Insulin requirements throughout pregnancy in women with type 1 diabetes mellitus: three changes of direction.

AIMS/HYPOTHESIS: The aim of the study was to analyse the insulin requirements of women with type 1 diabetes mellitus throughout pregnancy. METHODS: We have examined the weekly mean blood glucose (mmol/l), insulin requirements (U kg(-1) day(-1)) and total insulin requirements (U/day) in 65 women with type 1 diabetes mellitus and tight metabolic control since before pregnancy (HbA(1c) < or =6.0%). RESULTS: Both insulin requirement and total insulin requirement displayed a peak in week 9, a nadir in week 16 and a second peak in week 37. For the change in insulin requirement (4.08% per week) and in total insulin requirement (5.19% per week), the sharpest slope was observed from week 16 to week 37. However, two changes of direction took place in the first 11 weeks and eight out of nine episodes of severe hypoglycaemia requiring treatment with glucagon or i.v. glucose took place in the first 16 weeks. CONCLUSIONS/INTERPRETATION: Pregnant women with type 1 diabetes mellitus and tight metabolic control since before pregnancy displayed changes in insulin requirement and total insulin requirement with successive changes of direction. The sharpest slope was observed between 16 and 37 weeks, but insulin requirements were more unstable in the first 16 weeks. This information could help patients and physicians to react to changes in glycaemic pattern in a prompt and adequate way.

Relationship of neonatal body composition to maternal glucose control in women with gestational diabetes mellitus.

OBJECTIVE: To determine whether neonatal fat mass, which may be a better estimate of fetal overgrowth, is correlated with maternal fasting, preprandial and/or postprandial glucose values in women with gestational diabetes mellitus (GDM). STUDY DESIGN: Women with GDM and no other medical or obstetric problems, and their infants, were the subjects of this study. Portable reflectance meters were used by all participants for self-monitoring of blood glucose levels. Average fasting, preprandial, 2-h postprandial and bedtime glucose values were determined for each subject. Neonatal body composition was obtained by total body electric conductivity and/or anthropometric measurements within 48 h after delivery. RESULTS: Eighteen women with their infants participated in this study. The age (mean +/- SD) of the mothers was 28.0 +/- 5.7 years. Nine were treated with diet and nine with diet and insulin. An average of 40 fasting (84 +/- 13 mg/dl), 50 preprandial (87 +/- 14 mg/dl), 80 2-h postprandial (106 +/- 19 mg/dl) and 17 bedtime (104 +/- 19 mg/dl) glucose values were obtained from each subject. The average gestational age of the infants at birth was 38.3 +/- 1.3 weeks with a mean weight of 3,356 +/- 526 g. Three infants were > 4 kg and seven infants were > 90th centile for gestational age. The strongest correlation with neonatal fat mass was maternal fasting glucose level (r = 0.71, p < 0.01). Neonatal fat mass was not found to be significantly correlated with any other mean glucose value. Additionally, the infant's per cent body fat (r = 0.71, p < 0.01), sum of skinfold thicknesses (r = 0.70, p < 0.01), fat-free mass (r = 0.50, p < 0.05), and weight (r = 0.61, p < 0.01) were also found to be correlated with maternal fasting glucose level. No other maternal glucose measurements were correlated with either birth weight or estimates of fat free mass. CONCLUSION: Maternal fasting glucose levels correlated best with neonatal fat mass and other estimates of neonatal body composition.

Altered lipid profile, leptin, insulin, and anthropometry in offspring of South Asian immigrants in the United States.

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.

Anthropometric estimation of maternal body composition in late gestation.

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.

Agreement of Medicare claims and tumor registry data for assessment of cancer-related treatment.

BACKGROUND: Although health claims data are increasingly used in evaluating variations in patterns of cancer care and outcomes, little is known about the comparability of these data with tumor registry information. OBJECTIVES: To evaluate the agreement between Medicare claims and tumor registry data in measuring patterns of diagnostic and therapeutic procedures for older cancer patients. RESEARCH DESIGN: Analysis of a database linking Surveillance, Epidemiology and End Results (SEER) registry data and Medicare claims in patients aged > or =65 years with cancer. SUBJECTS: 361,255 Medicare patients with invasive breast, colorectal, endometrial, lung, pancreatic, and prostate cancer diagnosed between 1984 and 1993. MEASURES: Concordance of SEER files with corresponding Medicare claims. RESULTS: Medicare claims generally identified patients who underwent resection and radical surgery according to SEER (ie, concordance > or =85%-90%) but less likely biopsy or local excision (ie, concordance < or =50%). In some instances, claims also categorized patients as having more invasive surgery than was listed in SEER and also provided incremental information about the use of surgical treatment after 4 months. SEER files and, to a lesser degree, Medicare claims identified radiation therapy not included in the other data source, and Medicare files also captured a significant number of patients with codes for chemotherapy. CONCLUSIONS: Medicare files may be appropriate for studies of patterns of use of surgical treatment, but not for diagnostic procedures. The potential benefit of Medicare claims in identifying delayed surgical intervention and chemotherapy deserves further study.

The utility of Medicare claims data for measuring cancer stage.

BACKGROUND: The validity of using claims data for measuring tumor stage, one of the most important determinants of choice of therapy and long-term survival, is unknown. OBJECTIVES: To determine the relative accuracy of both inpatient and hospital Outpatient Medicare claims for measuring the stage of disease of six commonly diagnosed cancers. RESEARCH DESIGN: Analysis of a database linking Surveillance, Epidemiology, and End Results (SEER) registry data and Medicare claims in patients aged 65 years with cancer. SUBJECTS: Three hundred twenty thousand, six hundred and thirty seven cases of invasive breast, colorectal, endometrial, lung, pancreatic, and prostate cancers diagnosed between 1984 and 1993. MEASURES: Using SEER files as the "gold standard," concordance with Medicare claims, as well as sensitivity and positive predictive value of coding for each stage was measured. RESULTS: Although Medicare data correctly categorized local, regional, and distant stage tumors in 97%, 33%, and 65%, respectively, the data substantially overestimated the proportion of localized tumors and underestimated the rate of regional stage disease. The highest concordance was observed for breast and colorectal cancer. However, the sensitivity and positive predictive values were never simultaneously 80% within one stage of a specific cancer. The accuracy of coding for stage in Outpatient files was inferior to inpatient data. CONCLUSIONS: With few exceptions, Medicare claims have limited utility as a measure of cancer stage. If tumor registry data are not available, investigators should consider the trade offs in sensitivity and predictive value when considering a study that will use claims data.

The sensitivity of Medicare claims data for case ascertainment of six common cancers.

BACKGROUND: Although Medicare claims data have been used to identify cases of cancer in older Americans, there are few data about their relative sensitivity. OBJECTIVES: To investigate the sensitivity of diagnostic and procedural coding for case ascertainment of breast, colorectal, endometrial, lung, pancreatic, and prostate cancer. SUBJECTS: Three hundred and eighty nine thousand and two hundred and thirty-six patients diagnosed with cancer between 1984 and 1993 resided in one of nine Surveillance Epidemiology and End Results (SEER) areas. MEASURES: The sensitivity of inpatient and Part B diagnostic and cancer-specific procedural codes for case finding were compared with SEER. RESULTS: The sensitivity of inpatient and inpatient plus Part B claims for the corresponding cancer diagnosis was 77.4% and 91.2%, respectively. The sensitivity of inpatient claims alone was highest for colorectal (86.1%) and endometrial (84.1%) cancer and lowest for prostate cancer (63.6%). However, when Part B claims were included, the sensitivity for diagnosis of breast cancer was greater than for other cancers (93.6%). Inpatient claim sensitivity was highest for earlier years of the study, and, because of more complete data and longer follow up, the highest sensitivity of combined inpatient and Part B claims was achieved in the late 1980s or early 1990s. CONCLUSIONS: Medicare claims provide reasonably high sensitivity for the detection of cancer in the elderly, especially if inpatient and Part B claims are combined. Because the study did not measure other dimensions of accuracy, such as specificity and predictive value, the potential costs of including false positive cases need to be assessed.

Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus.

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.

Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans.

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.

Analysis of risk factors associated with rupture of silicone gel breast implants.

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.

Race and sex differences in long-term survival rates for elderly patients with pulmonary embolism.

OBJECTIVES: The goal of this study was to provide estimates of race- and sex-specific survival rates over a 10-year period for a cohort of 49,752 Medicare patients admitted to the hospital in 1984 with a diagnosis of pulmonary embolism. METHODS: Data were derived from Medicare Provider Analysis and Review Record inpatient claims files and the National Death Index file. RESULTS: For a primary diagnosis of pulmonary embolism, median survival times among Black men and women were 2.5 years and 5.2 years, respectively; for White men and women, the median survival times were 4.3 years and 5.9 years, respectively. Median survival times for Black men and women and White men and women with a secondary diagnosis of pulmonary embolism were 0.4 years, 0.7 years, 0.8 years, and 1.4 years, respectively. Survival rates declined with advancing age. CONCLUSIONS: Overall, survival rates among Blacks were lower than those among Whites, and men had lower survival rates than women. These survival estimates provide new insights into outcomes following pulmonary embolism in hospitalized elderly people.

Longitudinal changes in body composition and energy balance in lean women with normal and abnormal glucose tolerance during pregnancy.

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.

The effect of oral terbutaline on maternal glucose metabolism and energy expenditure in pregnancy.

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.

Longitudinal changes in pancreatic beta-cell function and metabolic clearance rate of insulin in pregnant women with normal and abnormal glucose tolerance.

OBJECTIVE: To evaluate basal pancreatic beta-cell secretion and suppression during infused insulin and the metabolic clearance rate of insulin in women with normal and abnormal glucose tolerance prior to conception and during pregnancy. RESEARCH DESIGN AND METHODS: Seven women with normal glucose tolerance and nine women with abnormal glucose tolerance during gestation were evaluated prior to conception, in early (12-14 weeks) and late (34-36 weeks) gestation. Basal insulin and C-peptide were measured after an 11-h fast and during the last 40 min of a 2-h hyperinsulinemic-euglycemic clamp at 40 mU.m-2.m-1. Suppression of basal C-peptide was calculated as the steady-state C-peptide/basal C-peptide. The metabolic clearance rate of insulin was calculated by dividing the insulin infusion rate by the steady-state insulin concentration, which was corrected for residual beta-cell secretion. RESULTS: No significant differences were noted in the following parameters between women with normal and abnormal glucose tolerance with advancing gestation: increase in basal insulin (P = 0.20) and C-peptide (P = 0.12), ability of infused insulin to decrease basal C-peptide concentration (P = 0.22), and metabolic clearance rate of insulin (P = 0.76). There was a significant 65% increase in both basal insulin (P = 0.0005) and C-peptide (P = 0.0002) concentrations in all subjects with advancing gestation. There was a significant (P = 0.0001) decrease in the ability of the infused insulin to decrease basal C-peptide concentration. C-peptide as a percentage of the basal was 64% before conception, 74% in early pregnancy, and 108% in late pregnancy. The metabolic clearance rate of insulin significantly (P = 0.0005) increased with advancing gestation: pregravid 442 ml.m-2.min-1, early pregnancy 514 ml.m-2. min-1, and 526 ml.m-2.min-1 in late pregnancy. CONCLUSIONS: Pregnancy is accompanied by progressive alterations in insulin kinetics, which are partly responsible for the hyperinsulinemia of this condition. These alterations are more likely a homeostatic response to the increased physiological insulin resistance of pregnancy.

Altered expression of RET proto-oncogene product in prostatic intraepithelial neoplasia and prostate cancer.

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.

Barriers to adequate delivery of hemodialysis.

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.

Neonatal morbidity after elective repeat cesarean section and trial of labor.

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 overlying dermatofibroma.

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.

Identification of dysplasia in human colonic aberrant crypt foci.

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.

Effects of maternal exercise on fetal activity in late gestation.

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.