PubMed Health⌕ Search

Biomedical subjects

A K Hackshaw

Publications and source records attributed to A K Hackshaw.

14 recordsLinked to original sources
PubMed1998

The distribution of nuchal translucency at 10-13 weeks of pregnancy.

There is a need for a simple method of expressing nuchal translucency measurement in early pregnancy that will allow for gestational age and be useful in screening for Down's syndrome. To achieve this objective, we conducted a prospective study of 561 women with singleton pregnancies that were not affected by Down's syndrome at 10-13 weeks of gestation. Nuchal translucency measurements and crown rump length measurements were determined. Nuchal translucency measurement increased by about 17 per cent per week. Expressing the result as a multiple of the median (MOM) nuchal translucency for a given crown rump length allowed for this increase with gestational age and yielded a distribution of values that was approximately Gaussian. About 96 per cent of values lay between 0.5 and 2.0 MOM. The variance and therefore the false-positive rate of nuchal translucency were significantly reduced by recording several measurements and using the average: for example, the false-positive rate reduced from 8.3 per cent to 5.0 per cent if the average of six measurements were used instead of one--a potential 40 per cent reduction in the false-positive rate if the test were used in screening. Estimating the distribution of nuchal translucency in MOM values will assist in specifying the statistical parameters to be used in prenatal screening for Down's syndrome and the use of repeated nuchal translucency measurements is expected to have a useful effect on reducing the screening false-positive rate at a given MOM cut-off level.

Adult↗
PubMed1997

The accumulated evidence on lung cancer and environmental tobacco smoke.

OBJECTIVE: To estimate the risk of lung cancer in lifelong non-smokers exposed to environmental tobacco smoke. DESIGN: Analysis of 37 published epidemiological studies of the risk of lung cancer (4626 cases) in non-smokers who did and did not live with a smoker. The risk estimate was compared with that from linear extrapolation of the risk in smokers using seven studies of biochemical markers of tobacco smoke intake. MAIN OUTCOME MEASURE: Relative risk of lung cancer in lifelong non-smokers according to whether the spouse currently smoked or had never smoked. RESULTS: The excess risk of lung cancer was 24% (95% confidence interval 13% to 36%) in non-smokers who lived with a smoker (P < 0.001). Adjustment for the effects of bias (positive and negative) and dietary confounding had little overall effect; the adjusted excess risk was 26% (7% to 47%). The dose-response relation of the risk of lung cancer with both the number of cigarettes smoked by the spouse and the duration of exposure was significant. The excess risk derived by linear extrapolation from that in smokers was 19%, similar to the direct estimate of 26%. CONCLUSION: The epidemiological and biochemical evidence on exposure to environmental tobacco smoke, with the supporting evidence of tobacco specific carcinogens in the blood and urine of non-smokers exposed to environmental tobacco smoke, provides compelling confirmation that breathing other people's tobacco smoke is a cause of lung cancer.

Adenocarcinoma↗
PubMed1997

A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect.

OBJECTIVE: To determine the magnitude and importance of the relation between smoking, bone mineral density, and risk of hip fracture according to age. DESIGN: Meta-analysis of 29 published cross sectional studies reporting the difference in bone density in 2156 smokers and 9705 non-smokers according to age, and of 19 cohort and case-control studies recording 3889 hip fractures reporting risk in smokers relative to non-smokers. RESULTS: In premenopausal women bone density was similar in smokers and non-smokers. Postmenopausal bone loss was greater in current smokers than non-smokers, bone density diminishing by about an additional 2% for every 10 year increase in age, with a difference of 6% at age 80. In current smokers relative to non-smokers the risk of hip fracture was similar at age 50 but greater thereafter by an estimated 17% at age 60, 41% at 70, 71% at 80, and 108% at 90. These estimates of relative risk by age, derived directly from a regression analysis of the studies of smoking and hip fracture, were close to estimates using the difference in bone density between smokers and non-smokers and the association between bone density and risk of hip fracture. The estimated cumulative risk of hip fracture in women in England was 19% in smokers and 12% in non-smokers to age 85; 37% and 22% to age 90. Among all women, one hip fracture in eight is attributable to smoking. Limited data in men suggest a similar proportionate effect of smoking as in women. The association was not explained by smokers being thinner, younger at menopause, and exercising less nor by actions of smoking on oestrogen, but smoking may have a direct action on bone. CONCLUSIONS: Hip fracture in old age is a major adverse effect of smoking after the menopause. The cumulative excess bone loss over decades is substantial, increasing the lifetime risk of hip fracture by about half.

Adult↗
PubMed1997

Cigarette smoking, sex hormones and bone density in women.

It is known that among women over the age of 65, bone mineral density is lower, and the risk of hip fracture higher, in smokers than non-smokers. We report a study in 1334 health pre- and post-menopausal women aged 35-64 years, to determine whether this effect can be attributed to lower oestrogen levels in smokers. Among 676 premenopausal women forearm bone density was no lower in smokers (95% confidence interval 1% lower, 4% higher). Among 543 postmenopausal women who had not used hormone replacement therapy (HRT) for more than a year there was no statistically significant difference, but the lower confidence interval was consistent with a lower bone density in older smokers (by 8% at age 55-59, 16% at age 60-64). Measurements in 194 postmenopausal women not taking HRT showed that oestrone and oestradiol were similar in smokers and non-smokers, as were cortisol and FSH, LH and prolactin. Meta-analysis of the present study and previous studies confirmed significantly higher levels in smokers of the androgens DHEAS (by 37%) and androstenedione (by 34%). Oestrogens were no lower in smokers, and the lower confidence limit excluded more than a trivial effect of smoking in lowering oestrogen. These results indicate that the recognised lower bone density in elderly smokers cannot be explained by an effect of smoking on oestrogen, since in premenopausal women bone density is no lower in smokers and in postmenopausal women oestrogens are no lower in smokers. The data suggest a balance between higher androgen levels but lower rates of conversion of androgens to oestrogens in smokers. The effect of smoking on bone may be due to impaired response of bone and other target organs to oestrogen, or to actions independent of oestrogen.

Adult↗
PubMed1997

Combining ultrasound and biochemistry in first-trimester screening for Down's syndrome.

Data on pregnancies with and without Down's syndrome between 10 and 14 weeks of pregnancy were used to determine the performance of combined ultrasound and biochemical markers in prenatal screening for Down's syndrome. We used three datasets: one published by Pandya et al. (1995) on nuchal translucency measurement in 86 Down's syndrome pregnancies; one published by Wald et al. (1996a) on free beta human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in 77 affected pregnancies and 385 unaffected pregnancies; and the third from Schuchter et al. on 561 unaffected pregnancies with nuchal translucency measurement. Combining the data from these three datasets showed that screening between 10 and 14 weeks by combining the serum markers with nuchal translucency measurement had a detection rate of 80 per cent for a 5 per cent false-positive rate, better than maternal age with two serum markers (62 per cent for 5 per cent) or maternal age with nuchal translucency measurement (63 per cent for 5 per cent). At this time in pregnancy, it appears that screening using the combined test is better than second-trimester serum screening (76 per cent for 5 per cent), though these estimates do not allow for any association between the markers and spontaneous fetal loss, an issue that needs to be clarified by further research. Meanwhile, these results provide a reasonable working estimate of screening performance using different combinations of these markers.

Chorionic Gonadotropin↗
PubMed1996

Environmental tobacco smoke.

Environmental tobacco smoke is an important contaminant of indoor air. For a non-smoker living with a smoker the exposure is equivalent to about 1% of that from actively smoking 20 cigarettes a day (based on plasma cotinine). There is strong and consistent evidence that passive smoking increases the risk of lung cancer. It is estimated that there is an increase in risk of 24% (95% confidence interval 11-38%) compared to unexposed non-smokers, and several hundred lung cancer deaths per year in Britain are attributable to environmental tobacco smoke exposure. Passive smoking is associated with an increase in risk of chronic respiratory disease in adults of 25% (10-43%), and increases the risk of acute respiratory illness in children, by 50-100%. It is likely that passive smoking increases the risk of ischaemic heart disease, and that exposure in pregnancy lowers birthweight, but there is inconsistency between different estimates of the magnitude of risk. The overall hazard is sufficient to justify measures to restrict smoking in public places and workplaces, and to discourage people from smoking in their homes.

Adult↗
PubMed1996

Cigarette smoking: an epidemiological overview.

The detailed mortality and morbidity statistics on smoking tend to conceal the overall impact of the habit on health. About 3 million people die each year from smoking in economically developed countries, half of them before the age of 70. Cancers of eight sites are recognized as being caused by smoking--lung cancer almost entirely and the others (upper respiratory, bladder, pancreas, oesophagus, stomach, kidney, leukaemia) to a substantial extent. Six other potentially fatal diseases are also judged to be caused by smoking: respiratory heart disease, chronic obstructive lung disease, stroke, pneumonia, aortic aneurysm and ischaemic heart disease, the most common cause of death in economically developed countries. Non-fatal diseases, such as peripheral vascular disease, cataracts, hip fracture, and periodontal disease, which cause appreciable disability, cost and inconvenience are also caused by smoking. In pregnancy, smoking increases the risk of limb reduction defects, spontaneous abortion, ectopic pregnancy, and low birth weight. While there are some diseases for which smoking shows a protective effect, the 'benefits' of these are negligible in relation to the illness and premature mortality caused by smoking. About 20% of all deaths in developed countries are caused by smoking; an enormous human cost which can be completely avoided.

Aged↗
PubMed1996

Empirical validation of risk screening for Down's syndrome.

OBJECTIVE: To validate individual risk estimates in antenatal serum screening for Down's syndrome. METHODS: Women screened for Down's syndrome using maternal serum alpha fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) with maternal age (the triple test) or AFP, uE3, free beta subunit and free alpha subunit of hCG with maternal age (the quadruple test) were grouped according to their predicted risk of having an affected pregnancy. The mean predicted risk in each category was then compared with the observed prevalence based on the number of affected and unaffected pregnancies in each category. SUBJECTS: About 100,000 pregnant women screened for Down's syndrome from 1989 to 1995. RESULTS: There was close agreement between the predicted term risk and the prevalence at birth for both the triple test and the quadruple test. For example, with the quadruple test the predicted risk in the highest risk group was 1 in 3.3 and the prevalence was 1 in 2.6; in the lowest risk group these were 1 in 3000 and 1 in 2300 respectively. CONCLUSION: Risk estimates based on multiple marker screening for Down's syndrome are accurate. The technique used to demonstrate this is simple and offers a useful empirical check on screening performance.

Adult↗
PubMed1995

Repeat maternal serum testing for Down's syndrome screening using multiple markers with special reference to free alpha and free beta-hCG.

To determine the effect of routine repeat testing in serum screening for Down's syndrome, we compared estimates of the detection and false-positive rates. Five serum markers were measured--alpha-fetoprotein (AFP), unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG), and its two subunits, free alpha and free beta-hCG. First and repeat test marker levels were available from 142 women whose samples had been routinely collected and stored in an antenatal serum bank. Different repeat testing policies were compared for various combinations of the markers. If all women had repeat tests using the four markers AFP, uE3, and free alpha and free beta-hCG, the detection rate for a 5 per cent false-positive rate was 69 per cent compared with 65 per cent if no women were repeated. Policies of repeating selected women gave similar results. The small gain in screening performance with repeat testing performed routinely is not worthwhile. If a woman does happen to have a repeat test, her risk estimate should, however, be based on both results, not just the second.

Biomarkers↗
PubMed1995

First trimester serum screening for Down's syndrome.

Screening for Down's Syndrome has been shown to be effective at 10 weeks of pregnancy. A multicentre study (the first trimester serum screening study) has shown that there are two biochemical markers of choice at this time in pregnancy, namely pregnancy associated placental protein A (PAPP-A) and the free beta-sub-unit of human chorionic gonadotrophin (free beta-hCG). When used together with maternal age these two biochemical markers have an estimated detection rate of 62% and a 5% false-positive rate. The results are consistent with those obtained from a systematic review of the world literature. Other markers are less predictive of Down's syndrome though there is still some uncertainty over the value of dimeric inhibin-A at 10 weeks of pregnancy. Nuchal translucency measurement, from an ultrasound examination performed at about 10 weeks of pregnancy, is associated with Down's syndrome and is emerging as an important potential screening marker. At present there is uncertainty over its quantitative performance and performance when combined with biochemical markers. The resolution of these issues is currently the subject of active research. Ten week screening for Down's syndrome is an advance that is now technically possible though there is still insufficient information to justify its use in routine screening practice.

Biomarkers↗
PubMed1994

DNA variants at the LPL gene locus associate with angiographically defined severity of atherosclerosis and serum lipoprotein levels in a Welsh population.

Coronary artery disease (CAD) patients (n = 235), comprising minimal (CAD-, n = 124) and severe (CAD+, n = 111) CAD, were recruited on the basis of their angiographic scores. Male control subjects (n = 123) were selected randomly from the Caerphilly Heart Study cohort. Subjects were genotyped for the Ser447-Ter mutation and HindIII/Pvu II restriction fragment length polymorphisms of the lipoprotein lipase gene and investigated for associations with severity and development of CAD and lipid and lipoprotein levels. The Ser447-Ter mutation showed no significant associations with CAD or dyslipidemia but was related to favorable lipid and lipoprotein profiles. The H2H2 genotype (P < .05) and H2 allele (P = .05) were significantly more frequent in CAD+ versus CAD- and control subjects versus CAD-. H2H2 subjects, among the entire male cohort, had significantly higher levels of apolipoprotein B (P = .0002), total cholesterol (P < .004), and triglycerides (P < .04) than alternative genotypes. P2P2 associated with significantly lower high-density lipoprotein cholesterol levels (P < .01). The H2 allele had most significant associations with raised apolipoprotein B levels compared with other biochemical parameters. Our data suggest that the H2 allele may be a linkage marker for an etiologic mutation for dyslipidemia and the severity and development of atherosclerosis; this is not the Ser447-Ter mutation.

Alleles↗