选择性κ阿片激动剂K-Ⅱ与U-50488的药理作用比较

K-Ⅱ系k阿片激动剂U-50488的同类物。通过部分离体和整体实验比较了K-Ⅱ与U-50488的药理作用。实验发现,K-Ⅱ抑制电刺激兔输精管收缩的IC₅₀值为0.42 nmol/L,U-50488为26.5 nmol/L;K-Ⅱ抑制小鼠运动功能(横筛法)的ED₅₀值为1.7 mg/g,U-50488为15.3 mg/kg;K-Ⅱ的小鼠LD₅₀值为152.5 mg/kg,U-50488为118.4 mg/g;K-Ⅱ明显降低小鼠自发活动的作用比U-50488强5倍。结果表明,K-Ⅱ是一个药理作用较U-50488强的k受体激动剂。     

Giant aneurysm treated by bilateral cervical carotid artery to proximal middle cerebral artery bypass and balloon embolisation: a case report

The authors describe a case of a 59 year-old Chinese lady with a history of spontaneous left caroticocavernous fistula in 1988 treated by left internal carotid artery clipping and muscle embolisation. She subsequently presented with a subarachnoid haemorrhage in November 1997 secondary to rupture of an unclippable giant right internal carotid artery aneurysm. This was treated satisfactorily with bilateral cervical carotid artery to proximal middle cerebral artery bypass followed by balloon occlusion. Postoperatively, the patient has no neurological deficit and CT angiogram shows good patency of both grafts 6 months after surgery.     

The incubation period of kuru

BACKGROUND: Kuru is a transmissible spongiform encephalopathy that was identified in Papua New Guinea in the late 1950s. Several thousand cases of the disease occurred during a period of several decades. Epidemiologic investigations implicated ritual endocannibalistic funeral feasts as the likely route through which the infectious agent was spread. METHODS: We estimated the incubation period distribution of kuru using a back-calculation model and explored the relation among sex, age at infection, and incubation period. Key assumptions in the model were that the number of new kuru infections in a year was proportional to the number of kuru cases dying that year, and that the epidemic arose from a single case of sporadic Creutzfeldt-Jakob Disease occurring around 1900. RESULTS: The mean incubation period of kuru was estimated at between 10.3 and 13.2 years. Point estimates of the 90th percentile ranged from 21.1 to 27.0 years. The incubation period in females was estimated to be shorter than that in males. The shortest incubation periods were estimated in adult women, who may have been exposed to the largest doses of infectious material. CONCLUSIONS: Our findings suggest that the relatively young age of cases of variant Creutzfeldt-Jakob disease probably reflects increased levels of exposure in young people, rather than age-dependency in the incubation period.     

Chemoprevention of spontaneous tumorigenesis in nullizygous p53- deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro- 5-androsten-17-one

Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non- competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency.      

Prevalence and impact of chronic childhood conditions in Auckland, New Zealand

Objective : To establish the prevalence of specific chronic conditions of childhood in the Auckland area and to quantify resource use by these children.
Methodology : Estimates were made from available registry data and published data sources of the population of children with selected chronic conditions resident in the Auckland Area Health Board area. Resource use data were extracted for admissions to Auckland public hospitals and from providers of community based technology services.
Results : The largest community prevalence groups are those with asthma, intellectual handicap, congenital heart disease and epilepsy. Children aged 0-14 with chronic conditions accounted for at least 14340 hospital days stay in Auckland in 1992 at an estimated minimum cost of $7.9 million. Over 200 children are dependent on technological aids at home.
Conclusions : There are sparse data on the numbers and needs of children with chronic conditions in the population. A non-categorical approach which crosses disease entities may be the best method of meeting common needs.     

Glaucoma case finding: a cluster-randomised intervention trial

PURPOSE: To assess the effect of an intervention comprising training in optic disc assessment, explicit referral criteria and ophthalmologist feedback on referred patients, on the number of optometrist referrals for suspected glaucoma seen at a referral site and the positive predictive value of those referrals. METHODS: Optometric practices routinely referring to the Ealing Hospital Eye Clinic were randomly divided into two groups taking into consideration those practices, which shared an optometrist (a cluster) and the number of optometrist days worked per week.One group of practices acted as controls, while the other practices were invited to receive the intervention. Data on 397 new patients referred and presenting to Ealing Hospital with suspected glaucoma were collected over a 20-month period. The data on patients who had failed to attend their appointment were collected over 7 months of this period. The number of referrals seen, the positive predictive value of those referrals, and the attendance rate were calculated. Optometrist's opinions of the intervention were assessed qualitatively. Data relating to optometrist compliance with the intervention were also collected. RESULTS: The number of glaucoma referrals presenting to Ealing Hospital from the intervention practices was almost double that from the control practices (210 vs 119). When cluster randomisation, the number of optometrist days per cluster and the number of assessed referrals in the preintervention period are taken into consideration, it is estimated that the intervention is associated with a 52% increase in the number of referrals reaching Ealing Hospital. However, the design effect resulting from the cluster randomisation was unexpectedly high (of the order of 13-14)and so the confidence intervals around the estimate of 52% are very wide (95% c.i. 35% decrease to 253% increase, P = 0.34). There was no evidence of an association between optometrist compliance with the intervention and the number of referrals seen at Ealing Hospital. The positive predictive value (PPV)of referrals was similar for the intervention(0.49 (95% c.i. 0.42, 0.55)) and control groups(0.46 (95% c.i. 0.33, 0.60)). Optometrist opinions of the intervention were largely favourable. All expressed a willingness to participate in future programmes. CONCLUSION: A large difference in the number of referrals between the practice groups was observed. Since the PPV of referral was unchanged, the potential impact of the intervention in terms of numbers of new cases of glaucoma detected in the community is substantial. However, because of its large design effect, this trial does not provide conclusive evidence of an impact of the intervention on referral numbers. A considerably larger trial will be required to produce conclusive evidence of an effect.     

Blindness: how to assess numbers and causes?

BACKGROUND: Traditionally, blindness surveys have modelled themselves on the "gold standard" of a census and examination of a whole population. Blindness, however, is a relatively rare condition even in badly affected communities; hence, large sample sizes are required to gain adequate estimates of prevalence, particularly by cause. METHODS: Three assessments of blindness prevalence and aetiology in the same communities are reported. One involved asking individuals questions concerning their visual status during a census (perceived visual status, PVD), one involved examination of all ostensibly visually disabled people presenting to a central point within each community (examination of the visually disabled, EVD), and the final assessment involved a gold standard examination of the whole population (whole community examination, WCE). RESULTS: In a population of 8139 the blindness prevalence was 2.7% PVS, 3.6% EVD, and 3.1% WCE. Attributed causes of blindness were not representative in the PVS except for cataract. The END yielded cause specific estimates not far from those found at WE except for a relative under-representation of glaucoma and optic atrophy. CONCLUSION: Since cataract is, by a significant margin, the most common cause of blindness in the world such a simple method as asking individuals if they are blind and what they believe to be the cause may yield adequate estimates of the problem for planning eye care strategies for this condition. Alternatively, an ophthalmologist visiting villages and examining allcomers for visual disability may provide reasonably accurate cause specific prevalence estimates without the expense of a major blindness survey.     

Respiratory viral infection in lower airways of asymptomatic children

Aim: The aim of this study was to determine if asthmatic children have viruses more commonly detected in lower airways during asymptomatic periods than normal children. Methods: Fifty‐five asymptomatic children attending elective surgical procedures (14 with stable asthma, 41 normal controls) underwent non‐bronchoscopic bronchoalveolar lavage. Differential cell count and PCR for 13 common viruses were performed. Results: Nineteen (35%) children were positive for at least one virus, with adenovirus being most common. No differences in the proportion of viruses detected were seen between asthmatic and normal ‘control’ children. Viruses other than adenovirus were associated with higher neutrophil counts, suggesting that they caused an inflammatory response in both asthmatics and controls (median BAL neutrophil count, 6.9% for virus detected vs. 1.5% for virus not detected, p = 0.03). Conclusions: Over one‐third of asymptomatic children have a detectable virus (most commonly adenovirus) in the lower airway; however, this was not more common in asthmatics. Viruses other than adenovirus were associated with elevated neutrophils suggesting that viral infection can be present during relatively asymptomatic periods in asthmatic children.     

Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000–2013

ObjectiveTo estimate cause-of-death distributions in the early (0–6 days of age) and late (7–27 days of age) neonatal periods, for 194 countries between 2000 and 2013.MethodsFor 65 countries with high-quality vital registration, we used each country’s observed early and late neonatal proportional cause distributions. For the remaining 129 countries, we used multinomial logistic models to estimate these distributions. For countries with low child mortality we used vital registration data as inputs and for countries with high child mortality we used neonatal cause-of-death distribution data from studies in similar settings. We applied cause-specific proportions to neonatal death estimates from the United Nations Inter-agency Group for Child Mortality Estimation, by country and year, to estimate cause-specific risks and numbers of deaths.FindingsOver time, neonatal deaths decreased for most causes. Of the 2.8 million neonatal deaths in 2013, 0.99 million deaths (uncertainty range: 0.70–1.31) were estimated to be caused by preterm birth complications, 0.64 million (uncertainty range: 0.46–0.84) by intrapartum complications and 0.43 million (uncertainty range: 0.22–0.66) by sepsis and other severe infections. Preterm birth (40.8%) and intrapartum complications (27.0%) accounted for most early neonatal deaths while infections caused nearly half of late neonatal deaths. Preterm birth complications were the leading cause of death in all regions of the world.ConclusionThe neonatal cause-of-death distribution differs between the early and late periods and varies with neonatal mortality rate level. To reduce neonatal deaths, effective interventions to address these causes must be incorporated into policy decisions.