Lung function, smoking and survival in severe alpha1-antitrypsin deficiency, PiZZ

Lung function, smoking, age and mortality data in 158 adult severe alpha₁-antitrypsin deficient, PiZZ individuals, followed from 1963 to 1982 were analyzed. Low initial FEV₁ value was significantly associated with increased mortality (p < 0.005). A 3 yr mortality rate of 40% was found in individuals whose initial FEV₁ values were less than 30% of that predicted. In contrast, the corresponding 3-yr mortality among those whose initial FEV₁ values were between 30 and 65% of that predicted was only 7%. Smokers were found to have significantly lower FEV₁ levels (p = 0.008) and higher mortality (p < 0.005) than non-smokers. The difference between current and ex-smokers in mortality and FEV₁ level were not statistically significant (p = 0.9 and p>0.25, respectively). Cross-sectional analysis of the initial FEV₁ values indicated a significant decline (p < 0.005) of FEV₁ with increasing age. This decline was greater among smokers than non-smokers. Longitudinal analysis of FEV₁ rates of decline in 80 cases with follow-up FEV₁ measurements failed to detect any significant differences between smokers and non-smokers, but was performed late in the disease process. The application of these results to the planning of studies on replacement therapy, smoking intervention strategy and longitudinal follow-up is discussed.     

Levels of alpha 1-antitrypsin in children from areas with different air pollution

Summary A study of alpha 1-antitrypsin (A-1-AT) blood-serum levels was performed in children populations eleven year old at two urban areas in autumn season and at three towns in spring season. In whole 547 blood samples in 312 children were examined. The areas under observations differed especially by the grade of air pollution. The A-1-AT values distribution differed significantly among the children from different areas. The difference were due mostly'to the girl part of the population. A hypothesis was risen that the difference found may have relation to the polluted atmosphere.     

Family study of alpha 1-antitrypsin deficiency: effects of cigarette smoking, measured genotype, and their interaction on pulmonary function and biochemical traits.

To gain insight into the variable expression of lung disease in alpha 1-antitrypsin (alpha 1AT) deficiency, five quantitative variables including forced expiratory volume at 1 sec (FEV1), forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25-75), total serum alpha 1AT, oxidized serum alpha 1AT, and total serum immunoglobulin E (IgE) were measured in alpha 1AT deficient individuals and their families. The effect of a known, measured genotype (the Pi type) was estimated for each quantitative trait; the influence of mode of case ascertainment on the measured genotype effect was also assessed. These analyses showed that total alpha 1AT levels are strongly influenced by Pi type; IgE levels are unaffected by Pi type; and FEV1, FEF25-75, and oxidized alpha 1AT are moderately influenced by Pi type. The effect of genotype-by-environment interaction between Pi type and pack-years of cigarette smoking on the five quantitative phenotypes was studied using an analysis of covariance. Significant Pi x pack-years interaction was evident for FEV1, but this effect is confounded in this data set with the Pi x age interaction. Probands who were ascertained because they had chronic obstructive pulmonary disease (COPD) do not demonstrate the significant Pi x pack-years interaction effect of the Pi x pack-years subjects ascertained for other reasons demonstrate. The effect of the Pi x pack-years interaction on FEV1 was no longer significant on a transformed scale, (FEVf12,) thus providing an additive scale for future data analysis. The increased sensitivity of Pi MZ individuals in our sample to cigarette smoking reduced the Pi x packs-years interaction effect on FEF25-75 to borderline significance. This investigation has provided an opportunity to incorporate both measured genotype and genotype-by-environment interaction analyses into the study of the variable expression of lung disease in Pi Z individuals.     

Tea drinking, passive smoking, smoking deception and serum cotinine in the Scottish heart health study

Following a recent claim that the use of cotinine in body fluids, to assess passive smoking and smoking “deception”, was confounded by metabolic individuality, and by non-tobacco sources of dietary nicotine, particularly tea, data were examined from a large cross-sectional survey in a tea-drinking population. In 3383 men and women aged 44–59 years from the Scottish Heart Health Study, defined as non-smokers, both by self-report and by low thiocyanate and expired air carbon monoxide levels, serum cotinine showed minimal association with self-reported daily average tea consumption. However, there was a strong correlation between degree of self-reported passive tobacco smoke exposure and median serum cotinine level. In the same survey, serum cotinine in 4144 self-reported non-smokers and in 3326 smokers showed entirely different distributions, but the same range, suggesting heavy nicotine intake in some “non-smokers”. These analyses confirm that cotinine levels in true non-smokers reflect far more the nicotine in inhaled ambient tobacco smoke than they do nicotine in tea. Some smoking “deceivers” have the same degree of exposure to nicotine as heavy smokers. Despite individual variability, the claim of confounding is poorly supported, and cotinine is confirmed as an indicator both of passive smoking and of smoking deception.     

Biochemical intermediates in alpha 1-antitrypsin deficiency: residual family resemblance for total alpha 1-antitrypsin, oxidized alpha 1-antitrypsin, and immunoglobulin E after adjustment for the effect of the Pi locus

alpha 1-antitrypsin (alpha 1 AT) deficiency is variably associated with the development of pulmonary emphysema. To gain insight into the process which begins the Z point mutation at the Protease Inhibitor (Pi) locus and results in the variable development of emphysema, three quantitative phenotypes, including total alpha 1 AT, oxidized alpha 1 AT, and total immunoglobulin E (IgE), were measured in sera from alpha 1-antitrypsin-deficient individuals and their families. The mean and variance effects of the Pi locus on these biochemical phenotypes were removed, and path analysis of the residual phenotypes was performed by using a TAU model to investigate whether there was any additional multifactorial transmission. Significant transmission was demonstrated for total serum IgE and serum-oxidized alpha 1 AT, which could be due to major genes other than the Pi locus, polygenes, or familial environment. Segregation analysis of the residual phenotypes was performed to determine whether additional major gene effects, other than the Pi effect, influence these quantitative phenotypes. Convincing evidence for an additional major gene was not found for oxidized alpha 1 AT, total alpha 1 AT, or IgE.     

The influence of Microgynon and Diane-35, two sub-fifty ovulation inhibitors, on voice function in women

The early days of oral contraceptives showed some evidence that these medications may have caused undesirable side effects on the voice, mainly in terms of virilization. In a random study carried out at the university hospitals of Jena and Berlin (Charité), two more recent drugs were tested in this regard, one containing cyproterone acetate (Diane-35^®) and the other one levonorgestrel (Microgynon^®), both from Schering. Ninety-one patients took part in extensive clinical and instrumental phoniatric investigations of voice function over a period of one year. No significant side effects on the voice could be proven for the two preparations. Gynecological and clinical effects of both Diane-35^® and Microgynon^® were similar during the one-year study period. Women taking Diane-35^® had less intracyclic bleedings and amenorrhea. Also, acne was more favorably influenced by Diane-35^®.     

Structure activity relationship of some 2,3-diaryl-2H-1-benzopyrans to their anti-implantation, estrogenic and antiestrogenic activities in rat

In an endeavour to develop potent anti-implantation agents, a new antiestrogen, CDRI 85/287 (2-(4-2-piperidinoethoxy)phenyl-3-phenyl(2H)benzo(b)pyran), virtually devoid of agonistic activity, was identified. The present study deals with anti-implantation and estrogen agonistic-antagonistic activities of four structural analogues of 85/287. Results show that none of the compounds induced vaginal cornification, even at doses as high as 2.5 mg/kg. Compounds having p-hydroxyphenyl group at position-3 or hydroxy group at position- 7 showed better estrogen receptor affinity (6.6 and 25.3% E₂) as well as antiestogenic activity. When 3-p-hydroxyphenyl was replaced by 3-p-methoxyphenyl, a marked reduction in the receptor affinity was observed. However, this compound was relatively more potent as an anti-implantation agent, possibly due to its conversion to hydroxylated metabolite in vivo. The provision of aminoethoxy side chain at para-position and a shift in the piperidinoethoxy side chain from position-4 to position-2 in these molecules resulted in a decrease in estrogenicity and increase in antagonistic property. Results are discussed with regard to molecular configuration, relative binding affinity of these compounds to their biological profile.     

胸腺肽α1对老年重症医院获得性肺炎患者免疫功能的影响

目的 探讨胸腺肽α1治疗对老年重症医院获得性肺炎（SHAP）患者细胞免疫功能的影响及其临床意义。方法36例SHAP患者随机分为治疗组（n=20）和对照组（n=16）。治疗组在对照组基础上给予胸腺肽α1，1.6mg皮下注射。2次／日，持续1周，之后改为1，6mg，皮下注射，隔日一次，共2周。结果 治疗组治疗后单核细胞人类白细胞抗原（HIA）-DR、自然杀伤（NK）细胞、CD4^＋细胞及CD4^＋／CD8^＋比值明显上升；治疗组住院死亡率明显低于对照组，其存活者抗生素应用时间亦比对照组明显缩短。结论 胸腺肽α1能提高SHAP患者免疫功能，有利于感染控制，并降低住院死亡率。     

MACC1及c-met在前列腺癌中的表达及临床意义

摘要:目的　探讨前列腺癌组织中结肠癌转移相关基因1（MACC1）及肝细胞生长因子受体（c-met）蛋白的表达及临床意义。方法　应用免疫组化方法检测76例前列腺癌组织和16例前列腺增生组织中MACC1及c-met蛋白的表达情况。结果　前列腺癌组织中MACC1蛋白阳性率为59.2%,显著高于前列腺增生组织（18.8%）,（χ2＝8.671,P＝0.003）;c-met蛋白在前列腺癌组织中阳性率64.5%,显著高于前列腺增生组织（31.2%）,（χ2＝6.018,P＝0.014）;随访结果提示MACC1和c-met阳性患者生存率显著低于阴性患者,（χ2＝5.480,P＝0.019;χ2＝14.826,P＜0.001）;MACC1与c-met蛋白呈正相关。结论　MACC1及c-met蛋白表达增高与前列腺癌的临床分期、病理分级、患者预后密切相关。联合检测MACC1及c-met蛋白可以作为反映前列腺癌的生物学行为的客观指标,有助于判断患者预后。     

Respiratory disorders and atopy in cotton, wool, and other textile mill workers in Denmark.

A cross-sectional study of respiratory disorders and atopy in Danish textile industry workers was conducted to survey respiratory symptoms throughout the textile industry, to estimate the association of these disorders with atopy, and to study dose-response relationships within the cotton industry. Workers at cotton mills, a wool mill, and a man-made fiber (MMF) mill were examined. Four hundred nine (90%) of the 445 workers participated in this survey, i.e., 253, 62, and 94 workers at the cotton mills, the wool mill, and the MMF mill, respectively. An interview designed to assess the prevalence of common respiratory and allergic symptoms was given to all workers willing to participate, and blood samples were drawn. Lung function measurements determined a baseline FEV1, FVC and the change in FEV1 and FVC during work hours on a Monday. The working environment was examined for dust, bacteria, endotoxins, and molds, and the exposure was estimated for each participant. The mean personal samples of airborne respirable dust and respirable endotoxin were highest in the cotton industry, i.e., 0.17-0.50 mg/m3 and 9.0-126 ng/m3 respectively, whereas mold spores were found in the highest concentrations in the wool mill: 280-791 colony-forming units (cfu)/m3. Only small concentrations of microorganisms were found in the MMF mill. The mean change in FEV1% and FVC% was greatest among atopic individuals in both cotton and wool industry and other textile industries although the differences were not significant. FEV1% and FVC% in the cotton workers were significantly associated with the cumulative exposure to respirable endotoxin. Byssinosis was diagnosed only in the cotton industry. We found a dose-response relationship between endotoxin exposure and byssinosis, and a significant association between A-1-A serum concentrations less than or equal to 35 mumol/liter and byssinosis, a finding we are further evaluating in subsequent studies.     

Discriminative aspects of two generic and two asthma-specific instruments: relation with symptoms, bronchodilator use and lung function in patients with mild asthma

The objective of this study was to compare the two most frequently used asthma-specific quality of life (QOL) questionnaires and two generic QOL questionnaires with clinical data in order to establish their ability to discriminate in asthma severity, also referred to as cross-sectional construct validity. We conducted a multicentre, randomized, placebo-controlled study investigating the long-term effects of the long-acting ß2-agonist formoterol in asthma patients using inhaled corticosteroids and short-acting ß2-agonists. Before randomization, the peak expiratory flow (PEF) and use of ß2-agonists for relief of symptoms were recorded twice daily for 1 month. At the end of the run-in period, the forced expiratory volume in 1s (FEV1), airway hyper-responsiveness (PC20 methacholine) and QOL were measured, using two asthma-specific questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Living with Asthma Quality of Life Questionnaire (LWAQ), as well as two generic questionnaires, the Short Form 36 (SF-36) and the Psychological General Well Being (PGWB) index. The quality of life of the patients (n=110) was only mildly impaired. The mean symptom score was 3.6 on a scale of 0-21 and the mean FEV1 was 65% of that predicted. The correlations between the QOL parameters and objective measures of asthma severity, such as the FEV1, PEF and PC20, were low (0.01-0.37). The correlations between the QOL parameters and subjective measures of asthma severity, such as symptom scores (range 0.26-0.65) and ß2-agonist use for the relief of symptoms (0.09-0.39), were higher. The correlations of the activity and symptoms domains of the AQLQ with diary-obtained symptom scores were r=0.50 (p[lessthan]0.0001) and r=0.65 (p[lessthan]0.0001), respectively. The correlation between the physical construct of the LWAQ and symptom scores was r=0.42 (p[lessthan]0.001) and that between the physical sumscore of the SF-36 and symptom scores was r=0.50 (p[lessthan]0.001). The correlation between the PGWB and symptom scores was r=0.41 (p[lessthan]0.001). The relation between the FEV1, PEF and PC20 and QOL was very low. The QOL measurements related well to the symptom scores. The AQLQ had a better cross-sectional construct validity than the LWAQ. The cross-sectional construct validity of the SF-36 was surprisingly high for this group of patients and the SF-36 performed better than the PGWB and LWAQ.     

Attitudes to cuts in expenditure and increased fees in health care

The aim of this postal questionnaire study was to measure attitudes to cuts and increased fees in health care in various Finnish population groups. Four groups were identified: a population sample of 2000 subjects, aged 18–70 y; a random sample of 1500 medical doctors of working age; a random sample of 1000 nurses of working age; and a sample of 2200 politicians involved in health and social care administration, mostly at the municipal level (altogether 6700 subjects). The main questionnaire included, among other things, the following questions: (1) Which of 18 specified medical activities at the primary health care level could be cut without causing severe harm to the population? (2) For which of 13 specified medical activities should clients pay at least 50% of the real cost? All the groups indicated the greatest willingness to cut expenditure on health education, occupational health sevices, hygienee inspection, substance abuse care, rehabilitation services for war veterans, and family planning. All the groups were least willing to make cuts in home care for disabled and elderly people, maternity services and clinics for under-fives. Most respondents in all groups felt that the activities for which clients should pay at least 50% of the cost were visits to physicians, occupational health services and dental services, whereas clinics for under-fives and home care for disabled and elderly persons should be kept free of charge. As a conclusion, primary health care and prevention of diseases for small children, mothers, the elderly and disabled persons, were prioritised by all the groups.     

Pulmonary function,smoking habits,and high resolution computed tomography (HRCT) early abnormalities of lung and pleural fibrosis in shipyard workers exposed to asbestos

To evaluate the presence of asbestos-related pleural and parenchymal abnormalities and their correlation with pulmonary function and smoking habits, 119 asbestos-exposed asymptomatic workers (mean age, 46.2 years; mean duration of asbestos exposure, 8.6 years; mean latency time, 21.6 years) with normal standard P-A chest radiographs were submitted to HRCT, CO-diffusing capacity, and pulmonary function tests. HRCT scans were normal only in 31 (26%) examined workers; 31 (26%) subjects showed both pleural and parenchymal involvement, and 50 (42%) and seven (6%) had exclusively pleural and parenchymal abnormalities, respectively. Based on CO-diffusing capacity and pulmonary function tests, no significant difference was demonstrated between workers with pleural lesions and subjects with normal pleura; however, lower values of FVC were observed in the nonsmoking workers with parenchymal abnormalities in comparison with nonsmoking subjects with normal parenchyma (78.2 vs. 89.7% of predicted values; p = 0.03 by student's two-tailedttest), and lower values of FEV₁/FVC in the smokers with parenchymal lesions with respect to smokers with normal parenchyma (93.7 vs. 100.2% of predicted values; p = 0.005 by student's two-tailedttest). In conclusion, our results demonstrate that HRCT may detect early parenchymal abnormalities which correlate with exposure to asbestos and respiratory function impairment, including a reduction in obstructive indices in smokers occupationally exposed to asbestos, without any clinically evident disease. © 1996 Wiley-Liss, Inc.     

Enzyme exposure, smoking and lung function in employees in the detergent industry over 20 years

This study was undertaken to examine the long term relationshipbetween lung function, smoking and exposure to enzymes in thedetergent industry. A total of 731 male workers from five locationsin the United Kingdom were subject to respiratory health surveillanceincluding lung function testing over a period of 4–20years. Exposure groups were defined by job history. Significantlydifferent rates of fall in FEV1 and FVC with time were fourtdby geographical location and by smoking habit, but there wereno consistent trends with enzyme exposure.     

保定市社区老年人日常生活活动能力 及其影响因素分析

摘要:目的　探讨保定市社区老年人日常生活活动能力及其影响因素。方法　采用自制的一般情况、躯体状况问卷及日常生活活动能力评定量表（ADL）对符合要求的555例社区老年人进行一般情况、躯体状况及日常生活活动能力的调查。结果　保定市社区老年人日常生活活动能力整体得分均值为18.1045,多因素分析显示对社区老年人日常生活活动能力的主要影响因素是年龄、性别、文化程度、BMI、职业、听力障碍、视力障碍、慢性病、用药。结论　保定市社区老年人日常生活活动能力明显存在障碍,应根据影响因素进行有效干预,以提高该地区老年人的生存质量。     

Maternal smoking during pregnancy, polymorphic CYP1A1 and GSTM1, and lung-function measures in urban family children

Purpose

Understanding the interplay between genes and in-utero tobacco exposure in affecting child lung development is of great significance. In this study, we tested the hypothesis that tobacco-related lung-function reduction in children differs by maternal polymorphic genes Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase Mu 1 (GSTM1).

Materials and methods

Data were collected among 370 children (6–10 years old, 81.6% African-Americans) and their biological mothers visiting a large children’s hospital. Study hypotheses were tested using multiple regression method.

Results

Among the study sample, 143 mothers smoked throughout pregnancy and 72 smoked on a daily basis. Spirometric measures (mean±SD) included were: forced vital capacity (FVC)=1635±431 mL, forced expiratory volume in the first 1 s (FEV₁)=1440 ±360 mL, percent FEV₁/FVC ratio=89±12, and forced expiratory flow between the 25% and 75% of FVC (FEF_25–75)=1745±603 mL. In addition to a tobacco effect on FVC (−131 mL, 95% CI: −245, −17) and FEV₁/FVC ratio (42, 95% CI: 1, 83), regression analysis controlling for covariates indicated that for the subsample of children whose mothers were CYP1A1?2A homozygous, maternal daily smoking was associated with −734 mL (95% CI: −1206, −262) reductions in FEV₁ and −825 mL (95% CI: −909, −795) reductions in FVC; reduced smoking was still associated with −590 mL (95% CI: −629, −551) reductions in FVC. For children of mothers with GSTM1 deletion, persistent daily smoking was associated with −176 mL (95% CI: −305, −47) reductions in FVC.

Discussion and conclusions

Maternal smoking during pregnancy was significantly associated with lung-function reduction in children, particularly for those whose mothers possessed the polymorphic CYP1A1*2A and GSTM1 deletion.     

APP/PS1双转基因小鼠的认知功能、炎症与肠道菌群特征分析

目的 探究阿尔茨海默症动物模型APP/PS1双转基因小鼠的认知功能、炎症及肠道菌群特征。方法 15只3月龄WT雄性小鼠为对照组,15只3月龄APP/PS1双转基因小鼠为模型组,饲养6个月后进行水迷宫实验,观察潜伏期。实验结束后采集小鼠血清、海马组织和粪便,测定小鼠血清细胞因子、海马Aβ蛋白沉积和细胞因子表达情况以及肠道菌群多样性和群落结构。结果 APP/PS1组小鼠海马中有明显的Aβ蛋白沉积、水迷宫潜伏期显著增加(t=-2.16;t=-3.20,P<0.05)。WT组小鼠血清LPS水平显著高于APP/PS1组(t=2.97,P<0.01),IL-1β水平显著低于APP/PS1组(t=-3.69,P<0.01)。APP/PS1组小鼠海马组织中BDNF mRNA表达水平显著高于WT组(Z=-2.79,P<0.01)。APP/PS1双转基因小鼠的肠道菌群Alpha多样性显著低于WT组(t=3.01,P<0.05),Beta多样性分析表明两组群落结构具有显著差异(R=0.45,P<0.05);APP/PS1组的疣微菌门和阿克曼氏菌属的相对丰度显著低于WT组(Z=2.61,P<0.05)。结论 APP/PS1组出现明显的认知功能下降、炎症反应以及肠道菌群结构的异常改变。肠道菌群可能是防治阿尔茨海默症的新靶点,值得进一步研究。     

胃腺癌组织中P33ING1b、FXYD3、PINCH蛋白的 相关性分析

摘要:目的　探讨P33ING1b、FXYD3、PINCH蛋白在胃腺癌组织中的表达及意义。方法　采用免疫组化SP法,检测P33ING1b、FXYD3、PINCH在30例正常胃黏膜及73例胃腺癌组织中的表达,并分析其与临床病理特征之间的关系及相关性。结果　P33ING1b蛋白的阳性表达与PINCH蛋白的阳性表达之间趋于存在正相关关系（r＝0.279,P＝0.007）;胃腺癌中FXYD3蛋白的阳性表达与P33ING1b 蛋白的阳性表达之间并无相关性（r＝0.131,P＝0.257）。结论　P33ING1b蛋白在胃腺癌细胞胞质中的表达,可能更方便通过细胞内、外的信息传递而与间质中表达的PINCH蛋白相互作用,共同参与肿瘤的发生。     

Endotoxins isolated from the air of a Danish paper mill and the relation to change in lung function: an 11-year follow-up

BACKGROUND: A decline in lung function has been associated with farming, cotton spinning, and work in the animal feed industry. The aim of the study was to reveal if loss of lung function was associated to work at a paper mill. METHODS: Ninety-seven male paper workers (PW), and 55 control workers were examined. Hygiene samples included total dust, endotoxins, and microorganisms. Interview, pulmonary function testing, and skin prick test (SPT) were performed and yearly decline in lung function was calculated. RESULTS: The exposure for endotoxin (LPS) ranged from Median (Max-Min) 69 (370-6) EU/m3, in the wet-end of the paper machines to 6 (19-16) in the pulping area. The lung function decline among the controls was comparable to the decrements among the maintenance and repair workers at the paper factory, around 51-54 and 37-38 ml/year among smokers' and non-smokers, respectively. After adjustment for baseline FEV1, the variables associated to an increased loss of FEV1 were age smoking and cough. For FVC we found an inverse relation between exposure and yearly decline. CONCLUSION: No increase in loss of lung function is seen among workers exposed to up to 200 EU/m3 of LPS.     

MMP2、MMP9、TIMP1、TIMP2在非小细胞肺癌中的表达及临床病理学意义

目的探讨基质金属蛋白酶MMP2、MMP9及其抑制剂TIMP1、TIMP2在非小细胞肺癌(NSCLC)中的表达及临床病理学意义。方法采用免疫组织化学S-P法,分别检测43例NSCLC组织、15例正常支气管粘膜上皮组织中MMP2、MMP9、TIMP1及TIMP2的蛋白表达。结果MMP2、MMP9、TIMP1及TIMP2在43例NSCLC中的阳性表达率(分别为79.1%、74.4%、55.8%及60.5%)明显高于正常支气管粘膜上皮组织(分别为26.7%、26.7%、20.0%及26.7%)(P<0.01或P<0.05);MMP2、MMP9的表达随着病理分级和临床分期增加而有增高趋势;而TIMP1、TIMP2的阳性表达则呈下降趋势。MMP2、MMP9、TIMP1及TIMP2的阳性表达率与患者淋巴结转移和3年生存期密切相关(P<0.05),但与患者的临床参数均无明显关系(P>0.05)。结论MMP2、MMP9、TIMP1及TIMP2的过度表达与NSCLC的发展、淋巴结转移及预后有密切关系,可作为临床评估NSCLC的进展及预测其转移潜能和预后的重要指标之一。