Efalizumab therapy resulted in significant improvements in plaque psoriasis in subjects with moderate-to-severe disease. Extending treatment from 12 to 24 weeks resulted in both maintenance and improvement of responses.

The performances of patients with dementia of the Alzheimer type (DAT), patients with Huntington's disease (HD), and demented and nondemented patients with Parkinson's disease (PD) were compared on 2 tests of implicit memory that do not require the conscious recollection of prior study episodes: (1) a pursuit-rotor motor learning task and (2) a lexical priming test. The HD patients were found to be impaired on the motor learning but not the lexical priming task, whereas the DAT patients evidenced the opposite relationship on these tasks. The demented, but not the nondemented, PD patients were found to be impaired on both tests of implicit memory. For both the HD and PD patients, deficits on the motor learning task correlated significantly with severity of dementia but not with level of primary motor dysfunction. The noted double dissociation between HD and DAT patients indicates that different forms of implicit memory, all of which are intact in amnesia, are dependent upon distinct neuroanatomic systems. Motor skill learning may be mediated by a corticostriatal system, whereas verbal priming may depend upon the integrity of the neocortical association areas involved in the storage of semantic knowledge. The results for the PD patients suggest that the demented PD patients have endured damage to the neurologic systems subserving both motor learning and lexical priming.

Context Because T-cell interactions are involved in the pathophysiology of psoriasis, therapy with a T-cell modulator may have beneficial effects on psoriasis severity and health-related quality of life (HRQL). Objective To assess the efficacy and safety of efalizumab, a T-cell modulator, in patients with plaque psoriasis. Design, Setting, and Patients Phase 3 randomized, double-blind, parallelgroup, placebo-controlled trial involving 556 adult patients with stable, moderate to severe plaque psoriasis and conducted at 30 study centers in the United States and Canada between January and July 2002. Interventions Patients were randomly assigned in a 2:1 ratio to receive 12 weekly doses of subcutaneous efalizumab, 1 mg/kg (n=369), or placebo equivalent (n=187). Main Outcome Measures At least 75% improvement on the Psoriasis Area and Severity Index (PASI-75); improvement on the overall Dermatology Life Quality Index (DLQI), Itching Visual Analog Scale (VAS), and Psoriasis Symptom Assessment (PSA) at week 12 vs baseline. Results Efalizumab-treated patients experienced significantly greater improvement on all end points than placebo-treated patients. Twenty-seven percent of efalizumabtreated patients achieved PASI-75 vs 4% of the placebo group (PϽ.001). Efalizumabtreated patients exhibited significantly greater mean percentage improvement than placebo-treated patients on the overall DLQI (47% vs 14%; PϽ.001), Itching VAS (38% vs −0.2%; PϽ.001), and PSA frequency and severity subscales (48% vs 18% and 47% vs 17%, respectively; PϽ.001 for both) at the first assessment point. Efalizumab was safe and well tolerated, with primarily mild to moderate adverse events. Conclusion In this 12-week study, efalizumab resulted in significant improvements in clinical end points, including physician-assessed and dermatology-specific patientreported HRQL measures, in patients with moderate to severe plaque psoriasis.

Basic fibroblast growth factor (FGF) has been found to increase neuronal survival and neurite e on in a highly purified population of fetal rat hippocampal neurons under well-defined serum-free cell culture conditions. In the presence of FGF, neuronal survival after 7 days in culture on a simple plastic substrate is increased 4-fold, to 54% of the Initial population. Survival is increased 2-fold to 40% on polyornithine-laminin. When FGF was bound to plastic or heparin substrates, neurite outgrowth was sgnflcantiy increased to lengths comparable to those seenwith lamin; however, FGF produced no further increase in neurite outgrowth on laminin. Half-maximal survival was observed at FGF concentrations of about 15 pg/nl (1 pM); half-maximal process outgrowth occurred at about 375 pg/ml (20 pM). The responsive cells were identified as neurons by their labeling with tetanus toxin and by antibodies to neurofilAments and to the neuron-speciflc enolase. Astrocytes, identified by the presence of glial fibrillary acidic protein, constituted about 10% of cells present at 1 week both in the presence and in the absence of FGF. These results strongly suggest that, in addition to its known mitogenic effects on nonneuronal cells, FGF possesses neurotrophic activity for hippocampal neurons.The discovery that during normal development substantial numbers of nerve cells in most regions of the central and peripheral nervous systems die and that the proportion of neurons that survive in any given region is closely related to the size of their target field has led to the hypothesis that all nerve cells are dependent for their growth and maintenance on the availability of specific trophic (growth) factors (1-3). The first neurotrophic factor to be identified was "nerve growth factor" (NGF), and the critical role it plays in supporting the survival and growth of sympathetic and certain sensory neurons has been well documented (4,5 Until recently very few systems have been described in which it is possible to reproducibly obtain adequate cultures of virtually pure neuronal (as opposed to mixed neuronal and glial) cultures. One such system involves the use of dissociated hippocampal neurons from late fetal rats (9-12). The main advantage of this system is that the cell population is unusually homogeneous, the overwhelming majority of the cells at embryonic day 18 being pyramidal neurons (9), and with appropriate controls the proportion of nonneuronal cells in the cultures can be kept to less than 10%1 (10,11). Previous studies have established that virtually all the neurons degenerate within 72-96 hr ifthey are maintained at low density and in a chemically defined medium (10-12), but they can be maintained for periods of several weeks in the presence of explants of hippocampal tissue or a feeder layer of astrocytes, or in medium conditioned by astrocytes (9, 10, 12). We have used this system to examine the effects of highly purified basic fibroblast growth factor (FGF) on the survival of the isolated neurons and on their capacit...

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