High incidence of language disorder in children with focal epilepsies

To investigate the relationship between the presence of language disorder, type of epilepsy, and epileptic seizures in childhood, language levels, types of language impairment, and aetiologies were examined in 109 children, aged between 5 and 17 years, attending a national children's epilepsy assessment unit over a 4-year period. There were 70 males and 39 females. Median age was 11 years 4 months (range 5 to 18 years 9 months). In addition to neurological assessment, simultaneous video and EEG monitoring and prolonged ambulatory EEG, each child underwent a comprehensive series of multidisciplinary tests, including intelligence, language, and communication assessments. Classification of seizures and epilepsy syndromes was agreed in conference by a physician specializing in childhood epilepsies, a paediatric neurologist, and a neuropsychiatrist. Other test procedures were administered by a speech and language pathologist with assistance from a neuropsychologist when relevant. Level of language disability in these children was associated with a range of aetiological factors. Evidence was found of a significant number of associations between focal epilepsies, certain seizure types, and language disorder. Of the 46 (42.2%) children with language disorders in the research sample, 30 had localization-related epilepsies and a further three had epilepsies which were undetermined as to whether focal or generalized. Children with focal epilepsies were 30% more likely to have language disorder than other language disability subtypes. The research demonstrated a clear though often subtle association between focal (localization-related) epilepsy and language disorder, indicating an increased risk in this patient group. Children with simple or complex partial seizures were more likely to have language disorder than other language disability subtypes; they also tended to have the lowest number of seizure types per case. This is of importance to clinicians managing children with epilepsy and has implications for their educational and social welfare.     

Nucleus accumbens dopamine depletion impairs both acquisition and performance of appetitive Pavlovian approach behaviour: implications for mesoaccumbens dopamine function

The involvement of mesoaccumbens dopamine in adaptive learning and behaviour is unclear. For example, dopamine may act as a teaching signal to enable learning, or more generally modulate the behavioural expression, or selection, of an already-learned response. The present study investigated the involvement of the mesoaccumbens dopamine system in a fundamental form of learning: Pavlovian conditioning. In this case, the temporal association of a previously neutral visual stimulus and a biologically significant unconditioned stimulus (US), subsequently led to the production of the conditioned response (CR) of discriminated approach behaviour directed toward the conditioned stimulus (CS+), relative to a control (CS-) stimulus. 6-hydroxydopamine lesions of the nucleus accumbens (NAcc), leading to approximately 80% reductions in tissue dopamine, were made at varying time points in four experimental groups of rats, either before or subsequent to the acquisition of the CR. NAcc dopamine depletion produced long-term neuroadaptations in dopamine function 2 months after surgery, and profoundly impaired discriminated Pavlovian approach regardless of when the lesion was made. Thus, NAcc dopamine not only plays a role in conditioned behavioural activation, but also in making the appropriate discriminated response i.e. the direction of response. Further, acquisition lesions produced a far greater impact on discriminated approach than performance lesions. This difference in lesion-induced impairment implies that mesoaccumbens dopamine may play differential roles in the learning and performance of preparatory Pavlovian conditioning.     

Growth hormone receptor antagonists: discovery,development, and use in patients with acromegaly

An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This molecule has been designed to compete with native GH for the GHR and to prevent its proper or functional dimerization-a process that is critical for GH signal transduction and IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed. This review charts the discovery and development of GHR antagonists and details the experience gained in patients with acromegaly.     

Anterior prostate cancer: is it more difficult to diagnose?

OBJECTIVE; To determine whether anterior prostatic tumours are adequately sampled using the Stamey sextant protocol, as a fifth of prostate cancers are anterior in distribution at radical prostatectomy. MATERIALS AND METHODS: All tumours (62) with an anterior distribution (>or=75% of the tumour anterior to the urethra) on radical prostatectomy whole-mounts, and in which the number and results of the sextant biopsies were available, were extracted from a prostate cancer database. Sixty-one posterior tumours (>or=75% of the malignant tissue posterior to the urethra) and their corresponding sextant biopsies were also retrieved for comparison. The number of biopsy sessions, the number of cores involved and the summated tumour length were recorded, together with the prostate gland weight, the tumour volume and the site of >or=75% of tumour in the superior-inferior axis. RESULTS: Anterior tumours required significantly more biopsy sessions to diagnose prostate cancer than posterior neoplasms (anterior, one set 47; > one set 15; posterior, one set 57; > one set, four, P=0.007). Anterior tumours had fewer cores with tumour involvement and less summated tumour length than had posterior cancers. The mean (sd) number of positive cores was; anterior 1.8 (1.01), posterior 2.50 (1.30) (P=0.001); the summated tumour length was; anterior 5.05 (4.10) mm, posterior 9.25 (7.80) mm (P<0.001). There was no significant difference in gland weight (mean anterior 43.8 g; posterior 48.3 g, P=0.3) or tumour volume (mean anterior 1.85 mL; posterior 1.49 mL, P=0.11) between the groups. There was no significant difference between the incidence of anterior and posterior neoplasms with respect to their position in the superior-inferior axis (P=0.96). CONCLUSIONS: Anterior prostate tumours account for 21% of all prostate cancers. They more often require multiple sets of sextant biopsies for diagnosis, and yield smaller areas of cancer on core biopsies than do posterior tumours in glands of similar weight and tumour volume. If prostate cancer is suspected clinically but biopsies are negative, targeting the anterior gland at subsequent prostatic biopsy should be considered.     

Cell Kinetic Analysis in Pediatric Brain and Spinal Tumors: A Study of 117 Cases with Ki-67 Quantitation and Flow Cytometry

We present cell kinetic data including Ki-67 quantitation and flow cytometry on 117 pediatric brain/spinal cord tumors and review the literature. Although, in general, these proliferation indices are in agreement with the histologic grade, they are useful in prognostication in some instances when the histological features of malignancy are equivocal. Specific examples in which flow cytometry may prove particularly useful in this context are childhood ependymomas, which do not show frank anaplasia but have cellular foci with focal increase in mitoses, and choroid plexus neoplasms, where elevated S phase fractions have been associated with an adverse outcome. Thus Ki-67 quantitation and flow cytometry not only serve as useful adjuncts to conventional histologic grading but also in specific instances may provide new information on tumor prognosis.     

Carboxypeptidase H in bovine pituitary gland: soluble forms are not processed at the C-terminus.

Carboxypeptidase H (CP-H) has been characterized in anterior and posterior lobes of bovine pituitary with regard to subcellular distribution, enzymatic properties, nature of membrane association, number of forms and C-terminal processing. Anterior lobe contained both soluble and membrane forms of CP-H with similar enzymatic properties after extraction at pH 5.5. The soluble forms represented about 70% of the total activity. Two soluble and two membrane forms, of 53 and 56 kDa, were demonstrated by immunoblotting and after purification. The amount of the 56 kDa soluble form increased with the salt content of the extraction buffer. Endoglycosidase digestions showed that the difference in size was not due to differential N-linked glycosylation and also showed that CP-H oligosaccharides do not become resistant to endoglycosidase H. CP-H in posterior lobe was also composed from about 70% soluble and 30% membrane forms. Only 53 kDa CP-H was detected in soluble and membrane fractions of posterior lobe. All forms of CP-H from both lobes reacted with antiserum directed to the C-terminus. These results do not support previous observations that soluble and membrane forms of CP-H can be distinguished by size and C-terminal processing.