Metaphase-arrest technique applied to human cervical epithelium. II. Cell production rates in normal and pathological cervical epithelium

An application of the metaphase-arrest technique to human cervical epithelium, in vivo, was utilized to obtain cell birth rate data for seventy-six patients with normal and pathological cervical epithelium. Mean cell production rates for basal and parabasal layers of normal epithelium were 0.91 and 0.92 cells/1000 cells/hr respectively. Histologically normal epithelium adjacent to CIN (cervical intra-epithelial neoplasia) had a significantly higher rate for the parabasal layer compared to the 'normal' group (P less than 0.05). Values for the lower two-thirds of CIN III were 8-10 times higher than for normal epithelium, with microinvasive carcinoma having the highest rates of all. Values for wart-affected cervical epithelium (NCWVI) were intermediate between normal and CIN, but there was activity in the superficial layer, possibly reflecting activity of the papilloma virus. Large variation in birth rates between individuals in the same histological category was noted for each group, this being particularly the case in six patients with early invasive carcinoma. The data is used to attempt to elucidate some of the uncertainties surrounding the aetiology and biological behaviour of cancer of the cervix and its precursors. Sources of inaccuracy are emphasized and practical difficulties discussed.     

Children's coughs related to parental smoking.

A survey of the smoking habits, attitudes, and background of over 15 000 8-19 year olds in northern England in December 1982 showed a positive correlation between parental smoking and the reporting of frequent coughs by children who had never smoked. This was especially pronounced in the youngest children. Thirty five per cent of boys under 11 who had never smoked and whose parents did not smoke reported frequent coughs; with one parent smoking this increased to 42%, and when both parents smoked the proportion was 48%. Girls under 11 showed the same pattern, with 32%, 40%, and 52% respectively reporting frequent coughs. Fewer older children in general reported frequent coughs. Mothers'' smoking had more influence on children''s coughs than had fathers'' smoking. Social area type had no significant effect. No significant effect of passive smoking was observed when the children themselves were smokers. These results are clear evidence of a definite link between smoking in the home and coughs in young children, which not only may present immediate problems but may also be a cause of illness in the future.     

Attitudes to tobacco smoking among Warsaw's physicians

Physicians in the majority of countries in which tobacco-smoking has successfully been reduced stopped smoking themselves as the first professional group. Physician's attitude towards smoking patients plays an important role. Sometimes a single medical consultation helps some tobacco-abused patients to quit smoking for ever. However, the time of such a consultation should be adequately long. Out of all methods to control smoking such a consultation has the widest social extend and produces the most favourable effect; about 3% of the tobacco abusers quit smoking. These results are even better if physician consultation is supplemented with other activities such as supply with proper literature, reference to antinicotine center and return to the subject at any further consultation. It means that half a million smokers would quit this habit if every physician employed in the primary carek in Poland would have consulted each smoking patient. We attempted to check physician's attitude towards tobacco-smoking and their activity in this field.     

Bronchial malondialdehyde DNA adducts, tobacco smoking, and lung cancer

Tobacco smoking is a major risk factor for lung cancer causing, among other effects, oxidative stress and lipid peroxidation. Malondialdehyde (MDA)-DNA adducts can be induced by direct DNA oxidation and by lipid peroxidation. We measured the relationship between bronchial MDA-DNA adducts and tobacco smoking, cancer status, and selected polymorphisms in 43 subjects undergoing a bronchoscopic examination for diagnostic purposes. MDA-DNA adducts were higher in current smokers than in never smokers (frequency ratio (FR) = 1.51, 95% confidence interval (CI) 1.01-2.26). MDA-DNA adducts were also increased in lung cancer cases with respect to controls, but only in smokers (FR = 1.70, 95% CI 1.16-2.51). Subjects with GA and AA cyclin D1 (CCND1) genotypes showed higher levels of MDA-DNA adducts than those with the wild-type genotype (FR = 1.51 (1.04-2.20) and 1.45 (1.02-2.07)). Lung cancer cases with levels of MDA-DNA adducts over the median showed a worse, but not statistically significant, survival, after adjusting for age, gender, and packyears (hazard ratio = 2.48, 95% CI 0.65-9.44). Our findings reinforce the role of smoking in lung carcinogenesis through oxidative stress. Subjects who carry at least one variant allele of the CCND1 gene could accumulate DNA damage for altered cell-cycle control and reduced DNA repair proficiency.     

Retrospective DNA analyses in cervical dysplasia as related to neoplastic progression or regression

Intracellular DNA distribution was measured in cells from two groups of patients with moderate cervical dysplasia. One group consisted of patients who subsequently developed carcinoma in situ; the other consisted of patients whose lesions regressed to normality. Papanicolaou-stained slides were examined cytologically, and dysplastic cells were located. The slides were then destained and restained by means of the Feulgen DNA staining method, after which they were analyzed in a microspectrophotometer. The DNA distribution pattern of both groups was different from that of normal cells and exhibited the same characteristics observed earlier in premalignant cervical cellular atypias. There was no significant difference between the two groups. The results indicate that quantitative DNA determinations in cytomorphologically equivalent dysplastic cervical cells do not offer additional means of predicting the outcome of the lesions.     

Recovery of bronchial epithelium on stopping smoking.

Bronchial biopsy specimens were studied from 19 patients, comprising five non-smokers, eight current smokers, and six people who had given up smoking between two and 16 years previously. By using a recently developed morphometric technique the structural state of the bronchial epithelium was assessed and described by a score, which specifies the extent to which the epithelial histology departs from the normal, through the changes of mucous-cell hyperplasia and squamous-cell metaplasia. The epithelium was nearer normal in former smokers than current smokers in each of six pairs matched for smoking history. The numerical scale permitted statistical analysis with a precision that is not possible with data based on subjective diagnosis alone: the results of comparing histology with pack-years of cigarette consumption were consistent with the hypothesis that structural recovery occurs in bronchial epithelium in people who stop smoking for over two years.     

Absence from school related to children's and parental smoking habits.

A sample of 2885 children aged 12 and 13 who completed a questionnaire survey in school in January 1987 were given a second questionnaire on a specified date in May 1987. The smoking habits, parental smoking habits, sex, and social background of the children who were present on both dates were compared with those of the children who were absent on the second occasion. Regular smoking was significantly more common among those absent for the second questionnaire: among boys 181/877 (21%) who never smoked, 109/486 (22%) who sometimes smoked, and 21/45 (47%) who regularly smoked were absent, and among girls the figures were 157/947 (17%), 117/487 (24%), and 17/43 (40%) respectively. Thus the odds ratio for those who sometimes smoked was 1.29 and for regular smokers 3.09 against those who never smoked. Whatever the children''s smoking habits, the proportion who were absent was higher when both parents or at least the mother smoked, the odds ratio being 1.39; the proportions absent were 203/1180 (17%) if neither parent or only the father smoked v 135/644 (21%) if both parents or only mother smoked for children who never smoked; 105/529 (20%) v 121/444 (27%) for those who sometimes smoked; and 10/27 (37%) v 28/61 (46%) for those who regularly smoked. Sex and social background had little effect, though there was an overall higher rate of absence among boys from industrial areas. The findings show a higher rate of minor ailments in children who smoke and in children whose mother smokes. If children are having frequent days off school for minor ailments possibly they or their parents would benefit from advice and help in stopping smoking.     

The metaphase-arrest technique applied to human cervical epithelium. I. Technique and dose-response studies

In order to study cell proliferation in intact human cervical epithelium, a technique involving metaphase arrest has been utilized. Metaphase accumulation is observed following intraepithelial administration of vincristine sulphate, at a predetermined optimum dose of 50 micrograms/ml. A significant delay before the onset of stathmokinetic activity is demonstrated; thereafter linearity of accumulation is apparent over a 4-hr period following injection. The technique appears applicable to the estimation and comparison of cell production rates in vivo of normal cervical epithelium, cervical intraepithelial neoplasia, wart-affected cervical epithelium and early invasive carcinoma. However, individual values are likely to be imprecise in isolation, indicating the need to study relatively large numbers of subjects in each group. Some practical difficulties are discussed.     

Damage to DNA concurrent with lipid peroxidation in rat liver slices.

Lipid peroxidation and DNA damage were evaluated in liver slices incubated for 2 h at 37 degrees C with 1 mM-t-butyl hydroperoxide (t-BOOH), 1 mM-BrCCl3 or 50 microM-ferrous iron. t-BOOH induced the greatest amount of damage to DNA and increased the production of thiobarbituric acid-reactive substances (TBARS). Both phenomena depended on the incubation time. Ferrous iron induced both DNA damage and TBARS production, and BrCCl3 did not induce significant DNA damage and was the weakest TBARS inducer. Butylated hydroxytoluene at 1 mM inhibited both DNA damage and TBARS production. DNA damage and lipid peroxidation in liver slices were correlated, indicating that these events were concurrent.     

Changes of smoking habits and cough in men smoking cigarettes with 30% NSM tobacco substitute.

The effects of smoking cigarettes with 30% of the tobacco replaced by NSM tobacco substitute, which lowered their tar and nicotine delivery, were studied by comparing them with the effects of conventional cigarettes in a controlled crossover trial lasting 20 months. Chest symptoms, cigarette consumption, and forced expiratory volume in one second (FEV1) were measured each month. Two-hundred men began the trial and 159 completed it. The test cigarettes were acceptable to all but one of the men. In a subsample of 35 men estimates of nicotine intake were obtained from monthly analyses of cigarette stubs. On changing from NSM to control cigarettes six of the 17 men, who were accustomed to low nicotine, kept their nicotine intake down by some change in smoking habit. Before the crossover and this change in smoking habit the men smoking NSM cigarettes had a small but significant reduction of cough. Cigarettes containing 30% NSM and delivering only 1 mg of nicotine are likely to be acceptable to smokers and may reduce coughing. Further trials are needed to confirm these findings and establish what long-term effects such cigarettes may have on smokers'' health.