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Epidemiology of lung cancer with special reference to genetics, bioassays, women, and developing countries.

The twentieth century may be looked back upon as the century of lung cancer. At the beginning of the century lung cancer was quite rare, but this century the rates have increased approximately 10-fold and it is the second most common type of cancer and has become the leading cause of death due to cancer in the United States. The rate of lung cancer among U.S. women continues to rise, in contrast rates in U.S. men have been declining since about 1990. Cigarette smoking accounts for 85-90% of lung cancer deaths in the United States. However, only 10-15% of smokers eventually develop lung cancer. In the past 25 years, since the U.S. Surgeon General's ground breaking report in 1964, overall smoking rates have been declining, but smoking still remains a significant behavior. More troubling, the rates of smoking continue to increase in many parts of the world. Advances in molecular biology and early diagnosis have increased the understanding of lung cancer etiology and may be effective in uncovering more efficient detection and treatment regimens. These advances will hopefully make lung cancer as uncommon at the end of the twenty-first century, as it was at the beginning of the twentieth century.

Journal Article↗

Positive association of farm or rural residence with acute myeloid leukemia incidence in a cohort of older women.

The etiology of acute myeloid leukemia (AML) is relatively unknown. Incidence rates are highest in the agricultural Midwest region compared with other regions of the United States. Many studies have examined the relationship between farming and leukemia, but most have mainly focused on men. We examined the potential association between farm or rural residence and AML in the Iowa Women's Health Study. In 1986, 37,693 women who were free of prior cancer completed a lifestyle and health questionnaire, which included a question on the place of residence. Women were subsequently followed until 2002 for cancer incidence; 79 women developed AML during the time period. Women who lived on a farm at baseline were more likely (relative risk, 1.91; 95% confidence interval, 1.19-3.05) to develop AML compared with women who did not live on a farm. Further, women who reported living on a farm or in a rural area were twice as likely (relative risk, 2.38; 95% confidence interval, 1.33-4.26) to develop AML compared with women who lived in a city with a population of >10,000 people. These results provide evidence that women who live on farms or rural areas are at an increased risk of AML.

Female↗

Antenatal waist circumference and hypertension risk.

OBJECTIVE: To assess whether waist circumference at the first antenatal visit predicts risk of developing hypertension later in pregnancy. METHODS: Pregnant women with singleton pregnancies (n = 1142, median age 29 years, interquartile range 25-32 years, 387 primigravidas) were recruited at their first antenatal visits. Using standardized methods, midwives determined the weights, heights (for calculation of body mass index [BMI]), and waist circumferences of all women. Eighty-two women developed pregnancy-induced hypertension, and 21 developed preeclampsia (hypertension with proteinuria). RESULTS: The median waist circumference between 6 and 16 weeks' gestation was 79 cm (interquartile range 72-84 cm), and there was no significant relationship between waist circumference and gestational age. Greater waist circumference was noted in subjects who subsequently developed pregnancy-induced hypertension (median 81 versus 77 cm, Mann-Whitney U test, P =.002) or preeclampsia (median 80 versus 77 cm, P =.02). The conventional, nonpregnant waist circumference action level of 80 cm gave a Mantel-Haenszel odds ratio (OR) for pregnancy-induced hypertension of 1.8 (95% confidence interval [CI] 1.1, 2.9) and for preeclampsia of 2.7 (95% CI 1.1, 6.8), compared with waists of less than 80 cm. Body mass index values were higher in women who developed pregnancy-induced hypertension (median 26 versus 24, P =.001) or preeclampsia (median 26 versus 24, P =.02). The conventional action limit for a BMI of 25 had an OR for pregnancy-induced hypertension of 2.0 (95% CI 1.2, 3.4) and for preeclampsia of 1.9 (95% CI 0.7, 4.8). Results were similar when the analysis was restricted to data from primigravidas. CONCLUSION: We conclude that waist circumference up to 16 weeks' gestation can predict pregnancy-induced hypertension and preeclampsia. Therefore, waist circumference could form the basis for health promotion involving raising awareness of the importance of or urging weight reduction for women planning pregnancies.

Adult↗

Residential environmental risks for reproductive age women in developing countries.

Published research suggests there is an association between maternal inhalation of common ambient air pollutants and adverse birth outcomes, including an increased risk for preterm delivery, intrauterine growth retardation, small head circumference, low birth weight, and increased rate of malformations. The air pollutants produced by indoor combustion of biomass fuels, used by 50% of households worldwide, have been linked to acute lower respiratory infections, the single most important cause of mortality in children under the age of 5. This report describes a hypothesis-generating study in West Wollega, Ethiopia, conducted to assess airborne particulate matter concentrations in homes that combust biomass fuels (biomass homes). Respirable suspended particulate matter was measured in biomass homes and nonbiomass homes using NIOSH method 0600. Measured airborne particulate concentrations in biomass homes were up to 130 times higher than air quality standards. These findings, in part, confirm that exposure to indoor air pollutants are a major source of concern for mother/child health. Midwives are encouraged to raise awareness, contribute to research efforts, and assist in interventions.

Adult↗

Alterations of left ventricular function in women with insulin-dependent diabetes mellitus during pregnancy.

AIMS/HYPOTHESIS: During pregnancy, eminent cardiovascular changes occur. The aim of the following study was to investigate the course of haemodynamic parameters under the increased volume load during pregnancy and delivery in women with insulin-dependent diabetes mellitus. METHODS: We examined 51 pregnant diabetic women and 51 healthy pregnant women. The control group consisted of 51 healthy non-pregnant women. In all women, left ventricular mass and fractional shortening were calculated. To evaluate left ventricular diastolic function, mitral inflow and pulmonary venous flow profiles were analysed. RESULTS: During pregnancy left ventricular mass increased, fractional shortening decreased and diastolic dysfunction was found. While the healthy pregnant women developed signs of disturbed relaxation during pregnancy, pregnant diabetic women showed signs of a disturbed relaxation at the beginning of gestation. Of the pregnant diabetic women, 29 developed a restrictive filling pattern at the 24th week of gestation. The remaining 22 diabetic women had a comparable restrictive filling pattern only during vaginal delivery. In 10 of the 29 pregnant diabetic women dangerous complications were documented, while there were no complications in the healthy pregnant women and the other 22 diabetic pregnant women. CONCLUSION/INTERPRETATION: In healthy women pregnancy results in a reversible physiologic left ventricular hypertrophy, a disturbed relaxation pattern and a temporary decrease of left ventricular systolic function. In contrast, pregnant diabetic women showed a delayed relaxation at the beginning of pregnancy and developed a restrictive filling pattern. The early development of a restrictive filling pattern could indicate complications during delivery in pregnant diabetic women.

Adult↗

Gender development in women with congenital adrenal hyperplasia as a function of disorder severity.

Prenatal-onset classical congenital adrenal hyperplasia (CAH) in 46,XX individuals is associated with variable masculinization/defeminization of the genitalia and of behavior, presumably both due to excess prenatal androgen production. The purpose of the current study was threefold: (1) to extend the gender-behavioral investigation to the mildest subtype of 46,XX CAH, the non-classical (NC) variant, (2) to replicate previous findings on moderate and severe variants of 46,XX CAH using a battery of diversely constructed assessment instruments, and (3) to evaluate the utility of the chosen assessment instruments for this area of work. We studied 63 women with classical CAH (42 with the salt wasting [SW] and 21 with the simple virilizing [SV] variant), 82 women with the NC variant, and 24 related non-CAH sisters and female cousins as controls (COS). NC women showed a few signs of gender shifts in the expected direction, SV women were intermediate, and SW women most severely affected. In terms of gender identity, two SW women were gender-dysphoric, and a third had changed to male in adulthood. All others identified as women. We conclude that behavioral masculinization/defeminization is pronounced in SW-CAH women, slight but still clearly demonstrable in SV women, and probable, but still in need of replication in NC women. There continues a need for improved instruments for gender assessment.

Adrenal Hyperplasia, Congenital↗

Maternal health services--the developing world.

Women in developing nations run 100 to 200 times the risk of dying in pregnancy and childbirth compared to women in affluent countries. The vast majority of these deaths are preventable. We examine 3 models of health development for their potential impact on maternal mortality. Although universal primary maternal health care would be ideal, resource limitations render its implementation impractical in many regions. The nonavailability of transport and referral services limits the impact of community-based programs. Selective primary health interventions have some role, but more costly and complex services are required to deal with hemorrhage, the complications of illegal abortion and to provide operative deliveries. Public health workers should focus on intersectoral programs at the community level which mobilize women around health issues. Sustainable development has the greatest potential to produce lasting changes in the risks of childbearing.

Developing Countries↗

An audit of assessment procedures in women who develop breast cancer after a negative result.

OBJECTIVES: A case audit was undertaken to determine the extent to which the early diagnosis of cancer could be improved by better adherence to screening guidelines, and to estimate the effect that this might have on breast cancer survival. Although affecting only a small proportion of the cancers of the screening programme, this exercise had an educational function for screening radiologists. SETTING: The East Anglian breast screening programme, a group of seven centres offering screening to a total population of 2.2 million inhabitants. Women were screened every three years between the ages of 50 and 64. METHODS: Adherence to the guidelines of the UK National Breast Screening Programme (as published in 2001) was tested in women assessed between the start of screening on 1 April 1989 and 31 December 1999, in cases where the screen was negative but who were subsequently diagnosed with breast cancer. RESULTS: In this period the programme screened 503,493 women, recalled 25,346 and diagnosed 3689 with cancer. 194 cancers in 193 women were reviewed, comprising those cancers that arose at the site of the lesion previously assessed. 96 women (49.5%) had calcifications, 48 (24.7%) had opacities. 139 of 194 cases were judged to have been inadequately assessed. A recurring theme showed that biopsies not undertaken or with false negative findings led to failure to diagnose lesions which were subsequently shown to be cancer. Microcalcifications and opacities were more likely to have been inadequately assessed than spiculate masses, parenchymal deformities, or asymmetric densities. In the earliest time period (1989-1993), there were a larger proportion of inadequately assessed cases than in the period 1994-1999. CONCLUSION: Scrupulous adherence to good guidelines will result in a greater proportion of cancers being diagnosed. Failure to perform effective percutaneous biopsy was the usual cause of missed diagnoses. Although an infrequent occurrence this may have an effect on subsequent survival from breast cancer.

Adolescent↗

[Pathophysiological aspects of adipose tissue development in women].

The fat cell, the functional entity of adipose tissue, is mainly involved in energy storage and mobilization. The deposition of fat in, and the mobilization of fat from, adipose tissue are precisely controlled by enzyme activities: LPL and HSL. These functions are under control of hormones such as insulin, catecholamines and, to some extent, steroid hormones. The adipocytes have been recently identified as the source of many factors that may act like hormones either in the local environment or at distant sites, are also target cells for many more hormones. Adipose tissue metabolism varies from one region of the body to another. The metabolic activity is the lowest in the subcutaneous gluteofemoral area, followed by the abdominal subcutaneous area, and the highest in the visceral region. The metabolic activity of gluteofemoral fat is activated in lactating mothers. Body fat content changes with female age. Puberty, parity and menopause seems to increase accretion of adipose tissue. Obesity is defined as an increase in body fat content. There is general agreement that obesity develops as an interaction between a genetic susceptibility and environment which is expressed when the subject is exposed to a certain set of environmental conditions. Obesity develops when energy intake exceeds energy expenditure over a prolonged period. Excess body weight is associated with several diseases which can shorten life expectancy. The prevalence of obesity is high and increases steadily. Approximately 20-40% of women are overweight (BMI 25-30 kg/m-2) and 5-20% are obese (BMI > 30 kg/m-2).

Adipocytes↗

The prevalence of anti-phospholipid antibodies in a selected population of Kenyan women and development of a non-human primate model.

The mechanisms by which anti-phospholipid antibodies (aPLs) may induce pregnancy losses, intrauterine growth retardation and pregnancy-induced hypertension are not clearly understood. Moreover, there is a controversy regarding the possible direct effects of these antibodies on the physiology of the placenta since the target antigens of these antibodies are intracellular antigens and are potentially inaccessible to the antibody. Also, controversy exists regarding the usefulness of the treatment regimens currently available. In this study, we present preliminary data on the prevalence of aPLs in a selected population (n = 80) of Kenyan women visiting Kenyatta National Hospital, Nairobi, Kenya for obstetrical complications including recurrent pregnancy losses. Our results showed approximately 13.8% of the patients were positive for anti-cardiolipin antibodies whereas 33.8% were positive for aPS. Additionally, we screened 72 non-human primates for presence of aPLs and our results showed that the olive baboon (Papio anubis) had the highest prevalence rate (52.2%, n = 23). Overall, our results suggest that the olive baboon may be a suitable animal model for studying the mechanism of action of the anti-phospholipid antibody and pregnancy complications associated with aPLs.

Animals↗

[Swedish women have developed more risky and more harmful alcohol drinking habits. A survey of alcohol drinking changes among Swedes between 1997-2001].

A random sample of 1,250 persons from the general Swedish population responded to the Alcohol Use Disorders Identification Test, AUDIT. The results (72.5% response rate) were compared to the results from an identical survey made 1997 (79.8% response rate). The factor structure and the internal reliability showed good correspondence with those of 1997, indicating a stable and satisfactory psychometric quality of the Swedish AUDIT version. The female prevalence of hazardous or harmful alcohol use had increased from 11 to 15 percent between 1997 and 2001. Thus, women, particularly 28-38 years old, reported drinking more often and in greater amounts. Furthermore, the prevalence of female teetotallers had decreased from 18 to 13 percent. The corresponding trends among men were not significant but might have been underestimated due to a greater dropout, particularly among young men in the year of 2001.

Adolescent↗

Increased risk of Graves' disease after pregnancy.

The improvement in autoimmune thyroid disease during pregnancy and the subsequent exacerbation postpartum is secondary to immune system changes necessary to a normal pregnancy. Prior studies have shown that a clinically significant number of women develop Graves' disease (GD) in the postpartum period. The aim of this study was to examine the risk of post pregnancy GD and define patient characteristics that may impact the diagnosis and treatment strategies for this group. We performed a retrospective review of 152 consecutive women, aged 18-39 years when diagnosed with GD, to examine the relation between disease diagnosis and prior pregnancy. Differences in patient characteristics and treatment outcomes of women were analyzed. New York City population data were used to estimate a relative risk for the development of postpartum GD. We found that in parous women, 45% were diagnosed with GD in the postpartum period and 55% had an onset in subsequent years. No significant differences were noted in patient characteristics or treatment outcomes. We found that the risk of women developing post pregnancy GD was greatest in the older patients (35-39 years), with 56% developing GD compared to 42% of nulliparous women. These data, therefore, suggest an increased risk for older women. We were able to calculate the increase in estimated relative risk for postpartum disease by using control population data. The risk maximized at 5.6 for the age group 35-39 years when compared to the control population. These data support earlier studies that showed that a clinically significant number of women develop GD after childbirth compared to nulliparous women and extends this risk for many years. The mechanism of this long-standing increased susceptibility requires further delineation.

Adolescent↗

Predictive value of increased plasma levels of fibronectin in gestational hypertension.

Blood pressure, proteinuria, and plasma fibronectin and plasminogen activator inhibitor-1 levels were measured in 120 apparently healthy normotensive primigravid women during the first, second, and third trimesters of pregnancy and 2 days post partum. Thirty-two women developed hypertension (diastolic blood pressure greater than or equal to 90 mm Hg) that in 17 women was associated with proteinuria (greater than 0.3 gm/day). Fibronectin levels were 83% +/- 22% of normal (mean +/- SD) during the first trimester and 75% +/- 20% at term in the healthy women but increased from 94% +/- 36% to 187% +/- 36% in the women who developed gestational hypertension (with or without proteinuria) (p less than 0.0001). Plasminogen activator inhibitor-1 levels increased from 26 +/- 19 ng/ml to 110 +/- 86 ng/ml in healthy women and from 32 +/- 35 ng/ml to 290 +/- 90 ng/ml in hypertensive women (p less than 0.001). Increased levels of fibronectin at 25 to 36 weeks of pregnancy (greater than or equal to mean + 2 SD of the healthy women, or greater than 140%) were found in 31 of the 32 women with gestational hypertension with or without proteinuria and in 5 of the 88 healthy women (sensitivity 96%, specificity 94%). Fibronectin levels increased 3.6 +/- 1.9 weeks earlier than the onset of hypertension and/or proteinuria. Increased levels of plasminogen activator inhibitor-1 at 25 to 32 weeks (greater than or equal to 280 ng/ml) were found in 16 of the 32 women who developed gestational hypertension with or without proteinuria and in 4 of the 88 healthy women (sensitivity 50%, specificity 95%). We conclude that increased fibronectin levels are the best predictor of gestational hypertension with or without proteinuria and that its level in plasma increases several weeks before the development of hypertension.

Female↗

Randomised placebo-controlled trials and HIV-infected pregnant women in developing countries. Ethical imperialism or unethical exploitation?

The maternal-fetal HIV transmission trials, conducted in developing countries in the 1990s, undoubtedly generated one of the most intense, high profile controversies in international research ethics. They sparked off a prolonged acrimonious and public debate and deeply divided the scientific community. They also provided an impetus for the revision of the Declaration of Helsinki--the most widely known guideline for international research. In this paper, I provide a brief summary of the context, outline the arguments for and against the controversial use of placebo controls, and focus on particular areas that I believe merit further discussion or clarification. On balance, I argue that the researchers failed in their duties to protect the best interests of their research subjects, and to promote distributive justice. I discuss the difficulties of obtaining valid consent in this research context, and argue that it is unethical to inform women of their HIV status without at least offering them prophylactic treatment for their unborn children. A global view of justice, which endorses international equity, cannot be squared with international research guidelines that allow 'local conditions' to define the scope of duty to the control group. Finally, I suggest that the heated debate reflects a tension, if not an outright war, between two conflicting meta-ethical systems, or incommensurable paradigms, that underpin scientific research involving human subjects.

Developing Countries↗