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[A prospective study of antipyrine pharmacokinetics in pregnancy].

Pharmacokinetics of a single dose of antipyrin (10 mg/kg) subjected to biotransformation at the expense of microsomal oxidation of its molecule in the liver was studied in 6 healthy nonpregnant women and in 24 women within the frames of a prospective follow-up starting from the early terms of gestation; 7 of these women developed edemas, proteinuria and/or hypertension in the course of follow-up. The results permit us consider that a test with a single antipyrin dose may be used as a marker to characterize drugs with similar metabolic transformations when used in pregnant women. The identity of pharmacokinetic regularities of antipyrin in samples of blood plasma and saliva permit the use of saliva as biological material for assessment of the metabolic profile of pregnant women. The problem of drug therapy in the third trimester is closely connected with specific features of pharmacokinetic profile detected by antipyrin test both in normal and complicated gestation. Our data evidence that the third trimester is characterized by special tension of the metabolic processes. A complicated course is associated with unambiguous changes in the metabolic activity of drugs, this necessitating special attention of a physician to drug dose.

Adult↗

Estrogen replacement and migraine aura.

OBJECTIVE: To assess the association between estrogen replacement therapy and migraine aura. BACKGROUND: Estrogen replacement therapy is increasingly used by perimenopausal and postmenopausal women for management of menopausal symptoms and for long-term protection against osteoporosis and arterial disease. There are few reports about the effects of estrogen replacement therapy on migraine. METHOD: Case reports were collected from women developing migraine aura related to use of estrogen replacement therapy. RESULTS: Four patients who developed migraine aura associated with the use of estrogen replacement therapy are described. In all cases, reducing the dose of estrogen or changing the route of delivery was associated with loss of aura. CONCLUSION: These findings suggest that high levels of estrogen in women using replacement therapy can trigger migraine aura.

Adult↗

Lower hypertension risk in Mexico City than in San Antonio.

BACKGROUND: We examined the effects of blood pressure (BP), weight, and weight gain on hypertension risk in two similar ethnic origin populations, subjects in Mexico City and Mexican Americans in San Antonio. METHODS: The Mexico City Diabetes Study and San Antonio Heart Study are population-based, epidemiologic studies with identical survey protocols. Incident hypertension (BP > or = 140/90 mm Hg or current antihypertensive treatment) was analyzed in subjects aged 35 to 64 years of Mexican ethnicity living in low-income neighborhoods (n = 1467 in Mexico City, n = 628 in San Antonio). RESULTS: In Mexico City, 10.6% of men and 13.1% of women developed hypertension in a 6.5-year period; in San Antonio, 28.6% and 28.7% in a 7.5-year period, respectively. Poisson regression analysis demonstrated a greater hypertension risk in San Antonio for both men (risk ratio [RR] = 1.75, 95% confidence interval [CI]: 1.19-2.56) and women (RR = 1.40, 95% CI: 1.05-1.86). In a multiple linear regression analysis, systolic BP change was associated with weight gain in Mexico City (P < .001 in men and women) and San Antonio (P = .045 in men, and P = .027 in women) independently of age, BP, obesity, alcohol consumption, cigarette smoking, diabetes, and antihypertensive treatment. These covariates did not fully explain greater increments of systolic BP in San Antonio than in Mexico City (P < .001 in men and women). CONCLUSIONS: Hypertension risk is lower in Mexico City than in San Antonio. Systolic BP increases with weight gain, independently of other determinants of hypertension.

Adult↗

Iron status and coronary heart disease: negative findings from the NHANES I epidemiologic follow-up study.

The potential association between iron status and coronary heart disease has received increased attention recently. The authors examine this hypothesis in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study. The study consisted of 4,237 respondents (1,827 men, 2,410 women) aged 40-74 years at baseline. During the average 13-year follow-up, 489 persons (289 men, 200 women) had an acute myocardial infarction, and 1,151 persons (633 men, 518 women) developed coronary heart disease (included myocardial infarction and other forms of chronic ischemic heart disease). In logistic regression analyses, adjusting for baseline age, systolic blood pressure, serum cholesterol, smoking status, and education, serum iron was inversely associated with the risk of myocardial infarction in women (relative risk = 0.82 for an increase of 5.4 mumol/liter (equivalent to about 1 standard deviation), 95% confidence interval (CI) 0.70-0.95), but not in men. Total iron-binding capacity and transferrin saturation were not related to myocardial infarction in either sex, while serum iron and transferrin saturation were inversely associated with coronary heart disease in both sexes. Among men, the relative risk was 0.92 (95% CI 0.85-1.00) for a 5.4-mumol/liter increase in serum iron, while a relative risk of 0.91 (95% CI 0.83-1.00) was observed for a 10% increase in transferrin saturation. For women, the corresponding relative risks were 0.86 (95% CI 0.77-0.95) and 0.88 (95% CI 0.79-0.98), respectively. Dietary iron intake based on 24-hour recall was not associated with the two disease end points. These findings from a large national sample do not support the hypothesis of a positive iron-coronary heart disease relation.

Adult↗

Gender differences in insulin-induced free fatty acid suppression: studies in an African American population.

This study of African Americans (AA) was designed to investigate gender differences in insulin-induced free fatty acid (FFA) suppression. Sixty AA (34 women, mean age 34 +/- 7.6 years, and 26 men, mean age 30 +/- 2.9 years) participated. All subjects had an oral glucose tolerance test (OGTT). Nineteen women and 18 men also underwent a euglycemic hyperinsulinemic clamp (IC) study. Plasma insulin and FFA concentrations were obtained during both tests at 0, 60, and 120 min. While there was no gender difference in body mass index (P = 0.21), women had greater percent body fat (P < 0.001) calculated by the Siri formula. There was no gender difference in fasting FFA levels, but during the OGTT, women compared to men had significantly greater FFA suppression. Both nonobese and obese women suppressed FFA concentration by 88%, and nonobese and obese men suppressed FFA concentration by 80 and 66% respectively. This gender difference in FFA suppression was significant (P = 0.001) and independent of obesity and insulin concentration. During the IC studies, there were no gender or obesity differences in FFA suppression, with women and men suppressing FFA levels by 87-89% (P = 0.7). Fasting insulin concentrations were higher in obese vs. nonobese (P = 0.03), but fasting FFA concentrations were not different (P = 0.15). For nonobese and obese females, fasting FFA levels were 0.55 +/- 0.24 and 0.44 +/- 0.26 mEq/L, respectively, and for nonobese and obese males, 0.45 +/- 0.2 and 0.35 +/- 0.18 mEq/L, respectively. In women, development of obesity may be enhanced by greater sensitivity to insulin-induced FFA suppression as measured during an OGTT. To detect gender differences in FFA metabolism, the OGTT is superior to the IC. The lack of elevation in fasting FFA levels in obese AA women and men has not been reported in other racial groups and may indicate a greater adipocyte sensitivity to insulin in AA.

Adipocytes↗

Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine.

We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with 131I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after 131I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.

Adult↗

[The epidemiology and pathogenesis of postpartum depression].

Mood disorders--maternity blues, depression and bipolar disorders with psychotic features--are common and increased in rate during the postpartum period as compared to the non-postpartum period. Several authors showed a frequent recurrence of postpartum depression in women with a history of postpartum depression. Bloch, et al: (2000) showed that 5 of 8 women(62.5%) with a history of postpartum depression and none of the 8 control women developed significant mood symptoms during the withdrawal from high serum levels of progesterone and estradiol. These findings indicate that a history of postpartum depression produces hypersensitivity or reverse tolerance to subsequent exposure to an acute decrease of gonadal steroids at least for a subgroup of women with a past postpartum depression.

Adult↗

Elevated C-reactive protein is a predictor of the development of diabetes in a general Japanese population: the Hisayama Study.

OBJECTIVE: We examined the association between high-sensitivity C-reactive protein (CRP) levels and the development of diabetes in a general Japanese population. RESEARCH DESIGN AND METHODS: A total of 1,759 Japanese subjects, aged 40-79 years and without diabetes (according to American Diabetes Association fasting criteria), were stratified into three groups according to CRP tertiles by sex and followed up prospectively for a mean of 9.0 years. RESULTS: During the follow-up, 131 subjects (67 men and 64 women) developed diabetes. In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly as the tertiles of CRP levels increased. In multivariate analyses, the risk of developing diabetes was significantly higher in the highest CRP tertile than in the lowest after adjustment for a number of confounding factors (odds ratio 2.63 [95% CI 1.23-5.65] for men and 2.25 [1.01-5.01] for women). In stratified analyses, this CRP-diabetes association was stronger in subjects without obesity or other risk factors related to insulin resistance and in nondrinking subjects. CONCLUSIONS: Our findings suggest that elevated CRP concentration is a significant predictor of diabetes in the general Japanese population, independent of obesity and insulin resistance.

Adult↗

Comparative study on age-related changes and atherosclerotic involvement of the coronary arteries of male and female subjects up to 40 years of age.

In an unselected population sample of Bucharest, including 536 subjects (284 males and 252 females) aged up to 40 years, sex appeared as one of the most important factors influencing the pattern of coronary artery growth and remodelling, as well as the pattern of atherosclerotic involvement. The internal elastic membrane of the female coronary arteries of neonates, children, juveniles and adolescents manifested a lesser tendency to fragment, to interrupt and to exhibit elastolysis than did the corresponding internal elastic membrane of male subjects. In the anterior descending and circumflex arteries, female subjects had less intima than males of similar age. Women developed the first atherosclerotic plaques a decade later than men and at a similar age showed fewer atherosclerotic plaques and atheromas. These sex differences were statistically significant for the anterior descending and circumflex arteries, but not for the right coronary artery. During adulthood, the number of women with a three vessel involvement was half that of men. In successive age groups, the degree of luminal narrowing by atherosclerotic plaques was constantly and consistently lower in female than in male subjects.

Adolescent↗

Wide local excision and radiotherapy for the treatment of ductal carcinoma in situ of the breast: the Hong Kong experience.

AIMS: Breast conservation treatment for ductal carcinoma in situ (DCIS) was unpopular in the Chinese population and the outcome was seldom reported. We conducted a single-centre retrospective study to examine the clinical outcome of women in Hong Kong. MATERIALS AND METHODS: Seventy-five Chinese women were treated with wide local excision and radiotherapy for DCIS of the breast between 1994 and 2003. Only 26 (34.7%) women had non-palpable DCIS detected by screening mammograms. All women were treated with whole breast irradiation of 50 Gy in 2 Gy daily fractions, with 50 (66.7%) women receiving an additional electron boost of 10-16 Gy. RESULTS: The median follow-up was 5.1 years (range 2.0-10.7). At the last assessment, four women developed local recurrences, but all remained disease-free after salvage mastectomy. The 5-year actuarial local failure-free rate and cause-specific survival rate were 92.9% (95% confidence interval 89.4-96.4) and 100.0%, respectively. Cosmetic results were rated as good to excellent in all women. On univariate analysis of prognostic factors for local failure, only a close (< or = 2 mm) final resection margin approached statistical significance (hazard ratio 9.108; 95% confidence interval 0.946-87.655; P = 0.056). The 5-year actuarial local failure-free rates for women with a close (< or = 2 mm) final resection margin and women with wider margins were 77.0 and 98.2%, respectively. CONCLUSIONS: Despite geographical and demographic differences, the clinical outcome after wide local excision and radiotherapy for DCIS of the breast in Chinese women is comparable with that in Western series. Efforts are needed to achieve cosmetically acceptable tumour-free margins greater than 2 mm.

Adult↗

Low-dose oral contraceptives and 24-hour ambulatory blood pressure.

OBJECTIVE: To evaluate in normotensive women the influence of low-dose oral contraceptives (OC, monophasic formulations containing 30 microg of estrogen) on 24-h blood pressure. METHODS: We evaluated prospectively in 15 normotensive healthy women (three smokers) the influence of OC on 24-h ambulatory blood pressure monitoring (ABPM). ABPM was performed (SpaceLabs 90207) before and after 6-9 months of use of OC. We also evaluated ABPM in eight women (two smokers) before and after 6-8 months on an intrauterine device (IUD) as contraceptive method--these were used as control subjects. RESULTS: OC produced a significant increase in 24-h ABPM values (from 120+/-3/75+/-2 to 128+/-4/81+/-2 mmHg, P < 0.04) which was particularly evident for night-time values (from 108+/-2/64+/-2 to 120+/-4/73+/-2 mmHg, P < 0.02). After OC, two normotensive women developed 'hypertensive values'. In OC users there was a slight but significant increase in body weight which did not correlate with the increase of blood pressure. In contrast, in the control group (IUD) neither ABPM values nor weight were modified by the contraceptive maneuver. CONCLUSIONS: In normotensive women, low-dose OC may increase blood pressure to an extent that, at least in some women, may affect blood pressure control towards 'hypertensive values'. This stresses the importance of monitoring blood pressure values during OC treatment.

Adult↗

A discriminant function for preeclampsia: case-control study of minor hemoglobins, red cell enzymes, and clinical laboratory values.

A case-control study was performed in eight pairs of women to determine whether preeclamptic women developed abnormalities in minor hemoglobins, glycolytic enzymes, or other blood components that might provide insight into the pathophysiology of preeclampsia, or that in combination might be used as a marker for the condition. These variables and standard clinical tests were analyzed as discriminators between preeclamptic and control women. The subjects were matched for age, ethnicity, parity, and gestational age. Blood samples were taken at the time of diagnosis of preeclampsia and at comparable gestational ages for matched normal controls. Variables differing significantly between groups included increases in uric acid (UA), low-density lipoproteins (LDL), phosphoglycerate kinase (PGK), and mean platelet volume (MPV), and decreases in glyceraldehyde phosphate dehydrogenase (G3PD) in preeclamptic women compared to normal controls. Discriminant analysis revealed the following function to separate the groups: 0.7764 (UA) + 0.8086 (PGK) -0.7032 (G3PD) + 0.1399 (LDL) -0.2386 (MPV). A discriminant score of > or = 275 indicated a > or = 90% probability of preeclampsia. The results are consistent with perturbations in red cell glycolysis in preeclampsia. Further prospective studies are warranted to test the efficacy of this discriminant function in predicting preeclampsia.

Adult↗

Effects of the postpartum period on nortriptyline pharmacokinetics.

The objective of this research was to investigate sequential serum levels and level/dose ratios of the tricyclic antidepressant nortriptyline (NTP) through the first 17 postpartum weeks. The initial NTP dose was given immediately postpartum to 16 mothers and increased gradually to 70 mg over the first week. A dose of 75 mg was prescribed until adjustment according to serum levels. Serum levels of NTP and its metabolites Z- and E-OH-NTP were determined. At postpartum Week 2, the women developed a mean level/dose (L/D) ratio for NTP of 1.11 (range 0.37 to 3.23), and subsequently experienced an increase in the L/D ratios which continued through Week 6. At Week 8, the NTP L/D ratios declined, and became relatively stable at Week 11 and beyond. For postpartum women treated with NTP, side effect profiles should be carefully followed during the first 6 weeks after delivery as a clinical marker for elevation of serum levels. Since our highest L/D ratios for NTP occurred at Week 6, a serum level is recommended at this time. If the dose needs to be lowered to maintain a nontoxic level, a repeat serum level should be obtained at Week 11, at which time an increase in dose may be required.

Adult↗

Who gets alcoholic liver disease: nature or nurture?

The factors determining why fewer than 10% of drinkers develop advanced alcoholic liver disease remain largely unknown. There is a weak relationship between disease risk and the dose and pattern of alcohol consumed. Obesity increases the risk of all stages of alcoholic liver disease, probably reflecting the role of steatosis in the pathogenesis of more advanced disease. Women develop disease at a lower intake than men due, in part, to their lower volume of distribution for alcohol, but also potentially to increased gut permeability to endotoxin. Recent studies suggest a non-gender-linked genetic component to disease susceptibility and recent case-control studies have suggested that polymorphisms of genes encoding cytokines and other immunoregulatory molecules may exert a significant effect. The pattern of polymorphisms associated with risk suggests that antibody-mediated mechanisms play a role in disease pathogenesis. This has implications for treatment and for identifying high risk individuals at an early stage.

Adult↗

Blood pressure changes and oral contraceptive use: a study of 2676 black women in the southeastern United States.

Blood pressure (BP) and weight were measured on 2676 black women attending a large southeastern family planning clinic. Repeat measurements were made after a minimum of six and upt to 24 months on 673 women who continuously used nonhormonal contraceptive (OC) therapy, and 1390 women who continuously used OCs. The mean change in systolic blood pressure (SBP) adjusted for initial BP and change in per cent ideal body weight is +1.44 mmHg in the new users of OC. This slight increase in SBP is statistically significant (p = 0.04) relative to the +0.41 mmHg increase observed in the control group. However, the adjusted diastolic blood pressure (DBP) change (+0.46 mmHg in new OC users and +1.54 mmHg in the control group) fails to support the hypothesis of a greater increase in DBP in new OC users. The adjusted mean rise in mean arterial BP does not differ significantly between new OC users and the control group. The proportion of women developing a DBP greater than or equal to 90 mmHg during the average follow-up interval of one year is 2.4% in the control group, 1.0% in the new OC users and 0.2% in the continued OC users. These results provide evidence that OC use has no significant effect on the level of mean arterial BP in black women followed for 6-24 months; and fail to support the hypothesis of a causal relationship between OC use and elevated BP in black women.

Adolescent↗

Plasma lipoproteins and the incidence of abnormal excretion of albumin in diabetic American Indians: the Strong Heart Study.

Animal studies suggest that lipids are risk factors for kidney diseases. Some prospective studies and clinical trials have reported predictive effects of lipoproteins on different stages of diabetic nephropathy in humans. We examined lipoprotein abnormalities to determine if they predict abnormal urinary excretion of albumin (> or = 30 mg albumin/g creatinine), using logistic regression. We followed 671 American Indians (211 men, 460 women) with Type II diabetes for a mean of 3.9 years (range 1.7-6.2). Participants were aged 45-74 years. They had normal excretion of albumin and normal serum creatinine at baseline. 67 men and 144 women developed abnormal excretion of albumin. In models controlled for age, treatment with oral hypoglycaemic agents or insulin, HbA1c, study site, degree of Indian heritage, mean arterial blood pressure, albumin excretion at baseline and duration of diabetes, a high HDL cholesterol was a protector for abnormal excretion of albumin in women [odds ratio (OR) comparing the 90th with the 10th percentile = 0.56, 95% confidence interval (CI) = 0.32-0.98], but not in men (OR = 1.5, 95% CI = 0.66-3.4). Further adjustment for obesity, insulin concentration, alcohol consumption or physical activity did not change the results. There was a tendency for high values of VLDL and total triglyceride and small LDL size to predict abnormal excretion of albumin in women only. We conclude that low HDL cholesterol was a risk factor for abnormal excretion of albumin in women, but not in men. Sex hormones may be responsible for sex differences in the association between HDL cholesterol and abnormal excretion of albumin.

Aged↗

Are randomized trials of hormone replacement therapy in symptomatic women with breast cancer feasible?

OBJECTIVE: To evaluate the feasibility of conducting a large randomized trial of HRT in symptomatic women with early-stage breast cancer. DESIGN: Open randomized study. SETTING: Outpatient clinics at The Royal Marsden and St. George's Hospitals, London. PATIENT(S): One hundred postmenopausal women with early-stage breast cancer, experiencing vasomotor symptoms and/or vaginal dryness. INTERVENTION(S): Randomization (1:1) to HRT or no HRT for 6 months. MAIN OUTCOME MEASURE(S): Acceptance, continuance rates, and the reasons eligible women declined study entry. RESULT(S): Acceptance (38.8%) and continuance rates (>80%) were encouraging. The efficacy of HRT did not appear to be antagonized with concomitant tamoxifen. Seventy-five percent of women continued HRT after the study ended. Three women developed metastatic disease. Two used HRT. CONCLUSION(S): Despite informed consent, a national UK randomized trial of HRT should be feasible and has now been planned. Successful implementation necessitates the provision of information about HRT and the estrogen deficiency side effects of breast cancer therapy to health professionals and women with breast cancer.

Adult↗

Randomised trial of nitric oxide donor versus prostaglandin for cervical ripening before first-trimester termination of pregnancy.

BACKGROUND: Vaginal administration of the nitric oxide donor isosorbide mononitrate can induce effective ripening of the human cervix. We investigated whether this drug is associated with fewer side-effects than prostaglandins when used to ripen the cervix before first-trimester surgical termination of pregnancy, and assessed whether the extent of cervical ripening it induces is clinically sufficient. METHODS: 66 primigravid women scheduled for surgical termination were assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg or 80 mg, or the prostaglandin analogue gemeprost 1 mg. The primary measured outcome was onset of new symptoms before termination of pregnancy. FINDINGS: More women remained symptom-free after isosorbide mononitrate than after gemeprost (28/44 [64%] vs 3/22 [14%], p<0.005). Pretreatment with gemeprost resulted in abdominal pain in 73% of women and vaginal bleeding in 32% compared with 3% and 0%, respectively, after isosorbide mononitrate, whereas, more women developed headache after isosorbide mononitrate (27%) than after gemeprost (0%). Cervical resistance and measured intraoperative blood loss were lowest after pretreatment with gemeprost. The measured cervical resistance and intraoperative blood loss with either dose of isosorbide mononitrate did not differ from those in a comparison group of 22 parous women not in the randomised trial. INTERPRETATION: Pretreatment with isosorbide mononitrate to ripen the cervix before first-trimester termination of pregnancy is associated with fewer side-effects than gemeprost treatment and adequately decreases cervical resistance. Isosorbide mononitrate could be used as an alternative to gemeprost for this indication.

Abortifacient Agents, Nonsteroidal↗