Reaction product imaging: the h + d2 reaction.

The differential cross section for the H + D(2) --> HD + D reaction has been measured using a technique called reaction product imaging. In this experiment, a photolytically produced beam of hydrogen (H) atoms crossed a beam of cold deuterium (D(2)) molecules. Product D atoms were ionized at the intersection of the two particle beams and accelerated toward a position-sensitive detector. The ion images appearing on the detector are two-dimensional projections of the three-dimensional velocity distribution of the D atom products. The reaction was studied at nominal center-of-mass collision energies of 0.54 and 1.29 electron volts. At the lower collision energy, the measured differential cross section for D atom production, summed over all final states of the HD(v,J) product, is in good agreement with recent quasi-classical trajectory calculations. At the higher collision energy, the agreement between the theoretical predictions and experimental results is less favorable.

Direct measurement of the preferred sense of NO rotation after collision with argon.

The preferred sense of product molecule rotation (clockwise or counterclockwise) in a bimolecular collision system has been measured. Rotationally inelastic collisions of nitric oxide (NO) molecules with Ar atoms were studied by combining crossed molecular beams, circularly polarized resonant multiphoton ionization probing, and velocity-mapped ion imaging detection. The observed sense of NO product rotation varies with deflection angle and is a strong function of the NO final rotational state. The largest preferences for sense of rotation are observed at the highest kinematically allowed product rotational states; for lower rotational states, the variation with deflection angle becomes oscillatory. Quantum calculations on the most recently reported NO-Ar potential give good agreement with the observed oscillation patterns in the sense of rotation.

Serum hormones and the alcohol-breast cancer association in postmenopausal women.

BACKGROUND: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. METHODS: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. RESULTS: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. CONCLUSIONS: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.

Dopaminergic modulation of 18-hydroxycorticosterone secretion in man.

This study was designed to investigate mechanisms of dopaminergic control of corticosteroid secretion and to determine on which step in the aldosterone biosynthetic pathway dopamine exerts its effects. Plasma concentrations of electrolytes, PRA, plasma cortisol, 11-deoxycorticosterone, corticosterone (18-OHB), and 18-hydroxy-11-deoxycorticosterone were not altered by the iv administration of 10 mg metoclopramide in six healthy male volunteers. Metoclopramide increased plasma aldosterone from 6.3 +/- 0.9 ng/dl to a maximum of 23.0 +/- 3.4 ng/dl, plasma 18-OHB from 11.4 +/- 1.1 ng/dl to a maximum level of 42.8 +/- 4.4 ng/dl, and PRL from 9.9 +/- 1.4 ng/ml to a maximum of 71.0 +/- 5.5 ng/ml. The aldosterone and 18-OHB responses displayed a parallel time course, with significant responses of both occurring with 5 min after metoclopramide administration. Dopamine infusions (3 micrograms/kg . min) begun 60 min before the administration of metoclopramide markedly decreased the 18-OHB as well as the aldosterone and PRL responses to the dopamine antagonist. A parallel time course of stimulation of 18-OHB and aldosterone secretion with no change in other aldosterone precursors suggests that dopamine may modulate the activity of the glomerulosa 18-hydroxylase enzyme. Thus, rather than simply affecting aldosterone secretion, dopaminergic mechanisms appear to modulate the biosynthesis of aldosterone.

The longitudinal study of adrenal maturation during gonadal suppression: evidence that adrenarche is a gradual process.

The physical changes that herald the onset of puberty result from the combination of adrenarche and gonadarche. To examine adrenal maturation and associated changes in growth without the confounding effects of changes in the gonadal steroid milieu, we performed a longitudinal study in 14 young girls with idiopathic central precocious puberty during long-term pituitary-gonadal suppression. Beginning at the mean age of 2.9 yr, dehydroepiandrosterone sulfate levels, linear growth, skeletal maturation, body mass index, and secondary sexual development were evaluated at 3- to 6-month intervals for up to 12.3 yr. In 12 of the girls, levels of dehydroepiandrosterone, androstenedione, 17-hydroxypregnenolone, and 17alpha-hydroxyprogesterone were determined before and after acute ACTH stimulation every 6 months to investigate the maturation of adrenal steroidogenic enzyme activity. Serum dehydroepiandrosterone sulfate levels rose progressively throughout the study. An exponential model fit the longitudinal datasets well and indicated that dehydroepiandrosterone sulfate levels increased approximately 22%/yr from the youngest age onward. Increasing activity of 17-20 lyase (CYP17) and decreasing activity of 3beta-hydroxysteroid dehydrogenase were also evident in preadrenarchal subjects. When controlled for chronological age, no significant associations were noted between weight, body mass index, or body surface area and dehydroepiandrosterone sulfate levels. However, similar analyses revealed modest correlations of both height and growth velocity with dehydroepiandrosterone sulfate levels. Our results suggest that adrenarche is not the result of sudden rapid changes in adrenal enzyme activities or adrenal androgen concentrations; rather, adrenarche may be a gradual maturational process that begins in early childhood.

Relationships of serum androgens and estrogens to prostate cancer risk: results from a prospective study in Finland.

Several lines of evidence suggest that sex hormones may be involved in the etiology of prostate cancer. We conducted a prospective nested case-control study to evaluate the relationships of serum androgens and estrogens to prostate cancer using serum collected at baseline for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The 29,133 male smokers who participated in the trial were 50-69 years old at baseline. During 5-8 years of follow-up, 246 men were diagnosed with prostate cancer, and 116 of these were randomly selected for inclusion in the current study. For each case, two controls matched on age, date of blood collection, intervention group, and study center were selected. Hormones were measured in serum by RIA using standard procedures. None of the individual androgens or estrogens was significantly related to prostate cancer. These findings were unaltered by simultaneous evaluation of serum androgen and estrogen concentrations in multivariate models. These results do not support a strong relationship of serum androgens and estrogens with prostate cancer in smokers. Within-person variation in concentrations of some hormones may have contributed to the lack of significant associations.

Reproducibility studies and interlaboratory concordance for assays of serum hormone levels: estrone, estradiol, estrone sulfate, and progesterone.

We conducted studies to measure sources of assay variability for estrone, estradiol, estrone sulfate, and progesterone for postmenopausal women (n = 5) and for women in the mid-follicular (n = 5) and mid-luteal (n = 5) phases of the menstrual cycle. A single blood sample from each woman was divided into 2.5-ml aliquots and stored at -70 degrees C, and sets of two aliquots were sent at monthly intervals to each of three laboratories (four for progesterone). Each aliquot was analyzed in duplicate. Thus, within each menstrual category, we were able to estimate the components of variance due to variation among women, variation among aliquots, variation among duplicate measurements, and variation among the 4 analysis days. Using the logarithm of assay measurements, we estimated the percentage of variance attributable to variation among women in each menstrual category, 100 rho, is the estimated intraclass correlation. For each assay, 100 rho exceeded 90% for mid-follicular and mid-luteal women. For postmenopausal women, values of 100 rho exceed 84% for estrone in two laboratories. Values of 100 rho were lower for progesterone in postmenopausal women, although a value of 84% was estimated from one laboratory. These studies indicate that estrogen assays over a period of 3 months permit reliable comparisons among women in a given menstrual category. Progesterone measurements are likewise reliable for women in the mid-follicular and mid-luteal phases but somewhat less satisfactory for postmenopausal women. These assessments of variability pertain only to laboratory techniques and do not allow for secular variation in intra-woman hormone levels. Moreover, although these measurements tend to be reliable enough for making comparisons among women, estimates of coefficients of variation for estrogens are about 10% for mid-follicular and mid-luteal phase women and about 11-20% for postmenopausal women. Coefficients of variation for progesterone are about 10% for mid-luteal, 20% for mid-follicular, and 30% for postmenopausal women.

Testosterone and aggression in children.

OBJECTIVE: A link between serum testosterone and aggressive behavior, which has been demonstrated in numerous animal studies and suggested in several studies of adult men, has never been investigated in children before the time of puberty. METHOD: We measured serum testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) in 18 highly aggressive prepubertal boys, ages 4 to 10, hospitalized for violent or unmanageable behavior at a state children's psychiatric facility in New York City (the Bronx). We compared them with a group of age and race matched controls from the same demographic area, screened negative for aggressive behavior problems. All the aggressive subjects met DSM-III-R criteria for conduct disorder and scored higher than the 98th percentile on the aggression subscale of the Child Behavior Checklist (mean T = 80 for the group). RESULTS: There were no significant differences between aggressive and nonaggressive children for T, SHBG, DHEA, DHEAS, or ratios of combinations of these variables. CONCLUSIONS: These findings raise questions about inferences from adult studies that testosterone may play a causal role in the development of human aggression. Testosterone does not appear to be a useful biological marker for aggressivity in early childhood.

The measurement of 18-hyroxy-11-deoxycorticosterone in human plasma by radioimmunoassay.

A radioimmunoassay method for the measurement of plasma levels of 18-hydroxy-11 -deoxycorticosterone (18 -OH-DOC) has been developed. The antiserum against 18-OH-DOC was produced in rabbits immunized against 18-OH-DOC-3-oxime-bovine serum albumin. Plasma (1-2 ml) was extracted with dichloromethane and chromatographed on paper. The purified extracts were incubated with antiserum at a 1/22,000 dilution for 1/2 hour at 37 degrees C and for 2 hours at 4 degrees C. Saturated ammonium sulfate was used to separate free from bound 18-OH-DOC. 1,2-3H-18-OH-DOC was added to all samples to correct for losses and to determine the percent free. Pyridine (0.1%) was added to solvents to maintain the stability of 18-OH-DOC. Recovery after extraction was 58 +- 8 (S.D)%. The accuracy and precision of the method were acceptable, and a sensitivity of 2 pg per sample enabled the measurement of very low levels of 18-OH-DOC. High specificity was demonstrated by a low blank value (0 +- 0.2 pg) and by demonstrating that alternative paper chromatography separation systems gave results not differing significantly from those obtained by the present method. The mean 8AM plasma 18-OH-DOC level was 8.5 +- 1.2 ng per 100 ml in18 normotensive control subjects. There was a marked response of plasma 18-OH-DOC to ACTH stimulation and dexamethasone suppression and a significant increase after 3 hours upright posture.

Differences in cAMP levels in the gingival fluid of diabetics and nondiabetics.

Gingival fluid from eight control subjects and ten diabetics was collected and the content of cAMP and protein in the fluid was assayed to determine the nature of the biochemical changes occurring in the gingival fluid due to diabetes. The gingival fluid of the control subjects had a cAMP concentration of 2.4 X 10(-6) M, which was a hundredfold greater than that seen in serum, thus suggesting that the cAMP in the fluid resulted from active synthesis by the gingival cells and was not merely a transudate from the blood. The gingival fluid of the diabetics contained only one-seventh the level of cAMP seen in the control group. It is suggested that the decreased level of cAMP seen in the givgival fluid of diabetics may be a manifestation of a defect in the cAMP forming mechanism of the gingival tissue, which may reflect the systemic etiology of diabetes. It was also found that in the control subjects the content of cAMP in the gingival fluid was in inverse proportion to the volume of exudate in the gingival crevice. No such relationship was seen in the diabetic group. It appears that the level of cAMP present in the gingival fluid of normal individuals without any generalized endocrine deficiencies may be used as an additional indicator of the inflammatory status of the gingival tissues, along with the clinical evaluation based on gingival index.

Effects of blast overpressure on the ear: case reports.

The case histories of five patients who experienced blast overpressure in excess of 200-dB peak pressure level are presented. Despite the significance of the sound pressure levels received in a military training accident and the severe injuries that resulted from the blast, these individuals experienced substantial improvement of hearing 1 year later. Undoubtedly, successful surgical intervention and medical management were the primary contributors to the restoration of hearing. Audiometric data are presented documenting hearing status within 2 to 3 weeks postinjury and following final surgical remediation of the resulting middle ear damage. A review of these cases offers insight into the possible prognosis of patients with similar injuries.

Androgen dynamics and serum PSA in patients treated with abiraterone acetate.

BACKGROUND: We analyzed the potential of abiraterone acetate (henceforth abiraterone) to reduce androgen levels below lower limits of quantification (LLOQ) and explored the association with changes in PSA decline in metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: COU-AA-301 is a 2:1 randomized, double-blind, placebo-controlled study comparing abiraterone (1000 mg q.d.) plus low-dose prednisone (5 mg b.i.d.) with placebo plus prednisone in mCRPC patients post docetaxel. Serum testosterone, androstenedione and dehydroepiandrosterone sulfate from baseline to week 12 were measured by novel ultrasensitive two-dimensional liquid chromatography coupled to tandem mass spectrometry assays in a subset of subjects in each arm (abiraterone plus prednisone, n=80; prednisone, n=38). The association between PSA response (< or =50% baseline) and undetectable androgens (week 12 androgen level below LLOQ) was analyzed using logistic regression. RESULTS: A significantly greater reduction in serum androgens was observed with abiraterone plus prednisone versus prednisone (all P < or = 0.0003), reaching undetectable levels for testosterone (47.2% versus 0%, respectively). A positive association was observed between achieving undetectable serum androgens and PSA decline (testosterone: odds ratio=1.54; 95% confidence interval: 0.546-4.347). Reduction of androgens to undetectable levels did not occur in all patients achieving a PSA response, and a PSA response did not occur in all patients achieving undetectable androgen levels. CONCLUSIONS: Abiraterone plus prednisone significantly reduced serum androgens, as measured by ultrasensitive assays and was generally associated with PSA response. However, androgen decline did not uniformly predict PSA decline suggesting ligand-independent or other mechanisms for mCRPC progression.

Testosterone and bioavailable testosterone help to distinguish between mild Cushing's syndrome and polycystic ovarian syndrome.

Women with Cushing's syndrome (CS) and polycystic ovarian syndrome (PCOS) may present with similar symptoms. Subjects with mild CS lack clinical stigmata of classical CS and often have normal laboratory tests measuring hypercortisolism. Thus, distinguishing mild CS from PCOS may be difficult. We hypothesized that either total testosterone (TT) or bioavailable testosterone (BT) levels or the calculation of the free androgen index (FAI) would be low in patients with mild CS and elevated in patients with PCOS, and could help differentiate the two conditions. TT, BT, and FAI were measured in a group of 20 patients of reproductive age with mild CS and 20 PCOS patients matched for age and BMI. We used receiver operator characteristic (ROC) curves to assess the sensitivity and specificity of these measurements for the diagnosis of CS. TT (p<0.0001), BT (p=0.02), and FAI (p=0.003) were significantly elevated in PCOS patients compared to mild CS patients. Sex hormone-binding globulin was similar in both groups. The optimal cut-point for TT was 1.39 nmol/L, yielding a sensitivity of 95% and a specificity of 70%. The cut-point for BT was 0.24 nmol/L, resulting in a sensitivity of 75% and a specificity of 80%. The cut-point for FAI was 5.7, with a sensitivity of 88% and a specificity of 60%. We conclude that TT levels may be useful to discriminate between mild CS and PCOS. In patients with signs and symptoms consistent with CS and PCOS, a TT level of <1.39 nmol/L warrants a workup for CS.

Differential cross sections for collisions of hexapole state-selected NO with He.

The first measurements of differential inelastic collision cross sections of fully state-selected NO (j=12, Omega=12, epsilon= -1) with He are presented. Full state selection is achieved by a 2 m long hexapole, which allows for a systematic study of the effect of parity conservation and breaking on the differential cross section. The collisionally excited NO molecules are detected using a resonant (1+1') REMPI ionization scheme in combination with the velocity-mapped, ion-imaging technique. The current experimental configuration minimizes the contribution of noncolliding NO molecules in other rotational states j, Omega, epsilon--that contaminates images--and allows for study of the collision process at an unprecedented level of detail. A simple method to correct ion images for collision-induced alignment is presented as well and its performance is demonstrated. The present results show a significant difference between differential cross sections for scattering into the upper and lower component of the Lambda-doublet of NO. This result cannot be due to the energy splitting between these components.

Reconstruction of an axisymmetric image from its blurred and noisy projection.

The 3-D velocity distribution of ionized photofragments resulting from the dissociation of methyl iodide is recovered by digitally deblurring and Abel inverting a single measured 2-D projection. The reconstructed distribution reveals two rings which are the dissociation channels corresponding to ground state and excited state iodine. A factor of 1.6 in resolution improvement of the channels is achieved by deconvolving the 2-D projection using a line-by-line implementation of Kawata's reblur algorithm. This technique guarantees noise-smoothed projections for the notoriously sensitive Abel inversion procedure, which in this paper is implemented using discrete Fourier and Hankel transforms.