Biomedical subjects

W M Leisenring

Publications and source records attributed to W M Leisenring.

8 recordsLinked to original sources

PubMed2004

Relationship of maternal plasma leptin and risk of pre-eclampsia: a prospective study.

OBJECTIVE: We measured maternal plasma leptin concentrations in 55 women with pre-eclampsia and 487 normotensive women to determine whether elevated leptin concentrations were associated with the occurrence of pre-eclampsia. METHODS: Maternal blood samples were collected at 13 weeks' gestation, on average. Plasma leptin concentrations were determined using immunoassay. Logistic regression procedures were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Leptin concentrations were 78% higher in cases than control subjects (median 34.6 vs. 19.5 ng/ml; p < 0.001). Relative to women with leptin concentrations of < 27.4 ng/ml, those with elevated leptin concentrations (> or = 27.4 ng/ml) experienced a 2.3-fold increased risk of pre-eclampsia (OR 2.3; 95% CI 1.1-4.6). We observed evidence of a strong linear component of trend in risk of pre-eclampsia with increasing maternal plasma leptin concentration. Each 10-ng/ml increase in leptin concentration was associated with a 30% increase in pre-eclampsia risk (OR 1.3; 95% CI 1.1-1.5). Overweight women with elevated leptin concentrations experienced the highest risk of pre-eclampsia (OR 6.4; 95% CI 3.1-13.2) as compared with lean women with no leptin elevations. CONCLUSION: Elevated plasma leptin concentration and maternal overweight status appear to be independently associated with an increased risk of pre-eclampsia.

Female↗

PubMed2001

Plasma concentrations of carotenoids, retinol, and tocopherols in preeclamptic and normotensive pregnant women.

This case-control study was conducted in Lima, Peru, from June 1997 through January 1998 to assess whether plasma concentrations of carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin), retinol, and tocopherols (alpha-tocopherol and gamma-tocopherol) are decreased in women with preeclampsia. A total of 125 pregnant women with preeclampsia and 179 normotensive pregnant women were included. Plasma concentrations of antioxidants were determined using high performance liquid chromatography. After adjusting for maternal demographic, behavioral, and reproductive characteristics and total plasma lipid concentrations, the authors found a linear increase in risk of preeclampsia with increasing concentrations of alpha-tocopherol (odds ratio of the highest quartile = 3.13; 95% confidence interval: 1.06, 9.23, with the lowest quartile as the reference group; p value of the test of linear trend = 0.040). The risk of preeclampsia decreased across increasing quartiles of concentrations for retinol (odds ratio of the highest quartile = 0.32; 95% confidence interval: 0.15, 0.69, with the lowest quartile as the reference group; p value of the test of linear trend = 0.001). Some of these results are inconsistent with the prevailing hypothesis that preeclampsia is an antioxidant-deficient state. Preliminary findings confirm an earlier observation of increased plasma concentrations of alpha-tocopherol among women with preeclampsia as compared with normotensive pregnant women.

Adolescent↗

PubMed2000

Respiratory distress syndrome and maternal birth weight effects.

OBJECTIVE: To study traditional risk factors and the intergenerational risk factor maternal low birth weight (LBW) for respiratory distress syndrome (RDS) in infants in multiple ethnic groups. METHODS: The population-based database consists of hospital records linked to Washington state maternal and infant vital records. Four racial-ethnic groups were studied, whites, blacks, Native Americans, and Hispanics. Poisson regression models were used to estimate relative risks of various factors for RDS. RESULTS: Rates for RDS were whites 1.2%, blacks 1.9%, Native Americans 1.3%, and Hispanics 1.0%. Maternal LBW was associated with increased relative risk (RR) for RDS in whites (2.6, 95% confidence interval [CI] 1.6, 4.2) and blacks (3.3, 95% CI 1.9, 5.6) for infants born vaginally. Compared with mothers of normal infants, birth weights of mothers of infants with RDS and delivered vaginally were significantly lower in whites, blacks, and Native Americans. The association of maternal LBW with RDS persisted in blacks even when multiple risk factors were added to the model (RR 2.4; 95% CI 1.1, 5.1). CONCLUSION: The association of maternal LBW with RDS is probably due in part to the association of maternal LBW with infant LBW and preterm birth. The strong persistent association of maternal LBW with RDS in blacks suggests that improvement of perinatal outcomes in that group will require improvement of long-term birth weight distribution.

Adult↗

PubMed1999

Pre-eclampsia disrupts the normal relationship between serum leptin concentrations and adiposity in pregnant women.

The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of < or = 25 kg/m2, pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, pre-eclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m2. Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and pre-eclamptic pregnancies.

Adipose Tissue↗

PubMed1999

A population-based cohort study of the relation between maternal birthweight and risk of gestational diabetes mellitus in four racial/ethnic groups.

Intrauterine growth retardation and low birthweight have been associated with an increased risk of insulin resistance and type II diabetes later in life. We hypothesised that maternal low birthweight is associated with an increased risk of gestational diabetes mellitus (GDM). Study subjects comprised women giving birth in Washington State between 1987 and 1995. Information for 21,528 births to non-Hispanic white women, 6359 to African-American women, 7456 to Native American women and 6496 to Hispanic women was available for analysis. All information was derived from statewide computerised vital records and hospital discharge summaries of obstetric and neonatal admissions with linkage to birth certificates of mothers. Maternal birthweight was collected from subjects' birth certificates. Information from both the birth certificates and the obstetric and neonatal admissions database was used to determine whether subjects developed GDM. Poisson regression models were estimated to calculate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for GDM by categories of maternal birthweight. The cumulative incidence of GDM among non-Hispanic white, African-American, Native American and Hispanic women was 2.8, 2.6, 2.7 and 3.0% respectively. After adjusting for maternal age, parity, cigarette smoking, history of chronic hypertension and participation in the Medicaid programme, non-Hispanic white women with a birthweight < 2000 g were 1.7 times more likely to have had their pregnancy complicated by GDM (RR = 1.7; 95% CI 0.8, 3.3) than those with a birthweight 3000-3999 g. The corresponding adjusted RRs for African-American, Native American, and Hispanic women were 2.8 [95% CI 1.2, 6.1], 3.1 [95% CI 1.2, 8.2] and 2.4 [95% CI 0.9, 6.0] respectively. Among African-American women, those with a birthweight > or = 4000 g also experienced a twofold increased risk of GDM (RR = 2.1; 95% CI 1.0, 4.1). This association of high birthweight and increased GDM risk was not found among women in the other three racial/ethnic groups. These findings suggest that individuals with low birthweight constitute a group at increased risk for GDM.

Adolescent↗

PubMed1998

Avascular necrosis following bone marrow transplantation: a case-control study.

The role of specific immunosuppressive agents in the development of avascular necrosis (AVN) following hematopoietic stem cell and solid organ transplantation remains unclear. To further explore this question, we conducted a case-control study of patients who underwent bone marrow transplantation (BMT) at the Fred Hutchinson Cancer Research Center. 96 of 1939 long-term survivors transplanted between May 1976 and October 1993 were identified as having AVN. Eight patients were excluded because AVN developed before transplant and one was excluded due to restrictions on reviewing follow-up records. The remaining 87 patients developed AVN a mean of 26.3 +/- 2 months posttransplant and were matched for age, gender, and date of transplant to other BMT recipients. Records were reviewed for corticosteroid and cyclosporine use, pretransplant conditioning with total body irradiation (TBI), and other information including disease for which the transplant was indicated, type of transplant, the occurrence of acute and chronic graft-vs.-host disease, and steroid use prior to transplant. Adjusted odds ratios (ORs) were obtained from conditional logistic regression for 87 matched pairs. Posttransplant steroid use was a risk factor for the occurrence of AVN (adjusted OR, 14.4; 95% CI, 2.8-73.2), with the greatest risk associated with those receiving steroids at the time of diagnosis of AVN (adjusted OR, 31.9; 95% CI, 4.4-248.9). There was no further increasing risk associated with increasing duration of steroid use. Conditioning with TBI was also associated with the occurrence of AVN (adjusted OR, 3.2; 95% CI, 1.1-9.7); however, cyclosporine was not a risk factor for AVN (adjusted OR, 0.5; 95% CI, 0.1-1.9). Our results support the hypothesis that AVN following BMT has a strong association with the administration of corticosteroids. TBI may be an additional risk factor, and cyclosporine does not appear to contribute to an increased incidence of AVN.

Adult↗

PubMed1996

A biologically-based dose-response model for developmental toxicology.

The methods currently used to evaluate the risk of developmental defects in humans from exposure to potential toxic agents do not reflect biological processes in extrapolating estimated risks to low doses and from test species to humans. We develop a mathematical model to describe aspects of the dynamic process of organogenesis, based on branching process models of cell kinetics. The biological information that can be incorporated into the model includes timing and rates of dynamic cell processes such as differentiation, migration, growth, and replication. The dose-response models produced can explain patterns of malformation rates as a function of both dose and time of exposure, resulting in improvements in risk assessment and understanding of the underlying mechanistic processes. To illustrate the use of the model, we apply it to the prediction of the effects of methylmercury on brain development in rats.

Abnormalities, Drug-Induced↗

PubMed1994

Increased birth weights of National Wilms' Tumor Study patients suggest a growth factor excess.

An analysis of over 1800 patients with Wilms' tumor revealed significantly higher birth weights than newborns in the general United States population. The highest birth weights were found not only in patients diagnosed with the Beckwith-Wiedemann syndrome (mean, 3.78 kg), as had been expected, but also in those with hemihypertrophy (3.80 kg) or perilobar nephrogenic rests (3.56 kg) in addition to their Wilms' tumor. The birth weights of Wilms' tumor patients with intralobar nephrogenic rests (3.43 on average kg) and of those without associated anomalies (3.45 kg) were slightly but still significantly higher on average than national birthweights (overall mean, 3.35 kg) adjusted for gender, race, and year of birth in each subgroup. Birth weights of children with aniridia and Wilms' tumor (2.99 kg) were lower than the national mean. Among more than 3000 patients with Wilms' tumor, heights and weights at diagnosis were significantly higher for the subgroups of patients with Beckwith-Wiedemann syndrome or hemihypertrophy, and height was lower for those with aniridia or characteristic genitourinary anomalies, when compared to other patients with Wilms' tumor. These data suggest prenatal effects of growth factors on the development of Wilms' tumors, or vice versa, and provide further epidemiological support for heterogeneity in the pathogenesis of Wilms' tumors associated with perilobar nephrogenic rests versus intralobar nephrogenic rests.

Beckwith-Wiedemann Syndrome↗