Periosteal Reaction Possibly Induced by Pazopanib: A Case Report and Literature Review.

BACKGROUND: Although complications associated with pazopanib, a multitarget tyrosine kinase inhibitor, are known, periosteal reaction as a side effect has never been reported. OBSERVATION: We present a case involving a male pediatric patient with desmoid tumors treated for 6 months with pazopanib who presented with pain and periosteal reaction in the ilium and scapula. Three months after termination of pazopanib therapy, the periosteal reaction in the scapula resolved and that in the ilium improved. CONCLUSION: Children receiving pazopanib presenting with focal pain should be examined for the periosteal reaction; this knowledge may facilitate correct diagnosis of symptoms as a drug-associated finding.

Effect of antioxidants on BPA-induced stress on sperm function in a mouse model.

In the past few years, bisphenol A, (BPA) an endocrine-disrupting chemical, has received increasing attention because of its detrimental health effects. There is ample evidence to support that BPA interferes with the reproductive health of humans and animals. In spermatozoa, BPA-induced adverse effects are mostly caused by increased oxidative stress. Using an in vitro experimental model, we examined whether antioxidants (glutathione, vitamin C, and vitamin E) have defensive effects against BPA-induced stress in spermatozoa. The results showed that antioxidants inhibit the overproduction of reactive oxygen species (basically cellular peroxides) and increase intracellular ATP levels, thereby preventing motility loss and abnormal acrosome reaction in BPA-exposed spermatozoa. In particular, glutathione and vitamin E reduced the protein kinase A-dependent tyrosine phosphorylation in spermatozoa and, thus, prevented the precocious acrosome reaction from occurring. Furthermore, we found that the compromised fertilisation and early embryo development mediated by BPA-exposed spermatozoa can be improved following their supplementation with glutathione and vitamin E. Based on these findings, we suggest that antioxidants reduce oxidative stress in BPA-exposed spermatozoa, thus preventing detrimental effects on their function and fertility.

Comparison of Anterior Suprascapular, Supraclavicular, and Interscalene Nerve Block Approaches for Major Outpatient Arthroscopic Shoulder Surgery: A Randomized, Double-blind, Noninferiority Trial.

BACKGROUND: The interscalene nerve block provides analgesia for shoulder surgery, but is associated with diaphragm paralysis. One solution may be performing brachial plexus blocks more distally. This noninferiority study evaluated analgesia for blocks at the supraclavicular and anterior suprascapular levels, comparing them individually to the interscalene approach. METHODS: One hundred-eighty-nine subjects undergoing arthroscopic shoulder surgery were recruited to this double-blind trial and randomized to interscalene, supraclavicular, or anterior suprascapular block using 15 ml, 0.5% ropivacaine. The primary outcome was numeric rating scale pain scores analyzed using noninferiority testing. The predefined noninferiority margin was one point on the 11-point pain scale. Secondary outcomes included opioid consumption and pulmonary assessments. RESULTS: All subjects completed the study through the primary outcome analysis. Mean pain after surgery was: interscalene = 1.9 (95% CI, 1.3 to 2.5), supraclavicular = 2.3 (1.7 to 2.9), suprascapular = 2.0 (1.4 to 2.6). The primary outcome, mean pain score difference of supraclavicular-interscalene was 0.4 (-0.4 to 1.2; P = 0.088 for noninferiority) and of suprascapular-interscalene was 0.1 (-0.7 to 0.9; P = 0.012 for noninferiority). Secondary outcomes showed similar opioid consumption with better preservation of vital capacity in the anterior suprascapular group (90% baseline [P < 0.001]) and the supraclavicular group (76% [P = 0.002]) when compared to the interscalene group (67%). CONCLUSIONS: The anterior suprascapular block, but not the supraclavicular, provides noninferior analgesia compared to the interscalene approach for major arthroscopic shoulder surgery. Pulmonary function is best preserved with the anterior suprascapular nerve block.

Comparison of nanoparticular hydroxyapatite pastes of different particle content and size in a novel scapula defect model.

Nanocrystalline hydroxyapatite (HA) has good biocompatibility and the potential to support bone formation. It represents a promising alternative to autologous bone grafting, which is considered the current gold standard for the treatment of low weight bearing bone defects. The purpose of this study was to compare three bone substitute pastes of different HA content and particle size with autologous bone and empty defects, at two time points (6 and 12 months) in an ovine scapula drillhole model using micro-CT, histology and histomorphometry evaluation. The nHA-LC (38% HA content) paste supported bone formation with a high defect bridging-rate. Compared to nHA-LC, Ostim® (35% HA content) showed less and smaller particle agglomerates but also a reduced defect bridging-rate due to its fast degradation The highly concentrated nHA-HC paste (48% HA content) formed oversized particle agglomerates which supported the defect bridging but left little space for bone formation in the defect site. Interestingly, the gold standard treatment of the defect site with autologous bone tissue did not improve bone formation or defect bridging compared to the empty control. We concluded that the material resorption and bone formation was highly impacted by the particle-specific agglomeration behaviour in this study.

Does the Use of Ibuprofen in Children with Extremity Fractures Increase their Risk for Bone Healing Complications?

BACKGROUND: Despite being an effective analgesic for children with fractures, some clinicians may avoid prescribing ibuprofen due to its potentially harmful effect on bone healing. OBJECTIVE: To determine if exposure to ibuprofen is associated with an increased risk of bone healing complications in children with fractures. METHODS: We performed a retrospective study of children aged 6 months to 17 years who presented to the pediatric emergency department (PED) with a fracture of the tibia, femur, humerus, scaphoid, or fifth metatarsus and who followed up with the orthopedic service. We chose these fractures due to their higher risk for complications. We classified patients as exposed if they received ibuprofen in the PED or during hospitalization or were prescribed ibuprofen at discharge. The main outcome was a bone healing complication as evidenced by nonunion, delayed union, or re-displacement on follow-up radiographs. RESULTS: Of the 808 patients included in the final analysis, 338 (42%) were exposed to ibuprofen. Overall, 27 (3%) patients had a bone healing complication; 8 (1%) developed nonunion, 3 (0.4%) developed delayed union, and 16 (2%) developed re-displacement. Ten (3%) patients who were exposed to ibuprofen, and 17 (4%) who were not, developed a bone healing complication (odds ratio 0.8, 95% confidence interval 0.4-1.8; p = 0.61). There was no significant association between ibuprofen exposure and the development of a bone healing complication despite adjustment for potential confounders. CONCLUSION: Children with extremity fractures who are exposed to ibuprofen do not seem to be at increased risk for clinically important bone healing complications.

Comparison of the therapeutic effects of intramuscular subscapularis and scapulothoracic bursa injections in patients with scapular pain: a randomized controlled trial.

Scapulothoracic bursitis contributes to considerable morbidity in some patients with scapular pain. A scapulothoracic bursa injection can induce symptomatic relief; however, blind injections into the scapulothoracic bursa may involve injecting into the subscapularis muscle itself. The aim of this study was to compare the therapeutic effects of intramuscular injections into the subscapularis under ultrasound (US) guidance with those of blind scapulothoracic bursa injections in patients with scapular pain. This study was a single-center, prospective, randomized, single-blinded, controlled clinical trial. Thirty-six patients with suspected scapulothoracic bursitis, who met the inclusion criteria, were recruited between January 2009 and December 2012. We performed three US-guided intramuscular injections into the subscapularis muscle or three blind scapulothoracic bursa injections at 1-week intervals. A visual analogue scale (VAS) and the Rubin scale at baseline and at 1, 2, and 3 weeks after the last injections were examined and again at 3 months after the last injections by a blinded investigator. Adverse effects were monitored. The VAS scores at baseline were 7.7 ± 1.3 and 7.8 ± 1.4 in the intramuscular injection and scapulothoracic bursa injection groups, respectively. Mean VAS scores after the intramuscular injections were 3.8, 2.7, 1.3, and 3.5, and mean VAS scores after scapulothoracic bursa injections were 4.1, 2.4, 1.6, and 2.9 at 1, 2, 3 weeks and at 3 months after the last injections. VAS scores decreased significantly after the injections in each group (p ≤ 0.05). However, no significant difference was observed between intramuscular injection into the subscapularis and the scapulothoracic bursa injection. No serious complications were encountered. In conclusion, injections at the scapulothoracic bursa without US guidance did not exclude the possibility of an effect of steroid on the subscapularis muscle, as both intramuscular injections into the subscapularis and scapulothoracic bursa injections in patients with scapular pain provided equal symptomatic relief, and all patients developed tenderness in their subscapularis muscle.

A neurophysiological evidence of capsaicin-sensitive nerve components innervating interscapular brown adipose tissue.

Neurophysiological basis for the heterogeneity of the nerve components in the brown adipose tissue (BAT) was examined in this experiment. Efferent nerve signals were recorded from the central cut end of the small nerve filament dissected from the nerve fibers innervating the interscapular BAT (IBAT). By focusing on qualitative aspects of observed compound action potentials (spikes), we found two distinctive types of spikes exhibited by the intercostal nerves innervating IBAT. The spikes mainly appeared upon sympathetic stimulations (cold stimulation and glucose administration) were characterized by low amplitude with relatively short duration (small spike) and their sensitivity to the ganglion blocker, hexamethonium (C6). On the other hand, the spikes seen throughout the experiments were characterized by high amplitude with long duration (large spike) and their insensitivity to C6. Since BAT is activated by cold and feeding via sympathetic nervous system, the small spikes seemed to be exhibited by sympathetic fibers. On the other hand, appearance of the large C6-insensitive spikes was strongly attenuated in capsaicin-desensitized rats. Even though the functional link between IBAT and C6 insensitive fibers remains unanswered, our results suggest that IBAT is under control of various nerve types including capsaicin-sensitive fibers in addition to the control of sympathetic nervous system.

Apoptosis in mouse fetuses from dams exposed to T-2 toxin at different days of gestation.

T-2 toxin (2 mg/kg b.w.) was orally inoculated to pregnant mice at gestational day (GD) 8.5, 9.5, 10.5, 11.5, 12.5, 13.5, 14.5, 15.5 and GD 16.5, respectively, and the fetuses were examined 24 hours later. The number and region of pyknotic or karyorrhectic cells varied according to inoculation date. In the GD 13.5-subgroup, a moderate to high number of pyknotic or karyorrhectic neuronal cells were observed in the central nervous system, peri-ventricular zone to subventricular zone, and pyknosis or karyorrhexis were also observed in a small number of chondroblasts and chondrocytes. In the GD 16.5-subgroup, a moderate to high number of pyknotic or karyorrhectic cells were observed in the thymus and renal subcapsular parenchyma. The nuclei of these pyknotic or karyorrhectic cells were strongly stained by the terminal deoxy nucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling method widely used for the in situ detection of apoptotic nuclei. In addition, a few fetuses from dams which were given T-2 toxin at GD 13.5 or GD 14.5 and killed at GD 17.5 showed skeletal abnormalities such as wavy ribs and short scapula. From the present findings and the well known fact that T-2 toxin readily crosses the rat placenta, it seems that T-2 toxin-induced apoptosis in the developing mouse fetuses might be a direct effect of T-2 toxin on fetuses.

Perturbation of BMP signaling in somitogenesis resulted in vertebral and rib malformations in the axial skeletal formation.

Axial skeletons such as vertebrae, ribs, and scapulae develop from the embryonic somitic mesoderm through interactions with neural tube/notochord and skin ectoderm. Bone morphogenetic proteins (BMPs) seem to play important roles in these tissue interactions; however, the relationship between BMP signaling and the early development of axial skeletons is poorly understood. In this report, we investigated possible roles of BMP signaling in axial skeletal formation. First, we describe the expression patterns of BMP4 and type I receptors for BMP during somitogenesis in chick embryos based on whole mount in situ hybridization. Next, the effects of BMP on axial skeletal morphogenesis were investigated by implantation of BMP proteins into the dorsal mesoderm at the time of somitogenesis. Transcripts for both BMP4 ligand and its receptors are expressed in the dorsal ectoderm and mesoderm. Implantation of BMP4 and BMP2 into the dorsal regions of embryos result in subsequent anomalies of vertebrae, ribs, and scapulae. The effects of BMP implantation on the skeleton are shown to be dependent upon the somitic stage. Vertebral anomalies are restricted to the dorsolateral elements of the vertebrae and specifically observed after BMP implantation into embryonic day 2 (E2) embryos, but not E3 embryos. These results indicate that implantation of BMP into the dorsal part of embryos where endogenous BMP ligand and BMP receptors are expressed perturbs BMP signaling and causes axial skeletal malformations. The findings presented here suggest that BMP signaling may be involved in the early developmental process of the axial skeleton.