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Root growth in the teeth of 46,XY females.

The subjects of this study are women with a male sex chromosome complement or 46,XY females who show the complete form of the testicular feminization syndrome (CTF). The basic endocrine defect is end organ insensitivity to androgens. They are on average tall individuals and also show an increase in head and face dimensions relative to normal females. A size increase is likewise evident in permanent tooth crowns and here we report permanent tooth root lengths in eight 46,XY females, their five female relatives and population control females and males. Measurements were made from panoramic radiographs by a digital calliper according to established procedures on both sides of the jaws. The results show increased root lengths of 46,XY females relative to control females with values similar to those in population control males. The root and crown findings point to evident irreversible growth excesses in 46,XY females beginning 3 years after birth up to the age of 14 years expressing an effect which apparently is influencing in a continuous way. Excess root growth conceivably would develop independently of the possible androgen influence, and it is suggested that the increase results from the direct effect of the genes on the Y chromosome. It is possible that these genes on the Y chromosome are the same that promote tooth crown growth.

Androgen-Insensitivity Syndrome↗

Lung cancer risk in relation to the CYP2C9*1/CYP2C9*2 genetic polymorphism among African-Americans and Caucasians in Los Angeles County, California.

CYP2C9 is involved in the metabolism of warfarin and a wide array of other therapeutic agents. It also appears to play a role, along with other cytochrome P450 enzymes, in the metabolism of benzo[a]pyrene, a carcinogen in tobacco smoke. A relatively common allelic variant (termed R144C, Cys144 or more recently CYP2C9*2) has been described that results in the substitution of cysteine for arginine at residue 144 and appears to reduce enzyme activity. We therefore examined the possible association between the presence of the CYP2C9*2 variant allele and risk of lung cancer using peripheral blood DNA from 329 incident cases of lung cancer (152 African-American and 177 Caucasian) and 700 (239 African-American and 461 Caucasian) population controls in Los Angeles County, California. Among the population controls the frequency of the CYP2C9*2 variant allele was lower (p = 0.00002) among African-Americans (0.036) than among Caucasians (0.100). The presence of the CYP2C9*2 variant allele was not associated with a decreased risk of lung cancer; slight but nonstatistically significant elevations in risk were observed for both African-Americans [odds ratio (OR) 1.22, 95% confidence interval (CI) 0.48-3.11] and Caucasians (OR = 1.55, 95% CI 0.96-2.48). The ORs were slightly and nonsignificantly elevated for all histologic types without substantive variation. The association also did not vary materially according to smoking history or whether subjects had the homozygous deletion of the GSTM1 gene. We found no support for the hypothesis that the CYP2C9*2 variant allele decreases the risk of lung cancer. The role of P450s, including CYP2C9, in benzo[a]pyrene metabolism is not fully defined, and CYP2C9 catalyses detoxication as well as activation steps. Thus it is not inconceivable that diminished CYP2C9 activity could increase metabolic activation of benzo[a]pyrene to carcinogenic intermediates. Nonetheless, the small increased risk associated the CYP2C9*2 variant allele in our data is consistent with chance and should not be overinterpreted.

Adenocarcinoma↗

The road to abortion (II): how government got hooked.

The first part of this series traced close links between eugenics (the effort to breed a "better" human race) and population control throughout the greater part of this century up to the 1960s. It stressed the population work of early eugenicists and eugenics sympathizers such as Frederick Osborn, Margaret Sanger, Gunnar Myrdal, Alan Guttmacher, Garrett Hardin and John D. Rockefeller 3rd. This second and concluding part will show how population controllers, from the 60s onward increasingly added economic and foreign-policy concerns to their original "eugenics" motive of improving human genetic stock. Working in both Democratic and Republican administrations, they gained major government backing for their programs and also played a key role in the legalization of abortion. I will use President Richard Nixon's administration as an example of heavy government involvement.

Abortion, Legal↗

Age, alcoholism and depression are associated with low levels of urinary melatonin.

Two normal control populations, separated by 8,000 miles and 24 degrees of latitude, had similar six-month mean values for overnight urinary melatonin concentrations. These values were significantly higher than six-month values for depressed subjects and abstinent alcoholic subjects, while the means for the two clinical populations were similar. Age and urinary melatonin concentration in the control and clinical populations were inversely related, but the slopes of the linear regression equations were ten times steeper for the control populations than for the clinical populations. Differences in age and sex distributions accounted for some of the differences in values between controls and the clinical populations, although controls still differed from the clinical populations, even after sex and age were factored out. The disparate slopes for age and melatonin concentrations may contribute to some of the conflicting findings of studies comparing populations of different ages. The total melatonin content in the samples from alcoholic subjects, but not the depressed subjects, was lower than that for controls. The difference in the urinary melatonin concentration between the controls and the two patient groups was not accounted for by difference in duration of urine collection period, hours of sleep or body weight.

Adult↗

The politics of birth control, 1920-1940: the impact of professionals.

Before the 1920s, a birth control movement arose in the United States out of socialist, feminist, and other radical groups concerned with women's rights and sexual freedom. After 1920 the birth control movement became gradually transformed into a respectable, nonradical reform cause, the recipient of large grants from big business, with women's rights secondary to an overriding concern with medical health and population control. This transformation was achieved through the professionalization of the birth control movement-that is, its takeover by professional experts, almost all male, in place of the radical amateur women, fighting for their own interests, who initiated it. The article examines two groups of professionals who were particularly influential in this transformation: doctors and academic eugenists. The former made birth control a medical issue, held back the development of popular sex education, and stifled a previously developing feminist approach to women's birth control needs. The later contributed racism to the birth control movement, helping to transform it into a population control movement with racist and anti-feminist overtones. Both groups, while they made contributions to the technology of contraception, simultaneously held back the spread of birth control by transforming the campaign for it from a popular, participatory cause to a professional staff lobbying operation.

Attitude↗

Empirical study of parental recall bias.

Recall bias is a major concern in case-control studies in which questionnaire data are used to assess past exposure. The authors conducted a validation substudy within the framework of a parent case-control study on risk factors for acute lymphoblastic leukemia in children aged < or =9 years diagnosed in 1980-1993 in Quebec, Canada. Parental recall bias for two variables was assessed: reported distance from home to power lines compared with measured distance and reported prenatal radiographic examinations compared with hospital medical record data. For reported distance, sensitivity was 62% for a subgroup of cases living in an area in which an excess of childhood acute lymphoblastic leukemia was perceived and was attributed to power lines. However, for other cases, sensitivity (35%) was similar to that measured for hospital controls (36%) and was relatively close to that for population controls (22%). Specificity was high for all groups except cases from the area with a perceived excess. Sensitivity for reported prenatal radiographic examinations was similar for cases (64%) and population controls (71%) but was lower for hospital controls (50%). Results confirm that under special circumstances, such as those resulting from enhanced public concern, parental recall can be differential but otherwise is most often nondifferential, with low sensitivity. Choosing the best type of controls to ensure comparable recall accuracy remains difficult.

Adult↗

Association of NOD1 polymorphisms with atopic eczema and related phenotypes.

BACKGROUND: Interactions with microbial pathogens are crucial for the maturation of the immune system. The nucleotide-binding oligomerization domain protein 1 (NOD1) is a cytosolic receptor sensing a muropeptide found mostly in gram-negative bacterial peptidoglycans. NOD1 is located on chromosome 7p14-p15, a region that has been linked with atopy. Recently, polymorphisms of the closely related NOD2 have been associated with atopy-related traits. OBJECTIVES: Within a large population-based cohort of German adults (n = 1417), a case-control population for atopic eczema (n = 454), and a large cohort of parent-offspring trios for atopic eczema (189 trios), we evaluated 11 NOD1 polymorphisms for associations with atopic phenotypes. Methods Subjects were phenotyped by standardized questionnaires and interviews, skin examination, and serum IgE measurements. Genotyping was performed by using matrix-assisted laser desorption ionization-time of flight mass spectrometry. RESULTS: Analyses revealed significant association of one NOD1 haplotype with atopic eczema in the population-based cohort ( P = .004) and the case-control population ( P = .003). Another NOD1 haplotype was associated with decreased total IgE ( P = .008). In addition, significant associations with total serum IgE levels were observed for polymorphisms rs2907748 ( P = .006), rs2907749 ( P = .012), and rs2075822 ( P = .018). These polymorphisms were significantly associated with atopic eczema and asthma in the family-based association analyses ( P = .001-.043). Seven polymorphisms showed significant transmission distortion for total IgE levels ( P values < .0001-.029). CONCLUSION: These data indicate that genetic variants within NOD1 are important determinants of atopy susceptibility.

Adaptor Proteins, Signal Transducing↗

Significant reduction in advanced breast cancer. Results of the first seven years of mammography screening in Kopparberg, Sweden.

A population-based, randomized, controlled breast cancer screening trial with single-view mammography as the only means of primary detection has been under way in Kopparberg county, Sweden, since October 1977. The 7-year results of the study show (1) a significant change in the stage distribution of breast cancers in the cohort invited to undergo screening (ASP) as compared to the control group. (2) This change is seen as an initial decrease in the proportion of advanced (stage II and more advanced) cancers in the ASP as compared to the control population, followed in the second and third round of screening by a significant decrease in the absolute number of these advanced cancers in the ASP relative to the control group. (3) A thorough follow-up of both populations will answer whether these preliminary findings will result in decreased breast cancer mortality in the population invited to screening.

Adult↗

Lung cancer risk in relation to the CYP2E1 Rsa I genetic polymorphism among African-Americans and Caucasians in Los Angeles County.

Genetic polymorphisms in the activation or detoxication of carcinogens, such as those in tobacco smoke, may produce differences in individual susceptibility to lung cancer. The cytochrome P450 CYP2E1 is an enzyme involved in the metabolism of nitrosamines in tobacco smoke. A polymorphism of CYP2E1 detectable by the restriction enzyme Rsa I may be functionally important because it is located in a putative binding site for the transcription factor HNF-1 and has been associated with higher levels of CYP2E1 transcription. It is conceivable that this CYP2E1 Rsa I polymorphism might contribute to differences in susceptibility to lung cancer. We conducted a case-control study of patients with incident lung cancer and population controls in Los Angeles County to examine the association between the CYP2E1 Rsa I polymorphism and lung cancer risk among African-Americans and Caucasians. Samples of white blood cell DNA sufficient for determination of the CYP2E1 Rsa I genotype by a polymerase chain reaction-based assay were obtained from 341 cases and 706 controls with data on lifetime smoking history. No subjects were homozygous for the CYP2E1 Rsa I rare c2 allele. The rare c2 allele was not associated with an increased risk of lung cancer (adjusted odds ratio, OR 0.72; 95% confidence interval, CI = 0.35-1.46). Among the population controls the percentage of subjects carrying the rare c2 allele was lower (p = 0.002) among African-Americans (2%) compared with Caucasians (8%). However, the association between the CYP2E1 Rsa I genotype and lung cancer risk did not differ between ethnic groups. There was no important association between the CYP2E1 Rsa I genotype and lung cancer risk in analyses stratified by cell-type, smoking history, gender, occupational asbestos exposure, and dietary intake of antioxidants vitamin C, vitamin E or beta carotene. Due to the low frequency of the c2 allele in these populations, larger studies would be necessary to rule out a modest association between the CYP2E1 Rsa I polymorphism and lung cancer risk.

Adult↗

Systemic diseases associated with various types of retinal vein occlusion.

PURPOSE: To investigate systemic diseases associated with various types of retinal vein occlusion. METHODS: We investigated prospectively in 1090 consecutive patients with retinal vein occlusion, almost all Caucasian (consistent with the racial pattern here), the prevalence of associated systemic disorders before or at the onset of various types of retinal vein occlusion. The patients were categorized into six types of retinal vein occlusion based on defined criteria: nonischemic and ischemic central retinal vein occlusion, nonischemic and ischemic hemi-central retinal vein occlusion, and major and macular branch retinal vein occlusion. The patients had a detailed ophthalmic and systemic evaluation according to our protocol. For data analysis, patients were divided into three age groups: young (younger than 45 years), middle-aged (45 to 64 years), and elderly (65 years or older). The observed prevalence rates of major systemic diseases were compared among central retinal vein occlusion, hemi-central retinal vein occlusion, and branch retinal vein occlusion using a polytomous logistic regression analysis adjusting for gender and age. Logistic regression adjusting for age and gender was also used to compare the observed prevalence of systemic disease between nonischemic and ischemic in central retinal vein occlusion and hemi-central retinal vein occlusion and between major and macular branch retinal vein occlusion. These observed prevalence rates were also compared with those expected in a gender-matched and age-matched control population from estimates from the US National Center for Health Statistics. RESULTS: There was a significantly higher prevalence of arterial hypertension in branch retinal vein occlusion compared with central retinal vein occlusion (P < .0001) and hemi-central retinal vein occlusion (P = .028). Branch retinal vein occlusion also had a significantly higher prevalence of peripheral vascular disease (P = .0002), venous disease (P = .011), peptic ulcer (P = .031), and other gastrointestinal disease (P < .0001) compared with central retinal vein occlusion. The proportion of patients with branch retinal vein occlusion with cerebrovascular disease was also significantly (P = .049) greater than that of the combined group of patients with central retinal vein occlusion and patients with hemi-central retinal vein occlusion. There was no significant difference in prevalence of any systemic disease between central retinal vein occlusion and hemi-central retinal vein occlusion. A significantly greater prevalence of arterial hypertension (P = .025) and diabetes mellitus (P = .011) was present in the ischemic central retinal vein occlusion compared with the nonischemic central retinal vein occlusion. Similarly, arterial hypertension (P = .0002) and ischemic heart disease (P = .048) were more prevalent in major branch retinal vein occlusion than in macular branch retinal vein occlusion. Relative to the US white control population, the combined group of patients with central retinal vein occlusion and patients with hemi-central retinal vein occlusion had a higher prevalence of arterial hypertension (P < .0001), peptic ulcer (P < .0001), diabetes mellitus (in ischemic type only, P < .0001), and thyroid disorder (P < .0001). The patients with branch retinal vein occlusion showed a greater prevalence of arterial hypertension (P < or = .005), cerebrovascular disease (P = .007), chronic obstructive pulmonary disease (P = .012), peptic ulcer (P < .0001), diabetes (in young only, P = .0005), and thyroid disorder (P = .003) compared with the US white control population. CONCLUSIONS: The findings of our study revealed that a variety of systemic disorders may be present in association with different types of retinal vein occlusion and in different age groups, and that their relative prevalence differs significantly, so that the common practice of generalizing about these disorders for the entire group of patients with retinal vein occlusion can be misleading. The presence of a particular associated systemic disease does not necessarily imply a cause-and-effect relationship with that type of retinal vein occlusion; the particular disease may or may not be one of the risk factors in a multifactorial scenario predisposing an eye to develop a particular type of retinal vein occlusion. Based on our study, we think that apart from a routine medical evaluation, an extensive and expensive workup for systemic diseases is unwarranted in the vast majority of patients with retinal vein occlusion.

Adult↗

[Association of parents' occupational exposure to cancer in children. A case-control study of acute lymphoblastic leukemia].

The objectives of the present study were to evaluate the preconceptual, prenatal, and postnatal environmental factors as possible etiologic agents of childhood neoplasms. An exploratory case-control study was conducted on parents of children less than 15 yr of age with acute lymphocytic leukemia (ALL). Data were obtained on 147 identified cases by interview from their mothers and by mail questionnaire from their fathers. Hospital control cases were matched by sex and age, while population control cases were matched by place of residence, and sex. The following results were obtained. 1) As for the occupation of the parents, more fathers of the cases were engaged in occupations related to agriculture, medicine, and science than those of the controls, and more mothers of the cases were engaged in agriculture than those of the controls. 2) No significant relation could be demonstrated between ALL and occupations related to hydrocarbon and ionizing radiation. 3) The results of multivariate analysis showed that in comparison with the hospital control cases the preconceptual exposure to chemicals and the prenatal exposure to pesticides of the fathers and the prenatal exposure to benzine and spray pesticides of the mothers were risks of high significance. In comparison with population control cases, the prenatal exposure of benzine and exposure to paints of the mothers prior to disease onset were risks of high significance. The foregoing results suggest that exposure to occupational and environmental factors of the parents may play an etiologic role in childhood leukemia.

Adolescent↗

The role of a common TNNT2 polymorphism in cardiac hypertrophy.

We found a five-basepair insertion/deletion polymorphism in intron 3 of TNNT2, one of the genes responsible for hypertrophic cardiomyopathy. These five bases may be part of an intronic polypyrimidine tract sequence that may affect splicing. The purpose of the study was to examine the association of the polymorphism with cardiac hypertrophy. The study population consisted of 151 subjects with prominent concentric left ventricular hypertrophy, and 987 healthy subjects recruited from medical checkups (control population). The deletion/deletion genotype tended to be associated with a larger left ventricular mass/height ratio in the HCM population ( p<0.0001). Multiple regression analyses indicated that the left ventricular mass/height ratio was determined ( p<0.0001, R=0.738) by the TNNT2 genotype. Moreover, the frequency of the deletion allele was significantly higher in the hypertrophy population than in the control population ( p<0.0001). In vitro expression study revealed the deletion allele significantly affected the mRNA expression pattern by skipping exon 4 during splicing. In conclusion, TNNT2 deletion allele could be associated with a predisposition to prominent left ventricular hypertrophy.

Aged↗

Risk factors for vulvovaginal candidiasis: a case-control study among university students.

Vulvovaginal candidiasis (VVC) is a common inflammatory condition caused by vaginal overgrowth of Candida albicans. Typical symptoms include pruritus and discharge. To test the association between several hypothesized risk factors and VVC, we conducted a case-control study among university students, with both clinic and population controls. Symptomatic, culture-proven VVC was associated with receptive oral sex twice or more in the previous 2 weeks [vs not at all, odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.7-7.0]; oral contraceptive use (OR = 1.8; 95% CI = 0.95-3.6); spermicide use (OR = 3.3; 95% CI = 1.6-6.8); a prior diagnosis of VVC in the previous year (OR = 3.0; 95% CI = 1.5-5.9); and black (OR = 6.8; 95% CI = 3.1-15) and "other" race (OR = 2.2; 95% CI = 1.0-4.6). Estimates are from a cases vs population controls logistic regression model including all five variables; results for cases vs clinic controls were similar. After adjusting for these factors, many other hypothesized risk factors, such as antibiotic use, menstrual hygiene practices, and vaginal intercourse, had little association with VVC.

Adult↗

Maternal use of nutritional supplements during the first month of pregnancy and decreased risk of Down's syndrome: case-control study.

OBJECTIVE: We studied the association between the use of nutritional supplements during the first gestational month and the origin of Down's syndrome. METHODS: We compared 781 subjects with Down's syndrome caused by pure trisomy 21 with their matched controls who had no defect. We also compared subjects who had Down's syndrome with groups of 22 843 patient controls (i.e., subjects with other congenital abnormalities) and 38 151 population controls (without defects). Subjects with Down's syndrome and other congenital abnormalities were identified in the large population-based dataset of the Hungarian Congenital Abnormality Registry between 1980 and 1996, and matched population controls were selected from the National Birth Registry. There were three sources of exposure data: 1) prospective and medically recorded data based on prenatal logbooks, 2) retrospective maternal information based on questionnaires, and 3) home visits in non-respondent cases of Down's syndrome and congenital abnormalities. A possible association between the use of nutritional supplements, mainly folic acid and antioxidant vitamins C and E, during the first month of pregnancy and the incidence of Down's syndrome was studied. RESULTS: A significant protective effect was seen with large doses of folic acid ( approximately 6 mg/d) and iron (150-300 mg/d of ferrous sulfate) during the first gestational month against Down's syndrome (adjusted odds ratio 0.4, 95% confidence interval 0.2 to 0.7 for both). In general, folic acid and iron were used together, so it was difficult to separate these effects due to the limited number of subjects and controls. Only iron alone showed a protective effect against Down's syndrome (odds ratio 0.4, 95% confidence interval 0.1 to 0.9). The use of antioxidant vitamins was a rare event in the first month of pregnancy. CONCLUSION: Pharmacologic doses of folic acid and iron appear to have a preventive effect against Down's syndrome.

Case-Control Studies↗

Case-control study of multiple system atrophy.

The epidemiology of multiple system atrophy (MSA) is scarcely known, and risk factors have not been definitely identified. We investigated the effect of family history for neurodegenerative diseases and environmental factors on MSA risk in a multicentric case-control study. A total of 73 MSA patients (42 men, 31 women; age, 64.3 +/- 8.1 years; disease duration, 4.8 +/- 3.9 years), 146 hospital controls (84 men, 62 women; age, 64.9 +/- 8.4 years), and 73 population controls (42 men, 31 women; age, 63.7 +/- 8.9 years) matched for sex, age (+/-3 years), and province of residence were enrolled consecutively at seven neurological centers from 1 January 1994 to 31 July 1998. The following variables were investigated: family history of neurodegenerative diseases, education, smoking habits, hobbies, and occupational history. Occupational history of farming was significantly more frequent among MSA cases than controls (OR adj = 2.52; 95% CI, 1.25 to 5.07, MSA vs. hospital controls; OR adj = 4.53; 95% CI, 1.68 to12.2, MSA cases vs. population controls). A dose-response analysis for years of farming corroborated this association. We recently found that smoking is significantly less frequent among MSA cases than controls (Vanacore et al. [2000] Neurology 54:114-119). Here, we report that the effects of farming and smoking on MSA risk do not interact. Our results suggest that occupational history of farming is a risk factor for MSA. Smoking and farming seem to influence MSA risk independently. Further epidemiological studies might provide clues on the etiopathogenesis of MSA.

Aged↗

Case-control study of colon cancer and drinking water trihalomethanes in Wisconsin.

A case-control study was conducted to test the hypothesis that chronic ingestion of trihalomethanes (THMs), occurring as chlorination byproducts in drinking water, carries a risk of colon cancer. Lifetime residential and water source histories and information on water-drinking habits, diet, sociodemographics, medical and occupation histories, lifestyle and other factors were obtained by questionnaire from a statewide sample of newly-diagnosed colon cancer cases (N = 347), controls with cancer of other sites (N = 639) and general population controls (N = 611). Since no data on past THM levels exists, it was necessary to devise a scheme to generate THM estimates for all Wisconsin water sources. For this, a statistical model based on quantitative THM measures and routinely-recorded data taken at 81 municipal water facilities was used in conjunction with individual residential histories to estimate lifetime and period-specific THM exposure for each case and control. Logistic regression was used to estimate odds ratios adjusted for age, sex and urban living, for colon cancer and THM exposure. The study results indicate that THM in Wisconsin drinking water does not pose a significant colon cancer risk. Odds ratios for exposure to the middle and highest category of lifetime cumulative THM were 1.05 (95% Cl = 0.66-1.68) and 0.93(95%Cl = 0.55-1.57) respectively, relative to the cancer control group, and 1.10 (95%Cl = 0.68-1.78) and 0.73 (95% Cl = 0.44-1.21) respectively, relative to the general population controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control study.

OBJECTIVE: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. METHODS: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (-5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. RESULTS: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1-9 years (OR 0.9; 95% CI 0.6, 1.5), for 10-19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). CONCLUSION: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.

Case-Control Studies↗