1-[Carbon-11]-glucose radiation dosimetry and distribution in human imaging studies

1-[Carbon-11]-D-glucose ([11C]-glucose) is an important imaging agent for PET studies that have been used to study the normal brain, encephalitis, epilepsy, manic-depressive disorder, schizophrenia and brain tumors. METHODS: Dosimetry estimates were calculated in subjects undergoing imaging studies to help define the radiation risk of [11C]-glucose PET imaging. Time-dependent radioactivity concentrations in normal tissues in 33 subjects after intravenous injection of [11C]-glucose were obtained by PET imaging. Radiation absorbed doses were calculated according to the procedures of the Medical Internal Radiation Dose (MIRD) committee along with the variation in dose based on the calculated standard deviation of activity distribution seen in the individual patients. RESULTS: Total body exposure was a median of 3.0 microGy/MBq in men and 3.8 microGy/MBq in women. The effective dose equivalent was 3.8 microGy/ MBq in men and 4.8 microGy/MBq in women. The critical organs were those that typically take up the most glucose (brain, heart wall and liver). CONCLUSION: The organ doses reported here are small and comparable to those associated with other commonly performed nuclear medicine tests and indicate that potential radiation risks associated with this radiotracer are within generally accepted limits.     

Oscillopsia: visual function during motion in the absence of vestibulo-ocular reflex

Inspiratory muscle function has been shown to be related to general muscle weakness, weight loss, blood gas tensions, airway obstruction and hyperinflation. The aim of this study was to define (1) the factor that is the main determinant of the tension-time index of the inspiratory muscles (TTmus), and which this increases the risk of inspiratory muscle fatigue; and (2) whether a breathing strategy is adopted to avoid inspiratory muscle fatigue. Twenty-seven normal volunteers and 35 stable COPD outpatients (FEV1% predicted, range: 21-89%; and FRC/TLC, range: 49-77%) were studied. The TTmus was determined as follows: TTmus = PI/PImax.TI/Ttot, where Pi is the mean inspiratory pressure calculated from the mouth occlusion pressure (P0.1), PImax is the maximal inspiratory pressure, TI is the inspiratory time, and Ttot is the total time of the breathing cycle. COPD patients showed significantly lower PImax and higher P0.1, PI, PI/PImax, and TTmus than normal subjects. No patient had a TTmus value higher than the inspiratory muscle fatigue threshold of 0.33. The FEV1 was significantly correlated with TTmus and all its components in the patients. The FRC/TLC was also correlated with all components except PI. Body weight was only correlated with PImax. In a forward and backward stepwise regression analysis, FEV1 appeared to be the only significant factor explaining the variance of log (PI/PImax) and log (TTmus), whereas FRC/TLC was the principal determinant of PImax. In COPD patients, a non-linear relationship was found between TI and P0.1. A negative linear relationship was found between TI/Ttot and PI/PImax. In conclusion, although hyperinflation predominantly affected inspiratory muscle strength in a group of stable COPD patients with a wide range of severity, airway obstruction was the principal factor determining the magnitude of TTmus. In addition, in order to remain below the inspiratory muscle fatigue threshold, as the severity of airway obstruction increased, patients adopted a breathing strategy characterized by decreased TI/Ttot as inspiratory pressure demand increased.     

Effect of biphosphonates on abnormal mandibular growth of rats intoxicated with uranium

The North Central Cancer Treatment Group designed a phase II trial to assess the efficacy and toxicity of topotecan in patients with unresectable malignant pleural mesothelioma. Twenty-two previously untreated patients with unresectable pleural mesothelioma and good performance status (Eastern Cooperative Oncology Group performance status 0, 1, or 2) were enrolled on this trial from October 1993 through July 1994. Nineteen men and three women, median age 66 years (range, 44-78 years), were treated with topotecan 1.5 mg/m2 intravenously over 30 minutes daily for 5 days at 3-week intervals until toxicity, progression of disease, or a patient decided to discontinue treatment. There were seven patients with measurable disease and 15 with evaluable disease; all were assessable for response and toxicity. A total of 113 cycles of treatment were given, for a median of three cycles (range, 1-26 cycles). Myelosuppression was the most frequent toxicity. Eighteen of 21 patients (86%) experienced grade 3 or 4 neutropenia during the initial treatment cycle. The median neutrophil nadir was 0.5 x 10(3)/microl (range, 0.1-1.6 x 10(3)/microl), and the median platelet nadir was 127 x 10(3)/microl (range, 18-460 x 10(3)/microl). Other toxicities more than grade 2 included malaise (two patients), and anorexia, infection, fever, pulmonary, and cardiac in one patient each. There were no objective responses, and 18 patients had stable disease for a median of 74 days. The median survival for all patients was 230 days, with 23% alive at 1 year. Topotecan as administered in this trial is reasonably well tolerated; however, the response rate was insufficient to warrant additional study in pleural mesothelioma.     

MR volumetric analysis of the human entorhinal, perirhinal, and temporopolar cortices

Cell-adhesion molecules (CAMs) are thought to play crucial roles in development and plasticity in the nervous system. This study tested for a role for cell adhesion and in particular, the recognition of two glycosyl epitopes (HNK-1 and oligomannoside) in the activity-driven sharpening of the retinotopic map formed by the regenerating retinal fibers of goldfish. HNK-1 is a prominent glycosyl epitope on many CAMs and extracellular matrix (ECM) molecules, including NCAM, L1, ependymin, and integrins, which have all been implicated in synaptic plasticity. To test for a role of HNK-1 in the sharpening process, we used osmotic minipumps to infuse HNK-1 antibodies for 7-21 days into the tectal ventricle starting at 18 days after optic nerve crush. Retinotopic maps recorded at 76-86 days postcrush showed a lack of sharpening similar to that seen previously with two antibodies to ependymin, an HNK-1-positive ECM component present in cerebrospinal fluid. The multiunit receptive fields at each point averaged 26 degrees versus 11-12 degrees in regenerates infused with control antibodies or Ringer's alone. The HNK-1 epitope also binds to the G2 domain of laminin to mediate neuron-ECM adhesion. To test for a role for laminin, a polyclonal antibody was similarly infused and also prevented sharpening to approximately the same degree. The results support a role for the HNK-1 epitope and laminin in retinotectal sharpening. The oligomannoside epitope (recognized by monoclonal antibody L3) on the CAM L1 interacts with NCAM on the same cell to promote stronger L1 homophilic interactions between cells. Both an L1-like molecule and NCAM are prominently reexpressed in the regenerating retinotectal system of fish. Infusion of oligomannosidic glycopeptides resulted in decreased sharpening, with multiunit receptive fields that averaged 22.7 degrees. Infusions of mannose-poor glycopeptides less prominently disrupted sharpening, with average multiunit receptive fields of 18 degrees. Thus, oligomannosidic glycans in particular may play a role in retinotopic sharpening. Blocking glycan-mediated interactions between CAMs and ECM molecules could decrease the extent of exploratory growth of retinal axon collaterals, preventing them from finding their retinotopic sites, or could interfere with L1 or NCAM and laminin binding at the synaptic densities preventing stabilization of retinotopically appropriate synapses. Together, these results support a prominent role for cell adhesion and glycan epitopes in visual synaptic plasticity.     

Peptide-amidating enzymes are expressed in the stellate epithelial cells of the thymic medulla

C-terminal amidation is a post-translational processing step necessary to convey biological activity to a large number of regulatory peptides. In this study we have demonstrated that the peptidyl-glycine alpha-amidating monooxygenase enzyme complex (PAM) responsible for this activity is located in the medullary stellate epithelial cells of the thymus and in cultured epithelial cells bearing a medullary phenotype, using Northern blot, immunocytochemistry, in situ hybridization, and enzyme assays. Immunocytochemical localization revealed a granular pattern in the cytoplasm of the stellate cells, which were also positive for cytokeratins and a B-lymphocyte-associated antigen. The presence of PAM activity in medium conditioned by thymic epithelial cell lines suggests that PAM is a secreted product of these cells. Among the four epithelial cell lines examined, there was a direct correlation between PAM activity and content of oxytocin, an amidated peptide. Taken together, these data provide convincing evidence that thymic epithelial cells have the capacity to generate amidated peptides that may influence T-cell differentiation and suggest that the amidating enzymes could play an important role in the regulation of thymic physiology.     

Leukocyte-endothelium interaction during the early stages of hypercholesterolemia in the rabbit: role of P-selectin, ICAM-1, and VCAM-1

The early effects of hypercholesterolemia on leukocyte-endothelium interaction were studied in vivo in the rabbit mesenteric microcirculation. Rabbits fed a 0.5% high-cholesterol (HC) diet showed elevated plasma cholesterol levels during the 1 to 2 weeks of HC feeding (P<0.001 versus control diet-fed rabbits). Intravital microscopy of mesenteric venules revealed that leukocyte rolling had increased 10-fold (P<0.001 versus control-fed group) at the end of the first week of the HC diet, which was sustained after 2 weeks of HC feeding (P<0.001 versus control-fed rabbits). Firm adherence of leukocytes to the endothelium was moderately increased after a 1-week period of hypercholesterolemia (P<0.05) but increased by 12-fold at 2 weeks (P<0.001 versus control diet-fed and P<0.01 versus 1-week HC-fed rabbits). Upregulation of the endothelial cell adhesion molecules P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was observed immunohistochemically on the intestinal microvascular endothelium of HC-fed rabbits. P-selectin was maximally expressed within the first week of the HC diet and remained elevated during the second week of cholesterol feeding (P<0.01 versus control). In contrast, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were moderately upregulated at 1 week but were highly expressed after 2 weeks of the HC diet (P<0.05 and P<0.001 versus control, respectively). Basal release of NO from both mesenteric microvascular and aortic endothelium in cholesterol-fed rabbits was progressively reduced after 1 (P<0.05) and 2 (P<0.01) weeks. Our data suggest that enhanced leukocyte-endothelium interaction occurs in vivo in the rabbit microcirculation during the first 2 weeks of hypercholesterolemia. This phenomenon is associated with impaired basal NO release and progressive endothelial surface expression of endothelial cell adhesion molecules (ie, P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1) in the microvasculature.     

The ratio of initial/residual DNA damage predicts intrinsic radiosensitivity in seven cervix carcinoma cell lines

The single-cell gel electrophoresis (comet) assay was used to measure radiation-produced DNA double-strand breaks (dsbs) in a series of seven cervical tumour cell lines (ME180, HT3, C33A, C41, SiHa, MS751 and CaSki). The proportion of DNA dsbs was measured immediately after radiation treatment (initial damage) and 16 h later after incubation at 37 degrees C (residual damage). Linear dose-response curves were seen for initial (slopes 0.23-0.66) and residual (slopes 0.16-0.87) DNA dsbs. Neither of the slopes of the linear regression analysis on the initial and on the residual DNA dsbs dose-response curves (range 0-80 Gy) correlated with SF2 (surviving fraction at 2 Gy) measured after high- (HDR) or low-dose-rate (LDR) irradiation. An association was evident between SF2 after HDR and LDR irradiation and the ratio of the absolute level of initial and residual damage after a single dose of 60 Gy. However, a significant correlation was found between HDR (r= -0.78, P = 0.04) and LDR (r = -0.86, P = 0.03) SF2 values and the ratio of the slopes of the initial and residual DNA dsbs dose-response curves (range 0.47-0.99), representing the fraction of DNA damage remaining. These results indicate that the neutral comet assay can be used to predict radiosensitivity of cervical tumour cell lines by assessing the ratio of initial and residual DNA dsbs.     

Factor structure of a measure of anxiety sensitivity in children

Anxiety sensitivity (i.e., the disposition to react to autonomic arousal with fear) has taken a central role in recent conceptualizations of anxiety. However, questions regarding the dimensional nature of anxiety sensitivity remain. In particular, the factor structure of anxiety sensitivity is unexplored in nonadult populations. The factor structure of the Anxiety Sensitivity Index for Children (ASIC) was examined in three studies. Study 1 (N = 95) used a sample of school children in Grades 4-8 to investigate the reliability of items and factor structure. Items with weak psychometric properties were eliminated, and subsequent analyses revealed that the ASIC was best viewed as a hierarchical scale with a higher order factor (Anxiety Sensitivity) and two first-order factors (Fear of Physiological Arousal and Fear of Mental Catastrophe). Study 2 (N = 112) and Study 3 (N = 144) used more distressed samples of youngsters, and they also found the ASIC to be a hierarchical scale. These findings add a developmental perspective to the Anxiety Sensitivity Index factor analytic discussion and are highly consistent with emergent thinking in the adult anxiety sensitivity literature.