Severe combined immunodeficiency (SCID) mouse modeling of P-glycoprotein chemosensitization in multidrug-resistant human myeloma xenografts

We have established a reproducible in vivo model of human multiple myeloma in the severe combined immunodeficiency (SCID) mouse using both the drug-sensitive 8226/S human myeloma cell line and the P-glycoprotein-expressing multidrug-resistant 8226/C1N subline. As demonstrated previously, the SCID mouse is well suited as a model for myeloma because: (a) human SCID xenografts are readily attained; (b) human myeloma xenografts are readily detected by their immunoglobulin secretion; and (c) differential therapy effects in drug-sensitive versus drug-resistant cell lines are readily demonstrable by monitoring mouse urinary human immunoglobulin output. In the current study, we have utilized this model to evaluate the in vivo efficacy of chemomodulators of P-glycoprotein-related multidrug resistance. In our initial experiments, doxorubicin alone was effective in treating the 8226/S human myeloma xenografts but had no effect on the drug-resistant 8226/C1N xenografts, in the absence of the chemosensitizing agent verapamil. In subsequent experiments, the combination of verapamil and doxorubicin resulted in both a decrease in human lambda light chain urinary excretion and an increase in survival of those animals bearing the 8226/C1N tumor. The median survival time of animals injected with 8226/C1N cells and subsequently treated with doxorubicin was 48.6 +/- 7 days, which compared to a survival of 89.6 +/- 18 days in animals receiving the 8226/S cell line and treated with doxorubicin alone (P < 0.001). When verapamil was added to the treatment regimen of those animals bearing the 8226/C1N xenografts, there was a 179% increase in their life span (P < 0.001), which corresponded with the observed decreased light chain in the urine. In animals receiving multiple courses of chemotherapy, an attenuated response to verapamil and doxorubicin was observed, in a manner analogous to the clinical setting of human drug-resistant myeloma escape from chemosensitivity. The SCID human myeloma xenograft model thus offers a means of evaluating the in vivo efficacy and potential toxicities of new therapeutic approaches directed against P-glycoprotein in multidrug-resistant human myeloma.     

Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates

Magnetic resonance imaging (MRI) has shown a great reduction in medial temporal lobe and hippocampal volume of patients with Alzheimer's disease as compared to controls. Quantitative volumetric measurements are not yet available for routine clinical use. We investigated whether visual assessment of medial temporal lobe atrophy (MTA) on plain MRI films could distinguish patients with Alzheimer's disease (n = 21) from age matched controls (n = 21). The degree of MTA was ascertained with a ranking procedure and validated by linear measurements of the medial temporal lobe including the hippocampal formation and surrounding spaces occupied by cerebrospinal fluid. Patients with Alzheimer's disease showed a significantly higher degree of subjectively assessed MTA than controls (p = 0.0005). Linear measurements correlated highly with subjective assessment of MTA and also showed significant differences between groups. Ventricular indices did not differ significantly between groups. In Alzheimer's disease patients the degree of MTA correlated significantly with scores on the mini-mental state examination and memory tests, but poorly with mental speed tests. This study shows that MTA may be assessed quickly and easily with plain MRI films. MTA shown on MRI strongly supports the clinical diagnosis of Alzheimer's disease, is related to memory function, and seems to occur earlier in the disease process than does generalised brain atrophy.     

Discriminability of random-dot stereograms in three-dimensional space

The discriminability of crossed-disparity (near) and uncrossed-disparity as a function of their location in the upper-left, upper-right, lower-left, and lower-right quadrants of the visual field. Discriminability was assessed using choice reaction-time (RT) and accuracy measures. While near targets were recognized equally well in the upper and lower fields, far targets were perceived more easily in the upper visual field. The discriminability of far targets was particularly poor in the lower left quadrant. These results point to the existence of fundamental asymmetries in perceiving crossed and uncrossed disparities along the vertical and lateral axes.     

Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT)

OBJECTIVE: Although there are many anecdotal reports that psychological intervention is effective in enhancing adjustment to spinal cord injury (SCI), there are little data to support this assertion. To date, reports of few longitudinal-based controlled trials that assessed psychological outcomes for SCI persons have been published. This study was conducted to determine long-term efficacy of cognitive behavior therapy during rehabilitation. DESIGN: The study employed a nonrandomized controlled trial, and measures were taken on three occasions: before, immediately after, and 12 months after treatment. SETTING, OUTCOME MEASURES, AND INTERVENTION: Anxiety, depressive mood, and self-esteem were assessed in 28 SCI persons consecutively selected on admission to hospital, who participated in specialized group cognitive behavior therapy (CBT) during rehabilitation. CONTROLS: The intervention group's responses on the measures were compared with a control group of 41 SCI persons who only received traditional rehabilitation services during their hospitalization. RESULTS: There were no overall group differences on anxiety, depressive mood, and self-esteem, although there was a trend for the treatment group to have greater levels of improvement in depression scores across time in comparison to the control group. However, those in the treatment group who reported high levels of depressive mood before the CBT treatment were significantly less depressed 1 year after injury, compared to similar persons in the control group. CONCLUSIONS: While it appears not everyone who experiences SCI needs CBT, at least in the hospital phase of their rehabilitation, those who report high levels of depressive mood benefited greatly from CBT.     

Networked multimedia: issues and perspectives

In this opinion article, we see digital multimedia communications of the future dependent on business vision, evolving networking and consumer electronics technologies, and public policies regarding intellectual property and investment in communications infrastructure. As always, it is easy to predict a rich networked multimedia future, but difficult to say when or exactly how. These will be determined by social and business understandings on the divisive issues, by still uncertain consumer tastes and willingness to pay, and by resolving some technical obstacles. This brief article gives our personal perspectives on the current status of networked multimedia, the most promising multimedia applications, and the social and technical bottlenecks.     

Diagnosis & management of pituitary tumors

Pharmacologic agents are useful in the management of some patients with pituitary tumors. The diagnosis and management of pituitary adenomas are discussed.     

Temperature dependence of the optical absorption spectra of InP/ZnS quantum dots

The optical-absorption spectra of InP/ZnS (core/shell) quantum dots have been studied in a broad temperature range of T = 6.5–296 K. Using the second-order derivative spectrophotometry technique, the energies of optical transitions at room temperature were found to be E ₁ = 2.60 ± 0.02 eV (for the first peak of excitonic absorption in the InP core) and E ₂ = 4.70 ± 0.02 eV (for processes in the ZnS shell). The experimental curve of E ₁(T) has been approximated for the first time in the framework of a linear model and in terms of the Fan’s formula. It is established that the temperature dependence of E ₁ is determined by the interaction of excitons and longitudinal acoustic phonons with hω = 15 meV.