头颈癌的靶向治疗：2007年发展及临床应用进展

头颈部鳞癌患者的肿瘤复发、第二原发及并发症导致肿瘤治疗失败，且各种治疗方法都有其自身的局限性。靶向治疗的应用，使肿瘤治疗方法的选择逐渐增多。表皮生长因子受体（EGFR）参与肿瘤的发生及发展，并与患者的不良预后有关，因此，第一个靶向治疗药物抗表皮生长因子受体的单克隆抗体西妥昔单抗应用而生。新近的研究资料表明，西妥昔单抗联合放疗能够提高晚期头颈癌患者的生存率及肿瘤局部控制率。单独应用西妥昔单抗，能够提高铂类耐药患者的生存率。最近的临床Ⅲ期实验结果表明，对复发性及转移性头颈癌，西妥昔单抗及铂类药物的联合应用能够提高患者生存率。西妥昔单抗的治疗副作用较其他细胞毒性药物轻，且不会加重放疗副作用。     

Mortality in Dutch hospitals: Trends in time,place and cause of death after admission for myocardial infarction and stroke. An observational study

Background  

Patterns in time, place and cause of death can have an important impact on calculated hospital mortality rates. Objective is to quantify these patterns following myocardial infarction and stroke admissions in Dutch hospitals during the period 1996–2003, and to compare trends in the commonly used 30-day in-hospital mortality rates with other types of mortality rates which use more extensive follow-up in time and place of death.     

The effects of two centrally-acting anti-hypertensive drugs on the quality of life

Summary The objectives of this study were to compare the effects of two centrally-acting antihypertensive drugs on measures of quality of life in a three-month double-blind trial of hypertensive patients randomized to methyldopa (n=79) or rilmenidine (n=78).We studied men and women aged over 21 y attending eight hospital out-patient clinics in the United Kingdom. They had average diastolic blood pressures between 95 and 110 mm Hg and systolic pressures below 210 mm Hg after a 4-week placebo run-in period. The doses ranged from 1 to 2 mg daily of rilmenidine and 500 mg to 1 g of methyldopa. Hydrochlorothiazide (25 mg daily) was added after 8 weeks when the diastolic blood pressure remained at 90 mm Hg or more in 29% of patients on rilmenidine and 35% of those on methyldopa. Quality of life was assessed from self-completed questionnaires using standardized instruments.Both drugs reduced blood pressure, but at the end of the trial the fall in the methyldopa group (19.3/13.0 mm Hg) was significantly greater than in the rilmenidine group (13.2/10.0 mm Hg). Ten patients in the methyldopa group withdrew from the trial compared with three in the rilmenidine group, primarily because of adverse effects. In both groups there was a significant increase in the overall reporting of adverse effects. Reports of dry mouth increased on both drugs, and sleepiness on rilmenidine but not methyldopa. There was no significant difference between the drugs in the overall reporting of adverse effects or of individual adverse effects.Psychological well-being tended to improve on rilmenidine, but was adversely affected by methyldopa, with increases in reports of depression and cognitive impairment. However, at the end of the trial there were no significant differences in overall psychological well-being between the two groups.     

Hiding in the Bunker: Challenges for a radiation oncology department operating in the Severe Acute Respiratory Syndrome outbreak

In February 2003, one woman returned from Hong Kong to Singapore with a previously undescribed atypical pneumonia. Two months later, Singapore is facing its greatest ever threat to its population's health and the country's economy. The government has taken strong action to break the chain of infection of Severe Acute Respiratory Syndrome (SARS). As a radiation oncology department in Singapore, we have faced challenges in keeping staff and patients safe while continuing to provide a service to our patients. In this article, we outline the measures taken to curb SARS in Singapore and discuss the implications for Australasian radiation oncology departments.     

Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase

Background and purpose:

Inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for the metabolism of the endogenous cannabinoid (CB) receptor ligand anandamide (AEA), are effective in a number of animal models of pain. Here, we investigated a series of isoflavones with respect to their abilities to inhibit FAAH.

Experimental approach:

In vitro assays of FAAH activity and affinity for CB receptors were used to characterize key compounds. In vivo assays used were biochemical responses to formalin in anaesthetized mice and the ‘tetrad’ test for central CB receptor activation.

Key results:

Of the compounds tested, biochanin A was adjudged to be the most promising. Biochanin A inhibited the hydrolysis of 0.5 µM AEA by mouse, rat and human FAAH with IC₅₀ values of 1.8, 1.4 and 2.4 µM respectively. The compound did not interact to any major extent with CB₁ or CB₂ receptors, nor with FAAH-2. In anaesthetized mice, URB597 (30 µg i.pl.) and biochanin A (100 µg i.pl.) both inhibited the spinal phosphorylation of extracellular signal-regulated kinase produced by the intraplantar injection of formalin. The effects of both compounds were significantly reduced by the CB₁ receptor antagonist/inverse agonist AM251 (30 µg i.pl.). Biochanin A (15 mg·kg⁻¹ i.v.) did not increase brain AEA concentrations, but produced a modest potentiation of the effects of 10 mg·kg⁻¹ i.v. AEA in the tetrad test.

Conclusions and implications:

It is concluded that biochanin A, in addition to its other biochemical properties, inhibits FAAH both in vitro and peripherally in vivo.This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x     

Stroke death and unemployment in London.

STUDY OBJECTIVE--The aim was to investigate the relationship between social factors and stroke mortality in men and women aged between 45 and 74 years using census and mortality data from 32 London boroughs in 1971 and 1981. DESIGN--Census data from 1971 and 1981 on type of accommodation, density of room occupation, male unemployment rate, and proportion of households without a car were linked with stroke mortality available for each London borough. SETTING--32 London boroughs excluding the City of London. MEASUREMENTS AND MAIN RESULTS--The main outcome measures were the association between age adjusted mortality from stroke and the proportion of households with no car, non-ownership of home, in council housing or rented accommodation, male unemployment rate, and living density of more than 1.5 people per room. There was no strong correlation between social variables and stroke mortality in 1971, but strong correlations were found for male stroke mortality in 1981. The highest correlation was with male unemployment (r = 0.64, p less than 0.001) even after adjusting for the proportion of the population born in the Caribbean and Africa (r = 0.56, p less than 0.01). Other social variables were also highly correlated with male stroke mortality: households without a car (r = 0.63, p less than 0.001), living density of more than 1.5 people per room (r = 0.053, p less than 0.001), council housing (r = 0.45, p = 0.01), and rented accommodation (r = 0.36, p = 0.05). After regressing male mortality on unemployment rate the other social variables were no longer significantly correlated with male stroke mortality. In women, the only significant correlation was found in 1981 between stroke mortality and the proportion of families living in council housing (r = 0.34, p = 0.05). CONCLUSIONS--Social factors are important indicators of stroke mortality. The major increases in unemployment over the decade may explain the generally stronger association in 1981 compared with 1971. Male stroke mortality increased by 0.062/1000 for every one percent increase in male unemployment (0.054/1000 after adjusting for place of birth).     

Prevalence of <Emphasis Type="Italic">Helicobacter pylori</Emphasis>infection and associated factors among adults in Southern Brazil: a population-based cross-sectional study

Background  

Helicobacter pylori (Hp) infection is associated with several upper gastrointestinal disorders. Local data on the epidemiology of the infection are scarce in Brazil. The purpose of this study is to measure the prevalence rate and to explore the associated factors among the adult population living in Pelotas, a southern Brazilin city.     

Breast cancer oestrogen independence mediated by <Emphasis Type="Italic">BCAR1</Emphasis> or <Emphasis Type="Italic">BCAR3</Emphasis> genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

Introduction  

Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known. The aim of this study was to investigate the growth control mediated by these BCAR genes by gene expression profiling.     

Reassessment of cochlear dead regions in hearing-impaired teenagers with severe-to-profound hearing loss

The aim of this study was to reassess cochlear dead regions after an interval of twelve months, using the Threshold Equalising Noise (TEN) test. Thirty-four ears of 24 teenagers (mean age of 14 years) with longstanding severe-to-profound sensorineural hearing impairment were tested. Testing was repeated after an interval of 12 months using the same experimental set-up. A total of eight (23.5%) out of 34 ears changed category on retest: this decreased to two (7.1%) out of 27 ears when the inconclusive category was removed from the analysis. In both of these ears (of the same participant) the criteria were met at a single frequency, and the masked threshold was only 10 dB above the TEN level per ERB_N. When all of the data were examined on a frequency-by-frequency basis, the instances that changed category ranged from 15 to 51%. The range decreased to between 4 and 34% when the inconclusive category was removed from the analysis.