A 51-year-old man with metastatic renal cell carcinoma whose fentanyl requirement was 3000-4000 µg/h in inpatient hospice presented for a thoracic (T) vertebral 4-10 posterior spinal fusion for a ...lytic T7 compression fracture. He underwent total intravenous (IV) anesthesia with propofol, remifentanil, and ketamine; liposome bupivacaine was locally infiltrated at the end of the case. Following extubation on postoperative day (POD) 1, he had severe pain refractory to high-dose IV fentanyl patient control analgesia and ketamine infusion. His pain dramatically improved after a dexmedetomidine infusion was added and titrated to the analgesic effect. He participated in neurological examinations and fulfilled both surgical and pain management goals without side effects. Dexmedetomidine was successfully weaned off on POD 3.
Transcriptional control by β-catenin and lymphoid enhancer-binding factor 1 (LEF1)/T cell factor regulates proliferation in stem cells and tumorigenesis. Here we provide evidence that transcriptional ...co repressor homeodomain interacting protein kinase 2 (HIPK2) controls the number of stem and progenitor cells in the skin and the susceptibility to develop squamous cell carcinoma. Loss of HIPK2 leads to increased proliferative potential, more rapid G₁-S transition in cell cycle, and expansion of the epidermal stem cell compartment. Among the critical regulators of G₁-S transition in the cell cycle, only cyclin D1 is selectively up-regulated in cells lacking HIPK2. Conversely, overexpression of HIPK2 suppresses LEF1/β-catenin-mediated transcriptional activation of cyclin D1 expression. However, deletion of the C-terminal YH domain of HIPK2 completely abolishes its ability to recruit another transcriptional corepressor CtBP and suppress LEF1/β-catenin-mediated transcription. To determine whether loss of HIPK2 leads to increased susceptibility to tumorigenesis, we treat wild-type, Hipk2⁺/⁻, andHipk2⁻/⁻ mice with the two-stage carcinogenesis protocol. Our results indicate that more skin tumors are induced in Hipk2⁺/⁻ and Hipk2⁻/⁻ mutants, with most of the tumors showing shortened incubation time and malignant progression. Together, our results indicate that HIPK2 is a tumor suppressor that controls proliferation by antagonizing LEF1/β-catenin-mediated transcription. Loss of HIPK2 synergizes with activation of H-ras to induce tumorigenesis.
Abstract Background Anterocollis is a form of cervical dystonia characterized by forward neck flexion. While botulinum toxin is the treatment of choice for cervical dystonia, patients with ...anterocollis, who receive injections into the sternocleidomastoid and anterior scalene muscles, represent a disproportionate number of treatment failures. Deep cervical muscles such as the longus colli likely play an important role in neck flexion but are not routinely injected. Objective To describe a technique for longus colli injection in cases of anterocollis and to report the clinical outcomes of 10 such injections of botulinum toxin. Methods Three patients were referred for evaluation and treatment of anterocollis. All had previous treatment failures with sternocleidomastoid/anterior scalene injections or no activity noted on needle EMG investigation of these muscles. All patients received injections of botulinum toxin into the longus colli under fluoroscopic and EMG guidance. Results All patients experienced symptomatic improvement (eight of 10 injections). Two patients reported mild dysphagia without serious complications after dose increases in botulinum toxin. Conclusions Incomplete muscle selection may be one cause of treatment failures in anterocollis. Deep cervical flexors such as the longus colli represent an under-recognized potential target for symptomatic treatment of anterocollis.
Transcriptional control by β-catenin and lymphoid enhancer-binding factor 1 (LEF1)/T cell factor regulates proliferation in stem cells and tumorigenesis. Here we provide evidence that transcriptional ...co repressor homeodomain interacting protein kinase 2 (HIPK2) controls the number of stem and progenitor cells in the skin and the susceptibility to develop squamous cell carcinoma. Loss of HIPK2 leads to increased proliferative potential, more rapid G...-S transition in cell cycle, and expansion of the epidermal stem cell compartment. Among the critical regulators of G...-S transition in the cell cycle, only cyclin D1 is selectively up-regulated in cells lacking HIPK2. Conversely, overexpression of HIPK2 suppresses LEF1/β-catenin-mediated transcriptional activation of cyclin D1 expression. However, deletion of the C-terminal YH domain of HIPK2 completely abolishes its ability to recruit another transcriptional corepressor CtBP and suppress LEF1/β-catenin-mediated transcription. To determine whether loss of HIPK2 leads to increased susceptibility to tumorigenesis, we treat wild-type, Hipk2..., and Hipk2... mice with the two-stage carcinogenesis protocol. Our results indicate that more skin tumors are induced in Hipk2... and Hipk2... mutants, with most of the tumors showing shortened incubation time and malignant progression. Together, our results indicate that HIPK2 is a tumor suppressor that controls proliferation by antagonizing LEF1/β-catenin-mediated transcription. Loss of HIPK2 synergizes with activation of H-ras to induce tumorigenesis. (ProQuest: ... denotes formulae/symbols omitted.)
A 51-year-old man with metastatic renal cell carcinoma whose fentanyl requirement was 3000-4000 µg/h in inpatient hospice presented for a thoracic (T) vertebral 4-10 posterior spinal fusion for a ...lytic T7 compression fracture. He underwent total intravenous (IV) anesthesia with propofol, remifentanil, and ketamine; liposome bupivacaine was locally infiltrated at the end of the case. Following extubation on postoperative day (POD) 1, he had severe pain refractory to high-dose IV fentanyl patient control analgesia and ketamine infusion. His pain dramatically improved after a dexmedetomidine infusion was added and titrated to the analgesic effect. He participated in neurological examinations and fulfilled both surgical and pain management goals without side effects. Dexmedetomidine was successfully weaned off on POD 3.
PDF
