Prepulse inhibition (PPI) of the startle reflex provides an operational measure of sensorimotor gating. Deficits in PPI are observed in schizophrenia patients and can be modelled in animals by administration of noncompetitive NMDA antagonists such as phencyclidine (PCP) or dizocilpine (MK-801). Previous studies indicate that the atypical antipsychotic clozapine restores PPI in PCP-treated animals while the typical antipsychotic haloperidol does not. Olanzapine (LY170053) is a novel putative atypical antipsychotic that shares many pharmacological and behavioral properties with clozapine. The present study assessed the ability of olanzapine (0, 1.25, 2.5, 5.0 or 10.0 mg/kg) to antagonize deficits in PPI produced by PCP (1.5 mg/kg) and dizocilpine (0.1 mg/kg). At the two highest doses, olanzapine significantly increased PPI in PCP- and dizocilpine-treated animals without affecting PPI or baseline startle reactivity by itself. These results support the notion that olanzapine is functionally similar to clozapine and may have utility as an atypical antipsychotic agent. 相似文献
OBJECTIVES: To evaluate the efficacy of oral lycopene therapy in patients with oral submucous fibrosis and to compare these effects with a placebo. STUDY DESIGN: Fifty-eight patients with oral submucous fibrosis formed the population for the study and were randomly divided into 3 groups, evaluated weekly over a 2-month period. Patients of group A (n = 21) received 16 mg of lycopene, those of group B (n = 19) received 16 mg of lycopene along with biweekly intralesional steroid injections, and those of group C (n = 18) were given a placebo. Paired and unpaired t tests were used for statistical evaluation. RESULTS: Mouth-opening values for the patients showed an average increase of 3.4 mm, 4.6 mm, and 0.0 mm for patients in groups A, B, and C, respectively. These values were statistically found to be highly significant. CONCLUSIONS: The observed effects suggest that lycopene can and should be used as a first line of therapy in the initial management of oral submucous fibrosis. 相似文献
OBJECT: This study evaluated the dose related effects of Cyclosporin A (CsA) alone and in combination with monoclonal antibodies (mAbs) directed against intercellular adhesion molecule-1 (ICAM-1) and the alpha subunit of leukocyte function-associated antigen (LFA-1 ) on peripheral nerve allograft rejection in a rat model. METHODS: Nerve regeneration was assessed using gait analysis of returning hind limb function, histology, and morphometry. RESULTS: Regeneration comparable to isograft controls and high dose CsA treatment groups was observed when mAbs were used in combi-nation with intermediate dose CsA. Intermediate dose CsA therapy without additional mAbs was insufficient to support this level of regeneration. Nerve allografts treated with high and low dose CsA demonstrated no increased benefit with the addition of mAb therapy. CONCLUSIONS: Thus, mAbs seem to have a dose dependent effect on immunosuppression when used in combination with CsA, and may have therapeutic promise as a rescue therapy when CsA levels fall or issues of toxicity become important. 相似文献
Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup. 相似文献
Intracranial lipomas are rare developmental lesions, predominantly occurring in the interhemispheric location. Osteochondrolipoma is an extremely rare variant of lipoma with osseous and chondroid differentiation. We present a case of interhemispheric osteochondrolipoma, in a 2.5‐years‐old male child which was detected antenatally, in association with corpus callosum agenesis. The lesion progressively increased in size with resulting compression of surrounding structures, and was subjected to microsurgical decompression. To the best of our knowledge, this is the first case of intracranial interhemispheric osteochondrolipoma in the existing medical literature. Peculiarities of this case and the diagnostic and surgical challenges are discussed. 相似文献
Patients undergoing elective PCI are traditionally admitted overnight, however day case PCI cuts costs and has been proposed as a safe method for selected patients. We evaluated the success and long term clinical outcomes of day case percutaneous coronary intervention (PCI) for outpatients with stable angina.In total, 484 consecutive patients treated over a five year period with planned day case PCI were studied and followed up for 12 months. Successful PCI with same day discharge was performed in 463 patients (95.7%). There were 21 patients (4.3%) who required hospital admission. Reasons for failed discharge were hematoma formation (n = 7, 1.4%), coronary dissection (n = 4, 0.8%), post-procedural chest pain (n = 3, 0.6%), prolonged procedure (n = 2, 0.4%), and 1 each of acute stent thrombosis, coronary perforation, anaphylaxis, minor drug reaction and a functional study for untreated disease. One year follow up was complete for 439/484 (90.7%). At 12 months there were 6 hospitalizations for angina (1.2%, 95% CI 0.6–3.0%), 20 repeat revascularisations (4.1%, 95% CI 2.7–6.3%), 3 myocardial infarctions (0.6%, 95% CI 0.2–2.1%) and 2 deaths (0.4%, 95% CI 0.1–1.6%). Event free survival at 1 year follow up was 93.6% (95% CI 90.7–95.6%).Selecting patients for day case PCI is safe, and can achieve a high rate of success with excellent long term outcomes. 相似文献
Objective: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin (ATTR) amyloidosis.
Patients and methods: We performed a retrospective analysis of patients with biopsy-proven ATTRwt (wild-type transthyretin amyloid protein) and genopositive ATTR V122I (valine-to-isoleucine substitution at position 122 of the TTR gene) amyloidosis evaluated at the Amyloidosis Center at Boston University and Boston Medical Center between 1 January 2003 and 31 December 2016.
Results: There were a total of 226 patients with ATTRwt and ATTR V122I amyloidosis evaluated during the specified time frame with 155 and 71 patients in each cohort, respectively. Those with complete medical records, 140 patients with ATTRwt and 57 V1221 ATTRm subjects, were included in the analyses. Fifty-five patients (39%) in the ATTRwt cohort and 28 patients (49%) in the ATTR V122I cohort had an MGUS, as indicated by an abnormality in the serum-free light-chain ratio and/or serum immunofixation electrophoresis.
Conclusion: These data confirm the high prevalence of coexistent MGUS with ATTR amyloidosis in this patient population, with an MGUS rate that is higher than the general population. These findings also highlight the importance of a thorough diagnostic evaluation in patients with amyloidosis to determine the precursor protein, as the clinical course and treatment of AL (light-chain amyloid protein) and ATTR amyloidosis are distinct. 相似文献
OBJECTIVE: To examine the longterm effect of etanercept (ETN) therapy on health-related quality of life (HRQOL) and utility in patients with ankylosing spondylitis. METHODS: Patients completing a 24-week placebo-controlled trial were continued on ETN in a 72-week open-label extension study. Short Form-36 (SF-36), EuroQOL-5D (EQ-5D), and EuroQOL visual analog scale (EQ-VAS) scores were collected at open-label baseline and every 12 weeks thereafter. Mental and physical component scores (MCS and PCS) of the SF-36, EQ-5D and SF-6D utility scores, and quality-adjusted life-years (QALY) were calculated. RESULTS: 257 patients [129 previous placebo (PLA) and 128 ETN recipients] enrolled in this open-label extension study, and 85% completed the 72-week followup. PCS, EQ-5D and SF-6D utilities, and EQ-VAS were significantly lower at open-label baseline in the previous PLA group (PLA/ETN group) than in the previous ETN group (ETN/ETN group; all p < 0.001). At week 12, PCS and MCS, EQ-5D and SF-6D utility scores, and EQ-VAS were similar in the PLA/ETN and ETN/ETN groups. As expected, mean change in EQ-5D in the PLA/ETN group was significantly greater than that for SF-6D (0.18 vs 0.06; p < 0.0001). HRQOL and utility improvements were maintained in both groups for up to 72 weeks. The average 72-week QALY gain per person in the PLA/ETN group was 0.24 and 0.10 for EQ-5D and SF-6D, respectively. CONCLUSION: Patients continuing ETN therapy sustained HRQOL and utility improvements attained during the original PLA-controlled trial. Patients previously taking PLA showed rapid and sustained improvements in HRQOL and utility and substantial QALY gain with ETN therapy. 相似文献