Antepartum detection of macrosomic fetus: clinical versus sonographic, including soft-tissue measurements

OBJECTIVE: To compare clinical and sonographic estimates of birth weights with five new estimation techniques that involve measurements of soft tissue, for identifying newborns with birth weights of at least 4000 g. METHODS: Over 1 year, each woman at or after 36 weeks' gestation and suspected of having a macrosomic fetus had clinical and sonographic estimates of fetal weight (EFW) based on femur length (FL) and head and abdominal circumference, followed by five additional ways to identify excessive growth: cheek-to-cheek diameter, thigh soft tissue, ratio of thigh soft tissue to FL, upper arm subcutaneous tissue, and EFW derived from it. Areas (+/- standard error) of receiver operating characteristic (ROC) curves were calculated and compared with the area under the nondiagnostic line. P <.05 was considered statistically significant. RESULTS: Among 100 women recruited, 28 newborns weighed 4000 g or more. The areas under the ROC curves with clinical (0.72 +/- 0.06) and sonographic predictions using biometric characteristics (0.73 +/- 0.06) had the highest but similar accuracies (P.05). Three of the five newer methods (upper arm or thigh subcutaneous tissue and ratio of thigh subcutaneous tissue to FL) were poor diagnostic tests (range of areas under ROC 0.52 +/- 0.06 to 0.58 +/- 0.07). Estimated fetal weight based on upper arm soft tissue thickness and cheek-to-cheek diameter (areas 0.70 +/- 0.06 and 0.67 +/- 0.06, respectively) were not significantly better than clinical predictions (P.05) for detecting macrosomic fetuses. About 110 macrosomic and nonmacrosomic infants combined would be needed to have 80% power to detect a difference between ROC curves with areas of 0.58 (thigh subcutaneous tissue) and 0.72 (clinical estimate). CONCLUSION: ROC curves indicated that measurements of soft tissue are not superior to clinical or sonographic predictions in identifying fetuses with weights of at least 4000 g.     

A novel immunological model for the study of prostate cancer.

The Dunning R-3327 rat prostatic adenocarcinoma is a widely accepted model for in vivo experimental studies of prostate cancer. We have previously derived phenotypically distinct cell lines from a s.c. tumor resulting from the inoculation of the R-3327-5 subclone into Copenhagen rats. In this study, we report studies using a gelatin sponge model for the delivery of tumor cells and the retrieval of tumor-specific leukocytes responsive to different prostatic cell lines. S.c. preimplanted sponges were inoculated with tumor cells previously selected for differential properties of tumor formation and metastasis and examined for leukocyte content at time points of 1, 3, and 5 weeks after tumor cell inoculation. Cytospin and flow cytometric analyses revealed fewer tumor-associated leukocytes present in sponges inoculated with tumorigenic R-3327-5' and R-3327-5'B lines, with lesser sponge degradation, than in experiments with the nontumorigenic R-3327-5'A line, suggestive of a tumor cell-induced immunomodulatory mechanism. Morphological studies indicate an intermittent tumor growth pattern that gradually disappears in sponges inoculated with the nontumorigenic R-3327-5'A cells but a robust growth pattern in sponges inoculated with the tumorigenic cell lines. Cytokine analyses show the secretion of higher levels of active transforming growth factor-beta by the more invasive and metastatic lines. Total transforming growth factor-beta levels are higher in the epithelial, tumorigenic R-3327-5'B line. Additionally, the more tumorigenic lines secrete interleukin 10, a potent immunosuppressive molecule. In this report, we demonstrate the ability to retrieve viable leukocyte populations from a prostate tumor line bearing sponges, which offers an important model for further in vitro and in vivo manipulations and holds promise for testing adoptive immunotherapeutic strategies.     

Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line.

Although the incidence of, and deaths due to, malignant melanoma are rising at a rapid rate, few experimental models mimic the highly metastatic properties associated with the pathogenesis of the human disease, making study of the disease difficult. Thus, new human models are required to understand melanoma biology, especially its metastatic properties. Here we describe C8161, a highly invasive and spontaneously metastatic human melanoma cell line, which grows progressively in the subcutis of athymic nude mice with an average doubling time of approximately 6 days. By the time the tumor reaches a diameter of 1 cm, amelanotic metastases in lymph nodes, skin, peritoneal wall, spleen and lungs have formed. By comparing C8161 to variants from other well-characterized human malignant melanomas (A375 and MeWo) with differing metastatic traits, properties presumed to be involved in metastatic propensity were examined. C8161 showed a 2- to 14-fold higher ability to invade reconstituted basement membrane barriers in the MICS and correspondingly high type-IV collagenase mRNA levels and collagenolytic activity, as compared with other melanoma cell lines. Likewise, differential adhesion to immobilized RBM or HUVEC monolayers was observed, but did not correlate to rank orders of malignant properties. Recently, a correlation between surface expression of ICAM-1 and secondary tumor formation by human melanomas has been described in several laboratories. Basal levels of ICAM-1 on C8161, A375 and MeWo human melanomas were compared, but no correlation with metastatic potential was noted. Proto-oncogene expression in C8161 cells was compared with A375P and A375M variants using Northern blot analysis. c-myc expression was 6-fold greater than both A375 variants; c-fos expression was 3.4-fold less than A375P and 1.7-fold less than A375M; c-jun in C8161 cells was 2.5-fold and 2.1-fold greater than expression in A375P and A375M, respectively. Because C8161 is so highly malignant, amenable to experimental manipulation, and its behavior in nude mice mimics the clinical course of malignant melanoma, this cell line will prove valuable for studying properties associated with human melanoma tumor progression.     

Glaucoma in large-scale population-based epidemiology: a questionnaire-based proxy

PurposeTo improve upon self-reported glaucoma status in population-based cohorts by developing a questionnaire-based proxy incorporating self-reported status in conjunction with glaucoma-specific visual complaints.MethodsA vision specific questionnaire, including questions from the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) was administered to 79,866 Lifelines participants, a population-based cohort study in the Northern Netherlands. We compared NEI-VFQ-25 responses between ‘definite’ glaucoma cases (n = 90; self-reported surgical cases) and an age- and gender-matched subset of controls (n = 1,800) to uncover glaucoma-specific visual complaints, using a case–control logistic regression. We defined ‘probable glaucoma’ as both self-reported disease status and visual complaints, and ‘possible glaucoma’ as either. To evaluate the resulting proxy, we determined age-stratified glaucoma prevalences in the remaining cohort and compared the result to the literature.ResultsPer unit increase in the vision subscales (range 0–100) distance, peripheral and low luminance, we observed significantly increased odds of definite glaucoma (2% [P = 0.03], 4% [P = 1.2 × 10⁻⁸] and 2% [P = 0.02], respectively); the associated area under the curve was 0.73. We identified 300 probable and 3,015 (1,434 by self-report) possible glaucoma cases. Standardised prevalences of definite, probable and possible glaucoma for 55+ were 0.4%, 1.1% and 7.3%, respectively. For self-reported glaucoma (combining definite, probable and possible by self-report), this was 5.2%.ConclusionsThe combination of self-reported glaucoma status and visual complaints can be used to capture glaucoma cases in population-based settings. The resulting prevalence of combined definite and probable glaucoma (1.5%) appears to be more consistent with previous reports than the prevalence estimate of 5.2% based only on self-report.Subject terms: Epidemiology, Epidemiology, Glaucoma     

Incidence of fractures compared to cardiovascular disease and breast cancer: the Women’s Health Initiative Observational Study

Summary  To compare the absolute risk of fracture to the risk of other conditions by race/ethnicity, we studied 83,724 women, aged 70–79. The projected number of fractures was similar to or exceeded the combined number of cardiovascular events and breast cancers. Osteoporosis prevention efforts should target women of all ethnicities. Introduction  The relative risk of fracture is lower in non-white compared to white women but the absolute risk of fracture in comparison to other common chronic conditions is uncertain. Methods  We performed a prospective cohort study of 83,724 women, age 50–79 years. Cardiovascular disease (CVD), invasive breast cancer and all fractures were identified over an average of 7.7 ± 2.6 years. Results  The incidence of fracture, breast cancer, stroke and CVD varied across ethnicity. The annualized (%) incidence of fracture was greatest in whites (2.4%) and American Indians (2.8%) and lowest among blacks (1.3%). The majority of hip fractures occurred in white women. The projected number of women who will experience a fracture in one year exceeded the combined number of women who would experience invasive breast cancer or a broad category of CVD events in all ethnic groups except blacks. In 10,000 black women, an estimated 153 women would experience CVD, and 35 women, breast cancer compared to 126 women expected to fracture in one year. Conclusion  The annual risk of suffering a fracture is substantial in women of all ethnicities. Osteoporosis prevention efforts should target all women irrespective of their race/ethnic backgrounds. This article is discussed in an editorial that is available at .     

Growth in semisolid agar of prostate cancer cells obtained from bone marrow aspirates

Thirty-one bone marrow aspirations were performed on patients with prostatic carcinoma metastatic to bone. After separation over a Ficoll-Hypaque gradient viable nucleated cells were cultured in semisolid agar. Colony formation occurred in 14 of 27 (52%) nonbacterially contaminated cultures. Characterization of cells from the colonies showed them to be consistent with malignant prostate cells. After staining, these cells were periodic acid-Schiff positive, prostatic acid phosphatase positive, and prostatic specific antigen positive. Other studies demonstrated the cells to be karyotypically abnormal, ultrastructurally similar to epithelial cells, and capable of secondary colony formation. Three bone marrow aspirate specimens did not have metastatic prostatic carcinoma detected by standard methods but did demonstrate colony formation. However, colony formation was most frequently seen when a radionuclide scan was positive at the aspiration site and when tumor cells were microscopically detectable by Wright staining of a smeared aspirate. The potential utility of colony forming cultures in prostate cancer is discussed. In working with bone marrow aspirates, additional cell separation procedures may be required to calculate and maximize plating efficiencies.     

Comparison of Hypertonic Glucose to Other Provocative Tests in Patients with Noncardiac Chest Pain

The effect of hypertonic glucose as a provocative test was studied in 51 patients with noncardiac chest pain, 15 patients with esophagitis, and 16 asymptomatic controls. It was compared to esophageal perfusion with 0.1 N HCl and saline and intravenous administration of 10 mg edrophonium. Continuous esophageal manometric recordings were performed at the time of testing. The patients' symptoms were monitored every minute. The effect of these solutions and edrophonium on lower esophageal sphincter (LES) pressure and amplitude of esophageal contractions was also evaluated. Esophageal perfusion with hypertonic glucose, saline, or acid had no significant effect on LES pressure or amplitude of esophageal contractions in most patients. Edrophonium, however, resulted in a significant rise in the amplitude of esophageal contractions and the LES pressure in all groups studied. Hypertonic glucose resulted in chest pain in 13.6% of patients with noncardiac chest pain and 20% of those with esophagitis, whereas edrophonium reproduced the pain in 38.7 and 37%, respectively. Our results indicate that hypertonic glucose is not effective as a provocative test for noncardiac chest pain nor does it contribute to the chest pain in esophagitis. They also had no significant effect on the amplitude of esophageal contractions or LES pressure. Edrophonium continues to be a relatively sensitive test for noncardiac chest pain.