RESUMEN
OBJECTIVE: After months of lockdown due to the COVID-19 outbreak, the US postsecondary institutions implemented different instruction approaches to bring their students back for the Fall 2020 semester. Given public health concerns with reopening campuses, the study evaluated the impact of Fall 2020 college reopenings on COVID-19 transmission within the 632 US university counties. STUDY DESIGN: This was a retrospective and observational study. METHODS: Bayesian Structural Time Series (BSTS) models were conducted to investigate the county-level COVID-19 case increases during the first 21 days of Fall 2020. The case increase for each county was estimated by comparing the observed time series (actual daily cases after school reopening) to the BSTS counterfactual time series (predictive daily cases if not reopening during the same time frame). We then used multilevel models to examine the associations between opening approaches (in-person, online, and hybrid) and county-level COVID-19 case increases within 21 and 42 days after classes began. The multigroup comparison between mask and non-mask-required states for these associations were also performed, given that the statewide guidelines might moderate the effects of college opening approaches. RESULTS: More than 80% of our university county sample did not experience a significant case increase in Fall 2020. There were no significant relationships between opening approaches and community transmission in both mask-required and non-mask-required states. Only small metropolitan counties and counties with a non-community college or a higher percentage of student population showed significantly positive associations with the case number increase within the first 21-day period of Fall 2020. For the longer 42-day period, the counties with a higher percentage of the student population showed a significant case increase. CONCLUSION: The overall findings underscored the outcomes of US higher education reopening efforts when the vaccines were still under development in Fall 2020. For individual county results, we invite the college- and county-level decision-makers to interpret their results using our web application.
Asunto(s)
COVID-19 , Teorema de Bayes , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Humanos , Estudios Retrospectivos , Estados Unidos/epidemiología , UniversidadesRESUMEN
This randomized, double-blind, placebo-controlled study evaluated whether lamivudine given during late pregnancy can reduce hepatitis B virus (HBV) perinatal transmission in highly viraemic mothers. Mothers were randomized to either lamivudine 100 mg or placebo from week 32 of gestation to week 4 postpartum. At birth, infants received recombinant HBV vaccine with or without HBIg and were followed until week 52. One hundred and fifty mothers, with a gestational age of 26-30 weeks and serum HBV DNA >1000 MEq/mL (bDNA assay), were treated. A total of 141 infants received immunoprophylaxis at birth. In lamivudine-treated mothers, 56 infants received vaccine + HBIg (lamivudine + vaccine + HBIg) and 26 infants received vaccine (lamivudine + vaccine). In placebo-treated mothers, 59 infants received vaccine + HBIg (placebo + vaccine + HBIg). At week 52, in the primary analyses where missing data was counted as failures, infants in the lamivudine + vaccine + HBIg group had a significant decrease in incidence of HBsAg seropositivity (10/56, 18%vs 23/59, 39%; P = 0.014) and in detectable HBV DNA (11/56, 20%vs 27/59, 46%; P = 0.003) compared to infants in the placebo + vaccine + HBIg group. Sensitivity analyses to evaluate the impact of missing data at week 52 resulting from a high dropout rate (13% in the lamivudine + vaccine + HBIg group and 31% in the placebo + vaccine + HBIg group) remained consistent with the primary analysis in that lower transmission rates were still observed in the infants of lamivudine-treated mothers, but the differences were not statistically significant. No safety concerns were noted in the lamivudine-treated mothers or their infants. Results of this study suggest that lamivudine reduced HBV transmission from highly viraemic mothers to their infants who received passive/active immunization.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis B/tratamiento farmacológico , Hepatitis B/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Lamivudine/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Anticuerpos Antivirales/uso terapéutico , Quimioprevención/métodos , Método Doble Ciego , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Vacunas contra Hepatitis B/administración & dosificación , Humanos , Recién Nacido , Placebos/administración & dosificación , Embarazo , Resultado del TratamientoRESUMEN
Synthetic oligonucleotides coding for the yeast invertase secretion signal peptide were fused to the gene for the mature form of human interferon (huIFN-alpha 2). Two plasmids (E3 and F2) were constructed. E3 contained the invertase signal codons in a reading frame with the mature huIFN-alpha 2 gene. F2 had a deletion of the codon for alanine at amino acid residue-5 in the invertase signal and an addition of a methionine codon located between the coding sequences for the invertase signal and mature huIFN-alpha 2. Both hybrid genes were located adjacent to the promoter from the 3-phosphoglycerate kinase gene on the multicopy yeast expression plasmid, YEp1PT. Yeast transformants containing these plasmids produced somewhat more IFN than did the same expression plasmid containing the IFN gene with its human secretion signal sequence. HuIFN-alpha 2, purified from the medium of yeast cells containing E3, was found to be processed at the correct site. The huIFN-alpha 2 made by plasmid F2 was found to be completely processed at the junction between the invertase signal (a variant) and the methionine of methionine-huIFN-alpha 2. These results strongly suggested that the invertase signal (or its variant) attached to huIFN was efficiently recognized by the presumed signal recognition particle and was cleaved by the signal peptidase in the yeast cells. These results also suggested that amino acid changes on the right side of the cleavage site did not necessarily prevent cleavage or secretion.
Asunto(s)
Glicósido Hidrolasas/genética , Interferón Tipo I/genética , Señales de Clasificación de Proteína/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Secuencia de Aminoácidos , Enzimas de Restricción del ADN , Escherichia coli/genética , Humanos , Interferón Tipo I/metabolismo , Saccharomyces cerevisiae/enzimología , beta-FructofuranosidasaRESUMEN
The anti-Tac antibody is known to bind to the p55 chain of the human interleukin 2 receptor. An immunotoxin was produced by genetically linking Clostridium perfringens phospholipase C (PLC) to the Fab domain of anti-Tac. For this purpose, the PLC gene, with its own promoter and signal sequence, was fused to the 5' end of the VHCH1 segment of the anti-Tac heavy chain gene. The anti-Tac light chain gene, with an attached bacterial signal sequence, was made part of the same transcriptional unit. Escherichia coli transformed with the construct secreted a recombinant immunotoxin, anti-Tac(Fab)-PLC, in an active form. Anti-Tac(Fab)-PLC bound to cells expressing the interleukin 2 receptor and inhibited protein synthesis, with a 50% inhibitory concentration of 0.02 nM (1.8 ng/ml).
Asunto(s)
Fragmentos Fab de Inmunoglobulinas/genética , Inmunotoxinas/metabolismo , Fosfolipasas de Tipo C/genética , Secuencia de Aminoácidos , Secuencia de Bases , Línea Celular , Supervivencia Celular/efectos de los fármacos , Clostridium perfringens/enzimología , Clostridium perfringens/genética , Escherichia coli/genética , Humanos , Fragmentos Fab de Inmunoglobulinas/metabolismo , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/metabolismo , Inmunotoxinas/farmacología , Datos de Secuencia Molecular , Plásmidos , Receptores de Interleucina-2/metabolismo , Proteínas Recombinantes/metabolismo , Mapeo Restrictivo , Linfocitos T/inmunología , Fosfolipasas de Tipo C/metabolismo , Fosfolipasas de Tipo C/farmacologíaRESUMEN
Hydroxyurea (HU) is currently used in the clinic for the treatment of chronic myelogenous leukemia, head and neck carcinoma, and sarcoma. One of its drawbacks, however, is the development of HU resistance. To study this problem, we developed a HU-resistant human KB cell line which exhibits a 15-fold resistance to HU. The characterization of this HU-resistant phenotype revealed a gene amplification of the M2 subunit of ribonucleotide reductase (RR), increased levels of M2 mRNA and protein, and a 3-fold increase of RR activity. This HU-resistant cell line also expressed a "collateral sensitivity" to 6-thioguanine (6-TG), with a 10-fold decrease in the dose inhibiting cell growth by 50% as compared to the KB parental line. The mechanism responsible for this supersensitivity to 6-TG is believed to be related to an increasingly efficient conversion of 6-TG to its triphosphate form, which is subsequently incorporated into DNA. After passage of the resistant cells in the absence of HU, the cell line reverts. The revertant cells lose their resistance to HU and concomitantly their sensitivity to 6-TG. This phenomenon is due to the return of RR to levels comparable to that of the KB parental cell line. These observations and their relevance to cancer chemotherapy will be discussed in this paper. Our results suggest that a clinical protocol could be designed which would allow for a lower dose of 6-TG to be used by taking advantage of the increased RR activity in HU-refractory cancer patients. Two drugs which display collateral sensitivity are known as a "Ying-Yang" pair. Alternate treatment with two different Ying-Yang pairs is the rationale for the "Ying-Yang Ping-Pong" theory in cancer treatment. This rationale allows for effective cancer chemotherapy with reduced toxicity.
Asunto(s)
Hidroxiurea/farmacología , Tioguanina/farmacología , Animales , Secuencia de Bases , ADN/metabolismo , Resistencia a Medicamentos , Humanos , Células KB , Ratones , Datos de Secuencia Molecular , ARN/metabolismoRESUMEN
Single-chain immunotoxins anti-Tac(Fv)-PE40 and anti-Tac(Fv)-PE40KDEL, composed of variable domains of the anti-Tac monoclonal antibody and truncated forms of Pseudomonas exotoxin, have shown potent cytotoxic activity against malignant peripheral blood mononuclear cells (PBMCs) from adult T-cell leukemia (ATL) patients originating from the Caribbean. However, several clinically important issues have not previously been addressed. These include the potential of soluble interleukin 2 receptor in ATL patients to block immunotoxin effectiveness, the relative sensitivity of malignant lymph node cells (LNCs) versus PBMCs, the effect of an immunotoxin with a prolonged half-life, and finally whether ATL cells from patients in Japan have toxin sensitivity equal to those of the Caribbean patients. To resolve these questions, we studied 32 malignant PBMC and LNC samples from 30 ATL patients from Japan. PBMCs from 27 of 27 patients were very sensitive with 50% inhibition of protein synthesis achieved with 0.02-0.85 ng/ml (0.3-13 pM) of anti-Tac(Fv)-PE40KDEL or anti-Tac(Fv)-PE40. LNCs had sensitivity very similar to that of PBMCs in the five patients tested. The fully recombinant immunotoxin, anti-Tac(Fab)-PE40, which has 8-10 times the t1/2 alpha and beta compared to the Fv-immunotoxins, was also very cytotoxic toward cells from 27 of 27 patients tested with 50% inhibition of protein synthesis of 0.08-25 ng/ml. It was found that purified soluble interleukin 2 receptor added to the cytotoxicity assay decreased the cytotoxic activity of anti-Tac(Fv)-PE40KDEL or anti-Tac(Fab)-PE40, but that 1 x 10(4) units/ml or less had minimal competitive effects. It was found that ATL patients who have responded even incompletely to conventional chemotherapy have soluble interleukin 2 receptor levels lower than this at posttreatment. We conclude that recombinant immunotoxins containing anti-Tac(Fv) are effective against Japanese ATL PBMCs or LNCs and might be most effective if used in vivo after conventional chemotherapy. If it is found in humans that the effectiveness of single-chain recombinant toxins is limited by short half-life, anti-Tac(Fab)-PE40 should be considered as an alternative agent.
Asunto(s)
ADP Ribosa Transferasas , Toxinas Bacterianas , Exotoxinas/farmacología , Fragmentos Fab de Inmunoglobulinas/farmacología , Inmunotoxinas/farmacología , Leucemia de Células T/tratamiento farmacológico , Receptores de Interleucina-2/fisiología , Factores de Virulencia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunotoxinas/uso terapéutico , Leucemia de Células T/patología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/patología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Receptores de Interleucina-2/análisis , Exotoxina A de Pseudomonas aeruginosaRESUMEN
The nucleotide sequence of the alkaline phosphatase (APase) gene (phoA) of Escherichia coli strain 294 has been determined. Pre-APase has a total of 471 amino acids (aa) including a signal sequence of 21 aa. The derived aa sequence differs from that obtained by protein sequencing by the presence of aspartic acid instead of asparagine at positions 16 and 36, and glutamic acid instead of glutamine at position 197. Two open reading frames (ORF1 and ORF2) located downstream from phoA or upstream from proC have been found. ORF1 encodes a putative presecretory protein of 106 aa with a signal sequence of 21 or 22 aa. If this protein is actually produced, it may be one of the smallest periplasmic proteins in E. coli.
Asunto(s)
Fosfatasa Alcalina/genética , Escherichia coli/genética , Genes Bacterianos , Genes , Secuencia de Aminoácidos , Secuencia de Bases , Escherichia coli/enzimologíaRESUMEN
A gene encoding the mature form of human growth hormone (hGH) was fused to the secretion signal coding sequence of the Escherichia coli heat-stable enterotoxin II (STII). This hybrid gene was preceded by two Shine-Dalgarno sequences derived from the trp and STII-coding genes and was expressed in E. coli under the transcriptional control of the E. coli alkaline phosphatase (phoA) promoter. In low-phosphate growth media, cells synthesized about 15 to 25 micrograms of hGH/ml/1 A550 unit of cells. This represents 6 to 10% of total cellular protein. The majority of the hGH produced (more than 90%) was processed precisely and secreted into the periplasmic space. These results demonstrate that E. coli cells are able to synthesize and secrete high levels of this human protein using a prokaryotic signal sequence.
Asunto(s)
Gonadotropina Coriónica/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes/metabolismo , Gonadotropina Coriónica/biosíntesis , Gonadotropina Coriónica/genética , Escherichia coli/genética , Escherichia coli/fisiología , Genes , Genes Sintéticos , Vectores Genéticos , Humanos , Regiones Promotoras Genéticas , Procesamiento Proteico-Postraduccional , Señales de Clasificación de Proteína/genética , Señales de Clasificación de Proteína/fisiología , Secuencias Reguladoras de Ácidos NucleicosRESUMEN
We have studied the synthesis, secretion, and processing of human growth hormone (hGH) in Escherichia coli transformed with plasmids engineered for the expression of hGH as a secreted product. In one plasmid, pPreHGH207-2, the coding sequence of the natural hGH precursor (pre-hGH) is placed under the control of the E. coli trp promoter. In a second plasmid, pAPH-1, a DNA fragment containing the E. coli alkaline phosphatase promoter and signal sequence codons is fused to the mature hGH coding sequence (pho-hGH). Most of the hGH was present in the osmotic shock fluids of E. coli cells containing either plasmid, indicating transport to the periplasmic space. Amino acid sequencing of the N termini of the pre-hGH and pho-hGH gene products revealed that both were processed correctly. Electrophoretic analysis of these polypeptides on reducing and nonreducing sodium dodecyl sulfate (SDS)-polyacrylamide (PA) gels indicates that periplasmic hGH is monomeric and contains the same two disulfide bonds as authentic hGH.
Asunto(s)
Escherichia coli/genética , Hormona del Crecimiento/genética , Señales de Clasificación de Proteína/genética , Compartimento Celular , ADN Bacteriano/genética , Disulfuros , Regulación de la Expresión Génica , Hormona del Crecimiento/metabolismo , Humanos , Procesamiento Proteico-Postraduccional , Especificidad de la EspecieRESUMEN
p53 mutation has been rarely reported in cerebral primitive neuroectodermal tumors (PNET). To determine the significance of p53 mutations in the development of cerebral PNET, we studied cerebral PNET samples from 14 patients, 8 females and 6 males with a mean age of 38 years (range 10 months to 77 years) who had total or subtotal surgical resection. Histological typing of PNET with neuronal (N) and non-neuronal (NN) differentiation groups revealed 8 and 6 cases, respectively. Six (43%) of the 14 patients had p53 mutation. The p53(+) and p53(-) groups had an age range of 19-77 with a mean of 49 years and 10 months to 57 years with a mean of 30 years, respectively. p53 expression between the PNET-N and PNET-NN groups was 5 of 8 (62.5%) and 1 of 6 (16.7%), respectively. The mutations contained 3 transitions, 2 transversions and 1 frameshift; none of them occurred at the site of 'hot-spot' residues (codons 175, 248, 273). The results suggest that: (1) p53 mutation in cerebral PNET tends to show a higher incidence of neuronal differentiation and occurs in the older age group in Taiwan, (2) there was no difference in survival time between the PNET-N and PNET-NN groups (7 months and 6 months) (P = 0.54), and between p53(+) and p53(-) groups (6 months and 7 months) (P = 0.57), and (3) PNET may be an entity of a heterogenous group of tumors with different genetic mechanisms controlling their trends of differential lineage. Further studies are needed to determine the significance of p53 mutations in PNET development, especially the role of carcinogens in the genesis of PNET in Taiwan.
Asunto(s)
Neoplasias Encefálicas/genética , Genes p53 , Mutación , Tumores Neuroectodérmicos Primitivos/genética , Adolescente , Adulto , Anciano , Secuencia de Bases , Neoplasias Encefálicas/epidemiología , Niño , Preescolar , ADN de Neoplasias/genética , Exones , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Tumores Neuroectodérmicos Primitivos/epidemiología , Adhesión en Parafina , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Taiwán/epidemiologíaRESUMEN
5-Iodo-2-pyrimidinone-2'-deoxyribose (IPdR) can be converted into 5-iodo-deoxyuridine (IUdR), a clinical radiosensitizer, by aldehyde oxidase in the liver. This conversion does not require exogenous cofactors and cannot be catalyzed by mixed-function oxidases, xanthine oxidase or many other oxido-reductases. This "IPdR oxidase" activity is enriched in the liver; thus, extensive conversion of IPdR to IUdR could be anticipated in the liver and the therapeutic index of IPdR could be better than that of IUdR as a radiosensitizer for primary liver cancers or tumors metastasized to the liver. Based on structure and activity relationship studies, nucleoside analogues which could be activated by this enzyme to compounds capable of inhibiting DNA synthesis could be designed and should be explored as agents against cancer, viruses or parasites in the liver.
Asunto(s)
Aldehído Oxidorreductasas/metabolismo , Idoxuridina/metabolismo , Nucleósidos de Pirimidina/metabolismo , Fármacos Sensibilizantes a Radiaciones/metabolismo , Aldehído Oxidasa , Animales , Diseño de Fármacos , Humanos , Riñón/enzimología , Ratas , Bazo/enzimología , Especificidad por Sustrato , Extractos de Tejidos/metabolismoRESUMEN
5-Fluorouracil (5-FU) is an effective antitumor agent used in treating various cancers. Because of its metabolism by intestinal and other cells, 5-FU has an inconsistent bioavailability that limits its oral use. 5-Fluoro-2-pyrimidione (5-FP), a 5-FU prodrug, was synthesized and found to be converted to 5-FU by aldehyde oxidase, an enzyme present in high concentrations in the livers of mice and humans but not in the gastrointestinal tract. Using BDF1 mice, the pharmacokinetics of 5-FP were studied and compared with those of 5-FU. The bioavailability of 5-FP given orally was 100% at a dosage of 25 mg/kg and 78% at a dosage of 50 mg/kg. The half-lives of both doses of 5-FP were at least 2-fold longer than the half-lives of the same doses of 5-FU, and the clearance rates of 5-FP were 3-fold slower. 5-FP was converted rapidly to 5-FU, in vivo. The resulting 5-FU was measured at a steady-state level of 40-70 microM in plasma, at a dosage of 25 mg/kg, that was sustained for at least 4 hr. Also, when given orally, 5-FP was shown to have potent activity against Colon 38 tumor cells and P388 leukemia cells in mice. The therapeutic index of 5-FP was similar to that of 5-FU in these mouse tumor models. The potential clinical use of 5-FP as a prodrug of 5-FU should be considered.
Asunto(s)
Flucitosina , Fluorouracilo/farmacocinética , Profármacos , Administración Oral , Aldehído Oxidasa , Aldehído Oxidorreductasas/metabolismo , Animales , Disponibilidad Biológica , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Flucitosina/farmacocinética , Flucitosina/uso terapéutico , Flucitosina/toxicidad , Fluorouracilo/química , Fluorouracilo/toxicidad , Semivida , Cinética , Leucemia P388/metabolismo , Hígado/metabolismo , Ratones , Profármacos/farmacocinética , Profármacos/uso terapéutico , Profármacos/toxicidadRESUMEN
To establish criteria for administration of the optimal dose of alpha-adrenergic receptor blocking drugs, we studied cardiac performance and tissue oxygen tension in three patients who underwent excision of pheochromocytoma. Subcutaneous oxygen tension was measured by the method of Niinikoski and Hunt. Cardiac function was assessed by thermodilution cardiac output, systemic and pulmonary arterial blood pressures, and continuous two-dimensional transesophageal echocardiography of a cross section of the left ventricle at the level of the papillary muscles. Despite large changes in cardiac output and systemic, pulmonary, and wedge pressures, intraoperative tissue oxygen tensions and ejection fractions remained normal (even at times of peak catecholamine excretion and very abnormal wedge pressures). Studies of healthy animals that received no alpha-adrenergic receptor blocking drugs showed major decrements of tissue oxygen in response to modest doses of epinephrine. We conclude that progressive administration of alpha-adrenergic receptor blocking drugs does not absolutely protect the patient from major changes in blood pressure during operation for pheochromocytoma, but that cardiac performance and oxygen supply to the tissues are unimpaired.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/cirugía , Corazón/fisiopatología , Oxígeno/metabolismo , Fenoxibenzamina/uso terapéutico , Feocromocitoma/cirugía , Cuidados Preoperatorios , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/fisiopatología , Hemodinámica , Humanos , Complicaciones Intraoperatorias/prevención & control , Feocromocitoma/metabolismo , Feocromocitoma/fisiopatologíaRESUMEN
The therapeutic effect of hyperbaric oxygen (HBO) on ischemic injury was investigated using in situ hybridization to detect the mRNA expression of neurotrophin-3 (NT-3), which is thought to play a crucial role in protecting against neuronal death induced by brain ischemia. The rats under investigation were subjected to 10 min transient forebrain ischemia, and subsequently exposed to HBO (100% oxygen, 2.5 atm absolute) for 2 h. Levels of NT-3 mRNA in the CA1, CA2 and CA3 regions, and the dentate gyrus of the hippocampus were measured after various reperfusion periods. Neuronal death in the hippocampal CA1 region was also measured by Nissl staining, seven days post ischemia. The results demonstrated that HBO treatment significantly reduced the ischemia-induced down-regulation of the NT-3 mRNA level at 4 h post ischemia, and significantly increased cell survival 7 days after reperfusion. The findings suggest that an HBO treatment maintaining the NT-3 mRNA level in the hippocampus can be beneficial to the ischemic brain within a certain time frame.
Asunto(s)
Isquemia Encefálica/metabolismo , Regulación hacia Abajo/fisiología , Hipocampo/metabolismo , Oxigenoterapia Hiperbárica , Neurotrofina 3/metabolismo , ARN Mensajero/metabolismo , Animales , Isquemia Encefálica/terapia , Oxigenoterapia Hiperbárica/métodos , Neurotrofina 3/antagonistas & inhibidores , Neurotrofina 3/genética , ARN Mensajero/antagonistas & inhibidores , Ratas , Ratas Sprague-DawleyRESUMEN
Dexamethasone (DEX) increases the expression of neurotrophin-3 (NT-3) in normal rat hippocampal neurons, whereas transient forebrain ischemia reduces the NT-3 mRNA level. The effect of DEX on the expression of NT-3 mRNA in injured brain cells after ischemia has not been investigated, however. Using in situ hybridization and ribonuclease protection assay methods, we studied NT-3 mRNA expression in rats with and without DEX administration after transient forebrain ischemia. Without DEX treatment, NT-3 mRNA was down-regulated in the hippocampal neurons at 2, 4, 12 h and returned to basal levels 24 h following ischemia. With DEX treatment, however, NT-3 mRNA showed no change at 2, 4 and 12 h and increased 24 h after ischemia. The results indicate that DEX inhibits ischemia-induced NT-3 mRNA down-regulation during the first 12 h and up-regulates NT-3 mRNA 24 h after ischemia. DEX administration might be effective in influencing some of the pathophysiological effects of ischemia in the hippocampus.
Asunto(s)
Antiinflamatorios/farmacología , Isquemia Encefálica/fisiopatología , Dexametasona/farmacología , Factores de Crecimiento Nervioso/genética , Neuronas/metabolismo , Animales , Química Encefálica/efectos de los fármacos , Química Encefálica/fisiología , Giro Dentado/irrigación sanguínea , Giro Dentado/citología , Giro Dentado/metabolismo , Expresión Génica/efectos de los fármacos , Hibridación in Situ , Masculino , Neuronas/efectos de los fármacos , Neurotrofina 3 , Prosencéfalo/irrigación sanguínea , Prosencéfalo/citología , Prosencéfalo/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND PURPOSE: Proton MR spectroscopy has recently been applied to the evaluation of seizures, but few comparisons have been made between different clinical spectroscopic techniques. Our goal was to determine whether there is a significant difference between hippocampal NAA/(Cho+Cr) ratios obtained by single-voxel spectroscopy (SVS) and by chemical-shift imaging (CSI). METHODS: Twelve healthy adults and eight patients with complex partial seizures were studied on a 1.5-T MR scanner using a proton SVS method. Another 12 healthy adults and 10 patients with complex partial seizures were recruited for a proton CSI study, which was performed on a different 1.5-T MR system. The NAA/(Cho+Cr) ratio was calculated from the integral peak areas by curve fitting. The two-tailed t-test was used for statistical analysis. RESULTS: The mean value +/- standard deviation of the hippocampal NAA/(Cho+Cr) ratio in healthy control subjects was 0.63 +/- 0.07 by SVS, with 0.62 +/- 0.15 for the anterior hippocampus and 0.65 +/- 0.11 for the posterior hippocampus by CSI. There was no significant difference between the control group data obtained by SVS and those by CSI, nor was there a regional difference in the CSI NAA/(Cho+Cr) ratio in the hippocampus. Relative to the control group, the patients with seizures had a significant decrease in the NAA/(Cho+Cr) ratio in the abnormal hippocampus: -28% by SVS, and -24% in the anterior hippocampus and -18% in the posterior hippocampus by CSI. Proton SVS and CSI detected hippocampal abnormalities, unilateral or bilateral, in all patients of each group. CONCLUSION: Under similar measurement conditions, proton SVS and CSI provide similar NAA/(Cho+Cr) ratios among healthy control subjects, and they possess comparable ability for detecting hippocampal abnormalities in patients with complex partial seizures.
Asunto(s)
Epilepsia Parcial Compleja/metabolismo , Hipocampo/metabolismo , Procesamiento de Imagen Asistido por Computador/métodos , Espectroscopía de Resonancia Magnética , Adolescente , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Colina/análisis , Creatina/análisis , Electroencefalografía , Femenino , Análisis de Fourier , Humanos , Imagen por Resonancia Magnética , Masculino , ProtonesRESUMEN
Endoscopic sympathectomy is a new trend for the treatment of hyperhidrosis palmaris. It is a simple and effective technique; however, it carries some recognized risks such as Horner's syndrome and pneumohemothorax. We recently encountered a case complicated by the development of a chylothorax. The patient was a 23-year-old healthy women with profuse palmar sweating. She developed an intractable dry cough after a transthoracic endoscopic sympathectomy. A chest x-ray revealed a left pleural effusion. A chylous effusion was found after thoracentesis and fluid analysis. The pleural effusion resolved after chest tube drainage and diet control. Although endoscopic sympathectomy is a simple and quick procedure, unusual complications, such as chylothorax, may occur. Appropriate early recognition and treatment can prevent a disastrous result.
Asunto(s)
Quilotórax/etiología , Hiperhidrosis/cirugía , Complicaciones Posoperatorias/etiología , Simpatectomía , Toracoscopía , Adulto , Tubos Torácicos , Quilotórax/terapia , Femenino , Humanos , Complicaciones Posoperatorias/terapiaRESUMEN
Seventy-four patients with a traumatic epidural hematoma (EDH) and a Glasgow Coma Scale score of more than 12 received expectant treatment; 14 subsequently underwent surgical evacuation of the EDH. A patient with initial brain computed tomograms (CT) showing an EDH volume of more than 30 ml, a thickness of more than 15 mm, and a midline shift beyond 5 mm tended to require surgery within 3 days of the injury when the brain had exhausted its compensatory mechanism and yielded to the expanding EDH. After the 3-day period, in the absence of neurological symptoms, the presence of the EDH may not be an indication for surgical evacuation or hospitalization beyond 7 days. In our patients, the presence of a skull fracture in the temporal bone, the heterogeneous density of the EDH in the CT scan, or the 6-hour period between the CT study and the injury did not significantly increase the failure rate of nonsurgical treatment. Although a zero mortality was achieved in this series, these guidelines may not be applicable to the management of an infratentorial EDH.
Asunto(s)
Hematoma Epidural Craneal/cirugía , Adulto , Femenino , Estudios de Seguimiento , Escala de Coma de Glasgow , Hematoma Epidural Craneal/diagnóstico , Hospitalización , Humanos , Masculino , Fracturas Craneales/diagnóstico , Fracturas Craneales/cirugía , Tomografía Computarizada por Rayos XRESUMEN
In most cases, intracerebral hemorrhage during pregnancy or puerperium results from cerebral aneurysms or arteriovenous malformations. The authors present a case of a 30-year-old woman whose symptoms from a traumatic carotid-cavernous fistula had completely resolved 1 1/2 years after the event, but recurred 4 years later, causing two hemorrhages during pregnancy (33rd and 35th week of gestation) and one during the postpartum period (10 days after Caesarean section). Partial thrombosis of the cavernous sinus with obliteration of most of the drainage from the fistula accounted for the resolution of clinical symptoms, but also promoted back-flow to the preserved drainage of superficial cortical veins. The hemodynamic changes and the hormonal effects due to the patient's subsequent pregnancy further aggravated the venous engorgement and finally caused rupture. All three hematomas occurred in the vicinity of the extremely dilated veins, suggesting that back-flow with venous hypertension was the probable cause for the intracerebral hematomas. Spontaneous healing of the carotid-cavernous fistula should be confirmed with cerebral angiography.
Asunto(s)
Fístula Arteriovenosa/complicaciones , Enfermedades de las Arterias Carótidas/complicaciones , Seno Cavernoso , Hemorragia Cerebral/etiología , Complicaciones Cardiovasculares del Embarazo/etiología , Trastornos Puerperales/etiología , Adulto , Hemorragia Cerebral/cirugía , Femenino , Hematoma/etiología , Hematoma/cirugía , Humanos , Embarazo , Complicaciones Cardiovasculares del Embarazo/cirugía , Trastornos Puerperales/cirugía , ReoperaciónRESUMEN
A review is reported of the seizure incidence in 726 patients who underwent 740 posterior fossa operations via a suboccipital craniectomy without prophylactic anticonvulsant agents. Thirteen patients (1.8%) experienced seizures within 2 weeks postoperatively. Five of these patients (0.7% of the series) had seizures within 24 hours after operation. The incidence was highest for patients with medulloblastoma (7.2%) followed by those with astrocytoma (2.3%). Also, a higher percentage was found in patients with preoperative ventriculoperitoneal shunt or intraoperative ventriculostomy (2.7%) than in those without (1%), but the difference was not statistically significant. Metabolic acidosis (80%) and hyponatremia (20%) were the major causes of the seizures that developed within 24 hours after operation. Follow-up computerized tomography showed no definite lesion in these patients. Hydrocephalus (75%) and supratentorial hemorrhage remote from the operative site (25%) were detected in the patients who developed seizures between the 2nd and 14th postoperative day. Two of these patients also had postoperative bacterial meningitis. This review suggests that seizures are a possible complication in the early postoperative period after suboccipital craniectomy for posterior fossa lesions.