ABSTRACT
Tethered cord syndrome results from adherence of the conus medullaris to the sacrum and may be associated with high complication rates from neuraxial anesthesia. We present the case of a 32-year-old gravida 2 para 0 patient with a history of lipomyelomeningocele (one of several types of spina bifida) and tethered cord status post repair, residual low-lying conus medullaris, supermorbid obesity (body mass index of 58), and Mallampati IV airway, who underwent successful fluoroscopically guided epidural catheter placement for vaginal delivery. Risks and benefits of epidural catheter utilization and methods of placement are reviewed.
Subject(s)
Anesthesia, Epidural , Neural Tube Defects , Obesity, Morbid , Female , Humans , Adult , Obesity, Morbid/complications , Spinal Cord , CathetersABSTRACT
As tyrosine kinase inhibitors (TKIs) fail to induce long-term response in blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL), novel therapies targeting leukemia-dysregulated pathways are necessary. Exportin-1 (XPO1), also known as chromosome maintenance protein 1, regulates cell growth and differentiation by controlling the nucleocytoplasmic trafficking of proteins and RNAs, some of which are aberrantly modulated in BCR-ABL1(+) leukemias. Using CD34(+) progenitors from CML, B-ALL, and healthy individuals, we found that XPO1 expression was markedly increased, mostly in a TKI-sensitive manner, in CML-BC and Ph(+) B-ALL. Notably, XPO1 was also elevated in Ph(-) B-ALL. Moreover, the clinically relevant XPO1 inhibitor KPT-330 strongly triggered apoptosis and impaired the clonogenic potential of leukemic, but not normal, CD34(+) progenitors, and increased survival of BCR-ABL1(+) mice, 50% of which remained alive and, mostly, became BCR-ABL1 negative. Moreover, KPT-330 compassionate use in a patient with TKI-resistant CML undergoing disease progression significantly reduced white blood cell count, blast cells, splenomegaly, lactate dehydrogenase levels, and bone pain. Mechanistically, KPT-330 altered the subcellular localization of leukemia-regulated factors including RNA-binding heterogeneous nuclear ribonucleoprotein A1 and the oncogene SET, thereby inducing reactivation of protein phosphatase 2A tumor suppressor and inhibition of BCR-ABL1 in CML-BC cells. Because XPO1 is important for leukemic cell survival, KPT-330 may represent an alternative therapy for TKI-refractory Ph(+) leukemias.
Subject(s)
Antineoplastic Agents/pharmacology , Gene Expression Regulation, Leukemic/drug effects , Hydrazines/pharmacology , Karyopherins/antagonists & inhibitors , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Triazoles/pharmacology , Adult , Animals , Antigens, CD34/genetics , Antigens, CD34/metabolism , Apoptosis/drug effects , Cell Proliferation/drug effects , Clinical Trials, Phase I as Topic , DNA-Binding Proteins , Drug Evaluation, Preclinical , Fusion Proteins, bcr-abl/antagonists & inhibitors , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/metabolism , Histone Chaperones/antagonists & inhibitors , Histone Chaperones/genetics , Histone Chaperones/metabolism , Humans , Karyopherins/genetics , Karyopherins/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Mice , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Protein Kinase Inhibitors/pharmacology , Protein Transport , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Ribonucleoproteins/antagonists & inhibitors , Ribonucleoproteins/genetics , Ribonucleoproteins/metabolism , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics , Transcription Factors/metabolism , Exportin 1 ProteinABSTRACT
This study examined how pediatrician-parent social status concordance related to communication patterns in medical encounters during which children received treatment for psychosocial problems indicating attention deficit disorder or attention deficit hyperactivity disorder. Using data from 28 pediatric medical encounters occurring in a large southeastern metropolitan city during 2003, we focused on concordance according to race, gender, and education, and its relation to laughter, concern, self-disclosure, question asking, and information-giving utterances, and patient-centeredness. Results indicated that race-concordant pediatricians and parents frequently laughed, whereas parents asked many biomedical questions in gender-concordant encounters. Education-concordant pediatricians and parents expressed concern repeatedly, exchanged biomedical information freely, and shared communication control. Pediatricians also self-disclosed when interacting with college-educated parents.
