RESUMEN
Doubly electrophilic pyrazabole derivatives (pyrazabole = [H2B(µ-C3N2H3)]2) combined with one equiv. of base effect the ortho-borylation of N-alkyl anilines. Initial studies found that the bis(trifluoromethane)sulfonimide ([NTf2]-) pyrazabole derivative, [H(NTf2)B(µ-C3N2H3)]2, is highly effective for ortho-borylation, with this process proceeding through N-H borylation and then ortho C-H borylation. The activation of pyrazabole by I2 was developed as a cheaper and simpler alternative to using HNTf2 as the activator. The addition of I2 forms mono or ditopic pyrazabole electrophiles dependent on stoichiometry. The ditopic electrophile [H(I)B(µ-C3N2H3)]2 was also effective for the ortho-borylation of N-alkyl-anilines, with the primary C-H borylation products readily transformed into pinacol boronate esters (BPin) derivatives. Comparison of borylation reactions using the di-NTf2-and the diiodo-pyrazabole congeners revealed that more forcing conditions are required with the latter. Furthermore, the presence of iodide leads to competitive formation of side products, including [HB(µ-C3N2H3)3BH]+, which are not active for C-H borylation. Using [H(I)B(µ-C3N2H3)]2 and 0.2 equiv. of [Et3NH][NTf2] combines the higher yields of the NTf2 system with the ease of handling and lower cost of the iodide system generating an attractive process applicable to a range of N-alkyl-anilines. This methodology represents a metal free and transiently directed C-H borylation approach to form N-alkyl-2-BPin-aniline derivatives.
RESUMEN
Electrophilic borylation of indoles with BX3 (X = Cl or Br) using directing groups installed at N1 can proceed at the C2 or the C7 position. The six membered heterocycle directing groups utilised herein, pyridines and pyrimidine, result in indole C2 borylation being the dominant outcome (in the absence of a C2-substituent). In contrast, C7 borylation was achieved using five membered heterocycle directing groups, such as thiazole and benzoxazole. Calculations on the borylation of indole substituted with a five (thiazole) and a six (pyrimidine) membered heterocycle directing group indicated that borylation proceeds via borenium cations with arenium cation formation having the highest barrier in both cases. The C7 borylated isomer was calculated to be the thermodynamically favoured product with both five and six membered heterocycle directing groups, but for pyrimidine directed indole borylation the C2 product was calculated to be the kinetic product. This is in contrast to thiazole directed indole borylation with BCl3 where the C7 borylated isomer is the kinetic product too. Thus, heterocycle ring size is a useful way to control C2 vs. C7 selectivity in N-heterocycle directed indole C-H borylation.
RESUMEN
The intramolecular C-H borylation of (hetero)arenes and alkenes using electrophilic boranes is a powerful transition metal free methodology for forming C-B bonds. These C-H borylation reactions are preceded by intermolecular bond (both dative and covalent) formation, with examples proceeding via initial C-B and N-B bond formation dominating this field thus both are discussed in depth herein. Less prevalent intramolecular electrophilic C-H borylation reactions that proceed by intermolecular O-B, S-B and P-B bond formation are also summarised. Mechanistic studies are presented that reveal two mechanisms for C-H borylation, (i) electrophilic aromatic substitution (prevalent with B-X electrophiles); (ii) σ-bond metathesis mediated (prevalent with B-H and B-R electrophiles). To date, intramolecular electrophilic C-H borylation is utilised mainly for accessing boron containing conjugated organic materials, however recent developments, summarized herein alongside early studies, have highlighted the applicability of this methodology for forming synthetically versatile organo-boronate esters and boron containing bioactives. The multitude of synthetic procedures reported for intramolecular electrophilic C-H borylation contain many common features and this enables key requirements for successful C-H borylation and the factors effecting regioselectivity and substrate scope to be identified, discussed and summarized.
RESUMEN
The development of painful peripheral neuropathy is a dose-limiting side effect of numerous cancer chemotherapeutic agents. The present study utilized a rodent model of vincristine-induced neuropathy to determine whether a glial modulating agent, propentofylline, could attenuate vincristine-induced mechanical allodynia. Intravenous vincristine administered on days 1 through 5 and days 8 through 11 produced mechanical allodynia using 2 and 12 g von Frey filaments. Lumbar spinal cord from animals on day 15 expressed mild bilateral microglial and astrocytic activation as compared to saline-treated animals. Daily intraperitoneal propentofylline at 10 mg/kg attenuated mechanical allodynia induced by vincristine administration. In addition, propentofylline was found to decrease spinal microglial and astrocytic activation on day 15. These data suggest that central glial cells may play an important role in the development of painful neuropathy following vincristine administration.
Asunto(s)
Antineoplásicos/efectos adversos , Hiperalgesia/inducido químicamente , Hiperalgesia/prevención & control , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Vincristina/efectos adversos , Xantinas/administración & dosificación , Animales , Combinación de Medicamentos , Hiperalgesia/diagnóstico , Masculino , Fármacos Neuroprotectores/administración & dosificación , Dimensión del Dolor/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Enfermedades del Sistema Nervioso Periférico/patología , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
The specific mechanisms by which nervous system injury becomes a chronic pain state remain undetermined. Historically, it has been believed that injuries proximal or distal to the dorsal root ganglion (DRG) produce distinct pathologies that manifest in different severity of symptoms. This study investigated the role of injury site relative to the DRG in (1) eliciting behavioral responses, (2) inducing spinal neuroimmune activation, and (3) responding to pharmacologic interventions. Rats received either an L5 spinal nerve transection distal to the DRG or an L5 nerve root injury proximal to the DRG. Comparative studies assessed behavioral nociceptive responses, spinal cytokine mRNA and protein expression, and glial activation after injury. In separate studies, intrathecal pharmacologic interventions by using selective cytokine antagonists (interleukin-1 [IL-1] receptor antagonist and soluble tumor necrosis factor [TNF] receptor) and a global immunosuppressant (leflunomide) were performed to determine their relative effectiveness in these injury paradigms. Behavioral responses assessed by mechanical allodynia and thermal hyperalgesia were almost identical in the two models of persistent pain, suggesting that behavioral testing may not be a sensitive measure of injury. Spinal IL-1beta, IL-6, IL-10, and TNF mRNA and IL-6 protein were significantly elevated in both injuries. The overall magnitude of expression and temporal patterns were similar in both models of injury. The degree of microglial and astrocytic activation in the L5 spinal cord was also similar for both injuries. In contrast, the pharmacologic treatments were more effective in alleviating mechanical allodynia for peripheral nerve injury than nerve root injury, suggesting that nerve root injury elicits a more robust, centrally mediated response than peripheral nerve injury. Overall, these data implicate alternate nociceptive mechanisms in these anatomically different injuries that are not distinguished by behavioral testing or the neuroimmune markers used in this study.
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Antígenos CD , Antígenos de Neoplasias , Antígenos de Superficie , Proteínas Aviares , Proteínas Sanguíneas , Citocinas/metabolismo , Ganglios Espinales/lesiones , Gliosis/metabolismo , Neuroglía/metabolismo , Dolor/fisiopatología , Enfermedades del Sistema Nervioso Periférico/metabolismo , Médula Espinal/metabolismo , Animales , Basigina , Citocinas/antagonistas & inhibidores , Citocinas/genética , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ganglios Espinales/patología , Ganglios Espinales/fisiopatología , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/etiología , Gliosis/fisiopatología , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatología , Inmunohistoquímica , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Vértebras Lumbares , Masculino , Glicoproteínas de Membrana/metabolismo , Neuroglía/efectos de los fármacos , Neuroglía/patología , Dolor/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/patología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Sialoglicoproteínas/farmacología , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
UNLABELLED: Impaired in vivo immunity is often observed after major surgery and is multifactorial. We conducted a randomized clinical study to determine the independent effects of general anesthesia (GA) and of lumbar epidural anesthesia (LEA) on human immune function in the absence of surgical trauma. Nineteen healthy volunteers were randomized to receive GA with thiopental and isoflurane, LEA with lidocaine, or no anesthesia (Control). Serial blood samples were tested for antibody responses to antigen inoculation, neutrophil and mononuclear cell antibody-dependent cell cytotoxicity (ADCC), natural killer cell cytotoxicity, and neutrophil phagocytic activity. Antibody responses were similar in the three groups. Mononuclear cell ADCC increased in the LEA group at the end of the anesthetic (P < 0.05 at effector/target [E/T] ratios of 10:1, 25:1, and 50:1). Natural killer cell cytotoxicity increased at the end of the anesthetic in both the LEA group (P < 0.05 at all E/T ratios) and the GA group (P < 0.05 at an E/T ratio of 5:1 and 10:1). No significant changes were observed for neutrophil ADCC or phagocytosis. General or epidural anesthesia alone, in the absence of surgery, seems to have only transient and minor effects on human immune function. IMPLICATIONS: General or epidural anesthesia alone, in the absence of surgery, seems to have only transient and minor effects on human immune function.
Asunto(s)
Anestesia Epidural , Anestesia General , Inmunidad , Adulto , Anticuerpos/sangre , Citotoxicidad Celular Dependiente de Anticuerpos , Femenino , Humanos , Células Asesinas Naturales/inmunología , Leucocitos Mononucleares/inmunología , Masculino , Neutrófilos/inmunologíaRESUMEN
The purpose of this study was to investigate the role of peripheral macrophages in the generation of mechanical allodynia utilizing a modification of the Chung rat model of neuropathy. Three distinct methods were used: (1) systemic and perineural macrophage inhibition utilizing CNI-1493; (2) depletion of the peripheral macrophage population by liposome-encapsulated clodronate; and (3) perineural administration of activated or inactivated bone marrow-derived macrophages (BMDM) in sham-surgery rats. Mechanical allodynia was tested on days 1, 3, 5, 7, and 10 post-intervention or surgery using von Frey monofilaments. In order to assess the role of spinal glia following these interventions, microglial (CNS macrophages) and astrocytic activation was assessed using immunohistochemistry. CNI-1493 did not attenuate mechanical allodynia, or spinal glial expression as compared to the saline control group. Similarly, the clodronate depletion of peripheral macrophages prior to nerve injury did not have any effect on the resultant mechanical allodynia or spinal glial activation. Perineural administration of activated or inactivated BMDM did not evoke mechanical allodynia in sham surgery rats. Of interest, we observed an ipsilateral, dorsal horn increase in microglial expression following perineural administration of activated macrophages. In summary, these data suggest a limited role of activated macrophages in the onset of mechanical allodynia in an animal model of neuropathy.
Asunto(s)
Hiperestesia/etiología , Macrófagos/fisiología , Nervios Espinales/lesiones , Heridas Penetrantes/complicaciones , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/farmacología , Animales , Trasplante de Médula Ósea , Recuento de Células , Ácido Clodrónico/administración & dosificación , Ácido Clodrónico/farmacología , Hidrazonas/farmacología , Hiperestesia/fisiopatología , Inmunohistoquímica , Liposomas , Macrófagos/efectos de los fármacos , Macrófagos/trasplante , Masculino , Neuroglía/patología , Dimensión del Dolor , Estimulación Física , Ratas , Ratas Sprague-Dawley , Médula Espinal/patología , Heridas Penetrantes/patología , Heridas Penetrantes/psicología , Heridas Penetrantes/cirugíaRESUMEN
We examined the distribution of cocaine and its metabolites benzoylecgonine (BE) and norcocaine (NOR) in pregnant Sprague-Dawley rats and fetuses following twice-daily subcutaneous (s.c.) injections of 20 mg/kg cocaine HCl from gestational day (GD) 8 through GD 20. On GD 21, the animals received a single injection and maternal trunk blood, fetal blood, fetal brains, and amniotic fluid were collected 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, or 12 h later for cocaine and metabolite analyses by high-performance liquid chromatography (HPLC) with UV detection. The highest concentrations of cocaine and BE were detected in maternal plasma at 1 h and 4 h respectively. Cocaine peaked at 2 h and BE at 4 h in both fetal plasma and brain. In amniotic fluid, cocaine levels peaked at 2 h, but the highest BE levels were found at 8 h postinjection. An additional group of chronically treated dams was given both cocaine injections on GD 21 and sacrificed 2 h later. Benzoylecgonine concentrations were increased in fetal plasma, fetal brain, and amniotic fluid when compared with the 2-h results following a single cocaine treatment. Moreover, NOR, which had not been previously detected, was now measurable in the amniotic fluid.
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Trastornos Relacionados con Cocaína/metabolismo , Cocaína/farmacocinética , Feto/metabolismo , Intercambio Materno-Fetal , Complicaciones del Embarazo/metabolismo , Animales , Cocaína/administración & dosificación , Cocaína/análogos & derivados , Femenino , Inyecciones Subcutáneas , Embarazo , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
The goals of dialytic therapy are to provide safe, effective care and to emphasize the continuous improvement of quality. To provide such effective care requires the availability of a functional dialysis access. This is a critical (and sometimes the most difficult) component of dialysis. Care should focus not only on the maintenance of function but also on the prevention of complications. This article will familiarize the healthcare professional with the types, uses, and management of peritoneal and hemodialysis catheters.
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Catéteres de Permanencia , Diálisis Peritoneal/instrumentación , Diálisis Renal/instrumentación , Antisepsia , HumanosRESUMEN
The three-detector TRIAD 88 is a variable cylindrical FOV whole-body SPECT system designed for both brain as well as body organ imaging. The system performance was assessed in terms of physical indices and clinical quality. Measures of low contrast resolution using contrast-detail curves, high contrast resolution using LSFs and associated frequency descriptors, display characteristics, system sensitivity, energy resolution and uniformity analysis were utilized. In addition, images of Carlson phantom, Hoffman brain phantom and clinical brain images were used to compare two collimators subjectively. Measurements and calculations were obtained for two sets of parallel hole collimators, i.e., LEUR_PAR and LEHR_PAR. Of special interest is the consistency among the three detectors. The planar and volume sensitivities for the LEUR_PAR collimator were about 58% of those of the LEHR_PAR collimator. The planar spatial resolution of the two collimators differed by about 14%. The display was characterized by a logistic model H & D curve. The planar contrast-detail curves demonstrated no statistical difference in lesion detectability between the two collimator types, however SPECT phantom and clinical images demonstrated improved performance with the LEUR_PAR collimator. Images of Hoffman single slice brain and Carlson phantoms and Tc-99m (HMPAO) brain images demonstrated excellent image quality. There was similarity in performance parameters of the three detector heads.
Asunto(s)
Tomografía Computarizada de Emisión de Fotón Único/instrumentación , Fenómenos Biofísicos , Biofisica , Encéfalo/diagnóstico por imagen , Estudios de Evaluación como Asunto , Humanos , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
Cerebral glucose metabolic rates were determined in normal control subjects (n = 26) and schizophrenic patients with tardive dyskinesia (n = 14). Globus pallidus and primary motor cortex (precentral gyrus) metabolic values divided by those of the cerebral hemispheres were significantly increased in the patient group. A similar metabolic pattern has not been reported for schizophrenic patients without tardive dyskinesia, and the abnormalities were demonstrated despite the normal appearance of the basal ganglia on X-ray CT. The findings differed markedly from the reduced metabolic rates of the basal ganglia previously identified in other choreiform disorders, including Huntington's and Wilson's diseases. The findings suggest that tardive dyskinesia is characterized by increased pallidal synaptic activity resulting from either altered striatopallidal input or increased pallidal interneuron firing.
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Antipsicóticos/efectos adversos , Glucemia/metabolismo , Encéfalo/efectos de los fármacos , Discinesia Inducida por Medicamentos/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológico , Tomografía Computarizada de Emisión , Adulto , Anciano , Antipsicóticos/uso terapéutico , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Dominancia Cerebral/efectos de los fármacos , Dominancia Cerebral/fisiología , Femenino , Globo Pálido/diagnóstico por imagen , Globo Pálido/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/diagnóstico por imagen , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiologíaRESUMEN
A method has been developed for co-registering three-dimensional multi-modality images of the human brain. The interactive program allows users to specify the interhemispheric fissure plane in three dimensions by identifying the endpoints of the centerline within transaxial slices. Translations and rotations within transaxial and coronal planes are determined to align the interhemispheric fissure planes of the two image sets to be co-registered. After reslicing the two partially co-registered image volumes, the intercommissural lines are detected by using three internal landmarks. A transformation including translation and rotation in the sagittal plane finally co-registers the two image sets in three-dimensional space. Single photon emission computed tomography (SPECT) images and magnetic resonance (MR) images have been used to validate the method for co-registering three-dimensional functional and anatomic brain images. This new co-registration method requires neither special head positioning procedures nor external fiducial markers, thereby making it appropriate for the routine clinical practice.
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Encéfalo/anatomía & histología , Procesamiento de Imagen Asistido por Computador , Encéfalo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Valores de Referencia , Reproducibilidad de los Resultados , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
OBJECTIVE: To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease. DESIGN: Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/- 9) months. SETTING: Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology. SUBJECTS: Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry. INTERVENTIONS: None. OUTCOME MEASURES: Onset of chorea and imaging results. RESULTS: The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently. CONCLUSIONS: The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism.
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Núcleo Caudado/patología , Corteza Cerebral/patología , Glucosa/metabolismo , Enfermedad de Huntington/metabolismo , Adulto , Núcleo Caudado/metabolismo , Corteza Cerebral/diagnóstico por imagen , Susceptibilidad a Enfermedades , Femenino , Marcadores Genéticos , Humanos , Enfermedad de Huntington/diagnóstico por imagen , Enfermedad de Huntington/genética , Enfermedad de Huntington/patología , Masculino , Persona de Mediana Edad , Tomografía Computarizada de EmisiónRESUMEN
We examined chorea-free subjects at risk for Huntington's disease (n = 52) for lifetime psychiatric diagnoses, present mood, genetic marker status, and caudate glucose metabolic rates with positron emission tomography. Based on previous work, a caudate-ipsilateral hemisphere ratio less than 1.15 was defined as abnormal and predictive of Huntington's disease. None of three methods used to segregate subjects into groups more and less likely to develop Huntington's disease gave significant group rate differences for any formal psychiatric diagnoses. On present mood testing, however, subjective "anger/hostility" was significantly higher in those likely, compared with those less likely, to develop Huntington's disease, as determined by all three methods.
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Enfermedad de Huntington/genética , Trastornos Mentales/epidemiología , Adulto , Anciano , Núcleo Caudado/metabolismo , Femenino , Marcadores Genéticos , Glucosa/metabolismo , Humanos , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/metabolismo , Funciones de Verosimilitud , Masculino , Trastornos Mentales/diagnóstico , Persona de Mediana Edad , Modelos Genéticos , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Tomografía Computarizada de EmisiónRESUMEN
The Renfrew Word Finding Scale (Renfrew, 1988) was administered to 30 Indian (Group A) and 30 White (Group B) Durban English speaking children aged between eight and nine years to determine its suitability for assessment of expressive vocabulary. Mean scores for both groups were statistically compared to the British norms in terms of mean raw scores and mean mental age. Mean scores for groups A and B were compared to each other. Item analyses were carried out to obtain further information regarding possible lexical characteristics for each group and common problems with certain items. Both groups performed significantly poorer than expected according to the British norms. Group A was significantly lower than Group B, thus indicating the test's unsuitability for use with these population groups in its present form.
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Trastornos de la Comunicación/diagnóstico , Etnicidad , Pruebas del Lenguaje/normas , Niño , Cultura , Femenino , Humanos , Masculino , Valores de Referencia , SudáfricaRESUMEN
We compared four diagnostic data sets for the assessment of individuals at risk for Huntington's disease. Fifty-four chorea-free persons were evaluated by neurological examination, positron emission tomography measurement of glucose metabolism, radiographic computerized tomographic measurement of caudate size, and genetic testing at the polymorphic DNA loci D4S10, D4S43, and D4S125. Twelve (22%) persons had abnormal caudate metabolism, 6 (11%) had subtle abnormalities of motor control, and 7 (13%) had computed tomographic evidence of caudate atrophy, compared with an expected gene frequency of 34% for this population. In 20 persons with unambiguous genetic test results or the subsequent phenotypic expression of Huntington's disease (chorea), there was a greater sensitivity of the positron emission tomographic measurement of caudate metabolism (75%) relative to computed tomography (33%) or the clinical examination (17%) for the determination of a subpopulation of probable Huntington's disease gene carriers. Hypometabolism of the putamen and globus pallidus, and hypermetabolism of the precentral gyrus were also associated with a high probability of carrying the Huntington's disease gene. The findings support the hypothesis that abnormalities of cerebral metabolism precede clinical or structural (computed tomographic) abnormalities in gene-positive individuals at risk for Huntington's disease.
Asunto(s)
Enfermedad de Huntington/metabolismo , Atrofia , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/metabolismo , Lóbulo Frontal/metabolismo , Globo Pálido/metabolismo , Glucosa/metabolismo , Heterocigoto , Humanos , Enfermedad de Huntington/diagnóstico por imagen , Enfermedad de Huntington/genética , Enfermedad de Huntington/fisiopatología , Examen Neurológico , Fenotipo , Polimorfismo de Longitud del Fragmento de Restricción , Valor Predictivo de las Pruebas , Putamen/metabolismo , Tomografía Computarizada de Emisión , Tomografía Computarizada por Rayos XRESUMEN
The gradual closure of a long-stay hospital is stressful for staff. Some may have doubts about the case for community care, and almost all are affected by uncertainty and by the provisional step-by-step changes as patients gradually move out. The maintenance of staff morale during the transition is therefore important and difficult. This article examines some of the stresses and misunderstandings, and suggests how they could be managed.
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Administración de Instituciones de Salud , Clausura de las Instituciones de Salud/organización & administración , Hospitales de Enfermedades Crónicas , Hospitales Especializados , Administración de Personal , Comunicación , Humanos , Moral , Medicina Estatal , Reino Unido , Recursos HumanosRESUMEN
The accuracy and decision criterion of 51 persons at-risk (AR) for Huntington's disease (HD) along with 36 age-matched, healthy controls were evaluated using a word recognition memory test. Analyses revealed that the AR group was less accurate than the controls at recognizing a previously learned word list. Within the AR group, 13 AR persons were identified who committed significantly more false alarms than the remaining AR and control people. The 13 AR persons also showed evidence of lower cerebral metabolic ratios in frontal, caudate, and insula regions, as evaluated by positron emission tomography using I8F-Fluoro-deoxyglucose, and were considered to be at high risk for HD. One of these 13 AR persons has become symptomatic since testing, confirming the high risk status. These results suggest that certain tests of cognition and decision-making together with measures of regional brain metabolism might show the subtle cognitive changes taking place in potential HD gene carriers years before the clinical symptoms are observed.