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1.
J Wound Care ; 23(2): 53-4, 56-7, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24526080

RESUMEN

OBJECTIVE: This study examines the effect of various wound dressings on the pH levels of a wound, using a simulated wound environment. METHOD: The pH levels of a 4 different wound dressings (manuka honey dressing, sodium carboxymethylcellulose hydrofiber dressing, polyhydrated ionogen-coated polymer mesh dressing, and a protease modulating collagen cellulose dressing) were tested in a simulated horse serum wound environment. The effect of local buffering was observed and pH changes in real time were measured. RESULTS: All dressings were found to have low pH (below pH 4), with the lowest being the protease modulating collage cellulose dressing, with a pH of 2.3. The dressing with the strongest acid concentration was the polyhydrated, ionogen-coated, polymer mesh dressing. CONCLUSION: The low pH and strong acidic nature of the dressing investigated indicate that they may play a role in influencing the healing process in a wound. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare. This study was funded by the EPSRC.


Asunto(s)
Apósitos Oclusivos , Cicatrización de Heridas/efectos de los fármacos , Animales , Carboximetilcelulosa de Sodio/farmacología , Materiales Biocompatibles Revestidos , Colágeno/farmacología , Miel , Caballos , Concentración de Iones de Hidrógeno , Suero , Mallas Quirúrgicas
2.
Clin Infect Dis ; 49(12): 1878-82, 2009 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-19911965

RESUMEN

BACKGROUND: Antigen detection, which has proven useful in diagnosis of disseminated histoplasmosis, has not been studied in acute pulmonary histoplasmosis (APH). Because treatment is indicated in most patients with moderately severe or severe APH, antigen detection for rapid diagnosis could be helpful. METHODS: Histoplasma antigen detection was evaluated in 130 patients with APH. RESULTS: Antigenuria was detected in 64.6%, antigenemia in 68.6%, and antibody in 64.3%. If both urine and serum specimens were tested, antigen was detected in 82.8%, of which 45.8% had antigenemia only; and if both antigen and antibody were measured, results were positive in 93.3%, of which antigen only was positive in 35.7%. CONCLUSIONS: Testing for antigenemia, antigenuria, and antibodies using the complement fixation test offers a sensitive, noninvasive method for diagnosis of APH.


Asunto(s)
Antígenos Fúngicos/análisis , Histoplasma/inmunología , Histoplasmosis/diagnóstico , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedad Aguda , Antígenos Fúngicos/sangre , Antígenos Fúngicos/orina , Humanos , Inmunodifusión , Masculino
3.
Spinal Cord ; 47(10): 773-5, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19308072

RESUMEN

CASE REPORT: A case report of a 58-year-old man who sustained a laceration of his left vertebral artery during a routine corpectomy for cervical myelopathy is reported. OBJECTIVE: To report iatrogenic injury of a tortuous vertebral artery during anterior cervical spine surgery and discuss appropriate diagnosis and treatment options for this complication. SETTING: UMass Memorial Medical Center, Worcester, MA, USA. BACKGROUND DATA: Vertebral artery anomalies, although rare, are typically present with degenerative processes and great care must be taken to avoid damage during a corpectomy. Cross-sectional imaging coupled with intraoperative angiography is helpful for the urgent evaluation of the injury site and identification of the contralateral vertebral artery's status. METHODS: This is a single case of a patient sustaining a laceration of the left vertebral artery during surgery, which resulted in a lateral medullary stroke. RESULTS: After the left vertebral artery laceration, hemostasis was achieved. With the intent to better visualize and possibly embolize or stent the injury, an angiographic study was carried out. The angiogram revealed a laceration of the left vertebral artery within the vertebral foramina at vertebral body level C6, but intact distal flow. The patient underwent angiographic embolization and a subsequent magnetic resonance imaging (MRI) revealed a left lateral medullary stroke consistent with the lack of flow through the left vertebral artery from C6 to the basilar artery. CONCLUSION: If a tortuous vertebral artery is suspected, then meticulous review of preoperative cross-sectional imaging should be implemented along with angiographic examination. If anomalies are detected and the standard procedure cannot be safely carried out, then alterations, such as preoperative stent placement, need to be considered.


Asunto(s)
Vértebras Cervicales/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Compresión de la Médula Espinal/cirugía , Espondilosis/cirugía , Arteria Vertebral/anomalías , Arteria Vertebral/lesiones , Angiografía Cerebral , Circulación Cerebrovascular/fisiología , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/patología , Humanos , Enfermedad Iatrogénica/prevención & control , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/prevención & control , Síndrome Medular Lateral/etiología , Síndrome Medular Lateral/patología , Síndrome Medular Lateral/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Cuidados Preoperatorios , Rombencéfalo/irrigación sanguínea , Rombencéfalo/patología
4.
Proc Inst Mech Eng H ; 223(5): 515-24, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19623905

RESUMEN

Coronary artery stents have become the medical device of choice for the treatment of coronary artery disease. Since their introduction in 1987, significant advances in stent technology have taken place. A major objective of these developments was the reduction of in-stent restenosis, the formation of neointimal tissue inside the stent triggered by vessel injury and the inflammatory response, which results in renarrowing of the coronary artery. Improvements in strut configuration, thickness, and materials have enhanced deliverability and reduced vessel damage. Currently available drug-eluting stents release drugs that reduce neointimal formation through the arrest of cell proliferation. Drug-eluting stents have significantly reduced rates of in-stent restenosis. However, concerns have been raised with respect to their long-term safety, particularly in relation to the occurrence of late thrombosis. The post-procedural monitoring of stent-related complications is also of interest, including the relative suitability of invasive techniques such as angiography and intravascular ultrasound, and non-invasive techniques such as computed tomography and magnetic resonance imaging scanning. This paper reviews the current issues in stent technology.


Asunto(s)
Prótesis Vascular/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , Reestenosis Coronaria/prevención & control , Oclusión de Injerto Vascular/prevención & control , Stents/tendencias , Biotecnología/instrumentación , Biotecnología/tendencias , Reestenosis Coronaria/etiología , Oclusión de Injerto Vascular/etiología , Humanos
6.
Eur Spine J ; 17(4): 585-91, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18196293

RESUMEN

We analysed the morbidity, mortality and outcome of cervical spine injuries in patients over the age of 65 years. This study was a retrospective review of 107 elderly patients admitted to our tertiary referral spinal injuries unit with cervical spine injuries between 1994 and 2002. The data was acquired by analysis of the national spinal unit database, hospital inpatient enquiry system, chart and radiographic review. Mean age was 74 years (range 66-93 years). The male to female ratio was 2.1:1 (M = 72, F = 35). The mean follow-up was 4.4 years (1-9 years) and mean in-hospital stay was 10 days (2-90 days). The mechanism of injury was a fall in 75 and road traffic accident in the remaining 32 patients. The level involved was atlanto-axial in 44 cases, sub-axial in 52 cases and the remaining 11 had no bony injury. Multilevel involvement occurred in 48 patients. C2 dominated the single level injury and most of them were type II odontoid fractures. Four patients had complete neurology, 27 had incomplete neurology, and the remaining 76 had no neurological deficit. Treatment included cervical orthosis in 67 cases, halo immobilization in 25, posterior stabilization in 12 patients and anterior cervical fusion in three patients. The overall complication rate was 18.6% with an associated in-hospital mortality of 11.2%. The complications included loss of reduction due to halo and Minerva loosening, non-union and delayed union among conservatively treated patients, pin site and wound infection, gastrointestinal bleeding and complication due to associated injuries. Among the 28.9% patients with neurological involvement, 37.7% had significant neurological recovery. Outcome was assessed using a cervical spine outcome questionnaire from Johns Hopkins School of Medicine. Sixty-seven patients (70%) completed the form, 20 patients (19%) were deceased at review and 8 patients (7%) were uncontactable. Functional disability was more marked in the patients with neurologically deficit at time of injury. Outcome of the injury was related to increasing age, co-morbidity and the severity of neurological deficit. Injuries of the cervical spine are not infrequent occurrence in the elderly and occur with relatively minor trauma. Neck pain in the elderly patients should be thoroughly evaluated to exclude C2 injuries. Most patients can be managed in an orthosis but unstable injuries require rigid external immobilization or surgical stabilization.


Asunto(s)
Vértebras Cervicales/lesiones , Traumatismos Vertebrales/diagnóstico , Traumatismos Vertebrales/terapia , Anciano , Anciano de 80 o más Años , Fijadores Externos , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , Morbilidad , Aparatos Ortopédicos , Pronóstico , Estudios Retrospectivos , Traumatismos Vertebrales/mortalidad , Resultado del Tratamiento
7.
New J Phys ; 10: nihpa49499, 2008 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-18677419

RESUMEN

We investigate Ornstein-Uhlenbeck and diffusion processes with variable drift rates as models of evidence accumulation in a visual discrimination task. We derive power-law and exponential drift-rate models and characterize how parameters of these models affect the psychometric function describing performance accuracy as a function of stimulus strength and viewing time. We fit the models to psychophysical data from monkeys learning the task to identify parameters that best capture performance as it improves with training. The most informative parameter was the overall drift rate describing the signal-to-noise ratio of the sensory evidence used to form the decision, which increased steadily with training. In contrast, secondary parameters describing the time course of the drift during motion viewing did not exhibit steady trends. The results indicate that relatively simple versions of the diffusion model can fit behavior over the course of training, thereby giving a quantitative account of learning effects on the underlying decision process.

9.
Biosens Bioelectron ; 110: 65-70, 2018 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-29602032

RESUMEN

Staphylococcus aureus infections are a cause of significant morbidity and mortality, in addition to representing a considerable economic burden. The aim of this study was to explore a low cost screen printed electrode as a sensor for the detection of S. aureus using impedance spectroscopy. S. aureus was incubated in chambers containing the electrodes and the results analysed using a novel normalisation approach. These results show that it is possible to detect the presence of S. aureus in LB media after 30 min incubation of a 1% growth culture, in addition to being able to see immediate cell concentration dependant changes in 0.9% NaCl. These observations imply that a number of electrochemical mechanisms cause a change in the impedance as a result of the presence of S. aureus, including adsorption to the electrode surface and the metabolism of the bacteria during growth. The study suggests that this detection approach would be useful in a number of clinical scenarios where S. aureus leads to difficult to treat infections.


Asunto(s)
Técnicas Biosensibles/instrumentación , Espectroscopía Dieléctrica/instrumentación , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/aislamiento & purificación , Carbono/química , Impedancia Eléctrica , Electrodos , Diseño de Equipo , Humanos , Staphylococcus aureus/crecimiento & desarrollo
10.
Ir J Med Sci ; 186(2): 441-445, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27804078

RESUMEN

BACKGROUND: The 2D:4D ratio is a sexually dimorphic trait. A lower ratio is correlated with sporting prowess, successful financial trading, risk taking behaviour, aggression, and aggression-related injuries, such as the fifth metacarpal fractures. AIMS: We aimed to assess if the ratio correlates to skeletally immature patient aggression. METHODS: Radiology reports were searched for the terms "5th metacarpal" or "boxer". Of 537 X-rays, 142 had fractures. The mechanism of injury was recorded in 102 patients, differentiating aggressive and non-aggressive injury groups. Bone age and chronological age were recorded. RESULTS: A clear male preponderance for aggression was identified with only 60% of non-aggressive injuries occurring in males compared to 95% in the aggression group (p < 0.001). Patients with aggression injuries were older chronologically (14.6 vs 12.7, p < 0.001) and by bone age (14.5 vs 13.0, p < 0.001). For male patients, there was no difference in the 2D:4D ratio (p = 0.94); however, for females, the difference was significant (p = 0.04). CONCLUSIONS: Aggression injuries occur at an older age and are more common in males. In the female cohort, there was a distinct difference in digit ratio.


Asunto(s)
Agresión , Servicio de Urgencia en Hospital , Traumatismos de los Dedos/epidemiología , Fracturas Óseas/epidemiología , Adolescente , Niño , Femenino , Humanos , Masculino , Radiografía , Estudios Retrospectivos , Factores Sexuales
11.
Resuscitation ; 68(3): 429-32, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16325317

RESUMEN

We present a case of severe cardiovascular instability which required intensive care management after a myocardial infarction had been diagnosed incorrectly. Unusual ECG findings were diagnostic of calcium antagonist toxicity as the cause of the cardiovascular collapse. A discussion of the potential pitfalls in the management of patients intoxicated with these agents is undertaken. Of particular interest is the prolonged period of supportive therapy required prior to the return of an unsupported circulation. The physiological variables encountered with this type of poisoning were confirmed by the use of a PiCCO device.


Asunto(s)
Bloqueadores de los Canales de Calcio/efectos adversos , Sobredosis de Droga/diagnóstico , Angina de Pecho/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/administración & dosificación , Gasto Cardíaco , Diagnóstico Diferencial , Errores Diagnósticos , Electrocardiografía , Bloqueo Cardíaco/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Infarto del Miocardio/diagnóstico
12.
Nat Commun ; 7: 10679, 2016 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-26882053

RESUMEN

Antarctica contains some of the most productive regions on Earth for collecting meteorites. These small areas of glacial ice are known as meteorite stranding zones, where upward-flowing ice combines with high ablation rates to concentrate large numbers of englacially transported meteorites onto their surface. However, meteorite collection data shows that iron and stony-iron meteorites are significantly under-represented from these regions as compared with all other sites on Earth. Here we explain how this discrepancy may be due to englacial solar warming, whereby meteorites a few tens of centimetres below the ice surface can be warmed up enough to cause melting of their surrounding ice and sink downwards. We show that meteorites with a high-enough thermal conductivity (for example, iron meteorites) can sink at a rate sufficient to offset the total annual upward ice transport, which may therefore permanently trap them below the ice surface and explain their absence from collection data.

13.
Arch Intern Med ; 152(9): 1877-80, 1992 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1520054

RESUMEN

OBJECTIVE: This study compared the efficacy and safety of quinine sulfate, vitamin E, and placebo in the treatment of nocturnal leg cramps. DESIGN: A random-order, double-blind, placebo-controlled crossover trial was performed. SETTING: The study was conducted at the Veterans Affairs Medical Center, White River Junction, Vt. PARTICIPANTS: Twenty-seven male veterans, aged 38 to 73 years, who experienced at least six leg cramps per month were recruited through the general medicine walk-in clinic or were referred from other clinics. Fifty-five subjects were contacted, 30 were enrolled consecutively, and 27 completed the study. INTERVENTION: Subjects received, in random order, quinine sulfate (200 mg at supper and 300 mg at bedtime), vitamin E (800 U at bedtime), or placebo for 4-week periods. These periods were separated by 4-week washout intervals. OUTCOME MEASURES: Patients reported cramp frequency, severity, and sleep disturbance caused by cramps. RESULTS: Compared with treatment with placebo, quinine reduced the frequency of cramps and sleep disturbance, but not the average cramp severity. Thirteen of 27 patients had at least a 50% reduction in the number of cramps while receiving quinine; the response was usually seen within 3 days. There was evidence of a mild increase in side effects while subjects received quinine. Vitamin E was not effective in reducing leg cramp frequency, severity, or sleep disturbance. CONCLUSIONS: Quinine sulfate, but not vitamin E, is superior to placebo in the treatment of nocturnal leg cramps.


Asunto(s)
Calambre Muscular/tratamiento farmacológico , Quinina/uso terapéutico , Vitamina E/uso terapéutico , Método Doble Ciego , Humanos , Pierna , Masculino , Persona de Mediana Edad , Trastornos del Sueño-Vigilia/prevención & control
14.
Radiat Prot Dosimetry ; 114(1-3): 135-42, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15933095

RESUMEN

The applications of information technology in health care are now widespread and continue to grow. Medical imaging is at the forefront of this revolution and the introduction of digital detection methods to replace film is now addressing the diagnostic X-ray market, the most routinely employed imaging modality. The introduction of picture archiving and communication systems, hospital and radiology information systems is well underway, and the integration of radiation protection initiatives into these developments is desirable. In north-west UK, a project aimed at developing and implementing IT-driven radiation protection strategies has been underway for the past 10 y. Such strategies are geared towards the support of European Commission patient dose directive 97/43 EURATOM, in particular the need to implement clinical audit, patient dose audit and to establish dose reference levels. This paper demonstrates the national and local requirements for establishing a central dose data management system for use in radiation protection strategies. In particular, such a system can help develop and support the role of a medical physics expert in optimisation. The scientific requirements for such an approach are presented in this paper, and a prototype system is described. Preliminary results obtained with the central data management facility are also presented and the implication for analysing multiple site dose data in optimisation strategies for digital radiographic technology is highlighted.


Asunto(s)
Diagnóstico por Imagen/métodos , Protección Radiológica/instrumentación , Protección Radiológica/métodos , Sistemas de Información Radiológica , Calibración , Computadores , Humanos , Vértebras Lumbares/diagnóstico por imagen , Dosis de Radiación , Monitoreo de Radiación , Radiografía , Radiología/métodos , Programas Informáticos , Reino Unido
15.
Radiat Prot Dosimetry ; 114(1-3): 201-7, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15933109

RESUMEN

The implementation of film replacement digital radiographic imaging systems throughout Europe is now gathering momentum. Such systems create the foundations for totally digital departments of radiology, since radiographic examinations constitute the most prevalent modality. Although this type of development will lead to improvements in the delivery and management of radiological service, such widespread implementation of new technology must be carefully monitored. The implementation of effective QA tests on installation, at periodic intervals and as part of a routine programme will aid this process. This paper presents the results of commissioning tests undertaken on a number of computed radiography imaging systems provided by different manufacturers. The aim of these tests was not only to provide baseline performance measurements against which subsequent measurements can be compared but also to explore any differences in performance, which might exist between different units. Results of measurements will be presented for (1) monitor and laser printer set-up; (2) imaging plates, including sensitivity, consistency and uniformity; (3) resolution and contrast detectability; and (4) signal and noise performance. Results from the latter are analysed in relationship with both system and quantum noise components.


Asunto(s)
Radiografía/instrumentación , Radiografía/métodos , Computadores , Relación Dosis-Respuesta en la Radiación , Estudios de Evaluación como Asunto , Dosimetría por Película/instrumentación , Dosimetría por Película/métodos , Humanos , Intensificación de Imagen Radiográfica , Reproducibilidad de los Resultados , Proyectos de Investigación , Sensibilidad y Especificidad , Pantallas Intensificadoras de Rayos X
16.
Trends Biotechnol ; 12(4): 123-7, 1994 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-7764808

RESUMEN

Cross-disciplinary activity among the fields of biology, chemistry and electronics has steadily gained momentum in recent years, and defined areas for cooperative research and development are emerging. At the technology level, this has lead to the possibility of adapting techniques developed for micro- or nanofabrication of integrated circuits for the manipulation of molecules on surfaces. There are wide-ranging applications for these methods in many areas; this article describes some of them and speculates on possible future developments.


Asunto(s)
Biotecnología , Química Física , Animales , Biotecnología/métodos , Química Física/métodos , Embrión de Pollo , Electrónica , Microelectrodos , Propiedades de Superficie
17.
Protein Sci ; 6(9): 1869-77, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9300486

RESUMEN

alpha t alpha is a 38-residue peptide designed to adopt a helical hairpin conformation in solution (Fezoui Y, Weaver DL Osterhout JJ, 1995, Protein Sci 4:286-295). A previous study of the carboxylate form of alpha t alpha by CD and two-dimensional NMR indicated that the peptide was highly helical and that the helices associated in approximately the intended orientation (Fezoui Y, Weaver DL, Osterhout JJ, 1994, Proc Natl Acad Sci USA 91:3675-3679). Here, the solution structure of alpha t alpha as determined by two-dimensional NMR is reported. A total of 266 experimentally derived distance restraints and 20 dihedral angle restraints derived from J-couplings were used. One-hundred initial structures were generated by distance geometry and refined by dynamical simulated annealing. Twenty-three of the lowest-energy structures consistent with the experimental restraints were analyzed. The results presented here show that alpha t alpha is comprised of two associating helices connected by a turn region.


Asunto(s)
Péptidos/química , Estructura Secundaria de Proteína , Secuencia de Aminoácidos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Datos de Secuencia Molecular , Soluciones
18.
Endocrinology ; 122(6): 2547-53, 1988 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-3371256

RESUMEN

Androgen receptors (AR) were determined in cytosol and nuclear extracts of pituitary and neural tissue from intact male guinea pigs by a binding assay using [3H]dihydrotestosterone as ligand. Saturation analyses of cytosol from hypothalamus-preoptic area (POA)-amygdala regions and anterior pituitary revealed receptors (ARc) with apparent Kd values of 2.52 and 3.83 X 10(-10) M, respectively. Nuclear salt extracts from the same tissues contained receptors (ARn) with Kd values of 4.38 and 5.12 X 10(-10) M. Reproductive behavior of 10 males was observed with receptive females for 10 min once a week. After 4 weeks, half of the animals received 10 mg progesterone (P)/day for an additional 4 weeks. P treatment significantly (P less than 0.05) increased latency to first mount and decreased mounts per test period. After behavioral testing, analysis of the AR content of specific brain regions revealed that the highest concentrations of ARc and ARn were in the POA and medial basal hypothalamus, and the lowest were in the cerebral cortex. The ARn content was significantly suppressed in POA and medial basal hypothalamus (P less than 0.05) from P-treated males compared to the control value. These data show that AR content is highest in areas thought to control behavior and gonadotropin release within the brain of the male guinea pig. In addition, the antiandrogenic actions of P on the central nervous system, which in this experiment were expressed as a significant decline in reproductive behavior, may be explained by its interference with the retention of the AR in the nucleus.


Asunto(s)
Encéfalo/metabolismo , Adenohipófisis/metabolismo , Progesterona/farmacología , Receptores Androgénicos/metabolismo , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/ultraestructura , Animales , Encéfalo/efectos de los fármacos , Encéfalo/ultraestructura , Núcleo Celular/metabolismo , Citosol/metabolismo , Dihidrotestosterona/metabolismo , Cobayas , Hipotálamo/metabolismo , Hipotálamo/ultraestructura , Cinética , Masculino , Adenohipófisis/efectos de los fármacos , Adenohipófisis/ultraestructura , Área Preóptica/metabolismo , Área Preóptica/ultraestructura , Receptores Androgénicos/efectos de los fármacos , Reproducción/efectos de los fármacos , Conducta Sexual Animal/efectos de los fármacos , Distribución Tisular
19.
Endocrinology ; 122(5): 1890-6, 1988 May.
Artículo en Inglés | MEDLINE | ID: mdl-3359967

RESUMEN

In this study we compared the binding characteristics of methyltrienolone (R1881) in pooled cytosols from the hypothalamus-preoptic area-amygdala-septum (HPAS) of adult and fetal rhesus macaques. In addition, we studied the ontogeny of cytosolic androgen receptors (AR) in fetal neural tissue. Intact adult males and fetal rhesus monkeys of known gestational age were our experimental subjects. Fetuses were delivered by cesarean section at 50, 65, 80, and 150 days gestation. HPAS cytosols from 150-day fetuses and adult males were incubated with the synthetic ligand, [3H]R1881, for determining AR characteristics and to validate the assay. A single high affinity, low capacity receptor for R1881 was found in HPAS cytosols. The apparent dissociation constant was similar between adult and fetal HPAS (1.09 X 10(-10) vs. 1.59 X 10(-10) M, respectively). Binding specificity was determined by the addition of excess radioinert testosterone (T), 5 alpha-dihydrotestosterone, estradiol, or progesterone to the incubation tube. R1881 binding was displaced by the addition of excess amounts of T and dihydrotestosterone, but not of estradiol or progesterone. There were no differences between fetal and adult animals. Single point analyses of AR numbers in fetal animals showed significant age and regional differences (P less than 0.05). Since no sex differences were apparent, data from males and females were combined. In the hypothalamus-preoptic area there was a significant increase in AR throughout gestation [1.3 +/- 0.4 (+/- SE) fmol/mg protein; n = 7 (50 days gestation) vs. 6.2 +/- 0.3 fmol/mg protein; n = 4 (150 days of gestation); P less than 0.01]. These values differed significantly from adult male hypothalamic-preoptic area (14.1 +/- 0.3 fmol/mg protein; P less than 0.01; n = 3). AR levels in frontal and temporal cortex were high on day 50 of gestation, but showed a significant decline by day 150 (P less than 0.05). The administration of testosterone propionate (25 mg/kg.day) to pregnant animals from 40-50 days gestation, which resulted in elevated levels of serum T in female, but not male, fetuses had no effect on AR in any brain region studied. These studies confirm the presence of AR in fetal monkey brain. New information is provided on the changes in AR numbers in cortical and hypothalamic tissues during the critical period for sexual differentiation of the primate brain.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Encéfalo/embriología , Animales , Unión Competitiva , Encéfalo/metabolismo , Núcleo Celular/metabolismo , Citosol/metabolismo , Dihidrotestosterona/sangre , Estradiol/sangre , Femenino , Sangre Fetal/análisis , Edad Gestacional , Cinética , Macaca mulatta , Masculino , Especificidad de Órganos , Embarazo , Progesterona/sangre , Testosterona/sangre
20.
Clin Infect Dis ; 33(11): 1910-3, 2001 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11692303

RESUMEN

In sequential clinical trials of treatment for histoplasmosis in patients with acquired immunodeficiency syndrome, therapy with fluconazole failed in a higher proportion of patients than did therapy with itraconazole. To determine the cause for failure with fluconazole, antifungal susceptibility testing that used modified National Committee on Clinical Laboratory Standards procedures was performed on all baseline and failure isolates. Failure occurred more frequently in patients with baseline isolates with fluconazole minimum inhibitory concentrations (MICs) > or =5 microg/mL versus lower MICs; 29% versus 3%, respectively. There was at least a 4-fold increase in fluconazole MIC in the isolates from 10 (59%) of 17 patients for whom paired pretreatment and failure or relapse isolates were available. Cross-resistance to itraconazole was not seen. In conclusion, fluconazole is less active than itraconazole for Histoplasma capsulatum and induces resistance during therapy, which accounted for treatment failure in some patients.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Antifúngicos/uso terapéutico , Farmacorresistencia Fúngica , Fluconazol/uso terapéutico , Histoplasmosis/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Antifúngicos/farmacología , Susceptibilidad a Enfermedades , Fluconazol/farmacología , Histoplasma/efectos de los fármacos , Histoplasma/aislamiento & purificación , Histoplasmosis/complicaciones , Histoplasmosis/microbiología , Humanos , Itraconazol/farmacología , Pruebas de Sensibilidad Microbiana , Recurrencia , Insuficiencia del Tratamiento
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