Since the early 1950s clinicians have been concerned about the impact of pregnancy on malignant melanoma (MM). Case reports and case series described a grave prognosis for women diagnosed with MM during pregnancy. Today MM in pregnancy takes on enhanced significance as more women delay childbearing into their 30s and 40s, and the incidence of MM during pregnancy may be expected to increase. In addition, relative immunosuppression during pregnancy theoretically may favor the potential for MMs to behave more aggressively. This article compiles the most recent clinical, epidemiologic, and laboratory studies to guide clinicians in addressing the issue of melanoma in pregnancy. Herein we address the prognosis, characteristics, evaluation, treatment, and how to counsel women diagnosed with MM during pregnancy, including the potential consequences for the fetus. Overall, our analysis reveals that there is no effect on survival in women diagnosed with localized MM during pregnancy; likewise, pregnancies prior or subsequent to a diagnosis of MM do not impact prognosis. Strong epidemiologic evidence shows no enhanced risk of developing MM associated with oral contraceptive pill use. Although a smaller number of studies have addressed hormonal replacement therapy and risk of MM, these studies do not suggest a higher risk of MM. As for the fetus, risk of metastasis to the placenta and/or fetus is extremely low, and seems to occur exclusively in women with widely metastatic MM.
Acanthosis nigricans is a lesion affecting localized areas of the skin in persons with obesity and/or hyperinsulinemia. Roughening of the skin correlates with histological papilomatosis and the apparent darkening is due to hyperkeratosis. Biochemical mechanisms for developing this hyperplastic lesion are unclear, but likely involve local cutaneous growth factors. Cross sectional surveys of unselected populations have demonstrated that young children have low prevalences of obesity and acanthosis nigricans, but the prevalences of both increase with increasing age until plateaus are reached after the age of ten. Nearly 40% of Native American teenagers have acanthosis nigricans, whereas about 13% of African American, 6% of Hispanic, and less than 1% of white, non-Hispanic children aged 10-19 have clinically apparent acanthosis nigricans. We conclude that the presence of this skin lesion is a clinical surrogate of laboratory-documented hyperinsulinemia. Acanthosis nigricans identifies a subgroup within an ethnic group who have the highest insulin concentration, the most severe insulin resistance, and thus the highest risk for the development of type 2 diabetes.
Routine clinical pharmacokinetic data collected prospectively from pediatric patients receiving theophylline were analyzed using the NONMEM (nonlinear mixed effects model) digital computer program. A total of 314 measured serum theophylline concentrations (STCs) were obtained from 84 hospitalized patients ranging in age from 4 months to 15.2 years with the majority of patients between the ages of 1 and 8 years. Fifty-six percent were male. The race/ethnicity distribution was 71.4% Latin, 15.5% black, 11.9% Caucasian, and 1.2% (one subject) Pakistani. Of the total number of observed STCs, 16.2% reflected some degree of outpatient dosing. The pharmacokinetic model used was a one-compartment open model with either zero-order or first-order absorption and first-order elimination. Age was the most important determinant of theophylline clearance (Cl); weight was inferior to age and did not statistically improve the model (p greater than 0.005) when combined with age. Total Cl increased by 10%/year over the age range of 1 to 15 years of age. Black race and male gender were associated with higher Cl values: for a given age, Cl was 34% higher for blacks than the reference population composed of the remaining patients, and Cl for males was 25% higher than that for females. The volume of distribution (Vd) for the population was estimated to be 0.62 L/kg. The interindividual variability in Cl and Vd expressed as coefficients of variation were 19 and 28%, respectively. The residual intraindividual error variance corresponded to a standard deviation of 2.8 micrograms/ml. The STCs that represented some degree of outpatient dosing were 21% lower than those reflecting only inpatient dosing. Alternate models that include weight as a determinant of theophylline clearance are also provided. The NONMEM method of determining population pharmacokinetics is well suited to the pediatric population since it does not require a large number of STCs per patient. In this study a mean of only 3.7 STCs per patient were utilized to provide information which should prove useful in the design and adjustment of theophylline dosage regimens in children.
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