ZK 91296, a partial agonist at benzodiazepine receptors

ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl--carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation.     

Deficiency Citations on Inappropriate Psychotropics Use Related to Care for Behavioral Symptoms of Dementia

ObjectivesThe Centers for Medicare and Medicaid (CMS) initiated the National Partnership to Improve Dementia Care in Nursing Homes in 2012, which helped decrease antipsychotics use. However, inappropriate use of antipsychotics and other psychotropic medications to control behavioral symptoms associated with dementia persists. Nursing homes (NHs) can be flagged for inappropriate psychotropics use as a deficiency of care citation (F-758 tag). The purpose of this study was to comprehensively explore inappropriate psychotropic medication use deficiency, F-758 citations, in caring for NH residents with dementia.DesignA mixed-methods study was performed.Setting and ParticipantsDuring the first quarter of 2018 (January–March), 3526 NHs were surveyed, of which 642 received F-758 tags. Of the 642, the sample was confined to the 444 NHs that received the citation for the care of residents with dementia. Information on deficiencies was obtained from 2018 Certification and Survey Provider Enhanced Reporting data. Inspection reports for deficiencies were obtained from Centers for Medicare and Medicaid Nursing Home Compare and ProPublica.MethodsQuantitative analysis was used to examine the frequency of involved psychotropic medications, scope/severity of F-758 deficiency citations, and reasons for the citations. Reasons for F-758 citations by psychotropic medication categories and scope/severity of the citations were also examined using χ² tests. Qualitative data analysis was conducted using content analysis with an inductive coding approach to summarize the inspection reports.ResultsAntipsychotics were the most involved drug category for F-758 tag citations. The 3 most common reasons for F-758 citations included failure to identify and/or monitor behavioral symptoms (178 NHs), attempt gradual drug reduction (131 NHs), and maintain 14-day limitations on Pro Re Nata (PRN) psychotropic orders (121 NHs). Compared with those with no involvement of antipsychotic drugs, facilities with antipsychotics-related F-758 tags had higher rates of failure to identify/monitor behavioral symptoms (P < .001), attempt gradual drug reduction (P < .001), and provide adequate indications for psychotropics use (P < .001). NHs with F-758 tags related to inappropriate antianxiety medication use had a higher prevalence of failure to maintain 14-day limitation on PRN orders (P < .001) and provide nonpharmacologic interventions (P < .001).Conclusions and ImplicationsThis study suggests areas for improvement that could potentially reduce inappropriate psychotropics use. Supporting quality of dementia care workforce and improving cooperation within healthcare staff and professionals are recommended to ensure proper nonpharmacologic and pharmacologic interventions.     

Symptomatic compression of the optic nerve by the carotid artery: clinical profile of 18 patients with 24 affected eyes identified by magnetic resonance imaging.

OBJECTIVE: To characterize the clinical features and course of patients with magnetic resonance imaging (MRI)-defined optic nerve compression by the supraclinoid carotid artery. DESIGN: Retrospective, observational case series. PARTICIPANTS: Eighteen patients with 24 affected eyes were identified by reviewing case records from the author's referral-based neuro-ophthalmology practice. Predetermined inclusion and exclusion criteria were applied to potential participants. MAIN OUTCOME MEASURES: The following variables were abstracted from the medical record: age, gender, presenting symptoms, past medical problems, visual acuity, color vision, visual field, pupillary reactions, optic disc appearance, other neurologic signs, and previously documented and follow-up examinations. RESULTS: There were eight women and ten men ranging in age from 28 to 86 years (median age, 72 years) at the time of diagnosis. Ten (56%) of 18 patients had hypertension. Twelve patients had unilateral optic neuropathy, whereas 6 patients had bilateral optic neuropathy. One patient presented with subacute superior orbital fissure syndrome due to mass effect of a dolichoectatic carotid artery. Another patient had oculomotor nerve palsy with signs of aberrant regeneration due to intracavernous mass effect of a dolichoectatic carotid artery. One patient had a bitemporal hemianopia associated with bilateral compression of the immediate prechiasmatic optic nerves by dolichoectatic carotid arteries. The predominant pattern of visual field loss in most patients reflected nerve fiber bundle injury. A central scotoma or absolute central visual field loss was noted in only 6 (25%) of 24 affected eyes. Most patients demonstrated saucerlike excavation of the optic disc. Progression of visual acuity loss occurred at a relatively slow rate. CONCLUSIONS: Although uncommon, intracranial compression of the optic nerve by the carotid artery should be considered in a patient with unexplained or progressive unilateral or bilateral optic neuropathy. This entity can be diagnosed using clinical skills to exclude more common causes of optic nerve injury and coronal-oriented MRI to confirm anatomic compression of the symptomatic optic nerve. Although many affected patients have excavation of the optic disc and nerve fiber bundle visual field defects, most have additional signs atypical for glaucoma, minimizing the potential for diagnostic confusion between the two disorders.     

Effect of Punarnavine,an Alkaloid from Boerhaavia diffusa,on Cell-Mediated Immune Responses and TIMP-1 in B16F-10 Metastatic Melanoma-Bearing Mice

Effect of Punarnavine on the cell-mediated immune (CMI) response in metastatic condition was studied using C57BL/6 mice model. Administration of Punarnavine enhanced Natural Killer (NK) cell activity, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement mediated cytotoxicity (ACC) and the activity was observed in treated group much earlier compared to the metastatic tumor-bearing control. Production of cytokines such as IL-2 and IFN-γ were significantly enhanced by the administration of Punarnavine compared to the untreated metastatic tumor-bearing control. Peaks of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α were significantly lowered by Punarnavine administration compared to metastatic control. The level and expression of TIMP-1 was also enhanced by the administration of Punarnavine compared to metastatic tumor bearing control. These results indicate Punarnavine could enhance the immune response against metastatic progression of B16F-10 melanoma cells in mice.     

18F-FLT增殖显像机制及前期临床研究

18F-3'-脱氧-3 '-L氟代胸苷(18F-FLT)作为一种增殖示踪剂,利用PET可将细胞增殖活动可视化并进行量化评估,为临床提供了一种非侵入性监测抗肿瘤疗效的检查方法.该文讨论了18F-FLT作为增殖示踪剂的机制,并回顾了目前18F-FLT PET临床前期研究的状况.虽然18F-FLT是一种可以反映细胞增殖活动的示踪剂,但也有很多限制:在大部分病例中,其摄取率显著低于目前临床广泛应用的18F-FDG,而且受化疗方案和肿瘤类型的影响,18F-FLT摄取与细胞增殖活动并不总是一致.     

Pericardial fluid analysis in scleroderma (systemic sclerosis)

A patient with scleroderma who presented with pericarditis and effusion is described. Aspirates from this pericardial effusion had the characteristics of an exudate with no evidence of autoantibodies, immune complexes or complement depletion. These findings suggest that the mechanisms operating in the production of pericardial effusion in scleroderma may be different from those found in rheumatoid arthritis and systemic lupus erythematosus.