The key challenges of discussing end-of-life stroke care with patients and families: a mixed-methods electronic survey of hospital and community healthcare professionals.

BACKGROUND: Communication between professionals, patients and families about palliative and end-of-life care after stroke is complex and there is a need for educational resources in this area. METHODS: To explore the key learning needs of healthcare professionals, a multidisciplinary, expert group developed a short electronic survey with open and closed questions, and then distributed it to six UK multiprofessional networks and two groups of local clinicians. RESULTS: A total of 599 healthcare professionals responded. Educational topics that were either definitely or probably needed were: ensuring consistent messages to families and patients (88%); resolving conflicts among family members (83%); handling unrealistic expectations (88%); involving families in discussions without them feeling responsible for decisions (82%); discussion of prognostic uncertainties (79%); likely mode of death (72%); and oral feeding for 'comfort' in patients at risk of aspiration (71%). The free-text responses (n = 489) and 82 'memorable' cases identified similar themes. CONCLUSION: Key topics of unmet need for education in end-of-life care in stroke have been identified and these have influenced the content of an open access, web-based educational resource.

CYP2D6-mediated catalysis of tamoxifen aromatic hydroxylation with an NIH shift: similar hydroxylation mechanism in chicken, rat and human liver microsomes.

1. 4-Tritiated-tamoxifen (4-[(3)H]-tamoxifen) and 4-deuterated-tamoxifen (4-[(2)H]-tamoxifen) were synthesized to examine tamoxifen metabolism by human P450 (CYP) forms and also for the possibility of determining tamoxifen-4-hydroxylation in humans in vivo. 2. Liver microsomes from several species and cDNA-expressed human P450s were incubated with 4-[(3)H]-tamoxifen and the reaction monitored by assaying 4-hydroxytamoxifen (4-OH-tam) and (3)H(2)O formed. However, tamoxifen-4-hydroxylation did not generate stoichiometric amounts of (3)H(2)O and the expected unlabelled 4-OH-tam but instead yielded radiolabelled 4-OH-tam, apparently from [(3)H]-migration to the ortho-position, referred to as the NIH shift. 3. CYP2D6 was the prime catalyst of tam-4-hydroxylation, whereas CYP2B6, 2C9 and 2C19 yielded only low levels of 4-OH-tam; nevertheless, in all cases the 4-OH-tam was radioactive, apparently resulting from reactions involving an NIH shift. 4. Chicken liver microsomal preparation, being catalytically the most active in tamoxifen-4-hydroxylation, was incubated with deuterated tamoxifen (4-[(2)H]-tamoxifen) in order to determine whether an NIH shift occurs. Ion-trap mass-spectrometry of the HPLC-purified 4-OH-tam, from that incubation, indicated about 60% of [(2)H]-retention in 4-OH-tam, signifying an NIH shift. These findings indicate that the aromatic hydroxylation of tamoxifen does not entail hydroxyl insertion with an Sn2-displacement of hydrogen or a hydrogen isotope ((2)H or (3)H), but apparently involves epoxidation followed by migration of the (3)H, (2)H or (1)H to the ortho-position, and dissociation of the (1)H in preference to (3)H or (2)H, i.e. retention of the hydrogen isotope appears to be related to the bond strengths: C-(3)H>C-(2)H>C-(1)H.

A pyridone analogue of traditional cannabinoids. A new class of selective ligands for the CB(2) receptor.

A pyridone analogue (5) of the potent bicyclic cannabinoid CP 47,497 (6) has been synthesized as a model for one conformational isomer of anandamide and to test the hypothesis that an amide carbonyl may serve as a hydrogen bond acceptor in interactions with the CB(1) cannabinoid receptor. Pyridone 5 was synthesized from 6-bromo-2-methoxypyridine (10) by palladium catalyzed coupling with 1-pentyne to provide 11. Catalytic hydrogenation of 11 and hydrolysis to pyridone 13 followed by N-alkylation gave 1-propyl-6-pentyl-2-pyridone (15). Bromination of 15 gave dibromide 18, which underwent Heck coupling with cyclohex-2-en-1-one to give enone 19. Catalytic hydrogenation of 19 gave ketone 20 which was reduced using NaBH(4) to alcohol 5. Reduction of 20 with K-Selectride gave the axial epimer of 5 (21). Neither alcohol 5 nor 21 have significant affinity for the CB(1) receptor (K(i) > 970 nM), but both have moderately high affinity for the CB(2) receptor (K(i) < 60 nM).

Target-directed enediynes: designed estramycins.

The goal of selective targeting of enediyne cytotoxins has been investigated using estrogenic delivery vehicles. A series of estrogen-enediyne conjugates were assembled, and affinity for human estrogen receptor [hERalpha] was determined. The most promising candidate induced receptor degradation following Bergman cycloaromatization and caused inhibition of estrogen-induced transcription in T47-D human breast cancer cells.

Neuropsychological aspects of pediatric sickle cell disease.

Sickle cell disease (SCD), a class of genetic disorders characterized by abnormal, sickled red blood cells, is a chronic illness that results in progressive cerebrovascular disease. Neurocognitive sequelae of clinically apparent cerebrovascular accidents in children with SCD are characterized by pervasive impairments, including decrements in general intellectual functioning, language and verbal abilities, visual-motor and visual-spatial processing, memory, academic achievement, and processing of subtle prosodic information. In contrast, subtle neurocognitive deficits in the areas of attention and concentration, executive function, and visual-motor speed and coordination appear to be associated with silent infarcts that are not necessarily detected on physical examination. Investigation of the disease course and associated neurocognitive sequelae suggest a disease-specific model of neuropsychological impairment. Recommendations are made for clinical and research efforts in the field of pediatric neuropsychology.

Injury severity and neuropsychological and balance outcomes of four college athletes.

Recent evidence suggests significant short-term neurocognitive deficits following mild traumatic brain injury (MTBI) in sports. However, sequelae of mild head injuries is complicated by many factors including a history of multiple head injuries and injury severity. Few studies have considered the influence these variables may have on proper classification of a MTBI and their meaning for return-to-play guidelines. This study presents the short-term neuropsychological and balance outcomes of four college athletes who sustained mild head injuries of different severity (grade I, grade II, grade III and multiple head injured with a grade II based on American Academy of Neurology guidelines). The results demonstrated that self-report symptoms of concussion were slow to resolve in the grade III and multiple concussed individuals. For neuropsychological testing, Trails A & B, Symbol Digit Modalities Test and Digits Span Backwards were the most sensitive in identifying differences between the injuries. For balance assessments using the Neurocom Smart Balance System, the Sensory Organization Test and Reaction Time were also important variables in detecting differences among the various injuries. When these data are used together, it can assist physicians in determining safe return-to-play for athletes who sustain MTBI. There are contradindications in the numerous grading systems and return-to-play guidelines for MTBI. The results from this study provides new evidence which can be assimilated into a valid grading scale for MTBI sustained in sport.

Rapid naming deficits in children and adolescents with reading disabilities and attention deficit hyperactivity disorder.

Seventy-one children in three groups (reading disabilities, ADHD without reading disabilities, and normal controls) were compared on their ability to rapidly name colors, letters, numbers, and objects (RAN Tasks) and alternating letters/numbers and letters/numbers/colors (RAS tasks). Children with reading disabilities were found to be slower on letter- and number-naming tasks and made more errors on all tasks than controls or children with ADHD. There was an age effect for the RAN/RAS tasks, with younger children with reading disabilities performing more poorly on all tasks, while the older children with reading disabilities showed poorer performance only on the letter- and number-naming tasks.

Sulcal/gyral pattern morphology of the perisylvian language region in developmental dyslexia.

Two systems for classification of morphology of the perisylvian cortical area have been suggested, that of Steinmetz et al. (1990) and that of Witelson and Kigar (1992). This study examines whether the variations in placement of these convolutions in the language cortex are related to diagnosis of dyslexia in a clinic-referred sample of 55 children ages 8 to 12 years. Additionally, the systems are compared to determine their relationship to neurolinguistic performance. In this study, the Steinmetz et al. (1990) system captured morphological distinctions which were relevant to performance on neurolinguistic measures, while Witelson and Kigar's (1992) system did not. Under neither system was morphology associated with diagnosis of dyslexia.

Protein-degrading enediynes: library screening of Bergman cycloaromatization products.

[structure: see text] A screening method based on Bergman cycloaromatization products was applied to a compact library of estrogenic-enediyne hybrids. An enediyne candidate identified from the screen was subsequently synthesized, and it induced temperature- and concentration-dependent degradation of human estrogen receptor alpha upon cycloaromatization.

Dyslexia, neurolinguistic ability, and anatomical variation of the planum temporale.

This article addresses the relationship between patterns of planum temporale symmetry/asymmetry and dyslexia and neurolinguistic abilities. Considerable research indicates that dyslexic individuals typically do not display the predominant pattern of leftward planum temporale asymmetry. Variable findings on the structural basis of symmetry are due partially to measurement issues, which are examined in some detail in this critical review. The physiological basis of symmetry may be reduced neuronal elimination in the right planum, although other alternatives are offered. Theories are offered to explain how symmetrical plana are related to dyslexia, and it is evident that symmetrical plana are not sufficient to produce dyslexia. However, some evidence suggests that nonleftward plana asymmetry is associated with deficits in verbal comprehension, phonological decoding, and expressive language. It is concluded that nonleftward asymmetry is associated with linguistic deficits, but that explanatory theories need to be further developed. Among the many issues that need to be addressed, future research needs to determine whether the relationship between patterns of planum temporale symmetry/asymmetry and linguistic ability is specific to dyslexia or if asymmetry covaries lawfully with linguistic abilities in nondyslexic populations.

Academic underachievement in ADHD subtypes.

Although a relationship between attention-deficit/hyperactivity disorder (ADHD) and academic underachievement has been widely reported, the nature of this relationship has not been specified. The present investigation addresses this relationship directly by comparing 24 students (20 males and 4 females) with ADHD and 20 students (15 males and 5 females) with attention-deficit disorder without hyperactivity (ADD/noH) referred to a university-based diagnostic clinic for comprehensive neuropsychological assessment. The students ranged in age from 6 years 0 months to 12 years 10 months. Consistent with previous reports, this study found that math achievement test scores for students with ADD/noH were significantly lower than those for students with ADHD. These findings support previous research suggesting the ADD/noH may represent a distinct ADD subtype. It is hypothesized that inattention interferes with students' ability to master abstract symbol systems, especially in the acquisition of basic arithmetic skills in the primary grades.

Validity of the age-of-onset criterion for ADHD: a report from the DSM-IV field trials.

OBJECTIVE: To examine the validity of the DSM-IV requirement of an age of onset of impairment due to symptoms before 7 years of age for the diagnosis of attention-deficit/hyperactivity disorder (ADHD). METHOD: The validity of this criterion was examined in a clinic sample of 380 youths aged 4 through 17 years by comparing youths who met symptom criteria for ADHD and either did or did not display impairment before age 7 years. RESULTS: Nearly all youths who met symptom criteria for the predominantly hyperactive-impulsive subtype also met the age of onset of impairment criterion, but 18% of youths who met symptom criteria for the combined type, and 43% of youths who met symptom criteria for the predominantly inattentive type, did not manifest impairment before 7 years. For the latter two subtypes, requiring impairment before age 7 years reduced the accuracy of identification of currently impaired cases of ADHD and reduced agreement with clinicians' judgments. CONCLUSIONS: These findings raise questions about the validity of the DSM-IV definition of age of onset of ADHD. Marked differences in the ages of onset of both symptoms and impairment for the three subtypes of ADHD support the validity of distinguishing among these subtypes in DSM-IV.

Diagnosing ADHD (predominantly inattentive and combined type subtypes): discriminant validity of the behavior assessment system for children and the achenbach parent and teacher rating scales.

Compared the effectiveness of discriminating attention deficit/hyperactivity disorder (ADHD) subtypes using the Parent Rating Scale (PRS) and Teacher Rating Scale (TRS) of the Behavior Assessment System for Children (BASC) and the Parent Report Form and Teacher Report Form (TRF) of the Achenbach Child Behavior Checklist (CBCL). To determine the extent to which these scales measured similar behaviors, Pearson Product-Moment Correlations were computed for the parent scales (PRS and CBCL) and for the teacher scales (TRS and TRF). Results indicated that correlations were significant for a number of scales. Discriminant analysis does not suggest a strong advantage of either measure in differentiating children with ADHD from those who do not meet criteria for ADHD, except for the BASC TRS which has better predictive ability for children who do not meet ADHD criteria. For subtypes of ADHD, and specifically the ADHD: Predominantly Inattentive subtype, however, results would favor the use of the BASC PRS and TRS.

Validity of the Auditory Continuous Performance Test in differentiating central processing auditory disorders with and without ADHD.

The use of continuous performance tasks has been examined as a potential measure for clinical/laboratory identification of Attention-deficit/hyperactivity disorder. The present study compared the performance of 30 children, 26 boys and 4 girls ranging in age from 9-0 to 12-11, with central auditory processing disorders (CAPD) who did not meet criteria for coexisting ADHD with the performance of children with CAPD coexisting with ADHD (CAPD/ADHD) on the Auditory Continuous Performance Test (ACPT). In interpreting the results, the variability as well as the actual counts for correct responses and total errors were considered. Results indicated limited potential for the use of the ACPT in the differential diagnosis of ADHD. Implications of the results as well as considerations for future research are discussed.

Validity of DSM-IV ADHD predominantly inattentive and combined types: relationship to previous DSM diagnoses/subtype differences.

UNLABELLED: Since 1980, three different diagnostic nomenclatures have been published regarding attention-deficit hyperactivity disorder (ADHD). These changing conceptualizations and diagnostic criteria have generated considerable confusion. OBJECTIVE: To examine the multidimensional DSM-IV ADHD criteria in relation to how children and adolescents with a previous DSM-III ADD diagnosis or a DSM-III-R ADHD diagnosis are diagnosed according to DSM-IV criteria. METHOD: Children whose original diagnoses were according to DSM-III and DSM-III-R criteria received retrospective diagnoses according to DSM-IV criteria. RESULTS: Predominantly inattentive (n = 30) and combined types (n = 26) were compared on their previous DSM-III and DSM-III-R diagnoses and on demographic, behavioral, cognitive, and comorbidity variables. Predominantly inattentive and combined type diagnoses corresponded with DSM-III ADD/WO and ADD/H diagnoses, respectively. The DSM-III-R ADHD diagnosis did not correspond with either DSM-IV subtype. Children with the combined type diagnosis had more externalizing codiagnoses, and their parents reported more externalizing, delinquent, and aggressive behaviors. Children with the predominantly inattentive type had more math learning disability codiagnoses. CONCLUSION: Results support a multidimensional conceptualization of ADHD. There exists close correspondence between the DSM-III ADD/WO type and the DSM-IV predominantly inattentive type and between the DSM-III ADD/H type and the DSM-IV combined type.

Prediction of group membership in developmental dyslexia, attention deficit hyperactivity disorder, and normal controls using brain morphometric analysis of magnetic resonance imaging.

This study explored the utility of using selected brain morphometric indices for predicting group membership for children with developmental dyslexia (n = 10), attention deficit hyperactivity disorder: combined type (n = 10), and a control group (n = 10). Subjects ranged in age from 6.1 to 16 years (M = 10.5 years, SD = 2.8). None of the subjects were diagnosed with mental retardation, nor did any of the subjects have a history of seizure disorder, head trauma, or other neurodevelopmental disorders. WISC-R Full Scale IQ ranged from 87 to 149 (M = 114.4, SD = 13.3) with no significant differences noted between the clinical groups. Six brain regions, as defined by MRI scans, were selected a priori for inclusion in a discriminant function analysis. Reliability of the morphometric measures ranged from 0.94 to 0.97. One significant discriminant function was generated which accounted for about 61.4% of the variance between groups. The predictive discriminant analysis using the six morphometric MRI measurements classified subjects with an overall 60% accuracy with the best accuracy found for the developmental dyslexia and control groups. A predictive discriminant analysis incorporating these six morphometric measures as well as chronological age and FSIQ increased the overall classification accuracy to 87% with the misclassfied subjects assigned to one of the clinical groups. The findings support the presumed neurological basis for many neurodevelopmental disorders. They also underline the importance of including brain morphometric measures in predictive models.

Anomic aphasia in childhood.

Documented cases of anomic aphasia in childhood are rare, due to their low prevalence and relatively subtle clinical manifestations and because of probable referral bias. Such cases are important, however, because they may shed light on the nature of lesions that produce anomia in children and because they may contribute to our understanding of brain-behavior relations in children. This case involves a 10-year-old girl who experienced a left temporoparietal hematoma. Recovery over an 8-month period was good, with near normal verbal-expressive (Verbal IQ = 86) and normal perceptual-motor abilities (Performance IQ = 100). Reading, spelling, and repetition were preserved. Spontaneous speech was good, although initially circumlocutory and marked by obvious word-finding difficulty. Consistent with reports involving adults, there was significant disturbance in naming characterized by frequent literal and semantic paraphasias. Although she had significant difficulty on confrontational naming, she could accurately spell and read the name of the objects presented to her. This case is discussed relative to localization of lesions producing anomic aphasia and regarding the course of recovery in childhood.

Academic achievement and attention-deficit/hyperactivity disorder in children with left- or right-hemisphere dysfunction.

The neuropsychological investigation of learning disabilities has contributed much toward a more complete understanding of how the hemispheres are functionally organized and how differences in this functional organization may affect differential patterns of learning and behavior. It has been suggested that right-hemisphere dysfunction increases the likelihood of difficulty with attention/concentration and of overactive behavior, and interferes with arithmetic calculation more readily than reading and spelling. The present study examined the influence of right-versus left-hemisphere neuropsychological dysfunction on academic achievement and attention using two groups of children with learning disabilities and a group of nondisabled children. Results provide limited support for the hypothesis that the right hemisphere subserves attention and concentration. No support was found for the hypothesis that right-hemisphere deficits are more frequently associated with deficient arithmetic calculation, as opposed to reading and spelling performance. Results are discussed in the context of previous research on right-hemisphere dysfunction and learning disabilities.

Dyslexia and corpus callosum morphology.

OBJECTIVE: There is evolving evidence that developmental dyslexia is associated with anomalous cerebral morphology in the bilateral frontal and left temporoparietal regions. This study examined the morphology of the corpus callosum, as possible deviations in other important structures are poorly understood in this behaviorally diagnosed syndrome. DESIGN: Magnetic resonance imaging scans were obtained from children with developmental dyslexia and from matched control children. Morphometric measurements were examined to determine if regional differences existed in the corpus callosum between these two groups of children. SETTING: Magnetic resonance imaging studies were completed at Athens (Ga) Magnetic Imaging. PATIENTS AND OTHER PARTICIPANTS: Sixteen developmental dyslexic children (mean age, 9.7 years) and a matched sample of children who were diagnosed as being normal were examined by using a reliable comprehensive diagnostic process. MAIN OUTCOME MEASURES: Using a midsagittal magnetic resonance imaging scan, corpus callosum morphology was evaluated by segmenting the corpus callosum into five regions of interest. RESULTS: Analysis of the corpus callosum revealed that the anterior region of interest (the genu) was significantly smaller in the dyslexic children. Significant correlations existed between reading achievement and the region-of-interest measurements for the genu and splenium. Measured intelligence, chronologic age, and gender were not related to region-of-interest measurements of the corpus callosum. Consistent with previous studies, the dyslexic individuals were characterized by significant psychiatric comorbidity, particularly attention-deficit disorder with and without hyperactivity. Reported familial left-handedness also distinguished the dyslexic children. CONCLUSIONS: Subtle neurodevelopmental variation in the morphology of the corpus callosum may be associated with the difficulty that dyslexic children experience in reading and on tasks involving interhemispheric transfer.