药物不良反应国内文献题录检索系统

本文报道了药物不良反应国内文献题录检索系统的设计原理、功能特点,以输入药名及不良反应类别为例,显示了检索系统操作简便,提供信息及时准确的特点。本系统可从药名、不良反应类别及作者等多方面进行检索,可为查询者提供所需的详细资料,弥补了人工查阅文献的不足。并将继续扩大文献资料库,由题录向电报文体文摘形式转化,以贮存更多的信息。     

Brain Stem and Cervical Cord Dysraphic Lesions in Iniencephaly

Iniencephaly is a rare, lethal, axial dysraphic malformation complex diagnosed on the basis of three cardinal features: deficiency of the occipital bone, cervicothoracic spinal retroflexion, and rachischisis. The majority of the patients also have various associated viscerae malformations. An iniencephalic female fetus delivered at 35^5/7 weeks of gestation revealed severe anomalies of the central nervous system and the spine: the cerebellar vermis was hypoplastic, the medulla oblongata was flattened and broadened, and the cervical canal was widely patent dorsally. The thoracolumbar spinal cord had a duplicated central canal and lacked a dorsal fissure, representing a minor degree of diastematomyelia. The cervicothoracic spine showed severe bony anomalies including aplasia and fusion of vertebral bodies.     

Electrical responses of the muscularis externa to distension of the isolated guinea-pig distal colon

Abstract Enteric reflex pathways were studied in isolated segments of guinea-pig distal colon by recording the electrical responses to distension from the muscularis externa with suction electrodes. The end of the electrode wire were in the circular muscle and thus the recordings discussed below are deduced to be primarily from this layer. Moreover, intracellular microelectrodes in circular muscle cells and suction electrodes recorded similar events. Spontaneous activity consisted of myogenic slow waves at about 25 min ^-1 and transient biphasic potentials at about 6 min^-1 and 3-sec duration which were dependent on a stimulus from the enteric nervous system as they were blocked by tetrodotoxin (0.5 μM), d-tubocurarine (30 μM) and hexa-methonium (100 μM). Atropine (0.8 μM) blocked the depolarizing part of the biphasic potentials and unmasked transient spontaneous inhibitory junction potentials (IJPs) (～2-sec duration) which appeared to be responsible for the hyperpolarizing part of the biphasic potential. Three different responses were observed at sites oral to distension of the colon: a transient depolarizing response that was cholinergic (blocked by atropine (0.8 μM); ascending cholinergic excitation) and, after atropine, a transient IJP (ascending inhibition) which was followed by a transient non-cholinergic depolarizaton (ascending non-cholinergic excitation) that was sometimes followed by several cycles of slow wave activity. The oral responses to anal distension were also blocked by the nicotinic antagonists and were similar to the neurogenic spontaneous events, which also appeared to originate from activity in ascending nervous pathways. Four different responses were observed following distension of the oral end of the segment: an IJP followed by a prolonged phase of hyperpolarization that lasted for the duration of the distension (descending inhibition); a burst of depolarizing potentials (for up to 30 sec) that followed the termination of distensions up to 25 sec and was blocked by atropine (0.8 μM) (delayed cholinergic excitation), and a transient non-cholinergic response that immediately followed the termination of distension (non-cholinergic ‘off’ response). Apamin (0.5 μM) reduced the amplitude of the spontaneous IJPs and evoked IJPs. After apamin, distension evoked a small transient hyperpolarization at oral sites, which was similar to spontaneous events, and the prolonged hyperpolarization at anal sites. A second distension given within 20 sec of the first evoked an IJP of reduced amplitude at oral sites in every preparation. In contrast, the amplitudes of the oral Cholinergic excitation and descending inhibition were relatively unaffected by reducing the interval between distensions. Thus distension stimulates excitatory and inhibitory motor neurons supplying the circular muscle both oral and anal to the stimulus. The polarity of the reflex relies in part on the differences in timing and duration of responses as well as the transmission characteristics of the nervous pathways.     

Expression of tyrosine hydroxylase and neuropeptide tyrosine in mouse sympathetic airway-specific neurons under normal situation and allergic airway inflammation

BACKGROUND: The traditional neurotransmitter catecholamine and the neuropeptide tyrosine in sympathetic airway nerves have been proposed to be involved in the pathogenesis of airway diseases. OBJECTIVE: The aim of the present study was to investigate the effect of allergic airway inflammation on the expression of catecholamine enzyme tyrosine hydroxylase (TH), neuropeptide tyrosine (NPY) and tachykinins in mouse sympathetic airway ganglia. METHODS: Using neuronal tracing in combination with immunohistochemistry, the present study was designed to characterize TH, NPY and tachykinin profiles of superior cervical (SCG) and stellate ganglia after allergen challenge. RESULTS: The vast majority of fast blue-labelled SCG neurons (allergen: 97.5+/-1.22% (mean+/-SEM) vs. controls: 94.5+/-1.48%, P=0.18) and stellate neurons (allergen: 95.3+/-1.01% vs. controls: 93.6+/-1.33%, P=0.34) were immunoreactive for TH. Of the TH immunoreactive and fast blue-labelled SCG neurons, 52.0+/-1.01% allergen vs. 51.2+/-3.58% controls (P=0.83) and stellate neurons, 57.3%+/-0.97 allergen vs. 56.4+/-1.65% controls (P=0.64) were positive for TH only but not NPY, whereas 45.3+/-1.05% allergen vs. 43.3+/-1.18% controls (P=0.47) of fast blue-labelled SCG neurons and 37.9+/-0.86% allergen vs. 37.1+/-1.24% controls (P=0.62) of fast blue-labelled stellate neurons were immunoreactive for both TH and NPY immunoreactivities. There was a trend of an increase, but not significant one, in the percentage of TH-/NPY-immunoreactive and fast blue-labelled neurons in allergen-treated animals in comparison with the controls. Tachykinins, however, were not expressed by sympathetic neurons and were also not induced in sympathetic neurons after allergen challenge. CONCLUSION: The present study indicates that allergic airway inflammation does not alter the expression of noradrenalin and NPY in sympathetic ganglia and also shows that sympathetic neurons do not respond to allergic airway inflammation with tachykinins induction. However, a participation of catecholamine and NPY in the pathogenesis of allergic airway inflammation cannot be excluded in the present study as a higher neurotransmitter output per neuron following allergen challenge could be possible.     

Health‐related quality of life in multiple system atrophy

Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health‐related quality of life (Hr‐QoL). We, therefore, assessed Hr‐QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA‐Study Group (EMSA‐SG) Natural History Study: Medical Outcome Study Short Form (SF‐36), EQ‐5D, Beck Depression Inventory (BDI), Mini‐Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty‐six percent of patients had moderate to severe depression (BDI ≥ 17); Hr‐QoL scores on the SF‐36 and EQ‐5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA‐P (predominantly parkinsonian motor subtype) than MSA‐C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr‐QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate‐to‐strong predictors for the SF‐36 physical summary score and the BDI and UMSARS motor scores for the SF‐36 mental summary score. This report is the first study to show that Hr‐QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr‐QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr‐QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease. © 2006 Movement Disorder Society     

The plasma kallikrein–kinin system and risk of cardiovascular disease in men

BACKGROUND: The plasma kallikrein-kinin system (PKKS) has been implicated in cardiovascular disease, but activation of the PKKS has not been directly probed in individuals at risk of coronary heart disease (CHD) or stroke. OBJECTIVE: To determine the involvement of the PKKS, including factor XI, in cardiovascular disease occurring in a nested case-control study from the Second Northwick Park Heart Study (NPHS-II). METHODS AND RESULTS: After a median follow-up of 10.7 years, 287 cases of CHD and stroke had been recorded and 542 age-matched controls were selected. When FXIIa-C1 esterase inhibitor (C1-inhibitor) concentrations were divided into tertiles (lowest tertile as reference), the odds ratios (ORs) at 95% CIs for CHD were 0.52 (0.34-0.80) in the middle tertile and 0.73 (0.49-1.09) in the highest tertile (P = 0.01 for the overall difference; P = 0.01 for CHD and stroke combined). For kallikrein-C1-inhibitor complexes, the ORs for stroke were 0.29 (0.12-0.72) and 0.67 (0.30-1.52) in the middle and high tertiles, respectively (P = 0.02). FXIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes were negatively related to smoking and fibrinogen (P < 0.005). FXIa-inhibitor complexes correlated strongly with FXIIa-inhibitor complexes. CONCLUSIONS: Lower levels of inhibitory complexes of the PKKS enzymes and particularly of FXIIa contribute to the risk of CHD and stroke in middle-aged men. This observation supports the involvement of the PKKS in atherothrombosis.     

MULTICENTER STUDY DESIGN OF THE EX VIVO EVALUATION OF ENDOCYTOSCOPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Optical technological innovations enable us to visualize cellular nuclei endoscopically. Herein is described a protocol design for a multicenter study for the ex vivo evaluation of endocytoscopy. The present study was performed by the Endoscopy Forum Japan study group.     

Vascular PET Prostheses Surface Modification with Cyclodextrin Coating: Development of a New Drug Delivery System

PURPOSE: Cyclodextrins (CDs) are torus shaped cyclic oligosaccharides with a hydrophobic internal cavity and a hydrophilic external surface. We performed and analysed an antibiotic binding on Dacron (polyethyleneterephtalate, PET) vascular grafts, previously coated with CDs based polymers. METHODS: The CDs coating process was based on the pad-dry-cure method patented in our laboratory. The Dacron prostheses were immersed into a solution containing a polycarboxylic acid, a cyclodextrin and a catalyst, and placed into a thermofixation oven before impregnation with an antibiotic solution (Vancomycin). Biocompatibility tests were performed with L132 human epithelial cells. The antibiotic release in an aqueous medium was assessed by batch type experiments using UV spectroscopy. RESULTS: Viability tests confirmed that the CDs polymers coating the Dacron fibers were not toxic towards L132 cell. Cell proliferation was similar on coated and uncoated grafts. A linear release of Vancomycin was observed over 50 days. CONCLUSION: Our results demonstrate the feasibility of coating CDs onto vascular Dacron grafts. Biological tests show no toxicity of the different cyclodextrins coated. A linear release of antibiotics was depicted over 50 days, demonstrating that cyclodextrin grafting was an efficient drug delivery system.     

AC/A ratios in myopic and emmetropic Hong Kong children and the effect of timolol§

Purpose: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta‐adrenergic antagonism with topical timolol application on AC/A ratios. Methods: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin‐Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell‐Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens‐ and distance‐induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). Results: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = ‐3 ± 1.14^A) but not in the emmetropes (0.69 ± 0.9^P) or progressing myopes (0.16 ± 0.43^A) and this difference between refractive groups was statistically s ignificant (F^2,27= 3.766; P= 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. Conclusions: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia.