherencias Tisulares/etiologíaRESUMEN
Intraoperative management of a 68-year-old man with a 3-month history of presyncopal attacks presenting for left carotid endarterectomy is reported. Preoperative angiograms revealed that the patient had a 90% stenosis of his left internal carotid artery and a 35% stenosis of right internal carotid artery, absent posterior communicating arteries, a totally occluded left vertebral artery, and a right vertebral artery that became compressed upon turning his head to the right, often precipitating the presyncopal attacks. The surgical procedure was managed with intraoperative monitoring of both brainstem auditory and somatosensory evoked potentials. The patient had an uneventful outcome. The anesthetic management is discussed.
RESUMEN
During induced hypotension for surgical procedures, cerebral blood flow (CBF) autoregulation and cerebrovascular responsivity to CO2 may be impaired-changes that appear to be agent-specific. Adenosine is a potent endogenous systemic vasodilator and has been investigated as a hypotensive agent. In this study in dogs we investigated cerebral vascular responses to graded decreases of cerebral perfusion pressure (CPP) (100%, 60%, 45%, and 35% of control CPP) during normocapnia (PaCO2 = 37 mm Hg) and hypocapnia (PaCO2 = 21 mm Hg). CBF was measured using the venous outflow technique. Six mongrel dogs were anesthetized with halothane (0.6% inspired) and nitrous oxide (70%) in oxygen and studied during both normocapnic and hypocapnic hypotension. The entry sequence was randomized with >/= 1 h of recovery between normocapnia and hypocapnia. Hypocapnia reduced control CBF from 60.6 +/- 7.1 to 45.1 +/- 5.4 ml 100 g min (mean +/- SEM, p <0.05) during normotension. CBF was unchanged from control values during both graded normocapnic and hypocapnic hypotension until CPP reached 60% of control CPP (50 and 47 mm Hg for normocapnia and hypocapnia, respectively). Thereafter CBF decreased significantly from control values at 45% (37 mm Hg for both groups) and 35% (29 mm Hg for both groups) of control CPP. The lower limit of CBF autoregulation derived by applying linear regression analysis to the CBF-CPP relationship above and below the inflexion point was similar under both experimental conditions (60 +/- 1% of control CPP during normocapnia and 63 +/- 3% of control CPP during hypocapnia). CBF was significantly greater during normocapnia compared with hypocapnia at all levels of CPP, except at 35% of control when the values were similar. Cerebral metabolic rate was unchanged throughout the study. We conclude that neither CBF nor CO2 responsivity is appreciably altered during adenosine-induced hypotension when GPP remains above the lower limit of autoregulation of CBF.
RESUMEN
We examined the effect of nitrous oxide on cerebral blood flow velocity (Vmca), arteriovenous oxygen content difference and cerebral use of glucose during propofol-induced electrical silence of the electroencephalogram (EEG) in 10 patients undergoing anesthesia for nonneurosurgical procedures. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 3 micrograms/kg (followed by an infusion of 2 micrograms/kg/h), vecuronium 0.1 mg/kg, and maintained with a propofol infusion (250-300 micrograms/kg/min) sufficient to induce EEG silence. A transcranial Doppler was used to measure the Vmca and a jugular bulb catheter was inserted for oxygen saturation and glucose use measurements. After a 15-period of isoelectric EEG and normocapnia (PaCO2 38 +/- 1 mm Hg), baseline arterial and jugular bulb venous blood gases were drawn, and mean arterial pressure (MAP), heart rate (HR), and Vmca were recorded. Nitrous oxide was then introduced and equilibrated to an end-tidal concentration of 70% for 15 min, after which MAP, HR, Vmca, arterial and jugular bulb venous blood gases were measured again. Nitrous oxide increased Vmca (29 +/- 4 to 35 +/- 4 cm/s, p < 0.01), cerebral use of oxygen (166 +/- 13 to 190 +/- 12 vol%-cm/s, p < 0.05) and glucose (245 +/- 38 to 290 +/- 48 g%-cm/s, p < 0.05) by approximately 20%. Occasional bursts of EEG activity were observed in eight patients studied during the N2O stage. We conclude that in patients with propofol-induced isoelectric EEG, the increase seen in Vmca with the introduction of N2O is mainly due to cerebral stimulation and increase in cerebral metabolic rate.