Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects

Seven normal subjects received 0.25 mg/kg D-amphetamine orally, both after an overnight fast and again after a standard breakfast. Plasma levels, subjective and cardiovascular effects, and observer-rated activation were assessed hourly for 5 hr. Food did not affect amphetamine levels. Plasma levels peaked at 2-3 hr. Maximum cardiovascular effects generally occurred at 1 hr, whereas maximum behavioral and subjective effects occurred at 2 hr. Subjective and behavioral effects declined thereafter, in spite of substantial amphetamine levels. A separate group of 8 subjects received 0.5 mg/kg D-amphetamine orally. Plasma levels, subjective and cardiovascular effects, and activation ratings were assessed hourly for 4 hr. Maximum plasma levels were approximately twice those seen in the first group. In this case, plasma levels peaked at 3-4 hr; blood pressure and subjective and behavioral effects were all maximal at 2-3 hr and were declining by 4 hr, in spite of stable or rising plasma levels.     

Lupus optic neuritis with negative serology

A 56-year-old woman with a 12-year history of systemic lupus erythematosus presented with severe optic-disc swelling and blepharitis. At the same time, she developed acute pancreatitis and ultimately died of gram-negative sepsis. Although it appeared that the ocular and systemic disorders were manifestations of lupus, her serum antinuclear antibody and complement levels remained normal throughout her hospital course. Optic neuritis may be secondary to lupus, but the diagnosis is difficult to make when the serology is negative.     

Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Rat posterior parietal cortex: topography of corticocortical and thalamic connections

Anatomical and functional findings support the contention that there is a distinct posterior parietal cortical area (PPC) in the rat, situated between the rostrally adjacent hindlimb sensorimotor area and the caudally adjacent secondary visual areas. The PPC is distinguished from these areas by receiving thalamic afferents from the lateral dorsal (LD), lateral posterior (LP), and posterior (Po) nuclei, in the absence of input from the ventrobasal complex (VB) or dorsal lateral geniculate (DLG) nuclei. Behavioral studies have demonstrated that PPC is involved in spatial orientation and directed attention. In the present study we used fluorescent retrograde axonal tracers primarily to investigate the cortical connections of PPC, in order to determine the organization of the circuitry by which PPC is likely to participate in these functions, and also to determine how the topography of its thalamic connections differs from that of neighboring cortical areas. The cortical connections of PPC involve the ventrolateral (VLO) and medial (MO) orbital areas, medial agranular cortex (area Fr2), portions of somatic sensory areas Par1 and Par2, secondary visual areas Oc2M and Oc2L, auditory area Tel, and retrosplenial cortex. The secondary visual areas Oc2L and Oc2M have cortical connections which are similar to those of PPC, but are restricted within orbital cortex to area VLO, and within area Fr2 to its caudal portion, and do not involve auditory area Te1. The cortical connections of hindlimb cortex are largely restricted to somatic sensory and motor areas. Retrosplenial cortex, which is medially adjacent to PPC, has cortical connections that are prominent with visual cortex, do not involve somatic sensory or auditory cortex, and include the presubiculum. We conclude that PPC is distinguished by its pattern of cortical connections with the somatic sensory, auditory and visual areas, and with areas Fr2, and VLO/MO, in addition to its exclusive thalamic connectivity with LD, LP and Po. Because recent behavioral studies indicate that PPC, Fr2 and VLO are involved in directed attention and spatial learning, we suggest that the interconnections among these three cortical areas represent a major component of the circuitry for these functions in rats.