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Objective: This study prospectively evaluated the longitudinal changes in insulin sensitivity, insulin response, and endogenous (primarily hepatic) glucose production and suppression during insulin infusion in women with normal glucose tolerance (control) and gestational diabetes mellitus before and during a planned pregnancy.Study Design: Eight control subjects and 7 subjects in whom gestational diabetes mellitus developed were evaluated with an oral glucose tolerance test, an intravenous glucose tolerance test, and hyperinsulinemic-euglycemic clamp with infusion of [6,6 (2)H2 ]glucose before conception and at 12 to 14 and 34 to 36 weeks' gestation. Insulin response was estimated as the area under the curve during the intravenous glucose tolerance test. Basal endogenous glucose production was estimated from isotope tracer dilution during steady state with [6,6 (2)H2 ]glucose and suppression during insulin infusion. Insulin sensitivity to glucose was defined as the glucose infusion rate required to maintain euglycemia during steady-state insulin infusion. Body composition was estimated with hydrodensitometry. Data were analyzed with 2-way analysis of variance with repeated measures for 2 groups.Results: There were increases in first-phase (P =.006) and second-phase (P =. 0001) insulin responses in both groups with advancing gestation, but the increase in second-phase response was significantly greater (P =. 02) in the gestational diabetes mellitus group than in the control group. Basal glucose production increased significantly (P =.0001) with advancing gestation, and there was resistance to suppression during insulin infusion in both groups (P =.0001). There was less suppression of endogenous glucose production however, in the gestational diabetes mellitus group than in the control group (P =. 01). Insulin sensitivity decreased with advancing gestation in both groups (P =.0001), and there was lower insulin sensitivity in the gestational diabetes mellitus group than in the control group (P =. 04). Significant decreases in insulin sensitivity with time (P =. 0001) and between groups (P =.03) remained when the data were adjusted for differences in insulin concentration or residual hepatic glucose production.Conclusion: Obese women in whom gestational diabetes mellitus develops have a significant increase in insulin response but decreases in insulin sensitivity and suppression of hepatic glucose production during insulin infusion with advancing gestation with respect to a matched control group. These metabolic abnormalities in glucose metabolism are the hallmarks of type 2 diabetes, for which these women are at increased risk in later life. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the longitudinal changes in energy expenditure and body composition in relationship to alterations in carbohydrate metabolism in women with normal and abnormal glucose metabolism. We hypothesized that women with decreased insulin sensitivity before conception would have less fat accretion and smaller increases in energy expenditure.Study Design: Six women with normal glucose tolerance and 10 women with abnormal glucose tolerance were evaluated before conception, and in early (12 to 14 weeks) and late (34 to 36 weeks) gestation. Body composition was estimated by hydrodensitometry, resting energy expenditure, and glucose and fat metabolism by indirect calorimetry, endogenous glucose production by infusion of [6-6 2H2] glucose, and insulin sensitivity using a hyperinsulinemic-euglycemic clamp (40 mU/m2/min).Results: There was a smaller increase in fat mass (1.3 kg [P = .04]) in early pregnancy in women with abnormal glucose tolerance before pregnancy. Indirect calorimetry measured gestational age-related increases in basal oxygen utilization, with or without correction for fat-free mass (VO2, P = .002), resting energy expenditure (expressed in kilocalories, P = .0001), and carbohydrate oxidation (P = .0003). The insulin-mediated elevation in VO2 increased in later gestation VO2 (P = .005), as did resting energy expenditure (P = .0001) and fat oxidation (P = 0.0001). However, there was a decrease in respiratory quotient (P = .0001), carbohydrate oxidation (P = .002), and nonoxidative carbohydrate metabolism (P = .0001) with advancing gestation during insulin infusion. In early pregnancy, changes in fat mass correlated inversely with changes in insulin sensitivity (r= -0.52, P = .04) and changes in basal VO2 correlated inversely with decreases in basal endogenous glucose production (r = -0.74, P = .01).Conclusion: In early gestation, the changes in maternal fat mass and basal oxygen consumption are inversely related to the changes in insulin sensitivity. This response in lean women with decreased insulin sensitivity before conception may have survival value by providing a larger amount of available substrate to meet fetoplacental needs during gestation. [ABSTRACT FROM AUTHOR]

Objective: Terbutaline, a selective beta2-agonist, is a frequently used tocolytic known to affect maternal metabolism. The purpose of this study was to evaluate the effect of oral terbutaline on maternal glucose metabolism and energy expenditure.Study Design: Six healthy pregnant women with normal glucose tolerance were evaluated between 30 and 34 weeks' gestation. Oral terbutaline was administered to determine the effects on hepatic glucose production with [6-6(2)H2] glucose tracer, insulin sensitivity (hyperinsulinemic-euglycemic clamp), and energy expenditure (indirect calorimetry). Terbutaline, insulin, and glucagon levels were also obtained. Subjects were randomly assigned to either oral terbutaline 5 mg every 6 hours for 24 hours or no medication. Repeat studies were conducted 1 week apart, each subject serving as her own control.Results: In the basal state terbutaline was associated with a trend toward increased basal glucose levels (81.6 +/- 6.6 vs 93.7 +/- 12.0 mg/dl, p = 0.06) but no significant increase in hepatic glucose production (3.2 +/- 0.3 vs 3.6 +/- 0.4 mg/kg fat-free mass/min, p = 0.23). However, there was a significant increase in basal insulin concentration (17.6 +/- 9.2 vs 25.6 +/- 10.4 microU/ml, p = 0.02). There was a 28% decrease in insulin sensitivity as measured by the glucose infusion rate during the euglycemic clamp plus residual hepatic glucose turnover (5.78 +/- 1.91 vs 4.16 +/- 1.49 mg/kg fat-free mass/min, p = 0.005). Glucagon concentration was significantly decreased both in the basal state (163 +/- 26 vs 144 +/- 27 pg/ml, p = 0.0007) and during the clamp (144 +/- 27 vs 133 +/- 27 pg/ml, p = 0.003). Basal oxygen consumption increased 9% (270 +/- 49 vs 294 +/- 50 ml oxygen/min, p = 0.007) and caloric expenditure 14% (1.32 +/- 0.23 vs 1.50 +/- 0.31 kcal/min, p = 0.025) or 260 kcal/day with terbutaline.Conclusion: Decreased peripheral insulin sensitivity, and to a lesser degree increased endogenous glucose production, may represent the pathophysiology of abnormal glucose tolerance observed in many women treated with oral terbutaline. Common side effects such as tremors and tachycardia experienced by many women on a regimen of terbutaline are consistent with our finding of a significant increase in basal energy expenditure. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to examine the pattern of growth of both fetal lean body mass incorporating bone, brain, and muscle and subcutaneous fat mass during the course of normal pregnancy. We hypothesized that there are detectable differences in the accretion of fat versus lean body mass.Study Design: To establish our method we correlated standardized cross-sectional ultrasonographic images of the fetal extremities with anthropometric assessment of neonatal body composition in 25 subjects. Subsequently 36 nonsmoking women with normal prepregnancy body mass index, normal glucose screening results, and no medical or obstetric complications were recruited. We performed 135 ultrasonographic examinations between 19 and 40 weeks' gestation (mean 3.8 scans per fetus, range 2 to 6) at 4-week intervals. Lean body mass measures included biparietal diameter, head circumference, and femur length. Fetal subcutaneous fat and lean body mass were examined both in the mid upper arm and midthigh by standardized cross-sectional images. All neonates were born between 37 and 42 weeks' gestation and had normal birth weight distribution. Stepwise regression analysis established best-fit equations for fetal measurements obtained ultrasonographically. Independent variables included gestational age, maternal age, weight gain in pregnancy, parity, fetal gender, and maternal prepregnancy weight.Results: Fetal bone growth was best described by a second-order quadratic equation demonstrating deceleration with advancing gestational age (p < 0.0001, R2 0.92 to 0.96). A quadratic equation that accelerates with advancing gestation best described lean body mass accretion in the extremities (p < 0.0001, R2 = 0.85 to 0.86). Fetal fat deposition in the extremities was characterized by an accelerating quadratic equation when plotted against gestational age with maternal age and prepregnancy weight contributing significantly (p < 0.0001, R2 = 0.80 to 0.81).Conclusion: Consistent with our hypothesis, fetal fat and lean body mass demonstrate unique growth profiles. We speculate that, as a result of an accelerated rate of growth in late gestation, the measurement of fetal fat will provide a more sensitive and specific marker of abnormal fetal growth when compared with index values of lean body mass. [ABSTRACT FROM AUTHOR]

South Asians who immigrate to the United States have a propensity toward insulin resistance, central obesity, and elevated total cholesterol:high-density lipoprotein (HDL) ratio. To evaluate whether these alterations are apparent at a younger age, we studied 32 offspring of South Asian immigrants and compared them with 29 of European descent between 18 to 30 years of age. American-born South Asian males had significantly higher total cholesterol, low-density lipoprotein (TC:LDL) ratios, triglycerides, and fasting insulin levels (13.9 +/- 7.1 and 10.0 +/- 5.5 microU/mL, P <.01) than their European counterparts. The South Asian females only had increased plasma insulin levels (15.3 +/- 8.8 and 10.0 +/- 5.1 microU/mL, P =.05). The entire South Asian group had higher truncal skinfold thickness (40.1 +/- 18.1 and 30.3 +/- 12.6 mm, P = <.05) and lower insulin-like growth factor binding protein (IGFBP)-1 levels (46.8 +/- 33.4 and 56.0 +/- 33.4 microg/L, P =.05). Plasma leptin levels were also significantly higher in both males (4.3 +/- 2.5 v 2.8 +/- 1.3 ng/mL, P =.0001) and females (20.5 +/- 10.3 v 10.3 +/- 6.3 ng/mL, P =.002) South Asian subjects. A significant correlation between plasma leptin and insulin, triglycerides, TC, and body mass index (BMI) was seen in the South Asian males. South Asians born in the United States show evidence for an altered metabolic profile in young adulthood. The relative contributions of inheritance and nutritional practices early in life to this alteration remain unclear., (Copyright 2001 by W.B. Saunders Company)

Objective: To construct a model to estimate maternal body composition in late gestation using anthropometric measurements., Methods: Twenty healthy pregnant women at 30 weeks' gestation had estimates of body composition using hydrodensitometry, with corrections for residual lung volume, and total body water using H(2)(18)O (development group). Total body water was estimated from (18)O abundances measured by gas-isotope-ratio mass spectrometry. Maternal age, height, weight, and seven skinfold sites were correlated with fat mass using stepwise regression analysis. The anthropometric model to estimate fat mass was then tested prospectively in a second group of 20 subjects and correlated with underwater weighing and total body water measurements (validation group). Statistical analysis used chi(2), paired t and Wilcoxon sign-rank tests., Results: There were no statistically significant differences in maternal demographics between groups. The fat mass of development group subjects using underwater weighing and total body water was 22.7 +/- 7.6 kg. Using the development group, a model was derived that explained 91% of the variance in fat mass by underwater weighing and total body water using maternal weight and triceps, subscapular, and suprailiac skinfolds (r(2) = 0.91, P <.001). When tested prospectively in the validation group, the correlation remained statistically significant (r(2) = 0.89, P <.001). There was no statistically significant (P =.88) difference between the anthropometric estimates of fat mass and underwater weighing and total body water measurements (95% confidence interval -2.476, 2.748 kg of fat mass)., Conclusion: This anthropometric model can be used to predict maternal fat mass in late gestation.

Despite many recent studies on breast implant rupture, there is no general consensus on causation or incidence. Existing studies have not reported a multivariate analysis of risk factors associated with breast implant rupture. Most studies lack adequate sample size to study the effect of implant type, manufacturer, and other patient-related factors that might affect rupture. This study addresses all of these shortcomings. Patients undergoing implant removal by a single surgeon between 1990 and 1996 were examined for rupture and for 16 potential risk factors. The association between rupture and various factors was analyzed by univariate and multivariate analyses. A total of 842 patients underwent removal of 1619 implants. Increasing age of implant [p < 0.0001; adjusted odds ratio (OR), 1.20; 95% confidence interval (CI), 1.15 to 1.23], retroglandular location (p = 0.0002; OR, 1.93; CI, 1.37 to 2.71), Baker contracture grades III and IV (p = 0.005; OR, 1.52; CI, 1.14 to 2.03), and presence of local symptoms (p = 0.05; OR, 1.37; CI, 1.00 to 1.89) were associated with rupture. When different implant types were compared with smooth gel implants, after adjustment, double-lumen (p < 0.0001; OR, 0.33; CI, 0.22 to 0.50) and polyurethane-covered implants (p < 0.0002; OR, 0.33; CI, 0.20 to 0.57) had significantly lower rupture rates. When various manufacturers were compared with Dow Corning after adjusting for other factors, rupture rates were significantly lower for McGhan (p < 0.0001; OR, 0.41; CI, 0.26 to 0.65), whereas higher for Surgitek (p < 0.019; OR, 1.52; CI, 1.05 to 2.18). Significant risk factors for breast implant rupture were identified: older implants, retroglandular implant location, implant contracture, local symptoms, certain implant type, and certain manufacturer. Although the results of this study are based on a nonrandomized explant population from a single surgeon's practice, knowledge of these risk factors will permit better interpretation of future data on rupture. The knowledge will enable the medical community to better advise their breast implant population regarding durability and appropriate time for removal or replacement.

Prostate cancer (PCA), the most commonly diagnosed cancer in males in the United States, is the second leading cause of cancer-related deaths of males in this country. Because of the poor success rate in the treatment of PCA, an intervention at an early stage may reduce the progression of small carcinoma to large metastatic lesion, thereby reducing PCA-related deaths. Concerted efforts are needed to establish mechanism-based approaches to develop: (a) the markers for early detection of the disease as well as toward monitoring the efficacy of treatment(s); and (b) novel chemopreventive strategies against PCA. Using unique samples of pair-matched benign and cancer tissue obtained from the same PCA patient, we showed that ornithine decarboxylase (ODC) activity is significantly (P < 0.001) elevated in PCA (1142 +/- 100; mean +/- SE) than in paired benign tissue (427 +/- 51; mean +/- SE). The immunoblot analysis also showed a significant elevation in the protein expression of ODC in the PCA tissues as compared with the paired benign tissue. Furthermore, our data showed that the ODC activity in the prostatic fluid obtained by a digital rectal massage from the patients with PCA (3847 +/- 162; mean +/- SE) was significantly higher than in the patients with benign prostatic hyperplasia (2742 +/- 167; mean +/- SE) or normal individuals (1244 +/- 67; mean +/- SE). This observation might be of significance because the prostatic fluid could be obtained noninvasively by digital rectal massage. We suggest that ODC could serve as a target for early detection of human PCA as well as for monitoring the efficacy of treatment(s). The development of ODC as a target for novel chemopreventive strategies against PCA is an intriguing possibility.

Background: The RET proto-oncogene encodes a protein that belongs to the tyrosine kinase growth factor receptor family. Germline point mutations in RET are found in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene rearrangements have been reported in papillary thyroid cancers. We recently identified transcripts of the RET proto-oncogene in human prostate cancer xenografts and prostate cancer cell lines by means of reverse transcription-polymerase chain reaction analyses. The purpose of this study was to investigate Ret protein expression in human prostate tissue., Methods: Ret protein expression was evaluated immunohistochemically in formalin-fixed, paraffin-embedded whole-prostate sections. The prostate specimens were obtained from 30 patients with prostate cancer after radical prostatectomies. Ret protein expression was compared in tumor foci and benign prostatic tissue. Medullary thyroid carcinoma tissue associated with an MEN syndrome and papillary thyroid cancer tissue served as positive controls., Results: Ret appeared to be overexpressed in high-grade (histopathologically advanced) prostatic intraepithelial neoplasia (PIN) and prostate cancer when compared with its expression level in benign prostatic secretory epithelium. In addition, there was an apparent increase in Ret protein expression with decreased cellular differentiation, i.e., increasing Gleason pattern., Conclusion: Expression of the RET proto-oncogene in benign prostatic epithelium, high-grade PIN, and histopathologically advanced prostate cancer suggests that RET may play a role in the growth of both benign and neoplastic prostate epithelial cells.

Mortality rates among American hemodialysis patients are the highest in the industrialized world. Measures of delivered dialysis (Kt/V) correspond strongly with survival and are estimated to be inadequate in one third of patients. We sought to determine the importance of potential barriers to adequate dialysis, including patient-related and technical factors. Using a cross-sectional study design, we abstracted the charts of 721 randomly selected patients from all 22 chronic hemodialysis units in northeast Ohio. For each of 1,836 treatments provided to these patients, we assessed delivered dialysis (Kt/V) and patient-related factors (ie, hypotension, intradialytic symptoms, and treatment time missed due to noncompliance or transportation problems) and technical factors (ie, dialysis prescription, type of vascular access, clotting, and dialyzer reuse). We used hierarchical regression analysis to determine which potential barriers were independently related to delivered dialysis after adjustment for patient demographic and medical characteristics. Barriers independently related to dialysis delivery (all P values < 0.001) included patient noncompliance, present in 3% of treatments; low dialysis prescription, 14%; use of a catheter for vascular access, 11%; and clotting, 1%. The prevalence of identified barriers varied dramatically across facilities (eg, the prevalence of low dialysis prescription ranged from 0% to 37%, while the prevalence of catheter use ranged from 3% to 28%). In conclusion, patient noncompliance, low dialysis prescription, catheter use, and clotting are the most important barriers to dialysis delivery. Further work is needed to develop interventions to overcome these barriers and to determine the effect of such interventions on dialysis adequacy and patient survival.

Objective: To evaluate neonatal outcomes after an elective repeat cesarean section (ERCS) compared with a trial of labor (TOL)., Population and Method: All mothers who underwent previous cesarean section and delivered singleton infants at term gestation were identified during a 1-year period. Neonatal outcomes were compared between infants delivered by ERCS (n = 497) and those delivered by TOL (n = 492), and between infants delivered by a successful (n = 336) and a failed (n = 156) TOL. A cohort of mothers and their term infants delivered by routine vaginal delivery were also identified., Results: Infants delivered by ERCS had an increased rate of transient tachypnea compared with infants born by TOL (6% vs 3%). Compared with routine vaginal deliveries, the adjusted odds ratio of developing any respiratory problem after an ERCS was 2.3 (95% confidence interval [CI]: 1.4, 3.8), and for developing transient tachypnea was 2.6 (CI: 1.5, 4.5). In addition, two infants delivered by ERCS developed respiratory distress syndrome. Infants delivered after a TOL had increased rates of suspected and proven sepsis (5% vs 2% and 1% vs 0.1%, respectively). Compared with a successful TOL, the infants delivered by cesarean section after a failed TOL had more neonatal morbidity and had a longer hospital stay (4.8 +/- 2 vs 3.1 +/- 2 days). The odds ratio for developing any respiratory illness after a failed TOL was 2.1 (95% CI: 1.1, 4.1), for suspected sepsis was 4.8 (95% CI: 2.6, 9.0), and for proven sepsis was 19.3 (95% CI: 2.0, 187). Neonatal outcomes after a successful TOL were similar to routine vaginal births., Conclusion: Infants born by ERCS are at increased risk for developing respiratory problems compared with those born by TOL. However, TOL is associated with increased rates of suspected and proven sepsis. This appears to be limited to infants delivered by cesarean section after a failed TOL.

Follicular basal cell hyperplasia (FBCH) overlying dermatofibroma represents aborted or impeded pilar differentiation. Historically, this hyperplasia has been misinterpreted as basal cell carcinoma. In a large series of dermatofibroma (258 cases), those that contained primitive or malformed follicular structures over the lesion (59 cases) were compared with those without such elements (199 cases). Statistical analysis of various clinicopathologic features showed that FBCH was significantly associated with younger age, trunk location, hypercellular dermatofibroma, loss of a Grenz zone, clear cell hyperplasia, and seborrheic keratosis-like change. There was an inverse correlation between epidermal atrophy, lichen simplex chronicus-like change, and lower extremity location with FBCH. Histologic features favoring a diagnosis of FBCH over basal cell carcinoma are the focal nature and superficial location of the lesion, lack of cytologic atypia and mitoses, recognizable components of hair follicle differentiation, focal condensation of mesenchymal cells around basal cell proliferation, and the association of epidermal hyperplasia. Our findings suggest that FBCH, clear cell hyperplasia, and seborrheic keratosis-like change all represent an expression of follicular differentiation overlying dermatofibroma.

Aberrant crypt foci (ACF) are grossly invisible putative premalignant lesions in the colon. As dysplasia is considered an important precursor of colon carcinoma, we wanted to determine the presence and severity of dysplasia in human ACF. Fifty ACF from 28 patients were embedded in paraffin, cut serially, and stained with hematoxylin and eosin. Multiple slides from each ACF were evaluated for dysplasia according to a defined set of criteria. Of 50 ACF, 3 (6%) contained focal areas with severe dysplasia, ie, carcinoma in situ, 4 (8%) contained focal areas with moderate dysplasia, and 20 (40%) contained focal areas with mild dysplasia. Twenty-three ACF (46%) contained no detectable dysplasia. In 15 of 27 ACF with dysplasia, less than 50% (eg, 4 of 28, 10 of 54, and 10 of 30 sections) of the sections cut and evaluated from each ACF demonstrated dysplasia. The presence of dysplasia in a large proportion of ACF supports the hypothesis that they may be precarcinomatous.

In order to test the effects of maternal exercise in late gestation on fetal biophysical activities as measured by fetal breathing, shoulder movement, and kick response, these parameters were monitored by ultrasound in ten healthy pregnant women at 35 weeks of gestation before and after 20 minutes of aerobic dance and before and after 20 minutes of rest. A randomized crossover design between exercise (sequence A) and rest (sequence B) that used each pregnant woman as her own control was used in this study. Cumulative means for each fetal activity were compared. Results indicated a significant decrease in fetal breathing after maternal exercise and no significant change in shoulder movements or kick response.

There is a great need for markers that distinguish slowly progressive from rapidly progressive prostate cancers in paraffin-embedded tissues. CD44, an adhesion molecule that has been useful for the prediction of prognosis in some other cancers, has not been described in prostate cancer. The expression of CD44 was investigated with the monoclonal antibody GKW.A3 in prostate cancer in formalin-fixed, paraffin-embedded tissue sections of (1) whole prostates from 50 patients with 74 prostate cancers; and (2) lymph node metastases from 14 patients. Sixty percent of primary prostate cancers expressed CD44 moderately to strongly. No metastases expressed CD44 moderately to strongly; only 14% of metastases expressed even low levels of immunohistochemically detectable CD44. There is a difference between primary and metastatic prostate cancer (P <.0006) in the expression of CD44 and an inverse correlation (P <.05) between histological differentiation (Gleason grade) and the expression of CD44. The magnitude of the differential expression of CD44 in primary and metastatic prostate cancers suggests it should be investigated as an indicator of prognosis in a large prospective study.

Most patients' prostate cancers respond to androgen deprivation but relapse after periods of several months to years. Only two prostate cancer xenografts, LNCaP and PC-346, have been reported to be responsive to androgen deprivation and to relapse subsequently. Both of these tumors shrink slightly, if at all, and relapse less than 5 weeks after androgen withdrawal. After androgen withdrawal, the human primary prostate cancer xenograft CWR22 regresses markedly, and prostate-specific antigen (PSA) falls up to 3000-fold in the blood of mice. PSA usually returns to normal. In some animals, the tumor relapses and is then designated CWR22R. In these animals, PSA starts to rise approximately 2-7 months, and tumor begins to grow 3-10 months after castration. Animals with CWR22 need to be euthanized because of large tumors 6-12 weeks after the transplantation of CWR22. Androgen withdrawal prolongs life approximately 3-4-fold.

Immunohistochemical studies have suggested that E-cadherin may be a useful prognostic marker in prostate cancer. Previous studies have depended on cryostat sections of tissues selected grossly. Many prostate cancers, even when extensive, are not visible grossly; many others cannot be demarcated sharply grossly. The wide applicability of prognostic markers after total prostatectomy will depend upon methods that can be applied to tissue selected based upon the histopathological examination of the entire prostate. Our purpose was to investigate the possibility that E-cadherin could be demonstrated in paraffin-embedded whole prostates and metastatic prostate cancer. Microwaving in citrate buffer was the best of five methods tested for the demonstration of E-cadherin in paraffin-embedded prostate and was used to investigate 53 primary prostate cancers from 44 patients and lymph node metastases from 14 patients. Metastases of prostate cancer to lymph nodes expressed less (P = 0.008) E-cadherin than primary prostate cancers. The expression of E-cadherin correlated with the histopathological differentiation (Gleason grade) of primary prostate cancers (P = 0.03, Ptrend = 0.003). The use of monoclonal anti-human E-cadherin (HECD-1) with microwaving in citrate buffer followed by immunoperoxidase staining with heavy metal enhancement for the demonstration of E-cadherin in paraffin-embedded tissue will, for the first time, allow the use of archival tissue for prognostic studies of E-cadherin in prostate cancer and other tissue. Our results are consistent with the hypothesis that aggressive prostate cancers exhibit decreased expression of E-cadherin and demonstrate the feasibility of long-term prognostic studies of this molecule in the usually multiple prostate cancers found in whole, formalin-fixed, paraffin-embedded resected prostates.

The purpose of this study was to examine the demographic and obstetrical outcomes of women with poor prenatal care. A 7-year (1987-1993) computerized perinatal database with 29,225 consecutive deliveries was collected prospectively from a single inner city tertiary medical center. Data from 23,181 women who had documented prenatal visits during their pregnancies were used in the analysis. Overall, 21,004 (90.6%) of the mothers had at least 3 prenatal visits (C), while 2,177 (9.4%) had 2 or fewer visits (NC). The proportion of NC did not change significantly over the years (P = 0.47, by trend test). The NC group was 2.3 times more likely to be unmarried (79.8% vs. 59.4%; P < 0.001), have greater parity (mean +/- SD 2.1 +/- 1.9 vs. 1.2 +/- 1.2; P < 0.001), 6.3 times more likely to be staff patients (have no private insurance), and 1.5 times more likely to be black. The average maternal age was 24 years for both groups (P = 0.65). NC mothers delivered at an earlier gestational age (37.3 +/- 3.3 vs. 39.0 +/- 2.6 weeks; P < 0.001), had lower birth weights (BW) (2,810 +/- 743 vs. 3,203 +/- 607 g for singleton births; P < 0.001), and their infants had longer neonatal hospital stays (8.4 +/- 17.3 vs. 4.8 +/- 10.4 days; P < 0.001) compared with C mothers. Moreover, after adjusting for various confounding factors known to effect BW, C mothers delivered infants which were on the average 550 g heavier than the NC mothers. The neonates of NC had consistently lower Apgar scores and were more likely be delivered in breech presentation (5.7% vs. 3.1%) and to be transferred to the neonatal intensive care unit (11.6% vs. 5.2%; P < 0.001). However, the NC group had fewer cesarean deliveries (9.4% vs. 14.2%; P < 0.001) but more thick meconium fluid (12.4% vs. 8.9%; P < 0.001). In conclusion, the women not seeking adequate prenatal care are more likely to be unmarried, black, and staff patients having several children at home. NC mothers tend to have poor obstetrical outcomes and on the average their neonatal stay in the hospital is twice as long as women obtaining adequate prenatal care.

Objective: Estimation of neonatal body composition can be useful in the understanding of fetal growth. However, body composition methods such as total body water and total body electric conductivity are expensive and not readily available. Our primary purpose was to develop an anthropometric model to estimate neonatal body composition and prospectively validate the model against total body electric conductivity and secondarily to compare our anthropometric model and a previously published anthropometric formula with total body electric conductivity., Study Design: A total of 194 neonates had estimates of body composition according to total body electric conductivity (group 1). Parental morphometrics, gestational age, race, sex, parity, and neonatal measurements including birth weight, length, head circumference, and skinfolds (triceps, subscapular, flank, and thigh) were correlated with body fat by use of stepwise regression analysis. The model was validated in a second group of 65 neonates (group 2)., Results: There were no significant differences in any of the parental or neonatal measurements between groups 1 and 2. In group 1, 78% of the variance in body fat with the use of total body electric conductivity was explained by birth weight, length, and flank skinfold (R2 = 0.78, p = 0.0001). When prospectively validated by the subjects in group 2, the model had significant and stronger correlation (R2 = 0.84, p = 0.0001) with body fat estimated by total body electric conductivity as compared with the other anthropometric model (R2 = 0.54, p = 0.0001). There was no significant (p = 0.11) difference between our anthropometric estimate of body fat and total body electric conductivity., Conclusions: The anthropometric model developed can be used to reasonably predict neonatal body fat mass at birth.

Objective: Our purpose was to identify factors affecting fetal growth with birth weight and body composition., Study Design: A total of 183 singleton infants had birth weights and estimates of body composition performed within 24 hours of birth. Independent variables included were (1) maternal height, weight, pregravid weight, weight gain, education, and parity, (2) paternal height and weight, and (3) neonatal sex and gestational age. Best-fit stepwise regression analysis was used to correlate the independent variables with birth weight, fat-free mass, and fat mass., Results: Compared with females, males had greater birth weight (p = 0.009) and fat-free mass (p = 0.0001) but not fat mass (p = 0.32). The strongest predictors were gestational age with birth weight (R2 = 0.10), neonatal sex with fat-free mass (R2 = 0.08), and parity with fat mass (R2 = 0.08). By use of the significant independent variables we explained 29% of the variation in birth weight, 30% in fat-free mass, and 17% in fat mass., Conclusion: These data support the concept that various genetic and environmental factors may modify fetal growth by differentially affecting growth of fetal fat and fat-free mass.

Objective: Our purpose was to correlate maternal carbohydrate metabolism and parental morphometric measurements with neonatal birth weight, body composition, and placental weight., Study Design: Sixteen singleton (six control and 10 abnormal glucose tolerance) infants had placental weight, birth weight, and estimates of body composition performed within 24 hours of birth. Independent variables considered were (1) maternal and paternal demographic and morphometric measures, (2) neonatal sex and gestational age, and (3) estimates of maternal carbohydrate metabolism, including basal hepatic glucose production, insulin response, and insulin sensitivity. All metabolic measurements were performed before conception and in early (12 to 14 weeks) and late (34 to 36 weeks) gestation. Best-fit stepwise regression analysis was used to relate the independent variables with placental weight, neonatal birth weight, fat-free mass, and fat mass., Results: Insulin sensitivity in late gestation had the strongest correlation with placental weight (R2 = 0.28), neonatal birth weight (R2 = 0.28), and fat-free mass (R2 = 0.33). In contrast, insulin sensitivity before conception had the best correlation with neonatal fat mass (R2 = 0.15). Including all significant independent variables in the model improved the correlations for placental weight (R2 = 0.58), birth weight (R2 = 0.48), fat-free mass (R2 = 0.53), and fat mass (R2 = 0.46)., Conclusion: Maternal insulin sensitivity had stronger correlations with fetoplacental growth in comparison with maternal demographic or morphometric factors.

Background/aims: Aberrant crypt foci are putative preneoplastic lesions that, by definition, are identified microscopically in whole-mount preparations of colonic mucosa. Because the identification of hexosaminidase as a marker for rat aberrant crypt foci in histological sections facilitated their characterization, a similar marker for human foci in histological sections was sought., Methods: Human aberrant crypt foci were marked in whole-mount preparations, embedded in paraffin, and evaluated for their expression of carcinoembryonic antigen with two monoclonal antibodies., Results: Elevated expression of carcinoembryonic antigen was detected in 39 of 42 (93%) aberrant crypt foci from 15 patients. The expression of carcinoembryonic antigen assisted in the evaluation of longitudinal sections of foci, where dysplasia is more readily detected in these small lesions. The expression of carcinoembryonic antigen was related to the sizes of the foci (P = 0.0085, generalized Fisher's Exact Test) but not to the presence or degree of dysplasia., Conclusions: The overexpression of immunohistochemically demonstrable carcinoembryonic antigen is, to date, the only described alteration in most of these putative precursors of human colon cancer that differs from the expression in contiguous, normal crypts at the histological level and thus facilitates the identification of aberrant crypts in histological sections for further characterization.

Objective: Our goal was to evaluate various trends including gestational age, birth weight, and mode of delivery in an inner-city obstetric patient population delivered at a tertiary medical center., Study Design: We used an 18-year computerized perinatal database collected prospectively since 1975 in an inner-city tertiary medical center. More than 63,500 deliveries from 1975 through 1992 were evaluated. Trends in gestational age, birth weight, and mode of delivery were investigated with Cox-Stuart, regression, and other trend analysis methods., Results: The number of deliveries increased from 2682 in 1975 to 4740 in 1991, an increase of 77%. The median maternal age has increased from 20 years in 1975 to 23 years in 1992 (p < 0.001). Overall, the mean gestational age has declined monotonically from 39.2 +/- 2.84 weeks in 1975 to 38.3 +/- 3.17 weeks in 1992 (p = 0.057). While the median and lower percentiles of birth weight for singleton births have declined, the 75th and higher percentiles of birth weight have increased during 18 years. Overall, the proportion of preterm births (< 37 completed weeks gestational age) has increased from 3.3% in 1975 to 7.8% in 1991 (p < 0.001). During this period the proportion of low-birth-weight infants (< 2,500 gm) increased significantly from 12.7% to 17.3% (p < 0.001). The proportion of cesarean section deliveries for private patients has declined from 37% in 1975 to 25% in 1992 (p = 0.025), while this proportion has increased monotonically for staff patients from 10% to 17% during this period (p < 0.001)., Conclusions: Considering the large size of the database and diverse background of the study population, we believe that these trends can provide a realistic characterization of an obstetric patient population for a large inner-city urban population.

Objective: To develop birth weight-for-gestational age nomograms based on a computerized perinatal data base collected prospectively from 1975-1992., Methods: Using information from over 60,000 singleton deliveries (January 1975 through October 1992) at the MetroHealth Medical Center in Cleveland, Ohio, standard curves for normal birth weights were computed. Nomograms were developed for the overall population and for subgroups determined by factors known to affect fetal growth, including sex, race, smoking status, and gestational diabetes. The nomograms included the tenth, 50th, and 90th percentiles of birth weights for 24-44 weeks' gestation. Gestational age was based on clinical obstetric estimates confirmed by Dubowitz assessment of the neonate. In addition, third-order regression models were developed to predict median birth weight using gestational age. These models were validated using delivery data for the months of November and December, 1992, which were not included in model development., Results: The most significant predictors of median birth weight were the first-, second-, and third-order gestational ages, which explained over 80% of the total variation in birth weight. Other significant factors influencing birth weight included infant gender, maternal race, parity, smoking, and diabetes status. Among the marginally significant factors influencing birth weight were pay status and maternal age. In general, before 33 weeks' gestation, there were few differences in the birth weight percentiles of various groups except for those with diabetes; infants of diabetic women exhibited greater birth weights as early as 26 weeks' gestation., Conclusions: Considering the large size of the data base and the diverse background of the study population, we believe that these nomograms provide useful norms of birth weight for an indigent urban population. These norms enhance the obstetrician's and neonatologist's ability to identify true cases of retardation or acceleration of intrauterine growth. Simple mathematical models provide easy calculation of the median birth weights for 24-44 weeks while adjusting for many confounding factors.

Objective: The purpose of this study was to evaluate the reproducibility of the 3-hour oral glucose tolerance test during pregnancy and the potential factors associated with nonreproducible results., Study Design: Thirty-eight women with a 1-hour glucose level > or 135 mg/dl had a 100 gm oral glucose tolerance test. During the test samples were obtained for glucose, insulin, cortisol, human placental lactogen, and norepinephrine levels. The oral glucose tolerance test was repeated 1 week later under similar metabolic conditions., Results: The intraassay coefficient of variation in glucose from week 1 to week 2 was < 2%. There were no significant differences in the paired fasting 1-, 2-, or 3-hour glucose concentrations (p = 0.51 to 0.96) or the area under the glucose curve (p = 0.43) from week 1 to week 2, although the mean absolute difference in glucose values ranged from 4 (fasting) to 18 (3 hours) mg/dl. Oral glucose tolerance test results were classified as either normal or abnormal from week 1 to week 2; 16 normal/normal, 13 abnormal/abnormal, seven abnormal/normal, and two normal/abnormal. Norepinephrine (p = 0.03) and insulin (p = 0.05) were significantly greater in week 1 but not in week 2 in the abnormal/normal versus normal/normal and abnormal/abnormal groups. There were no significant differences in cortisol or human placental lactogen levels among groups at any time., Conclusions: The oral glucose tolerance test was not reproducible for diagnosis in 24% (nine of 38) of pregnant women. We speculate that maternal stress (increased norepinephrine) may have been a factor for the abnormal results in week 1 in the abnormal/normal group.