ABSTRACT
INTRODUCTION: Extracorporeal life support (ECLS) has been reported to be more effective than conventional cardiopulmonary resuscitation (CPR). In ECLS, a shorter time from arrival to implantation of extracorporeal membrane oxygenation (ECMO; door-to-ECMO) time was predicted to be associated with better survival rates. This study aimed to examine the impact of the physician-based emergency medical services (P-EMS) using a rapid response car (RRC) on door-to-ECMO time in patients with out-of-hospital cardiac arrest (OHCA). METHODS: In this retrospective cohort study, adult patients with OHCA who were admitted to a Japanese tertiary care hospital from April 2012 to December 2016 and underwent venoarterial ECMO were included. Patients were either transferred by emergency medical service (EMS only group) or RRC (RRC group). Primary outcome was door-to-ECMO time. Wilcoxon rank-sum test was used to compare the outcome between the two groups. RESULTS: A total of 34 patients were included in this study, and outcome data were available for all patients. The door-to-ECMO time was significantly shorter in the RRC group than in the EMS only group (median, 23min vs. 36min; P=0.006). Additionally, the RRC was also associated with earlier successful intubation and intravenous adrenaline administration. CONCLUSION: The physician-based RRC system was associated with a shorter door-to-ECMO time and successful advanced procedures in prehospital settings. Combination of the RRC system with ECLS may lead to better outcomes in patients with OHCA.
Subject(s)
Emergency Medical Services/methods , Extracorporeal Membrane Oxygenation/methods , Out-of-Hospital Cardiac Arrest/therapy , Aged , Cardiopulmonary Resuscitation , Female , Humans , Intubation, Intratracheal , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Animal studies on inner ear development, repair and regeneration provide understanding of molecular pathways that can be harnessed for treating inner ear disease. Use of transgenic mouse technology, in particular, has contributed knowledge of genes that regulate development of hair cells and innervation, and of molecular players that can induce regeneration, but this technology is not applicable for human treatment, for practical and ethical reasons. Therefore other means for influencing gene expression in the inner ear are needed. We describe several gene vectors useful for inner ear gene therapy and the practical aspects of introducing these vectors into the ear. We then review the progress toward using gene transfer for therapies in both auditory and balance systems, and discuss the technological milestones needed to advance to clinical application of these methods.
Subject(s)
Ear, Inner/physiology , Genetic Therapy/methods , Hearing Loss, Sensorineural/therapy , Labyrinth Diseases/therapy , Animals , Disease Models, Animal , Gene Expression , Gene Expression Profiling , Gene Expression Regulation , Genetic Vectors , Humans , Mice , Mice, Transgenic , Nerve Regeneration , Neurons/physiology , Signal TransductionABSTRACT
The human deafness-pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia-White (Mitf(Mi-wh) /+) mice were studied and hearing function of these mice characterized. Mitf(Mi-wh) /+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. Mitf(Mi-wh) /+ embryos have fewer melanoblasts during embryonic development than their wild-type littermates. Although cochlear melanocytes are present at birth, they disappear from the Mitf(Mi-wh) /+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness-pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes.
Subject(s)
Albinism, Oculocutaneous/physiopathology , Deafness/physiopathology , Hearing/physiology , Heterozygote , Microphthalmia-Associated Transcription Factor/genetics , Waardenburg Syndrome/physiopathology , Action Potentials/physiology , Albinism, Oculocutaneous/genetics , Albinism, Oculocutaneous/pathology , Animals , Animals, Newborn , Deafness/genetics , Deafness/pathology , Disease Models, Animal , Embryo, Mammalian/metabolism , Embryo, Mammalian/pathology , Evoked Potentials, Auditory, Brain Stem/physiology , Hair Cells, Auditory, Outer/metabolism , Hair Cells, Auditory, Outer/pathology , Humans , Melanocytes/metabolism , Melanocytes/pathology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Otoacoustic Emissions, Spontaneous/physiology , Stria Vascularis/metabolism , Stria Vascularis/pathology , Waardenburg Syndrome/genetics , Waardenburg Syndrome/pathologyABSTRACT
Tinnitus is the sensation of sound inside the head and is a common symptom encountered daily by otorhinolaryngologists. Pulsatile tinnitus sufferers hear rhythmical noise at the same rate as a heartbeat and can present a diagnostic challenge. In this report, we present a 32-year-old patient with pulsatile tinnitus that led to the diagnosis of essential thrombocythemia. The symptom of pulsatile tinnitus allowed an early diagnosis of essential thrombocythemia and a more favorable prognosis. The case demonstrates the importance of blood tests for all patients who present with pulsatile tinnitus of unknown origin.
Subject(s)
Thrombocythemia, Essential/diagnosis , Tinnitus/diagnosis , Adult , Diagnosis, Differential , Early Diagnosis , Follow-Up Studies , Humans , Hydroxyurea/therapeutic use , Male , Nitrosourea Compounds/therapeutic use , Platelet Count , Risk Assessment , Severity of Illness Index , Thrombocythemia, Essential/drug therapy , Treatment OutcomeABSTRACT
Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is extremely rare; only four cases have been reported. Herein are presented the case reports of two Japanese male patients with thyroid-like LGNPPA. Macroscopically, these tumors were pedunculated polypoid masses on the roof of the nasopharynx. Microscopically, they were characterized by papillary and glandular epithelial proliferation. The papillae were complex and tightly packed with hyalinized fibrovascular cores and lined by columnar and pseudostratified cells with intervening spindle-shaped cells. Both cell types had round to oval vesicular nuclei with tiny nucleoli and mildly eosinophilic cytoplasm. Mitotic figures were not evident and necrosis was not observed. Psammoma bodies were seen focally in one of the patients. Transition from normal surface epithelium to tumor cells was identified in both cases. On immunohistochemistry the tumor cells were positive for cytokeratin (CK)7, CK19, thyroid transcription factor-1 (TTF-1) and vimentin. They were negative for CK5/6, CK20, thyroglobulin, S-100 protein and CD15. In situ hybridization for EBV was negative. Nasopharyngeal tumors with similar morphological appearance should be examined for TTF-1 immunoreactivity, and patients should be clinically followed to determine the course of this unusual disease and the significance of TTF-1 expression.
Subject(s)
Adenocarcinoma, Papillary/pathology , Nasopharyngeal Neoplasms/pathology , Nuclear Proteins/biosynthesis , Transcription Factors/biosynthesis , Adenocarcinoma, Papillary/metabolism , Adult , Biomarkers, Tumor/analysis , Humans , Immunohistochemistry , Male , Nasopharyngeal Neoplasms/metabolism , Thyroid Nuclear Factor 1ABSTRACT
The discovery and SAR of 2,3-diphenylpropionic acid derivatives as highly potent VLA-4 antagonists are described. One representative compound, 9cc has inhibited intercellular adhesion by a VCAM-1/VLA-4 interaction with an IC(50) of 1.7 nM, and has good pharmacokinetics and oral bioavailability.
