Re-organization of P2X3 receptor localization on epidermal nerve fibers in a murine model of cancer pain

To determine whether ATP and P2X3 receptors contribute to bone-cancer pain in a mouse model, immunohistochemical techniques were used to identify whether changes in the labeling of P2X3 receptors on epidermal nerve fibers (ENFs) occurred during tumor development. C3H mice were injected with osteolytic fibrosarcoma cells in and around the calcaneus bone. These mice exhibited mechanical hyperalgesia by day 10 post-implantation as assessed using von Frey monofilaments. Biopsies of the plantar skin overlying the tumor were obtained at days 10, 14, and 18 post-implantation. Confocal images were analyzed for the number of PGP 9.5, P2X3, and CGRP immunoreactive (ir) ENFs. The overall ENF population (PGP-ir) decreased progressively over time, whereas the subsets of P2X3-ir fibers demonstrated a modest increase and CGRP-ir nerve fibers remained fairly constant. Importantly, the proportion of CGRP-ir fibers that labeled for P2X3 increased from approximately 6% in control animals to nearly 30% at day 14 following tumor cell implantation. These studies demonstrate increased expression of P2X3 receptors on CGRP-ir ENFs during tumor growth and suggest a role for ATP in cancer-related pain.     

Steady-state pharmacokinetics of bupropion SR in juvenile patients

OBJECTIVE: To examine the steady-state pharmacokinetic properties of bupropion sustained release (SR) and their potential developmental differences in youths. METHOD: Eleven boys and eight girls aged 11 to 17 years old were prescribed bupropion SR monotherapy for attention-deficit/hyperactivity disorder (n = 16) and/or depressive disorders (n = 16). Bupropion SR was given in morning doses of 100 mg/day (n = 11) or 200 mg/day (n = 8) for 14 days or less, with five subjects studied on both doses. All subjects had blood draws from an intravenous port every 1 to 3 hours for 24 hours after their usual morning doses. Pharmacokinetic variables were determined by noncompartmental and compartmental analyses for bupropion and metabolites, respectively. RESULTS: Bupropion and its metabolites exhibited linear pharmacokinetics. Areas under the concentration curves for the hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were 20, 12, and 2.7 times higher, respectively, than for bupropion. Relative to adults, the mean half-lives of bupropion (12.1 hours) and threohydrobupropion (26.3 hours) were significantly shorter, and areas under the concentration curve ratios of metabolites to bupropion were 19% to 80% higher. CONCLUSIONS: Youths metabolize bupropion SR faster to hydroxybupropion and other active metabolites than adults. Until the clinical importance of bupropion's metabolites is clarified, bupropion SR should be given in divided doses to youths, as the manufacturer recommends for adults taking higher doses.     

Successful treatment of pure red cell aplasia associated with systemic lupus erythematosus with oral danazol and steroid

We describe a middle-aged Chinese systemic lupus erythematosus (SLE) patient developing steroid refractory and transfusion dependent red cell aplasia. Oral danazol 200 mg twice per day was started together with low-dose prednisolone therapy. There was no further recurrence of anemia 1 month after this combined therapy.     

Asymmetric limb loading with true or simulated leg-length differences

Unequal leg lengths result in asymmetric limb loading but opinions vary on the size of the difference inducing abnormal loading, and which limb sustains the greater load. Our study compared limb-loading asymmetries during walking for subjects with anatomic leg-length discrepancies between 1.0 and 3 cm, subjects without length discrepancies, and for subjects with a simulated a 1.31-cm leg-length discrepancy. Symmetry indices were calculated for peak ground reaction force during weight acceptance, rate of change of weight acceptance force, peak push-off force, and rate of change of push-off force. All symmetry measures were significantly different from normal for the simulated leg-length discrepancy. The shorter limb sustained a greater proportion of the load and loading rate. The anatomic leg-length discrepancy group showed the same trend with the exception of the push-off force rate. There were equivalent size-effect differences for both leg-length discrepancy conditions; however, for the anatomic leg-length discrepancy group, only the weight acceptance force symmetry value was statistically different from normal. The shorter limb sustains a greater proportion of load and loading rates; therefore, equalizing leg lengths should be considered even with bilateral differences less than 3 cm.     

Autofluorescence and diffuse reflectance properties of malignant and benign breast tissues

Background Fluorescence spectroscopy is an evolving technology that can rapidly differentiate between benign and malignant tissues. These differences are thought to be due to endogenous fluorophores, including nicotinamide adenine dinucleotide, flavin adenine dinucleotide, and tryptophan, and absorbers such as β-carotene and hemoglobin. We hypothesized that a statistically significant difference would be demonstrated between benign and malignant breast tissues on the basis of their unique fluorescence and reflectance properties. Methods Optical measurements were performed on 56 samples of tumor or benign breast tissue. Autofluorescence spectra were measured at excitation wavelengths ranging from 300 to 460 nm, and diffuse reflectance was measured between 300 and 600 nm. Principal component analysis to dimensionally reduce the spectral data and a Wilcoxon ranked sum test were used to determine which wavelengths showed statistically significant differences. A support vector machine algorithm compared classification results with the histological diagnosis (gold standard). Results Several excitation wavelengths and diffuse reflectance spectra showed significant differences between tumor and benign tissues. By using the support vector machine algorithm to incorporate relevant spectral differences, a sensitivity of 70.0% and specifcity of 91.7% were achieved. Conclusions A statistically significant difference was demonstrated in the diffuse reflectance and fluorescence emission spectra of benign and malignant breast tissue. These differences could be exploited in the development of adjuncts to diagnostic and surgical procedures.