Unintentional total spinal anesthesia during cervical epidural block with ropivacaine

We present a case of unintentional total spinal anesthesia, which occurred during cervical epidural block. A 34-year-old man with complex regional pain syndrome of the right upper arm was treated with epidural block at C7-T1 interspace. Immediately after test-dose injection of ropivacaine 1.5 ml, he complained of paresthesia of his upper extremities. He developed difficulty talking and breathing. Subsequently he showed a complete paralysis with the loss of consciousness, respiratory arrest, and bilateral midriasis. Mandatory ventilation was started and endotracheal tube was placed. Eighty minutes after the injection of ropivacaine, he recovered consciousness and spontaneous respiration resumed. Checking adequate ventilation, his trachea was extubated. Neurological dysfunction was not seen thereafter. Although test-dose injection is recommended especially in high-risk patients and case of difficulty of epidural space identification, it does not fully prevent complications. For cervical epidural block, local anesthetics should either be given at small doses or not be given as long as a possibility of spinal injection is remaining.     

Fibroblast growth factor 2 inhibits the expression of stromal cell-derived factor 1α in periodontal ligament cells derived from human permanent teeth in vitro

Although cells derived from periodontal ligament (PDL) tissue are reported to have stem cell-like activity and are speculated to play a crucial role for tissue healing and regeneration after injury or orthodontic treatment, mechanisms regulating their recruitment and activation remain unknown. Recently, stromal cell-derived factor 1α (SDF-1α) has been reported to be important for stem cell homing and recruitment to injured sites. The aim of this study was to evaluate whether fibroblast growth factor 2 (FGF-2) affects the expression of SDF-1α in PDL cells derived from human permanent teeth in vitro. Using real-time PCR, the expression of SDF-1α mRNA in PDL cells was inhibited by treatment with 10 ng/ml FGF-2. When PDL cells were treated with SU5402 (an inhibitor of FGF receptor 1) in combination with FGF-2, the FGF-2-reduced expression of SDF-1α was inhibited. In the presence of the JNK inhibitor SP600125, SDF-1α mRNA in PDL cells was not suppressed by the FGF-2 treatment. Western blot analysis also showed that SDF-1α production was suppressed by treatment with FGF-2, but it recovered with treatment by FGF-2 + SU5402. These findings suggest that SDF-1α from PDL cells plays an important role in the regeneration and homeostasis of periodontal tissues via the recruitment of stem cells.     

Differential effects of TGF-β1 and FGF-2 on SDF-1α expression in human periodontal ligament cells derived from deciduous teeth in vitro

Stromal cell-derived factor (SDF)-1α has been reported to play a crucial role in stem cell homing and recruitment to injured sites. However, no information is available about its role in periodontal tissues. The aim of this in vitro study was to investigate the effects of basic fibroblast growth factor (FGF-2) and transforming growth factor (TGF)-β1 on SDF-1α expression in immortalized periodontal ligament (PDL) cells derived from deciduous teeth (SH9 cells). Real-time PCR and western blot analyses showed that SDF-1α mRNA expression in SH9 cells was markedly inhibited by FGF-2 treatment for 48 h. SU5402, which directly interacts with the catalytic domain of the FGF receptor 1 (FGFR1) and suppresses its phosphorylation, inhibited the FGF-2-related decrease in SDF-1α expression. These results suggest that FGF-2 signaling via the FGFR1 pathway inhibits SDF-1α expression. Conversely, SDF-1α expression in SH9 cells was increased by TGF-β1 treatment for 12 h. Western blot analysis showed that this treatment induced Smad2/3 phosphorylation. A time-course experiment showed that SDF-1α expression levels reached a maximum 12 h after the TGF-β1 treatment and returned to basal levels by 48 h. Real-time PCR analysis showed that Smad7 mRNA expression peaked by 6 h after TGF-β1 treatment. Since Smad7 siRNA downregulated Smad7 expression by approximately 2.5-fold compared with the negative control siRNA, the induction of SDF-1α expression was prolonged. Furthermore, treatment of SH9 cells with TGF-β1 for 12 h induced transwell migration of UE7T-13 cells, which are mesenchymal stem cells derived from human bone marrow. Therefore, SDF-1α may play an important role in stem and progenitor cell recruitment and homing to injured sites in the periodontal ligament, and regulation of SDF-1α expression may be a useful tool in cell-based therapy for periodontal tissue regeneration.     

Antinociceptive effect of intrathecal administration of taurine in rat models of neuropathic pain

Purpose

Taurine is the most abundant amino acid in many tissues. Although taurine has been shown to be antinociceptive, in this report, our focus is to elucidate the mechanism and action site on neuropathic pain. This study used behavioural assessments to determine whether taurine attenuates neuropathic pain in the spinal cord.

Methods

Chronic constriction injury (CCI) to the sciatic nerve and streptozotocin-induced diabetic neuropathy were introduced to male Sprague-Dawley rats. We then assessed the antinociceptive effect of spinal injections of taurine (100, 200, 400, or 800 μg) using electronic von Frey, paw pressure, and plantar tests. To explore the effect of taurine on motor function, a rotarod test was performed, and in order to determine which neurotransmitter pathway is involved in taurine’s action, we examined how several antagonists of spinal pain processing receptors altered the effect of taurine 400 μg in a paw pressure test.

Results

Taurine alleviated mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia in CCI rats and suppressed mechanical allodynia and hyperalgesia in diabetic rats. Significant effects were observed at 200 μg in both models. On the other hand, taurine dose-dependently affected motor performance, and a significant effect was seen at 400 μg. The antinociceptive effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist.

Conclusion

The present study demonstrated that intrathecal administration of taurine attenuates different models of neuropathic pain, and these effects seem to be mediated by the activation of glycinergic neurotransmission. These findings suggest that taurine may be a candidate remedy for neuropathic pain.     

Anti‐FGF‐23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice

Fibroblast growth factor 23 (FGF‐23) plays causative roles in the development of several hypophosphatemic rickets/osteomalacia such as X‐linked hypophosphatemic rickets/osteomalacia (XLH) and tumor‐induced rickets/osteomalacia. Patients with hypophosphatemic rickets/osteomalacia often complain of muscle weakness and bone pain that severely affect daily activities of these patients. The purpose of this study was to examine whether anti‐FGF‐23 antibodies, which have been shown to improve hypophosphatemia and rachitic changes of juvenile Hyp mice in a murine model of XLH, also ameliorate hypophosphatemic osteomalacia and affect muscle force and spontaneous motor activity in adult Hyp mice. Repeated injections of anti‐FGF‐23 antibodies increased serum phosphate and 1,25‐dihydroxyvitmain D levels and enhanced mineralization of osteoid in adult Hyp mice, whereas bone length did not change. We found that grip strength was weaker and that spontaneous movement was less in adult Hyp mice than in wild‐type mice. In addition, FGF‐23 antibodies increased grip strength and spontaneous movement. These results suggest that the inhibition of excess FGF‐23 action not only ameliorates hypophosphatemia and impaired mineralization of bone but also improves muscle weakness and daily activities of patients with FGF‐23‐related hypophosphatemic rickets/osteomalacia. © 2011 American Society for Bone and Mineral Research.     

Considerations for general anesthesia combined with epidural anesthesia in a patient with stiff-person syndrome

We report the successful management of anesthesia in a patient with stiff-person syndrome (SPS) undergoing a thymectomy using a volatile anesthetic combined with epidural anesthesia. The anesthetic concern in patients with SPS is the possibility of postoperative hypotonia due to the presence of excessive γ-aminobutyric acid (GABA) resulting from an interaction between the anesthetic agents and preoperatively taken therapeutic drugs. Epidural anesthesia has the advantages of decreasing the required amount of anesthetics with GABAergic action, and relieving the postoperative pain that causes the symptoms of SPS. Epidural anesthesia could be a useful technique in SPS patients.     

Effect of acute changes of serum phosphate on fibroblast growth factor (FGF)23 levels in humans

Fibroblast growth factor (FGF)23 was identified as a humoral factor involved in the development of several hypophosphatemic diseases. Subsequent studies indicated that FGF23 is a hormone regulating serum phosphate level. However, it is still unknown how the production and serum level of FGF23 are regulated. This study was designed to determine whether acute changes of serum phosphate modulate FGF23 levels in human. Four healthy volunteers participated in the study. In the phosphate infusion study, dibasic potassium phosphate was infused at a rate of 10 mEq/h for 4 h, and serum FGF23 levels were measured for up to 6 h after the start of the infusion. In the carbohydrate study, partially hydrolyzed starch corresponding to 150 g glucose was ingested and FGF23 levels were measured similarly for 6 h. Phosphate infusion significantly increased and carbohydrate ingestion decreased serum phosphate levels, respectively. However, FGF23 did not change by these maneuvers. It is concluded that acute changes of serum phosphate do not modify FGF23 levels in the healthy human.     

Treatment of high-risk peripheral T-cell lymphomas other than anaplastic large-cell lymphoma with a dose-intensified CHOP regimen followed by high-dose chemotherapy. A single institution study

We investigated the efficacy of a dose-intensified double-CHOP regimen followed by high-dose chemotherapy with or without peripheral blood stem cell transplantation (PBSCT) in 11 patients with four types of peripheral T-cell lymphoma (PTCL). Three of the 4 patients with unspecified PTCL (PTCLu) achieved complete response (CR); 1 patient relapsed and 1 died of secondary leukemia after consolidation therapy. All angioimmunoblastic T-cell lymphoma (AILT) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients achieved CR; 5 of 6 have remained disease free for more than 3 years. The patient with hepatosplenic lymphoma did not achieve CR even after PBSCT and underwent allogenic bone marrow transplantation (allo-BMT). Thus, our regimen appears to be effective for high-risk AILT and SPTCL. However, allo-BMT should be considered for high-risk of PTCLu and hepatosplenic T-cell lymphoma.