Determining clinically meaningful cognitive impairment following traumatic brain injury.

AIMS: To study the reliability and validity of ratings of: neuropsychological impairment with test data from traumatically brain-injured patients. METHODS: Neuropsychological test results from 66 traumatically brain-injured adults and 27 orthopaedic controls were rated for neuropsychological impairment by an experienced neuropsychologist and three undergraduate students provided with brief training in test interpretation. Ratings were based on the discrepancy between a patient's current cognitive level and their estimated premorbid cognitive level. Decision making rules were utilised in making the ratings. The raters, who were blind with respect to the patients diagnostic group membership, independently rated test results. Test results were rerated using the same method approximately two weeks later. RESULTS: The ratings of novice raters were in good to very good agreement with the ratings of an expert. All raters evidenced very good to excellent test-retest reliability. Higher rates of neuropsychological impairment were found in the traumatically brain-injured group than in the orthopaedic control group. Discriminant function analysis suggested that raters employed information from all neuropsychological measures (with the exception of current intellectual level), in making their overall ratings of neuropsychological impairment. CONCLUSION: These findings provide encouraging preliminary evidence in support of the reliability and validity of individual case-based ratings of neuropsychological impairment. The high false positive rate in the control sample may reflect the relatively low specificity of neuropsychological impairment.

Mechanisms of action of a second generation growth hormone-releasing peptide (Ala-His-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2) in rat anterior pituitary cells.

The mechanism by which GH-releasing peptides elicit GH secretion has remained largely unknown. In this study, the effects of a second generation GH-releasing peptide, Ala-His-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2(GHRP-1), on cAMP, intracellular Ca2+ ([Ca2+]i), and GH release were examined using rat pituitary gland static monolayer cell cultures. It was found that GHRP-1 increased GH release in a dose-dependent manner up to 3-fold, while having no effect on cAMP levels. In contrast, simultaneous elevations of cAMP and GH were observed after treatment with GHRH. To further define the underlying mechanism of GHRP-1-mediated GH release, its effect on [Ca2+]i was determined using a fluorescent Ca2+ indicator, fura-2. GHRP-1 dose dependently increased [Ca2+]i up to 45.5 nM +/- 5.6 nM. A similar elevation of [Ca2+]i was observed after GHRH treatment. Similar to GHRH, GHRP-1-induced increases in [Ca2+]i and GH release were inhibited by somatostatin. Furthermore, the GHRP-1-induced increases in [Ca2+]i and GH were also suppressed by nifedipine. The interaction between the voltage-dependent Ca2+ channels and GHRP-1 was investigated in cells maximally stimulated by KCl. The addition of GHRP-1 had no effect on the KCl-stimulated GH release. To investigate the possible interaction between the adenylyl cyclase pathway and GHRP-1, cells were maximally stimulated with forskolin or (Bu)2cAMP. Addition of GHRP-1 stimulated GH release beyond that observed using cAMP elevating agents. Similar results were obtained in the presence of a protein kinase C, 4 beta-phorbol 12-myristate 13-acetate (PMA). The GHRP-1-stimulated GH release was additive to that observed with PMA stimulation. Based on these findings, it was concluded that 1) GHRP-1 treatment leads to an increase in [Ca2+]i; 2) unlike GHRH, GHRP-1 releases GH via a Ca(2+)-dependent, cAMP-independent mechanism; 3) GHRP-1-induced increases in [Ca2+]i and GH release are sensitive to somatostatin inhibition; and 4) cAMP-elevating agents and PMA have an additive effect on the GHRP-1-stimulated GH release, indicating these agents stimulate GH release via a mechanism separate from that of GHRP-1.