Interrater agreement and stability of the Functional Independence Measure for Children (WeeFIM): use in children with developmental disabilities

OBJECTIVE: Examination of the interrater agreement and stability of ratings obtained using the Functional Independence Measure for Children (WeeFIM) in a sample of children with developmental disabilities. DESIGN: A relational design was used in which two sets of WeeFIM scores were collected under four conditions: same rater-short interval; same rater-long interval; different rater-short interval; and different rater-long interval. SETTING: WeeFIM scores were collected in outpatient developmental rehabilitation centers, school programs, and the children's homes. PARTICIPANTS: Data were collected for 205 children ranging in age from 11 to 87 months. All children had a medical diagnosis of disability and were receiving habilitative-educational intervention or follow-along services including neurodevelopmental surveillance. INSTRUMENT: The WeeFIM instrument examines basic daily living and functional skills in children from birth to 7 years of age. The WeeFIM is modeled after the Functional Independence Measure (FIM) for adults and includes 18 items in the following subscales: self-care, sphincter control, transfers, locomotion, communication, and social cognition. RESULTS: Kappa values for items ranged from .44 to .82. Intraclass correlation coefficients (ICC) for the six subscales ranged from .73 to .98. Total WeeFIM ICC values were greater than .95 for all analyses. CONCLUSIONS: The WeeFIM ratings for the 205 children with developmental disabilities participating in this investigation were consistent across raters and time.     

Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth

Neurons within each layer of cerebral cortex express multiple members of the neurotrophin family and their corresponding receptors. This multiplicity could provide functional redundancy; alternatively, different neurotrophins may direct distinct aspects of cortical neuronal growth and differentiation. By neutralizing endogenous neurotrophins in organotypic slices of developing cortex with Trk receptor bodies (Trk-IgGs), we found that BDNF and NT-3 oppose one another in regulating the dendritic growth of pyramidal neurons. In layer 4, both endogenous and exogenous NT-3 inhibited the dendritic growth stimulated by BDNF. In contrast, in layer 6 both endogenous and exogenous BDNF inhibited dendritic growth stimulated by NT-3. These antagonistic actions of endogenous BDNF and NT-3 provide a mechanism by which dendritic growth and retraction can be dynamically regulated during cortical development, and suggest that the multiple neurotrophins expressed in developing cortex represent distinct components of an extracellular signaling system for regulating dendritic growth.     

Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine

Two families of small peptides that bind to the human thrombopoietin receptor and compete with the binding of the natural ligand thrombopoietin (TPO) were identified from recombinant peptide libraries. The sequences of these peptides were not found in the primary sequence of TPO. Screening libraries of variants of one of these families under affinity-selective conditions yielded a 14-amino acid peptide (Ile-Glu-Gly-Pro-Thr-Leu-Arg-Gln-Trp-Leu-Ala-Ala-Arg-Ala) with high affinity (dissociation constant approximately 2 nanomolar) that stimulates the proliferation of a TPO-responsive Ba/F3 cell line with a median effective concentration (EC50) of 400 nanomolar. Dimerization of this peptide by a carboxyl-terminal linkage to a lysine branch produced a compound with an EC50 of 100 picomolar, which was equipotent to the 332-amino acid natural cytokine in cell-based assays. The peptide dimer also stimulated the in vitro proliferation and maturation of megakaryocytes from human bone marrow cells and promoted an increase in platelet count when administered to normal mice.     

Role of growth hormone in ovarian physiology and onset of puberty

To evaluate the usefulness of transendoscopic sonography, we have studied the use of a new sonographic probe of 6 F diameter in 11 fresh specimens. We achieved a precise imaging of well known anatomic structures and, moreover, obtained an additional dimension in endoscopy, since the sonographic probe adds a transverse scan to the endoscopic view, like a mini-CT at the tip of the probe. In this way, we also examined the guiding characteristics of this imaging technique, both in real time and on-line. Our results promise further interesting aspects of this technique in minimally invasive neurosurgery and suggest that further development and clinical experience seem to be justified.     

Management of acute extrapyramidal effects induced by antipsychotic drugs

The management of acute extrapyramidal effects (EPEs) induced by antipsychotic drugs is reviewed. EPEs associated with antipsychotics include acute dystonias, pseudoparkinsonism, and akathisia. Acute dystonias consist of abnormal muscle spasms and postures and usually occur three to five days after antipsychotic therapy begins or the dosage is increased. Acute dystonias should be treated with anticholinergic medications or benzodiazepines. Antipsychotic-induced pseudoparkinsonism has the same clinical appearance as idiopathic parkinsonism. Symptoms generally appear within the first three months. Pseudoparkinsonism is managed by lowering the anti-psychotic dosage or by adding an anticholinergic agent or a mantadine; switching to a low-potency agent or an atypical antipsychotic may also help. Akathisia is characterized by subjective feelings of restlessness and anxiety and objective signs of motor activity, such as inability to sit still. This EPE appears days to weeks after antipsychotic exposure begins and can be difficult to manage. If reduction of the antipsychotic dosage or a switch to a less potent antipsychotic is not practical or effective, an anticholinergic, beta-blocker, or benzodiazepine may be added. Lipophilic beta-blockers, especially propranolol and metoprolol, appear to be the most effective treatments. Anticholinergic agents are commonly given to prevent acute dystonias, especially in high-risk patients, but long-term prophylaxis is controversial. Atypical antipsychotics may have less potential to induce EPEs. Options in the management of antipsychotic-associated EPEs include using the lowest effective dosage of antipsychotic, treating the reactions with medications, and changing the antipsychotic to one with less potential for inducing EPEs.