Bioavailability of oral vs. subcutaneous low-dose methotrexate in patients with Crohn's disease.

BACKGROUND: Oral methotrexate and folic acid are partly absorbed by a common intestinal transporter. AIM: : To determine the relative bioavailability of oral low-dose methotrexate administered with and without concomitant folic acid vs. subcutaneous administration in patients with stable Crohn's disease. METHODS: Ten patients were randomized to receive their regular maintenance dose of methotrexate (15-25 mg) for three consecutive weeks: orally, orally with 5 mg folic acid or subcutaneously. Blood samples were drawn at specified intervals during 24 h, and methotrexate levels were determined by fluorescence immunoassay. Areas under the curve extrapolated to infinity (AUC infinity ) were compared between the three routes. RESULTS: The geometric mean AUC infinity values (95% confidence intervals) were 360 nmol x h/L (301-430 nmol x h/L), 261 nmol x h/L (214-318 nmol x h/L) and 281 nmol x h/L (209-377 nmol x h/L) per milligram of methotrexate administered for subcutaneous, oral and oral with folic acid administration, respectively (P < 0.05 and P < 0.01 for oral with folic acid and oral vs. subcutaneous administration, respectively). The geometric mean relative bioavailabilities (95% confidence intervals) were 0.73 (0.62-0.86) and 0.77 (0.60-0.99) for oral and oral with folic acid administration, respectively (difference not significant). CONCLUSIONS: In patients with stable Crohn's disease, the oral bioavailability of methotrexate is highly variable and averages 73% of that of subcutaneous administration. Concomitant folic acid has no significant effect on the bioavailability. Dose adjustments based on individual pharmacokinetic assessment should be considered when switching patients from parenteral to oral therapy.

Early postpartum discharge: how are mothers managing?

OBJECTIVE: To describe maternal concerns at 2 weeks and mothers' ability to function in various roles at 4 weeks postpartum. DESIGN: Subjects were mailed questionnaires at 2 and 4 weeks postpartum. SETTING: A mid-Atlantic hospital that is a part of an academic health center. PARTICIPANTS: A convenience sample of 100 healthy women who were discharged < or = 48 hours postpartum and met the study criteria. MAIN OUTCOME MEASURES: Instruments included a demographic questionnaire, the Maternal Concerns Questionnaire, and the Inventory of Functional Status After Childbirth. RESULTS: Physiologic concerns during the early postpartum period related primarily to perineal sutures, breast care, body image, and fatigue. More than 25% of the women continued to experience depression at 2 weeks, and 40% had days at 1 month when they never got dressed. Much concern was expressed about the mothering role but little about interaction with the mate. Older maternal age was associated with a longer hospital stay, and the trend suggested improved functioning at 1 month with longer hospitalization. More than half of the participants said they would visit a nurse-run clinic during the 1st postpartum week if given the opportunity. CONCLUSIONS: The results provide descriptive information about effects of early hospital discharge. Mothers discharged in 48 hours or less adjust to motherhood without the education and assessment that was formerly possible with extended hospitalization. The current study reinforces the need for nurses to explore strategies in hospitals or communities to provide early care for postpartum mothers.

Decrease in birth weight in relation to maternal bone-lead burden.

OBJECTIVES: Birth weight predicts infant survival, growth, and development. Previous research suggests that low levels of fetal lead exposure, as estimated by umbilical cord blood-lead levels at birth, may have an adverse effect on birth weight. This report examines the relationship of lead levels in cord blood and maternal bone to birth weight. METHODS: Umbilical cord and maternal venous blood samples and anthropometric and sociodemographic data were obtained at delivery and 1-month postpartum. Blood-lead levels were analyzed by atomic absorption spectrophotometry. Maternal tibia and patella lead levels were determined at 1-month postpartum with use of a spot-source 109Cd K-X-ray fluorescence instrument. The relationship between birth weight and lead burden was evaluated by multiple regression with control of known determinants of size at birth. RESULTS: Data on all variables of interest were obtained for 272 mother-infant pairs. After adjustment for other determinants of birth weight, tibia lead was the only lead biomarker clearly related to birth weight. The decline in birth weight associated to increments in tibia lead was nonlinear and accelerated at the highest tibia lead quartile. In the upper quartile, neonates were on average, 156 grams lighter than those in the lowest quartile. Other significant birth weight predictors included maternal nutritional status, parity, education, gestational age, and smoking during pregnancy. CONCLUSIONS: Our results indicate that bone-lead burden is inversely related to birth weight. Taken together with other research indicating that lead can mobilize from bone into plasma without detectable changes in whole blood lead, these findings suggest that bone lead might be a better biomarker than blood lead. Because lead remains in bone for years to decades, mobilization of bone lead during pregnancy may pose a significant fetal exposure with health consequences, long after maternal external lead exposure has declined.

Successful use of a chicken-based diet for the treatment of severely malnourished children with persistent diarrhea: a prospective, randomized study.

OBJECTIVE: To evaluate the efficacy of a chicken-based diet for the treatment of persistent diarrhea in severely malnourished children. STUDY DESIGN: Prospective, randomized, double-blind study that compared a chicken-based diet with elemental (Vivonex) and soy (Nursoy) diets. Hospitalized children with third-degree malnutrition and persistent diarrhea, aged 3 to 36 months, were included. Diets were isocaloric and given nasogastrically at 150 ml/kg per day in progressively increasing concentrations. RESULTS: Fifty-six children were included (18 received Vivonex, 19 Nursoy, 19 chicken). They had a mean age of 6.4 +/- 4.4 months, a mean weight of 3604 +/- 1232 gm, and a mean weight-for-age percentage of 51.4% +/- 7.2%. Sixty-four percent had associated conditions on admission to the hospital. Forty-one children (73.2%) were successfully treated (13 Vivonex, 13 Nursoy, 15 chicken). There were no differences in diarrheal outcomes, and all groups had significant weight gain. Failure was independent of the diet and was associated with the presence of infection on admission. There was a significantly higher nitrogen balance in the children from the chicken group (358.2 +/- 13 mg/kg per day) than in those receiving Vivonex (226.6 +/- 61) or Nursoy (291-4 +/- 111.6; p < 0.05) groups. CONCLUSIONS: The chicken-based diet was as effective as Vivonex or Nursoy. It is well tolerated, inexpensive, and widely available and thus represents an effective and inexpensive alternative to the treatment of severely malnourished children with persistent diarrhea.

Dietary and environmental determinants of blood and bone lead levels in lactating postpartum women living in Mexico City.

Despite the recent declines in environmental lead exposure in the United States and Mexico, the potential for delayed toxicity from bone lead stores remains a significant public health concern. Some evidence indicates that mobilization of lead from bone may be markedly enhanced during the increased bone turnover of pregnancy and lactation, resulting in lead exposure to the fetus and the breast-fed infant. We conducted a cross-sectional investigation of the interrelationships between environmental, dietary, and lifestyle histories, blood lead levels, and bone lead levels among 98 recently postpartum women living in Mexico City. Lead levels in the patella (representing trabecular bone) and tibia (representing cortical bone) were measured by K X-ray fluorescence (KXRF). Multivariate linear regression models showed that significant predictors of higher blood lead included a history of preparing or storing food in lead-glazed ceramic ware, lower milk consumption, and higher levels of lead in patella bone. A 34 micrograms/g increase in patella lead (from the medians of the lowest to the highest quartiles) was associated with an increase in blood lead of 2.4 micrograms/dl. Given the measurement error associated with KXRF and the extrapolation of lead burden from a single bone site, this contribution probably represents an underestimate of the influence of trabecular bone on blood lead. Significant predictors of bone lead in multivariate models included years living in Mexico City, lower consumption of high calcium content foods, and nonuse of calcium supplements for the patella and years living in Mexico City, older age, and lower calcium intake for tibia bone. Low consumption of milk and cheese, as compared to the highest consumption category (every day), was associated with an increase in tibia bone lead of 9.7 micrograms Pb/g bone mineral. The findings of this cross-sectional study suggest that patella bone is a significant contributor to blood lead during lactation and that consumption of high calcium content foods may protect against the accumulation of lead in bone.

Survey results: academic courses of women's health across the lifespan.

1. Today's college women are older than college women of 10 or 20 years ago; women's health courses must reflect this demographic change. 2. An awareness of older women's health concerns must be an essential component of any women's health course. 3. Nurses' preparation and traditional advocacy roles make them ideal to teach women's health courses.

Women at midlife. The transition to menopause.

The advantage over men that women experience in life expectancy does not extend to morbidity. Although women live on average approximately 7 years longer than men, their later years are often filled with medical problems. Much is currently known that could influence and effect improved health for women. Menopause is not a dramatic event that signals an abrupt change in the health and well-being of women. Rather, it is a transitional time of perhaps a 25-year span when estrogen production gradually declines and results in a variety of bodily changes. Concurrent with the hormone changes are other effects of the normal cycle of aging. Comprehensive multidisciplinary health care clinics for adult women have the potential to provide health services that women seek.

Ownership of research data.

The author reviews the conventional "works for hire" principle that an institution, not its employees, owns the rights to its employees' written products or other forms of expression, including primary research data. This principle is not open to debate as a legal matter. The tough problems giving rise to debates regarding data ownership and access are ethical problems rather than legal ones; these will remain unsettled for some time because at present there is no consensus concerning what constitutes ethical conduct among scholars and scientists and how seriously and in what manner to penalize breaches of that conduct. Access to data is a thorny issue; case histories illustrate the legal and ethical difficulties involved in questions of who has access to information compiled in the course of academic inquiry, and for what purpose. Much depends on the ethics and established procedures of the employing institution, but current case law suggests that a faculty member or institutional researcher does not have any legal right to review the data developed by a colleague. The author recommends that institutions clearly state their policies regarding ownership of data, and presents guidelines for such a policy.

Predicting paternal involvement with a newborn by attitude toward women's roles.

Significant change in the social roles played by American women has occurred during the past two decades. Recent research literature suggests, however, that attitudinal change may be lagging significantly behind the profound changes in behavior. The purpose of this research was to investigate whether expectant couples who hold more egalitarian views toward women's roles prior to the birth of a first child expect the new father to be more involved in the care of his own infant. A demographic questionnaire, the Attitudes Toward Women Scale (Spence & Helmrich, 1972), and the Projected Paternal Behavior Scale (Alter, 1978) were administered to 103 prenatal couples between the sixth and eighth months of pregnancy. Findings confirmed a significant correlation between both expectant fathers' and expectant mothers' egalitarian views toward women's roles and their projections of the father's participation in the care of his infant. More liberal attitudes toward women's roles were also associated with increased age, higher combined family income, and increased levels of education.

How safe is exercise during pregnancy?

Increasing numbers of women include exercise even during pregnancy as an essential part of their daily routines. Because of the additional physiological demands imposed by pregnancy, health-care practitioners must determine whether or not aerobic exercise is, in fact, healthy for the expectant mother and developing fetus. This article examines whether or not the traditional advice that women receive regarding exercise during pregnancy is supported by the existing scientific literature.

Expectant father's stress--due to the mother's expectations?

Despite the increased attention to the role of the father in the childbearing family, relatively little is known of those factors that facilitate or hinder the transition to parenthood. To study the relationship between stress in the prospective father and congruence of attitudes between husband and wife regarding the projected role of the father with the newborn, 103 prenatal couples were studied. Results supported the position that anxiety in the father increased as discordance between husband and wife increased regarding the projected father role. No relationship was found between anxiety and the amount of projected involvement by the father in child care.

Cellular bases of the production of and response to interleukin-2 in man: role of autologous rosette-forming T-cell subsets defined with monoclonal antibodies.

In this paper we present experiments that indicate that, in man, most T-cell subpopulations produce interleukin-2 (IL-2), but that the main cell subpopulation which produces it, both upon activation with phytohaemagglutinin or in autologous mixed lymphocyte cultures, is that of autologous rosette-forming (Tar) T4+ T cells. Conversely, the main IL-2-responding T-cell subpopulation is that composed of T cells depleted of Tar (T-Tar) that are T8+. IL-2 was also found to be more effectively produced by Tar cells that do not bind peanut agglutinin (PNA) than by those that do. The PNA-T4+Tar cells were also found to respond best to interleukin-1 (IL-1).

Effect of pregnancy on functions of circulating T cells from patients with systemic lupus erythematosus: correction of T-cell suppression and autologous mixed-lymphocyte responses.

Pregnant systemic lupus erythematosus (SLE) patients with inactive disease were found to have normal spontaneously generated suppressor-cell function and slightly higher concanavalin A-induced suppressor function as compared to matched normal pregnant and nonpregnant females. In six SLE patients studied sequentially throughout pregnancy and postpartum, suppressor functions were found to fall sharply within the first week after delivery. One of these patients had been studied before she became pregnant and found to have a decreased suppressor function. Nonpregnant SLE patients had both suppressor functions diminished despite their disease being similarly inactive. This group was also the only one to have decreased responses in autologous mixed-lymphocyte cultures. Both pregnant and nonpregnant SLE patients had decreased absolute numbers of total lymphocytes, T cells, and their subpopulations, but the proportions of these cells were similar in all four groups. Despite this apparent normalcy of immune regulation, pregnant SLE patients had higher levels of Clq-binding immune complexes than did nonpregnant ones. Functional T-cell abnormalities found in SLE patients tend to be corrected by pregnancy. This may explain in part the disease remissions that occur in them during the second half of pregnancy.

Abnormalities in the content of nucleic acids of peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

We have completed 59 cytofluorographic studies of DNA/RNA content in acridine orange-stained peripheral blood mononuclear cells from 44 patients with systemic lupus erythematosus, most of whom received no medications. Most such cells were in resting phases of the cell cycle, particularly those from patients with inactive disease. Nine patients with systemic lupus erythematosus had increased percentages of these cells in the synthesis and postsynthesis phases of the cell cycle; the B lymphocyte had a greatest proportions of activated cells. In 11 patients, we found that cells, particularly T lymphocytes, had increased RNA content without a proportional increase in DNA. This DNA block occurred primarily in patients with serum antibodies to DNA and it could be reproduced in normal mitogen-stimulated mononuclear cells incubated in heat-inactivated sera from patients with systemic lupus erythematosus whose own cells showed abnormalities of DNA/RNA content or in purified native DNA antibody. The DNA blocking potential of the DNA antibody was dependent on its Fc portion and on the presence of Fc receptors on T cells. Thus, saturation of Fc receptors by pretreatment with aggregated IgG or incubation with the whole antibody in the cold prevented the DNA block, indicating that it was an active process.