Preliminary analysis of a randomized comparison of 5-fluorouracil versus 5-fluorouracil and high-dose continuous-infusion folinic acid in disseminated colorectal cancer

In this study, 50 patients were randomly assigned to treatment with 5-fluorouracil (FUra) or FUra plus high-dose continuous-infusion folinic acid. Five of 27 evaluable patients in the FUra group versus 10 of 21 patients in the FUra plus folinic acid arm of the study had objective partial remissions, P = 0.02. Time to progression was 3.9 months for FUra and 8.0 months for FUra and folinic acid, P = 0.006; however, median survivals (11.9 versus 14.5 months) were not different in this crossover study. Toxicity in both treatment arms was mild, although patients receiving FUra plus folinic acid experienced significantly more stomatitis than patients treated with FUra alone. This study suggests that high-dose, continuous-infusion folinic acid, which produces a steady-state level of biologically active folates of 10 microM, significantly increases the therapeutic activity of FUra.     

The relationship of the extrinsic blood supply to regeneration in graft reconstructed peripheral nerves

Median nerves of rats were reconstructed with conventional or vascular nerve grafts. After 2, 3 and 4 weeks, Allen Video-Enhanced Contrast, Differential Interference Contrast (AVEC-DIC) microscopy revealed axonal transport in most preparations, with varying degrees of myelination. Radio-isotope tracer was measured in the nerve. Two and 4 week measurements revealed no difference between the graft types. At 3 weeks the vascular graft group exhibited transport along the entire length of the nerve in contrast to a relatively abbreviated path length in the conventional graft group. Nerve conduction velocities (NCV) were measured proximal to, within and distal to the grafts. Three week NCV showed no difference between the graft types. The 4 week NCV revealed normal values in the vascular graft group at points distal to and within the graft. Significant slowing was seen in the conventional grafts at both points.     

Parental communication deviance: its relationship to parent, child, and family system variables

Audiotape recordings of family interaction samples from 30 nondistressed and 32 multiproblem families were coded for communication deviance (CD). Maternal CD was found to be higher in families high on measures of "preschizophrenic" child behavior, externalizing or "acting out" offspring behavior, overall family distress, and maladaptive marital and family alliance structures. Paternal CD was found to be higher in families in which offspring were rated high on externalizing behaviors.     

Prediction of rodent carcinogenicity utilizing a battery of in vitro and in vivo genotoxicity tests

The primary purpose of this study is to investigate the degree to which we can improve the prediction of rodent carcinogenicity (CA) by combining results from an in vitro and two in vivo genotoxicity tests. We used the Ames Salmonella assay (SAL) for the in vitro test and the micronucleus assay (MNC) and chromosome aberration assay (ABS) in mouse bone marrow cells for the two in vivo tests. We collected complete assay data for 82 chemicals (55 carcinogens and 27 noncarcinogens) from the NTP data base and the IARC monograph series. Our results indicate that: (1) only SAL affects the predictivity of CA, (2) MNC has a strong association with ABS, and (3) SAL predicts ABS. It has been known for some time that once the SAL assay result is available for prediction, other in vitro mutation tests provide little additional information for predicting CA. Our study indicates that the same conclusion holds for CA, SAL, MNC, and ABS.     

Increased CSF F2-isoprostane concentration in probable AD

OBJECTIVE: To quantify F2-isoprostane levels in CSF obtained from the lumbar cistern of patients with AD, ALS, and controls. BACKGROUND: Studies of human postmortem tissue and experimental models have suggested a role for oxidative damage in the pathogenesis of several neurodegenerative diseases, especially AD and ALS. F2-isoprostanes are exclusive products of free-radical-mediated peroxidation of arachidonic acid that have been widely used as quantitative biomarkers of lipid peroxidation in vivo in humans. Recently, we showed that F2-isoprostane concentrations are significantly elevated in CSF obtained postmortem from the lateral ventricles of patients with definite AD compared with controls. METHODS: F2-isoprostanes were quantified by gas chromatography/negative ion chemical ionization mass spectrometry. RESULTS: CSF F2-isoprostanes were increased significantly in patients with probable AD, but not in ALS patients, compared with controls. CONCLUSIONS: Increased CSF F2-isoprostanes are not an inevitable consequence of neurodegeneration and suggest that increased brain oxidative damage may occur early in the course of AD.     

Cognitive neuropsychology. Resolving enigmas about Wernicke's aphasia and other higher cortical disorders

Cognitive neuropsychology is a young branch of neuroscience whose ancestral influences include a rich pool of experimental (eg, cognitive, psychology), theoretical (eg, epistemology), and clinical (eg, neurology, neuropsychology) disciplines. An essential principle of cognitive neuropsychology is that disorders of higher cortical functions can be understood in terms of breakdowns of one or more information-processing modules. Each module is the most basic element of intelligence that can be defined based on current knowledge. This approach is a refinement of-not a fundamental departure from-the 19th-century "localizationist" view of language disorders. Wernicke's aphasia, for example, classical attributed to a single cognitive deficit (loss of word sounds), is shown in this review to require damage to multiple distinct information-processing modules. Cognitive neuropsychology provides the tools for the type of fine-grained analyses of behavior that are needed to capitalize on recent advances in neuroimaging techniques, including the development of more sophisticated models of brain-behavior relationships.