Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications

Persistence of alemtuzumab at lympholytic concentrations after reduced-intensity conditioning allogeneic stem cell transplantations (RITs) could impair immune reconstitution and reduce donor T-cell-mediated graft-versus-leukemia/lymphoma (GVL) effects, derived from the graft or subsequent adoptive immunotherapy. We have studied the pharmacokinetics of alemtuzumab in 2 different groups: RIT (100 mg alemtuzumab in vivo over 5 days) and myeloablative allografts (20 mg alemtuzumab added in vitro to the stem cells prior to return). Alemtuzumab concentrations in RIT patients were in excess of that required to kill infused donor CD52+ cells at the time of transplantation and remained at potentially lympholytic levels (> 0.1 microg/mL) for approximately 56 days after transplantation, 26 days longer than for the myeloablative group. Total lymphocyte counts were significantly lower in the RIT group persisting beyond 6 months after transplantation (P =.005), and median absolute CD4 counts higher than 200 x 106/L were delayed until 9 months after transplantation.     

Human enamel dissolution in citric acid as a function of pH in the range 2.30< or =pH< or =6.30--a nanoindentation study

The objective of this study was to investigate the dissolution of human enamel in citric acid solutions over a wide range of pH. The in vitro conditions are considered to be relevant to soft drink-induced enamel erosion. Nanoindentation was used to investigate changes in the nanomechanical properties of polished enamel surfaces after exposure to citric acid solutions. Solutions used had 38.1 mmol l-1 citric acid and pH greater than 2.3 but less than 6.3 (2.30 < or = pH < or = 6.30). Samples were exposed to rapidly stirred, constant composition solutions for 120 s. Statistically significant changes in enamel hardness and reduced elastic modulus were observed after exposure to all solutions. There was an approximately linear dependence of enamel hardness on solution pH for 2.90 < or = pH < or = 6.30. Below pH 2.90, enamel is thought to have reached the lowest possible hardness value. The reduction in enamel dissolution caused by an increase in pH of a soft drink is likely to be small. Product modification to reduce the erosive potential of drinks may require additional methods such as addition of calcium salts.     

On the Elusive Nature of Sex Differences in Cognition: Hormonal Influences Contributing to Within-Sex Variation

We argue that within-sex variation resulting from the prenatal organizational and adult activational effects of gonadal steroid hormones has the potential to obscure between sex differences in cognitive performance and functional cerebral asymmetry. Two putative markers for prenatal testosterone, finger ridge count (FRC) asymmetry and the 2D:4D finger length ratio, have been linked to within-sex variation in cognitive performance. In particular, FRC allows the identification of men and women who show a reversal of the typical sex-related pattern of task performance. Three paradigms for the study of activational effects—seasonal, menstrual, and diurnal hormonal cycles—have evaluated changes in task performance and functional cerebral asymmetry. The performance of sex-dimorphic, but not sex-neutral, tasks changes with estrogen across the menstrual cycle and with testosterone across its seasonal and diurnal cycles. Functional cerebral asymmetry also changes systematically across both the menstrual cycle and the diurnal testosterone cycle in such a way that suggests left hemisphere performance increases as testosterone levels decline whereas right hemisphere performance increases as estrogen levels decline. In studies of sex differences, such correlates of within-sex hormone-related differences are rarely measured or controlled. Whatever the explanation for the associations of putative markers and hormone cycles with differences in cognitive abilities and cerebral asymmetry, it is clear that these relationships have the potential to contribute to the elusive nature of sex differences in cognition and functional brain organization.     

Parent influences in the transmission of eating and weight related values and behaviors

Early adolescent boys (n = 587) and girls (n = 619) and a parent completed questionnaires, that assessed child dieting behaviors, body dissatisfaction and tendency to overeat, child's current and ideal size, mother and father dieting, and encouragement of the child to diet.     

Intensity-modulated radiation therapy: First reported treatment in Australasia

Intensity-modulated radiation therapy (IMRT) is an exciting new advance in the practice of radiation oncology. It is the use of non-uniform radiation beams to achieve conformal dose distributions. As a result of the high initial capital costs and the time and complexity of planning, IMRT is not yet a widely available clinical treatment option. We describe the process involved in applying this new technology to a case of locally advanced nasopharyngeal cancer.     

The relationship between lesion and normal appearing brain tissue abnormalities in early relapsing remitting multiple sclerosis

Background In multiple sclerosis (MS), pathological changes have been found both in macroscopic lesions and normal appearing tissue. Magnetisation transfer ratio (MTR) and T1 relaxation time are abnormal in normal appearing tissues in established MS. This study used these MR techniques in early MS to study normal appearing tissues and lesions. The purpose was to determine whether abnormalities are already detectable in normal appearing tissues in early MS, and if so how they correlate with lesion characteristics. Methods Twenty two patients with early relapsing remitting (RR) MS (median disease duration 2 years, range 7 months–3 years) and 11 age-matched controls were studied. MTR and T1 relaxation times were measured in 9 regions of normal appearing white matter (NAWM) and 7 of normal appearing grey matter (NAGM). Gadolinium enhancing, T1-hypointense and T2 lesion loads were measured in all patients. Results When all regions were combined, there was a significant difference between patient and control NAWM for both T1 and MTR; T1 was abnormal in 6/9 and MTR in 3/9 NAWM regions. Global assessment of NAGM revealed a significant difference between patients and controls for T1 but not for MTR; T1 was significantly abnormal only in frontal NAGM. There was no significant correlation between NAWM T1 or MTR and any of the lesion load measurements. Conclusions This study reveals quantitative MR abnormalities in both NAWM and NAGM in early RR MS, with more extensive changes in the former. The lack of correlation between NAWM and lesion abnormalities suggests that they have developed by at least partly independent mechanisms. T1 may be more sensitive than MTR in detecting subtle pathological changes in NAWM and NAGM. Received: 3 April 2001, Received in revised form: 15 June 2001, Accepted: 18 June 2001     

PC-based visual stimuli for behavioural and electrophysiological studies of optic flow field detection

A PC-based visual-stimulus-generation package for behavioural and electrophysiological studies of responses to optic flow is described. Developed for studies of crab vision, the package is particularly well suited for use with animals that have very large fields of view, i.e. +/-120 degrees. Programs, written in the Borland Delphi language, use the OpenGL graphics library to create realistic representations of motion in a three dimensional environment. Large-field stimuli include simulations of self-motion (rotation and translation, separately or in combination) relative to a square-wave grating or other, user-selected, background. The package also includes representations of approaching and receding objects, and rotating spiral patterns for the investigation of neural responses to looming/anti-looming. Additionally, the package provides local motion stimuli, translating or rotating targets presented at many points in the receptive field, which can be used to derive response maps of large-field motion-sensitive interneurones. In all these stimuli, inconsistencies in animation timing that have hitherto hindered the use of standard PCs running Microsoft Windows for such applications have been minimised by using an improved real-time clock to control the animation cycle.     

Isolation (from a basal cell carcinoma) of a functionally distinct fibroblast-like cell type that overexpresses Ptch

In this study we report on the isolation and characterization of a nonepithelial, nontumorigenic cell type (BCC1) derived from a basal cell carcinoma from a patient. The BCC1 cells share many characteristics with dermal fibroblasts, such as the expression of vimentin, lack of expression of cytokeratins, and insensitivity to agents that cause growth inhibition and differentiation of epithelial cells; however, significant differences between BCC1 cells and fibroblasts also exist. For example, BCC1 cells are stimulated to undergo DNA synthesis in response to interferon-gamma, whereas dermal fibroblasts are not. More over, BCC1 cells overexpress the basal cell carcinoma-specific genes ptch and ptch2. These data indicate that basal cell carcinomas are associated with a functionally distinct population of fibroblast-like cells that overexpress known tumor-specific markers (ptch and ptch2).