Biomedical subjects
Publications and source records attributed to D W Cramer.
A retrospective analysis of 231 couples undergoing 762 IUI cycles revealed that 63 of 64 pregnancies occurred within four IUI cycles. It is recommended that couples undergoing IUI treatment who fail to conceive within four cycles consider a modification of treatment strategy.
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Information on demographic characteristics, life-style, and reproductive, prenatal, and medical history was obtained from the prenatal records of 140 women with a preterm delivery (cases) and 280 women with a term delivery (controls) matched by age. Compared with controls, a greater proportion of cases were nonwhite, never married, and educated less than 12 years. When logistic regression was used to control for confounding variables, a number of risk factors were found to be associated with an increased risk for preterm delivery: a history of a prior preterm delivery (relative risk, 3.5; confidence interval, 1.6 to 7.8), smoking during the pregnancy (p value test of trends, 0.005), and a prepregnancy weight less than 61.5 kg (relative risk, 2.0; 95% confidence interval, 1.2 to 3.2). Seven (5%) cases and none of the controls indicated a history of maternal diethylstilbestrol exposure (p less than 0.001). A history of prior induced abortion was associated with a modest increase in risk for a spontaneous preterm delivery (relative risk, 1.6; confidence interval, 0.9 to 2.7), and this risk increased with increasing numbers of induced abortions (p value for chi 2 test of trend, 0.02).
The association between time to conceive reported by 2817 fertile women who had recently had a liveborn child and consumption of coffee, tea, and "cola" drinks has been investigated. No evidence for an adverse effect of caffeine was found. For levels of consumption ranging from less than one cup of coffee per week (501 mg caffeine per month) to more than two cups of coffee per day (7000 mg per month), the average time to conceive was similar. The fecundability ratio adjusted for known risk factors for time to conceive was 1.03 (95% confidence interval 0.92-1.16) between those who consumed more than 7000 mg caffeine per month and those who consumed 500 mg or less per month. Furthermore caffeine consumption was not associated with infertility in 1818 infertile women and their primiparous controls.
The concept of ovarian cancer as a consequence of hypergonadotropic hypogonadism implies that risk factors for early menopause may also be risk factors for ovarian cancer. Gonadal radiation and the oophoritis of mumps are possible examples of environmental risk factors for early menopause and ovarian cancer. Family history is a strong determinant for both early menopause and ovarian cancer, implicating genetic factors in these disorders. Case-control data suggest that galactose consumption through the ingestion of high-lactose dairy foods may be a dietary risk factor and that galactose metabolism, as measured by galactose-1-phosphate uridyl transferase, may be a genetic risk factor for early menopause and ovarian cancer. Supporting evidence includes animal studies, case reports, and ecologic studies. Avoidance of a high-galactose diet may decrease the risk for early menopause and ovarian cancer. Alternatively, hormonal agents that lower gonadotropins may block ovarian cancer as a consequence of oocyte toxins, even if they do not prevent the early menopause.
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In a case-control study, consumption of dairy foods by 235 white women with epithelial ovarian cancer and by 239 control women, and activity of red blood cell galactose-1-phosphate uridyl transferase (transferase) in a subset of 145 cases and 127 controls were determined. Yogurt was consumed at least monthly by 49% of cases and 36% of controls. The mean transferase activity of cases was significantly lower than that of controls. When a ratio of lactose consumption to transferase (L/T) was calculated, cases had a mean L/T of 1.17 compared with 0.98 for controls; there was a highly significant trend for increasing ovarian cancer risk with increasing L/T ratio. Lactose consumption may be a dietary risk factor and transferase a genetic risk factor for ovarian cancer.
Reproductive history was obtained and the activity and electrophoretic pattern of the blood enzyme galactose-1-phosphate uridyl transferase (transferase) was measured in 104 adult Caucasian women, less than 70 years of age, sampled from the general population. Fifteen women were identified as carriers for the Duarte (GtD) or galactosemia (gt) variants of transferase--genes associated with reduced transferase activity compared with normal (Gt+). The mean age at menopause for 8 women with a natural menopause who were GtD/Gt+ or gt/Gt+ was 44.8, significantly younger (P = 0.007) than the mean age of 49.2 reported by 31 naturally postmenopausal subjects with Gt+/Gt+ genotypes and normal transferase activity. Compared with the latter group, women who were Duarte or galactosemia carriers were 13.7 times more likely to have a menopause before age 48 (with 95% confidence limits of 2.0 to 95.5). Six of 13 (46%) married women who were GtD/Gt+ or gt/Gt+ reported more than 2 years' trying to achieve a pregnancy, compared with 11 of 74 (15%) with normal genotypes and activity (P = 0.02). The authors conclude that genetic deficiency of transferase may be associated with infertility and early menopause.
Using published data, largely from the 1970s, the author compared ovarian cancer incidence, per capita milk consumption, and population estimates of lactase persistence (the ability to digest lactose after infancy) in 27 countries. Significant positive correlations were noted between ovarian cancer incidence, per capita milk consumption, and lactase persistence. Lactase persistence showed a stronger association than milk consumption or animal fat consumption in multiple regression models. The author speculates that toxicity from the lactose component of milk and, more specifically, galactose, the digestion of which is facilitated by lactase persistence, may provide a biologic basis for the correlation.
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This study explores the relationship between gay men coming out to parents and specific perceived parental variables in an attempt to discriminate between parents who are more or less accepting. In addition, other factors such as how the disclosure occurs and reasons for coming out were investigated. Results indicate that most parents initially react negatively to the disclosure, but become more accepting over time. Parental values and characteristics associated with homophobia were found to be good predictors of the change in parent-son relationship following disclosure. However, the predictions were often in unexpected directions. The majority of respondents reported having a more positive relationship with their mothers than with their fathers, both before and after coming out.
We studied past contraceptive use in 283 nulliparous infertile women who had a diagnosis of tubal adhesions or occlusion and in 3833 women admitted for delivery at seven collaborating hospitals from 1981 to 1983. The relative risk of tubal infertility associated with barrier contraceptive use or oral contraceptive use was calculated using multivariate logistic regression to control for confounding by region, age, religion, education, smoking, number of sexual partners, time since menarche, and use of other contraceptive methods. Women who had ever used barrier methods of contraception were at a significantly decreased risk of tubal infertility (relative risk = 0.6; 95% confidence limits, 0.5 and 0.8). When type of barrier method used for the longest time was evaluated, those who used the diaphragm or condoms plus spermicides were at lower risk than those who used condoms or spermicides alone. Overall, past use of oral contraceptives neither increased nor decreased a woman's risk of tubal infertility, but there was evidence that the association between oral contraceptives and tubal infertility may vary by the amount of estrogen and type of progestogen in the oral contraceptive used. We conclude that contraceptive users who use barrier methods that combine both a mechanical and chemical barrier, such as diaphragms, cervical caps, and condoms plus spermicides, have the clearest protection against tubal damage.
The activity and electrophoretic pattern of galactose-1-phosphate uridyl transferase (transferase), a key enzyme in galactose metabolism, were analyzed in four patients with Müllerian aplasia (Rokitansky-Küster-Hauser syndrome) and their mothers. Mothers of two of the patients had genetic variations of their transferase enzymes with activities below the normal range. Affected daughters from these two mothers also had genetic variations of the transferase enzyme. In one of the patients whose Müllerian aplasia had been diagnosed 15 years previously, premature ovarian failure developed. These case reports suggest a possible association between errors of galactose metabolism, Müllerian aplasia, and premature menopause--an association that is supported by a rodent model in which female offspring of mothers fed a high-galactose diet were born with reduced oocyte numbers and delayed vaginal opening.
Smoking histories were compared in 901 women with infertility of different types and 1264 women admitted for delivery at seven collaborating hospitals. The relative risk for infertility associated with cigarette smoking prior to the infertility diagnosis for nulliparous cases or first live birth for controls was calculated using a multivariate logistic-regression model to control for potential confounding factors, including center, age, religion, education, number of sexual partners, and contraceptive use. The adjusted risk for infertility attributed primarily to cervical factor (n = 96) was 1.7 (P = 0.04), to tubal disease unrelated to endometriosis (n = 225) was 1.6 (P = 0.009), to ovulatory factor (n = 389) was 1.0 (not significant [NS]), and to endometriosis (n = 191) was 0.9 (NS). The authors conclude that cigarette smoking is significantly associated only with certain types of primary female infertility.
In an expanded series of patients a sonographic sign was found to correlate well with the diagnosis of Down syndrome in second-trimester fetuses. The sign is characterized by soft-tissue thickening at the back of the fetal occiput. Sonographic evaluation for this sign was done in 2,121 consecutive fetuses between 15 and 20 gestational weeks of age at the time of genetic amniocentesis. The mothers were 35 years old or older or were otherwise at increased risk for fetal trisomies. Ten fetuses had Down syndrome by karyotype and four of these (40%) had thickened soft tissues (6 mm or more) at the back of the neck or occiput. When these data are combined with those in series previously reported by the authors, similarly collected consecutively, total second-trimester fetuses studied equals 3,825. Nine of the 21 (42%) Down syndrome fetuses by karyotype from this 3,825 had the positive sonographic sign described.
This report reviews the results of therapy in 93 patients with metastatic gestational trophoblastic tumor treated from 1965-1985. Complete remission was achieved in all 42 patients with low-risk metastatic disease and in 34 of 51 patients (67%) with high-risk metastatic disease. Single-agent chemotherapy induced complete remission in 38 of 42 patients (91%) with low-risk metastatic disease. Survival of high-risk patients has improved markedly over the past two decades; complete remission was attained in 13 of 24 high-risk patients (54%) from 1965-1975, and in 21 of 27 (78%) from 1976-1985. Survival correlated with the number of high-risk factors, the prognostic score, and the type of treatment. From 1965-1975, 54% (13 of 24) of high-risk patients were treated with single-agent chemotherapy alone, while in the last decade only 7% (two of 27) were so treated. Twenty-one patients with traditional high-risk factors had a prognostic score of 7 or less, and all achieved remission, with 67% (14 of 21) treated with primary single-agent chemotherapy. The prognostic scoring system was more effective than traditional high-risk criteria at predicting which patients require intensive combination chemotherapy to attain remission.
We compared menstrual characteristics and constitutional factors in 268 white women with primary infertility due to endometriosis and in 3,794 white women admitted for delivery at seven collaborating hospitals from 1981 to 1983. Adjusting for confounding factors, including location, age, religion, and education, women with short-cycle lengths (less than or equal to 27 days) and longer flow (greater than or equal to one week) had more than double the risk for endometriosis compared with women with longer cycle lengths and shorter duration of flow. There was a trend for increasing risk for endometriosis to be associated with increasing menstrual pain. Adjusting for these menstrual characteristics, we found decreased risk for endometriosis associated with smoking or exercise that was largely confined to women who began either habit at an early age and were heavier smokers or more strenuous exercisers. We conclude that risk for endometriosis may relate to menstrual factors that predispose to greater pelvic contamination with menstrual products and to constitutional factors that influence endogenous hormonal levels.
Demographic, reproductive, and dietary histories for 90 white women with complete molar pregnancy were compared in a multivariate analysis with those of 90 parous controls matched to cases by residence, birth year, and race. Women with molar pregnancy were more likely to have been born outside North America (relative risk = 1.9, p = 0.05), were more likely to have been past age 30 at time of their molar pregnancy (relative risk = 1.6, p = 0.05), and were more likely to have diets deficient in the vitamin A precursor carotene. Women with dietary scores for carotene above the control median had a relative risk for molar pregnancy of 0.6 (p = 0.02). In addition, there was a significant trend for decreasing risk for molar pregnancy with increasing consumption of carotene. Although other nutritional deficiencies in patients with complete molar pregnancy may exist, carotene is a biologically plausible candidate for a nutritional risk factor that could explain the geographic distribution of molar pregnancy.