Effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites

The effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites were investigated in eight patients with epilepsy or trigeminal neuralgia. One patient dropped out of the study, presumably due to side-effects of dextropropoxyphene. Dextropropoxyphene did not affect the plasma levels of the principal active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. Since dextropropoxyphene is known to increase the plasma levels of carbamazepine, leading to toxicity, the findings of this study suggest that oxcarbazepine is a useful alternative to carbamazepine when concomitant dextropropoxyphene therapy is required.     

抗生素的合理使用

随着医药工业的发展,新药层出不穷。以抗生素为例,20世纪50年代临床用的抗生素只有青、链、红、氯四大素,现在常用临床的抗生素以有100多种,临床医生长期来忙与医疗任务,如何掌握新药信息,做到合理选药,合理用药,使药物的药理作用转化为治疗效应,已成为临床医生日益关心的问题。1抗生素在临床应用中存在问题1.1常规固定方案长期以来根据以往的经验或资料,正式或非正式采用抗生素治疗方案。如:氨苄西林+庆大霉素、青霉素+庆大霉素、红霉素+氯霉素。由于对致病菌针对性不强,以致延误治疗。1.2抗生素在选择中存在问题随着医药工业的发展,抗生素…     

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.     

法莫替丁治疗消化性溃疡60例

60例(男50,女10,年龄43±8a)经内窥镜证实的活动性消化性溃疡患者,口服法莫替丁40mg,qn,疗程2-4wk或延至6-9wk。溃疡愈合率DU2,4,6 wk分别为50％,84％,92％,SU2,4,6,8 wk分别为40％,68％,73％,82％。服药后3,7,14 d上腹痛缓解率DU为50％,80％,100％,SU为40％,75％,95％。未见严重不良反应。故法莫替丁对溃疡病,尤其是DU是一有效和安全药物。     

Drug pharmacokinetics in the obese

In the obese, modifications in body constitution (higher percentage of fat and lower percentage of lean tissue and water) can affect drug distribution in the tissues. For slightly liposoluble molecules (e.g., digoxin, antipyrine), the equilibrium distribution volume (V), total and per kilogram weight, is significantly less than that of control subjects. With lipophilic drugs (e.g., barbiturates, benzodiazepines), this parameter is significantly increased, explaining the prolongation of the plasma elimination half-life. For drugs that are almost equally soluble in water and oil (methyl xanthines, aminoglycosides), the V is slightly increased in the obese. The other main factors involved in drug diffusion in the tissues are binding to plasma and tissue proteins, and regional blood flow. In the obese the binding of drugs to albumin does not seem to be altered. A marked increase in plasma alpha-glycoprotein acid and in propranolol binding has been reported in some studies; this has not been corroborated by other authors. Although the cardiac output and total blood volume are increased in the obese, the blood flow per gram of fat is less than in nonobese subjects. This could limit diffusion in the tissues of some lipophilic drugs. Studies on hepatic clearance of drugs are not available in the obese, but hepatic histological alterations have been described. In most publications concerning drugs with biotransformation as the principal elimination route, the total plasma clearance is not reduced. Up to the present, there are no reports of any impairment involving renal elimination of drugs in the obese. Dose-adjustment of hydrophilic drugs is assessed according to the ideal weight of the individual obese subject; with lipophilic drugs the loading dose can be fixed according to the total weight; calculation of the maintenance dose depends on possible changes in the total clearance.     

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     

Prosthetic valve endocarditis due to candida albicans treated successfully with medical treatment alone

Prosthetic valve endocarditis (PVE) caused by Candida species is associated with high morbidity and mortality. A combination of surgical resection and antifungal drug therapy is the golden standard for treatment, yet surgical intervention is not possible in all cases of Candida PVE. We report a case of PVE due to Candida albicans cured by medical treatment alone. This case suggests that, in some instances, Candida PVE can be managed medically with antifungal therapy. Such a conservative approach should be applied with caution and necessitates very close follow-up on a long-term basis.     

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.