Progesterone as an autocrine/paracrine regulator of human granulosa cell proliferation. The present study examined the role of progesterone in regulating human granulosa cell proliferation. Human granulosa and luteal cells were obtained from follicular aspirates of women undergoing in vitro fertilization. Cells were plated at 5, 10, or 50 x 10(3) cells/mL and cultured for up to 6 days. At specific times, cells were harvested and assessed for cell number and morphology. The medium was assayed for progesterone. Cells plated at 50 x 10(3) cells/mL did not increase in number after 3 or 6 days of culture, but rapidly differentiated, secreting high amounts of progesterone (> or = 320 nmol/L). Conversely, cells plated at 5 x 10(3) or 10 x 10(3) cells/mL doubled in number over the first 3 days of culture and subsequently differentiated. The addition of 100 ng/mL progesterone or more to the medium inhibited proliferation. Aminoglutethamide blocked progesterone secretion and increased the number of cells present after 3 days of culture. The antiproliferative effects of progesterone were not mimicked by estradiol, testosterone, dihydrotestosterone, or dexamethasone and could not be overridden by epidermal growth factor, a potent mitogen. These data suggest that progesterone plays an autocrine/paracrine role in regulating granulosa cell proliferation.


Hyperinsulinemia in patients with hypercholesterolemia. An independent association between hypercholesterolemia and high insulin levels has not consistently emerged from large-scale epidemiologic observations. We selected 39 patients with elevated low-density (LDL) cholesterol levels but normal body weight, blood pressure, and glucose tolerance, and compared them to 36 normocholesterolemic, healthy control subjects accurately matched to the patients for age, gender, body mass index, and mean arterial blood pressure. Fasting serum total cholesterol concentrations and levels of LDL cholesterol, triglycerides, and apoprotein B were all higher in the patients with hypercholesterolemia than in controls (P < 0.025 or less), whereas high-density lipoprotein cholesterol and apoprotein A levels were significantly lower (P < 0.05 or less). Plasma insulin concentrations were elevated in hypercholesterolemic patients vs. controls both in the fasting state (86 +/- 6 vs. 59 +/- 8 pmol/L) and 2 h after a 75-g oral glucose load (412 +/- 16 vs. 276 +/- 18 pmol/L, P < 0.02 for both). Two-hour plasma glucose concentrations were also significantly raised in the patients (7.8 +/- 0.2 mmol/L) compared to controls (6.4 +/- 0.1 mmol/L, P < 0.025). In a multiple regression model including serum triglyceride concentrations, LDL cholesterol was still significantly related to both fasting and 2-h plasma insulin concentrations, contributing approximately 20% to the overall variability of these measures. Thus, in this group of patients with type IIa familial combined hyperlipoproteinemia hypercholesterolemia was associated with hyperinsulinemia even when controlling for other confounders (age, gender, body mass, glucose tolerance, and blood pressure).


Combining insulin-like growth factor-I and mean spontaneous nighttime growth hormone levels for the diagnosis of growth hormone deficiency. There is no gold standard for the diagnosis of GH deficiency. Recent data show that spontaneous GH levels may lack sensitivity, and that GH stimulation tests lack specificity as currently performed. Serum insulin-like growth factor-I (IGF-I) measurements lack both sensitivity and specificity. Some of these problems may be explained by nutritional effects. In children, overnutrition decreases GH and increases IGF-I, while undernutrition decreases IGF-I and increases GH. To overcome these difficulties and improve diagnostic accuracy, we combined mean spontaneous nighttime GH levels with IGF-I levels in a statistically based bivariate model. On a two-dimensional plot of mean spontaneous nighttime GH level (in SD units) vs. IGF-I level (in SD units), we defined a new variable, S (sum) score, where S = (1/square root of 2) x (nighttime mean GH SD+IGF-I SD). While IGF-I (SD) and the mean spontaneous nighttime GH (SD) showed a significant correlation with body mass index, the S score was independent of body mass. We, therefore, used the S score to define a new test for GH deficiency. A child failed this bivariate test if his S score was less than -2 SD. We applied this model to 47 normal children and 48 short or slowly growing children (all prepubertal). We measured spontaneous nighttime GH levels and IGF-I levels in all children. In addition, the short children underwent 3 GH stimulation tests. Forty-six of the 47 normal children passed the bivariate test for GH sufficiency. Twenty-three of the 48 short or slowly growing children failed the bivariate test, whereas only 11 children had an abnormally low mean spontaneous nighttime GH measurement alone. Sixteen of 23 children who were GH deficient by the bivariate test were also GH deficient by the stimulation tests. In summary, the bivariate test for GH deficiency appears 1) to be independent of body mass, unlike either IGF-I or GH individually; 2) to identify more children than the mean spontaneous nighttime GH level alone; and 3) to be highly specific in the normal population, unlike stimulation tests.


Insulin insensitivity in adrenal hyperplasia due to nonclassical steroid 21-hydroxylase deficiency. To determine whether hyperandrogenism caused by an inborn error of adrenal steroidogenesis could produce insulin resistance, we examined insulin sensitivity in females with 21-hydroxylase deficiency. Minimal modelling was used to analyze the results of tolbutamide-modified, frequently sampled, iv glucose tolerance testing. Insulin sensitivity [Si; (min-1) (microU/mL)-1] was plotted against body mass index (BMI; defined as kilograms per m2). Six patients with nonclassical 21-hydroxylase deficiency (mean age, 27 yr; mean BMI, 23.2) underwent testing. None of these patients was in active puberty, nor was any patient being treated with glucocorticoids at the time of the study. Twelve eumenorrheic nonhyperandrogenic young adult female control subjects (mean age, 27 yr; mean BMI, 22.4) were also tested. The basal 17-hydroxyprogesterone concentration, but not the total serum testosterone level, was significantly different in the two groups (mean +/- SEM, 11,987 +/- 2,761 vs. 4,059 +/- 802 pmol/L; P < 0.05). As a group the patients' Si values were significantly lower than those of the controls (mean +/- SEM, 4.1 +/- 0.6 vs. 9.7 +/- 1.2; P < 0.05). There was no correlation between Si and basal serum 17-hydroxyprogesterone, testosterone, delta 4-androstenedione, or dehydroepiandrosterone. We conclude that chronic hypersecretion of androgen precursors due to an inborn error of metabolism can induce a reduction in insulin sensitivity.


Identification and characterization of high molecular weight forms of basic fibroblast growth factor in human pituitary adenomas. Basic fibroblast growth factor (bFGF) extracted from 23 human pituitary adenomas and 2 nontumorous anterior pituitary glands was examined by Western blot analysis to elucidate their molecular forms. Four bands that specifically interacted with anti-bFGF antibody were identified at the regions of 16K, 18K, 22K, and 24K mol wt. These immunodetectable bFGFs were bound to a heparin-Sepharose affinity column and eluted with 1-2 M NaCl. These partially purified tumor extracts could stimulate dose-dependently the growth of FGF-responsive cells. Some tumors contained bFGF with a mol wt of 24 K as a dominant form. In contrast, a major form of bFGF at the region of 18K was identified in the nontumorous anterior pituitary glands. We also addressed the possible presence of FGF receptor mRNA using Northern blot analysis. Many, but not all, human pituitary adenomas were found to contain detectable levels of FGF receptor mRNA with a size of 3.5 kilobases. The present results suggest that the role of bFGF in growth and hormone secretion in human pituitary adenomas should be examined using high mol wt forms of bFGF.


The bio/immuno ratio of plasma luteinizing hormone does not change during the endogenous secretion pulse: reanalysis of the concept using improved immunometric techniques. The purpose of this study was to find out whether the ratio of bioactive (B)/immunoreactive (I) LH varies during pulsatile LH secretion in healthy men when I-LH is determined using novel immunometric methods with improved sensitivity and specificity. Blood samples were collected for LH measurements from eight healthy men (aged 20-26 yr) at 20-min intervals over a period of 10 h. LH was measured in all samples using two novel sensitive and specific immunometric methods [Delfia, Wallac (sensitivity, 0.04 IU/L); and Amerlite, Amersham (sensitivity, 0.1 IU/L)] and for comparison with a conventional RIA. In addition, the plasma samples representing the LH secretion peaks and the preceding interpulse nadirs (two to five pairs of samples per subject; n = 23) were measured for B-LH using the mouse interstitial cell in vitro bioassay. The three immunoassay methods demonstrated the well known pulsatile mode of I-LH secretion in all subjects. A good correlation of B- and immunometric I-LH levels was observed (bioassay vs. Delfia, r = 0.89), but independent of the immunometric method used, no difference could be demonstrated between the B/I ratios of the mean basal and peak levels of LH (1.72 +/- 0.19 and 1.63 +/- 0.19 with Delfia, and 2.18 +/- 0.32 and 2.10 +/- 0.26 with Amerlite, respectively). Only when I-LH was measured by RIA was there a significant (P < 0.001) 2-fold increase in the B/I ratio in the secretion pulses. In conclusion, the previously documented increase in the B/I ratio of LH during the endogenous secretion pulses could not be documented when I-LH was measured, instead of RIA, using the novel immunometric methods. This finding further emphasizes the need for reassessment of the B/I ratio changes in LH in various physiological and clinical conditions.


Use of ketoconazole to probe the pathogenetic importance of 1,25-dihydroxyvitamin D in absorptive hypercalciuria. Ketoconazole was used to probe the pathogenetic importance of the serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentration in 19 patients with well characterized absorptive hypercalciuria (AH). Patients were studied while receiving a constant metabolic diet before and after 2 weeks of ketoconazole administration (600 mg daily). Twelve of the patients were classified as ketoconazole responders, because in conjunction with a reduction of serum 1,25-(OH)2D from 113 +/- 36 to 70 +/- 26 pmol/L, intestinal 47Ca absorption decreased from 76.3 +/- 8.1% to 61.9 +/- 7.7%, and 24-h urinary Ca excretion declined from 7.6 +/- 1.4 to 5.7 +/- 1.1 mmol (P < 0.001 each). In these patients, intestinal 47Ca absorption was directly correlated with serum 1,25-(OH)2D levels and 24-h Ca excretion. In another group of 7 patients, termed ketoconazole nonresponders, despite reduction of 1,25-(OH)2D from 122 +/- 36 to 84 +/- 17 pmol/L (P = 0.015), there was no significant change in intestinal Ca absorption (76.0 +/- 8.2% to 72.1 +/- 10.6%) or 24-h urinary Ca excretion (7.3 +/- 1.3 to 7.2 +/- 1.0 mmol). In these patients, neither intestinal Ca absorption nor urinary Ca excretion was correlated with serum 1,25-(OH)2D levels. It, thus, appears that AH is a heterogeneous disorder comprised of both vitamin D-dependent and vitamin D-independent subsets. Although useful to probe the pathogenesis of AH, chronic treatment with ketoconazole is not recommended because of its generalized effects in inhibiting steroid synthesis.


Beta-endrophin immunoreactivity during human pregnancy. The human placenta has been implicated as a source of numerous peptide hormones during pregnancy. Since the immunoassay detection of the proopiomelanocortin derived peptide beta-endorphin (beta E) in placental extracts in 1978, it has remained uncertain whether placental beta E immunoreactivity (IR) is 1) secreted into the maternal circulation and 2) opiate receptor active during pregnancy. To elucidate the nature of beta E IR in the placenta, both beta E IR and N-alpha-acetylated beta E (Ac beta E) IR were simultaneously measured in extracts of human pituitaries, placentas, and plasma by two homologous RIAs. Pituitary extracts (n = 6) contained 38 +/- 7 nmol beta E IR per g wet wt tissue (mean +/- SEM), of which only 20 +/- 4 pmol/g were Ac beta E IR. Term placental extracts (n = 19) had 201 +/- 30 fmol/g wet wt total beta E IR and 30 +/- 3 fmol/g wet wt total Ac beta E IR, which comprised 15% of total beta E IR in placental extracts. Total plasma beta E IR rose from 28 weeks gestation (8.5 +/- 0.3 fmol/mL, n = 159) to peak at labor (50 +/- 4 fmol/mL, n = 98; P < 0.01) but total Ac beta E IR was found in only four 28-week (1.7 +/- 0.9 fmol/mL) and 42 labor plasma samples (0.9 +/- 0.1 fmol/mL). Gel filtration chromatography of placental and pituitary extracts showed that while less than 1% of the beta E31-size material was acetylated in the pituitary, up to 60% of the beta E31-size material in placental extracts was acetylated. In pooled third trimester plasma extracts, however, only 4% of the beta E31-size material was acetylated. Furthermore, the ratio of beta E31:beta-lipotropin in pituitary extracts (n = 3) was 0.5; pooled plasma-0.5, and placental extracts (n = 5)-1.2. These data indicate that 1) the placenta extensively N-alpha-acetylates beta E31 destroying its opiate bioactivity while the pituitary does not; 2) beta E IR in pregnant women's plasma is similar to pituitary beta E IR, being mostly nonacetylated and similar in size to beta-lipotropin. These findings are consistent with a pituitary source for the elevated plasma beta E IR found during late pregnancy which may, in turn, be a consequence of elevated plasma concentrations of placentally secreted plasma corticotropin-releasing factor IR present during the third trimester.


Serum growth hormone (GH)-binding protein/receptor: an important determinant of GH responsiveness. Individual growth rates (or responses to GH therapy) and adult heights vary over a wide range. The reasons for this variation are poorly understood. Based on the reciprocal relationship between GH production and serum GH-binding protein/receptor (GH-BP), we hypothesized that genetic growth potential was achieved by a specific combination of GH-BP/receptor and GH production in each individual. To address the question whether GH production regulates GH-BP, or vice versa, we studied GH-deficient children, where one of the parameters, GH exposure, could be controlled through exogenous administration. Forty-three untreated prepubertal GH-deficient children were studied before and after 6 and 12 months of GH replacement therapy (0.18 mg/kg.week). Growth velocity, height, bone age, weight and their respective Z scores, serum GH-BP, and serum insulin-like growth factor I (IGF-I) were measured at each time point. The patients responded with significant increases in serum IGF-I, age-adjusted growth velocity, and height (P < 10(-6) for all). Before therapy, GH-BP correlated directly with chronologic and bone age (P < 10(-4), but not with either growth velocity or IGF-I. In contrast, GH-BP correlated strongly with the response to therapy whether assessed as the incremental change in IGF-I (P < 10(-6)) or as the increase in growth velocity (P approximately 0.003). GH treatment had no consistent effect on GH-BP/receptor levels. These findings support the concept that the GH-BP/receptor endowment is characteristic for an individual and plays a pivotal role in somatic growth. The GH-BP/receptor system and its ontogeny appears relatively independent of regulation by GH. Differences in individual GH-BP/GH receptor complement account for some of the variability in the response to GH, and GH-BP levels may serve as a predictor for the degree of response. The reciprocal relationship between GH production and GH-BP in normal subjects probably results from adjustment of GH secretion to accommodate the prevailing GH-BP/receptor environment.


The role of body mass in the response to growth hormone therapy. Obesity is associated with normal or increased growth despite diminished GH secretion compared to lean children. The mechanism by which adequate growth is maintained in the presence of low GH levels is unknown, but is possibly mediated at the GH receptor level. To probe this hypothesis, we examined the relationship between GH responsivity, body mass index (BMI) and plasma GH-binding protein (GH-BP)/receptor level in 43 GH-deficient children during treatment with a fixed dose of GH (0.18 mg/kg.week). Before treatment, BMI [expressed as standard deviation score (SDS) for age (BMI-SDS)] did not correlate with either growth velocity or serum insulin-like growth factor-I (IGF-I). In contrast, after 12 months of GH therapy BMI-SDS correlated directly with plasma IGF-I (P < 10(-5)) and growth velocity (P < 10(-3)). These findings parallel those obtained for GH-BP vs. the response to GH, suggesting that BMI and GH-BP are covariants. The interrelationships among BMI, GH-BP, and response to GH were further probed by multiple regression analysis. Partial correlation coefficients vs. response to GH were consistently stronger for GH-BP than for BMI-SDS, indicating that GH-BP is the dominant factor between these two covariants in determining responsiveness to GH. The data suggest a primary role for GH-BP/receptor levels in determining GH action, with secondary but significant effects of nutrition and degree of adiposity. The latter may be mediated through the impact of nutrition and body mass on GH-BP/receptor levels.


Immunoreactive androgen receptor expression in subjects with androgen resistance. Individuals with androgen resistance encompass a spectrum of phenotypic abnormalities ranging from complete testicular feminization to undervirilized men. Such subjects have been classified according to the hormone-binding characteristics in genital skin fibroblasts and on the basis of the mutation in the androgen receptor (AR) gene. Antibodies to the amino-terminal region of the human AR were used to develop an immunoblot assay for the comparison of androgen binding with the amount of AR expressed in genital skin fibroblasts. In controls and 4 androgen-resistant subjects with DNA-binding domain mutations, levels of immunoreactive AR correlated closely with androgen-binding capacity. In 15 androgen-resistant subjects with qualitatively abnormal AR, immunoreactive AR levels tended to be higher than predicted from the ligand-binding capacity. Discordance between immunoreactivity and androgen binding also occurred in fibroblasts from 3 other subjects. One carries a stop codon in the AR gene and produces a truncated AR that is immunoreactive but does not bind androgen. Two carry single point mutations in the hormone-binding domain and produce immunoreactive AR that is normal in size but does not bind androgen.


Effect of improved assay sensitivity on luteinizing hormone pulse detection after gonadotropin-releasing hormone antagonist treatment in man. When serum levels of a hormone are at or below the detection limit of the measurement system, accurate characterization and quantitation of pulsatile hormone secretion may be difficult. This point is well illustrated in this study, which used two immunoassays with markedly different assay sensitivities to quantitate pulsatile LH secretion in men in whom serum LH levels had been suppressed by the administration of a GnRH antagonist. Five normal men received 5 mg Nal-Glu, sc, daily for 21 days. Blood was drawn at 10-min intervals over 8 h on days 0 and 21. Samples were assayed in triplicate in both a conventional LH RIA with a sensitivity of 0.6-1.0 IU/L and a two-site-directed ultrasensitive immunofluorometric assay (IFMA) with assay sensitivity ranging from 0.05-0.125 IU/L. LH pulses were analyzed by Cluster analysis (C) and were corroborated by the Detect algorithm (D). Nal-Glu suppressed LH (C) pulse amplitude from 4.0 +/- 0.7 to 0.40 +/- 0.03 IU/L by LH RIA and from 7.8 +/- 2.1 to 0.21 +/- 0.04 IU/L by LH IFMA. An apparent reduction in LH pulse number was observed in the RIA data on day 21 by both pulse detection methods [4.2 +/- 0.4 vs 2.4 +/- 0.2/8 h on days 0 and 21 by C (P < 0.005); 5.8 +/- 0.8 vs. 2.8 +/- 0.7 by D (P < 0.05)]. However, the IFMA measurements in the same samples using the more sensitive LH IFMA showed no difference in pulse number between days 0 and 21. The RIA data correlated well with the IFMA data, with a concordance coefficient ranging from 0.66-0.9. In summary, the Nal-Glu GnRH antagonist markedly decreases LH pulse amplitude, but not pulse frequency. These observations are consistent with competitive inhibition of GnRH action at the pituitary site by the Nal-Glu antagonist; they indicate that assay characteristics can significantly affect quantitation of hormone pulse pattern and underscore the need for ultrasensitive LH assays for accurate assessment of LH pulse characteristics when LH levels are low or suppressed.


Antithyroid hormone antibodies induced by interferon-alpha. A 40-yr-old woman known for a multinodular goiter had hyperthyroidism. Treatment with antithyroid drugs and iodine therapy was effective. One year later, she received interferon-alpha for treatment of essential cryoglobulinemia. At that time, the patient was euthyroid. Testing for antithyroglobulin, antimicrosome, anti-TSH receptor, and antithyroid hormone antibodies was negative. After a 1-yr course of interferon-alpha, goiter enlargement was noticed. Apparently elevated free T3 and T4 serum values were measured by RIA, contrasting with clinical euthyroidism and normal TSH values. High serum levels of antithyroid hormone antibodies were found in the patient's serum, using a radiolabeled hormone immunoprecipitation assay. Antithyroglobulin and antimicrosome antibodies titers were also elevated and paralleled antithyroid hormone antibodies. After cessation of interferon-alpha therapy, clinical status and TSH levels remained normal, while thyroid hormone values and antithyroid hormone antibody levels progressively normalized. To our knowledge, this is the first report of antithyroid hormone antibodies induced by interferon-alpha. Since thyroid dysfunction is described in 10-15% of treated patients, the fact that interferon-alpha can induce antithyroid hormone antibodies has important implications: 1) the prevalence or intensity of thyroid dysfunction could be overestimated; and 2) artifactually elevated free T3 and T4 serum values could lead to inappropriate therapy of thyroid disease or cessation of interferon treatment.


Renal clearance, metabolic clearance rate, and half-life of human growth hormone in young and aged subjects. We studied the renal clearance, MCR, and half-life of the synthetic 22K form of human GH [recombinant hGH (rhGH)] in seven healthy young and five aged men by means of the constant iv infusion technique. rhGH was infused at a rate of 2 micrograms/kg.2 mL/h for 150 min, after which its disappearance was followed for 50 min. Changes in GH levels in plasma and urine were measured by a highly sensitive enzyme immunoassay. The mean (+/- SD) renal clearance of GH was significantly greater in the aged group than in the young group (14.3 +/- 2.5 vs. 4.2 +/- 1.0 microL/min; P < 0.05). The mean MCR was greater in the young group than in the aged group (187.1 +/- 43.7 vs. 120.5 +/- 39.5 mL/min; P < 0.05), but the MCR adjusted for body weight was not different between the two groups (2.9 +/- 0.6 vs. 2.3 +/- 0.8 mL/min.kg). No difference was noted in the half-life of GH between the two groups (13.8 +/- 0.9 vs. 14.2 +/- 0.4 min). These findings indicate that GH reabsorption from the renal tubule may be impaired in elderly subjects, but the disappearance rate of GH is not influenced by age.


Estradiol stimulates cell growth and secretion of procathepsin D and a 120-kilodalton protein in the human ovarian cancer cell line BG-1. Ovarian cancers are highly invasive. In a first attempt to define the hormones and factors involved in the control of tumor invasion and metastasis, we have used the human ovarian cancer cell line BG-1 which contains both estrogen and progesterone receptors. Protein synthesis and secretion was assayed by [35S]methionine incorporation and polyacrylamide gel electrophoresis followed by fluorography. Three responses to estradiol were found: 1) procathepsin D secretion was increased, whereas the corresponding intracellular proteins were not significantly affected; 2) an abundant but nonidentified 120-kilodalton (kDa) estrogen-induced secreted glycoprotein, different from CA125, was detected for the first time; and 3) the number of cells as determined by DNA assay was markedly stimulated, reaching a higher level of confluency. The antiestrogen OH-tamoxifen was weakly agonist at low concentrations to stimulate cell growth but was a pure antagonist on the 120-kDa protein. The steroid specificity of these responses strongly suggests that they are mediated by the estrogen receptor. We conclude that cathepsin D secretion is specifically stimulated by estrogen in this ovarian cancer cell line as it is in estrogen receptor-positive breast cancer cells. Both cathepsin D and a newly described 120-kDa secreted glycoprotein are potential markers of hormone responsiveness and/or aggressiveness which deserve to be further studied in clinical ovarian cancers.


The effects of exogenous testosterone on sexuality and mood of normal men. The effects of supraphysiological levels of testosterone, used for male contraception, on sexual behavior and mood were studied in a single-blind, placebo-controlled manner in a group of 31 normal men. After 4 weeks of baseline observations, the men were randomized into two groups: one group received 200 mg testosterone enanthate (TE) weekly by im injection for 8 weeks (Testosterone Only group), the other received placebo injections once weekly for the first 4 weeks followed by TE 200 mg weekly for the following 4 weeks (Placebo/Testosterone group). The testosterone administration increased trough plasma testosterone levels by 80%, compatible with peak testosterone levels 400-500% above baseline. Various aspects of sexuality were assessed using sexuality experience scales (SES) questionnaires at the end of each 4-week period while sexual activity and mood states were recorded by daily dairies and self-rating scales. In both groups there was a significant increase in scores in the Psychosexual Stimulation Scale of the SES (i.e. SES 2) following testosterone administration, but not with placebo. There were no changes in SES 3, which measures aspects of sexual interaction with the partner. In both groups there were no changes in frequency of sexual intercourse, masturbation, or penile erection on waking nor in any of the moods reported. The Placebo/Testosterone group showed an increase in self-reported interest in sex during testosterone treatment but not with placebo. The SES 2 results suggest that sexual awareness and arousability can be increased by supraphysiological levels of testosterone. However, these changes are not reflected in modifications of overt sexual behavior, which in eugonadal men may be more determined by sexual relationship factors. This contrasts with hypogonadal men, in whom testosterone replacement clearly stimulates sexual behavior. There was no evidence to suggest an alteration in any of the mood states studied, in particular those associated with increased aggression. We conclude that supraphysiological levels of testosterone maintained for up to 2 months can promote some aspects of sexual arousability without stimulating sexual activity in eugonadal men within stable heterosexual relationships. Raising testosterone does not increase self-reported ratings of aggressive feelings.


Spontaneous pulsatile growth hormone release in male and female premature infants. Although premature infants have high umbilical cord GH levels, little is known about spontaneous GH release in these individuals. The purpose of our study was to investigate spontaneous 12-h GH release in appropriate for gestational age male and female premature infants. We studied 22 premature infants (15 males and 7 females) of appropriate length and weight for age. Gestational ages, birth weights, birth lengths, and ages at the time of study were similar in male or female infants. All infants were biochemically euthyroid. Blood was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double antibody RIA, using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor-I and -II (IGF-I and -II) levels were measured after separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences were found between males and females in the pulse characteristics of frequency, maximal amplitude, incremental amplitude, width, or area. The GH pulse frequency per 12 h was 3.2 +/- 0.3 (mean +/- SE) in males and 3.0 +/- 0.7 in females. The maximal pulse amplitude was 50.7 +/- 6.2 micrograms/L in males and 44.7 +/- 9.0 micrograms/L in females. The incremental pulse amplitude was 24.3 +/- 3.2 micrograms/L in males and 20.2 +/- 3.9 micrograms/L in females. The mean 12-h GH level was 37.1 +/- 4.8 micrograms/L in males and 35.8 +/- 8.5 micrograms/L in females; the average GH nadir was 26.1 +/- 4.0 micrograms/L in males and 24.4 +/- 8.3 micrograms/L in females. Both IGF-I and IGF-II concentrations were similar in males and females. The mean IGF-I levels were 10.7 +/- 1.5 ng/mL in males and 7.5 +/- 1.1 ng/mL in females; IGF-II levels were 96.0 +/- 12.0 ng/mL in males and 115.4 +/- 17.1 ng/mL in females. These results demonstrate similar pulsatile GH release in male and female premature infants at a mean age of 32-33 weeks. Compared with previously reported values for mean GH concentration and average GH nadir in older children, the values in these premature infants were much higher. We speculate that the higher GH levels in premature infants may result from decreased negative feedback associated with low IGF-I levels. The premature infant's somatotrophs may also not fully respond to the GH inhibitory action of somatostatin.


Tertiary hyperparathyroidism during high phosphate therapy of familial hypophosphatemic rickets. We report the development of severe tertiary hyperparathyroidism in three girls treated for familial hypophosphatemic rickets and characterize parathyroid function in vivo and in vitro. All patients had been previously treated with relatively large doses of inorganic phosphorus (125 mm/day) and ergocalciferol or calcitriol for several years and had radiographic evidence of long-standing hyperparathyroidism. Even in the presence of extremely elevated PTH levels, oral phosphate lowered serum calcium levels in vivo and further stimulated PTH secretion. Profound multiglandular parathyroid hyperplasia was found in each patient at surgery. Examination of the secretory characteristics of the excised parathyroid tissue revealed that either relatively high calcium concentrations were generally needed to suppress PTH secretion or PTH secretion was not suppressible. Caution is recommended when relatively large doses of phosphate are used to treat familial hypophosphatemic rickets.


Virilizing adrenal cortical neoplasm arising ectopically in the thorax. We describe a 44-yr-old woman with a 12-yr history of clinical virilization and serum testosterone levels up to 28.1 nmol/L (normal range, 1-3.3 nmol/L) in whom repeated clinical evaluation and surgical procedures failed to reveal the source of androgen production. At the time the patient was referred to the Clinical Center of the NIH, an intrathoracic mass was seen on upper cuts of an abdominal computer-aided tomography scan, confirmed by computer-aided tomography scan and magnetic resonance imaging of the chest. A 6 x 5 x 3.5-cm mass, attached to the posterior pericardium, was removed by thoracotomy. Pathological examination revealed an adrenal cortical neoplasm of uncertain malignant potential that contained testosterone, 11-deoxycortisol, progesterone, and 17-hydroxyprogesterone. After the operation, the patient's serum testosterone levels decreased to the normal range. Ectopic adrenal cortical rests in the thorax and neoplasms arising from these rests are extremely rare, and we are not aware of a similar case previously reported. In women with virilization, radiological studies of the thorax as well as other reported sites of ectopic adrenal cortex should be performed if radiological studies of the abdomen and pelvis fail to locate the source of the neoplasm.


Heritability of cortisol responses to human corticotropin-releasing hormone, ergometry, and psychological stress in humans. The present study investigated cortisol responses to three different stimulation procedures, with a focus on the contribution of genetic factors. Thirteen monozygotic (MZ) twin pairs and 11 dizygotic (DZ) twin pairs performed bicycle ergometry until exhaustion and were exposed to the psychological stress of public speaking and mental arithmetic in front of an audience. Furthermore, 9 MZ pairs and 10 DZ pairs were injected with 100 micrograms synthetic human CRH (hCRH). The adrenocortical response to these challenges was monitored by determination of cortisol in saliva. Significant intraindividual stability of baseline cortisol levels was found in females, but was less in males. Maximum cortisol responses to all three stimulation procedures were significantly intercorrelated in males, but in females only the cortisol responses to hCRH and ergometer exercise showed a significant correlation. While a decided influence of genetic factors was observed for all three baseline cortisol levels as well as for the response to hCRH, heredity appeared to be play a minor role in the adrenocortical response to psychological stress. Cortisol changes after bicycle ergometry revealed no impact of genetic factors on the secretion of cortisol in response to strenuous physical exercise.


Longitudinal changes in lumbar bone density among thyrotoxic patients after attainment of euthyroidism. Hyperthyroidism increases bone turnover, which, in turn, may lead to bone loss from the spine and hip. Treatment of thyrotoxicosis may restore bone mass, but there are few long term prospective studies. We examined lumbar bone mineral density (BMD) in 21 subjects [11 with hyperthyroidism (HT) and 10 controls of similar age] by dual photon absorptiometry in 1986 and by dual energy x-ray densitometry in 1991. All 11 HT patients were successfully treated and remained euthyroid (mean TSH, 2.25 +/- 0.80 mU/L) for more than 3 yr. Lumbar BMD increased 11.03 +/- 2.38% (P < 0.001) in HT patients, but only 2.6 +/- 2.15% (P = 0.10) in control subjects. Among HT patients, the higher the T3 concentration during hyperthyroidism, the greater the subsequent increase in lumbar BMD (r = 0.72; P < 0.03). Age at treatment, in contrast, was not a significant predictor of eventual spinal bone mass. In conclusion, successful treatment of hyperthyroidism produced a significant increase in lumbar BMD. Hence, bone loss associated with thyrotoxicosis may not be permanent. Future work designed to examine the effect of thyroid hormone on skeletal homeostasis should include large scale longitudinal studies of both men and women.


Different posttranslational processing of human preprothyrotropin-releasing hormone in the human placenta and hypothalamus. We scrutinized the possible existence of human prepro-THR messenger RNA (mRNA) and of its posttranslational processing products in the human placenta. Human placental mRNA of preproTRH was found to have a single species identical to that predicted from the hypothalamic mRNA, and could be reverse transcribed to complementary DNA (cDNA) encoding preproTRH in a size similar to the hypothalamic counterpart by means of reverse-transcriptase-polymerase chain reaction. Five different intervening peptides, designated human TRH-associated peptide (hTAP) [hTAP-1, preproTRH(90-111); hTAP-2, preproTRH(120-132); hTAP-3, preproTRH(141-149); hTAP-4, preproTRH(158-183); hTAP-5, preproTRH(192-224)], and a TRH precursor comprising the TRH progenitor sequence (octa-TRH) were synthesized, and six different antisera raised against individual peptides were used to develop specific RIA systems. Significant concentrations of hTAP-5 and octa-TRH-like immunoreactivities were quantitated in acid extracts of human placentae. In human hypothalamic extracts, immunoreactivities of hTAP-3, hTAP-4, hTAP-5, and octa-TRH, were apparently detected. Chromotographic analysis showed a single peak corresponding to each authentic peptide in RIA systems of hTAPs detected. In placentae, a single peak of octa-TRH-like substance was observed, and two octa-TRH-like substances with different molecular weights detected in hypothalami. The present data indicate that unique posttranslational processing steps of human preproTRH differ in human placentae and hypothalami, and that the human tissues involve profound amounts of several preproTRH-related peptides which do not comprise the TRH progenitor sequence.


Presence of messenger ribonucleic acid for endothelin-1, endothelin-2, and endothelin-3 in human endometrium and a change in the ratio of ETA and ETB receptor subtype across the menstrual cycle. The aim of the present study was to determine whether mRNA for the three endothelin peptides (endothelin-1, endothelin-2, and endothelin-3) and the two known receptor subtypes (ETA and ETB) was present in human endometrium at different stages of the menstrual cycle (menstrual, early and mid-proliferative, and early, mid-, and late secretory). Endometrium was obtained from women undergoing surgery for benign disease, and total RNA was extracted using a guanidinium isothiocyanate method. mRNA for endothelin peptide and receptor was detected using the reverse transcriptase-polymerase chain reaction with nested oligonucleotide primers. mRNA for endothelin-1, endothelin-2, and endothelin-3 was demonstrated throughout the menstrual cycle, and three splice variants of mRNA encoding endothelin-3 were found in all samples. The ratio of ETA to ETB receptor mRNA was found to change throughout the menstrual cycle. In the proliferative phase, amplified cDNA product was almost exclusively confined to the ETA receptor, whereas an increase in the amplified product of the ETB receptor cDNA was seen in the secretory and menstrual phases. These studies show that mRNA for endothelin-1, endothelin-2, and endothelin-3 is present in human endometrium at all stages of the menstrual cycle and suggest that different physiological actions of the endothelin peptides may be mediated through changes in the ratio of the ETA and ETB receptor subtypes.


The natural history of autonomous gonadal function, adrenarche, and central puberty in gonadotropin-independent precocious puberty. Gonadotropin-independent precocity (GIP) is a syndrome marked by precocious pubertal development in the absence of pubertal levels of gonadotropins. To investigate the discrete patterns of central nervous system, gonadal, adrenal, and skeletal maturation in this syndrome, we conducted longitudinal studies spanning up to 10 yr in two such affected individuals. A cross-sectional analysis of adrenal androgen secretion was performed in nine additional patients to assess further the time course of adrenarche in GIP. Serial evaluations revealed progression of secondary sexual characteristics, statural growth, and skeletal maturation, all consistent with ongoing exposure to pubertal gonadal steroid levels. On the other hand, adrenarche (n = 11) and spontaneous and GnRH-stimulated gonadotropin secretion (n = 2) progressed in chronological age-appropriate manners despite long term pubertal levels of gonadal sex steroid secretion. After the development of central puberty, as documented by the appearance of pulsatile gonadotropin secretion, we sought to determine whether the potential for gonadal autonomy persisted. Despite complete pituitary desensitization induced by administration of a GnRH agonist, both patients studied demonstrated an ongoing capacity to secrete pubertal levels of gonadal steroids. Our study suggests that the timing of adrenarche and central puberty in these subjects with GIP was apparently unaltered by prolonged exposure to gonadal steroids. Subsequent to the development of central puberty, pulsatile gonadotropin secretion may override and, thus, mask the underlying defect(s) in adolescents and adults with histories of GIP.


Relative effects of activin and inhibin on steroid hormone synthesis in primate granulosa cells. Ovarian granulosa cells produce inhibin and activin, structurally related proteins with potentials to directly modulate follicular steroidogenesis. The aim of the present study was to compare development-related effects of inhibin-A and activin-A on steroidogenesis in marmoset monkey (Callithrix jacchus) granulosa cells. Granulosa cells from "immature" (< 1.0 mm diameter) and "mature" (> 2 mm diameter) follicles were incubated in serum-free culture medium for 96 h with and without peptide (1-100 ng/mL), in the presence and absence of gonadotropins [human (h) FSH or hLH] (10 ng/mL). Spent medium was collected and stored frozen for progesterone assay. Aromatase activity was determined by incubating cells for a further 6 h in the presence of 1 mumol testosterone and assaying accumulation of oestradiol. Granulosa cells from immature follicles showed characteristically low basal rates of steroid synthesis that were unaffected by treatment alone with either inhibin or activin. Treatment with hFSH stimulated both progesterone production and aromatase activity. Cotreatment with activin and hFSH further enhanced aromatase activity by up to 4-fold. The progesterone response to activin plus hFSH was related to the effect of hFSH in the absence of activin: high-level responsiveness to hFSH was suppressed by activin while low-level responsiveness was enhanced. Inhibin had no significant effect on FSH-responsive progesterone production, but at high concentrations (> 10 ng/mL) it caused slight (up to 30%) reduction in FSH-induced aromatase activity. Granulosa cells from mature follicles showed relatively high basal rates of steroidogenesis, and treatment with inhibin did not influence either basal or gonadotropin responsive steroidogenesis. Treatment with activin had divergent effects on aromatase activity and progesterone synthesis in that it increased both basal and hLH-responsive aromatase activity (up to 11-fold), had no effect on basal progesterone production, and markedly suppressed (by more than 50%) the progesterone response to hLH. These data reveal development-dependent effects of inhibin and activin on granulosa cell steroidogenesis that are likely to have physiological relevance to ovarian function in vivo.


Both hyper- and hypogonadotropic hypogonadism occur transiently in acute illness: bio- and immunoactive gonadotropins. Previous reports of hypogonadotropic hypogonadism in critically ill men may not reflect the complexity of changes in the hypothalamic-pituitary-gonadal (HPG) axis during acute illness. We sampled blood throughout hospitalization in 55 men admitted to acute care units to delineate the spectrum of changes in circulating gonadotropin and sex steroid levels at the onset and during recovery from acute illness. Bioactive LH and FSH were measured in a subset of patients. Percent free testosterone was measured to assess changes in binding to sex hormone binding globulin. Medications and serum estrogen and prolactin levels were monitored as potential causes of hypogonadotropism. Sustained suppression of serum testosterone levels below the normal range occurred in 62% of men with varying diagnoses and disease severity. Percent free testosterone remained constant. Hypogonadotropism was observed in most men (60%) and occurred independently from head injury, surgery, medications, or hyperprolactinemia. In a subset of men (n = 16), LH and/or FSH rose transiently above the normal range. Bioactivity of both LH and FSH remained constant while serum testosterone levels decreased. In contrast to serum testosterone levels, mean serum levels of E1, E2 and androstenedione were not less than control values. We conclude that both primary and secondary hypogonadism occur transiently in acutely ill men and cannot be explained solely by medications, hyperprolactinemia, or hyperestrogenemia. Neither biopotency of gonadotropins nor binding of testosterone to SHBG change across the course of acute illness. The hypogonadism, often severe and prolonged, may contribute to the persistent catabolic state observed in many critically ill patients.


Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus. Glucokinase is thought to play a glucose-sensor role in the pancreas, and abnormalities in its structure, function, and regulation can induce diabetes. We isolated the human glucokinase gene, and determined its genomic structure including exon-intron boundaries. Structure of the glucokinase gene in human was very similar to that in rat. Then, by screening Japanese diabetic patients using polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) and direct-sequencing strategies, we identified a missense mutation substituting arginine (AGG) for glycine (GGG) at position 261 in exon 7 of the glucokinase gene in a patient with early-onset non-insulin-dependent diabetes (NIDDM).


Glucose regulation of the autoantigen GAD65 in human pancreatic islets. Recent data suggest that the enzyme glutamic acid decarboxylase (GAD) may be a primary beta-cell antigen involved in the autoimmune response leading to insulin dependent diabetes mellitus (IDDM). Following three days culture of human islets at different glucose concentrations (5.6, 11 or 28 mM), there was a single 65 kDa/GAD band in the islet extracts, as assessed by immunoprecipitation both with serum from a newly diagnosed IDDM patient and a sheep anti-GAD serum. The synthesis of GAD was strongly stimulated at the higher glucose concentrations. Likewise, Western blot analysis indicated a glucose-induced increase of GAD in the islets. The data suggest that an enhanced function of human islet cells increases expression of GAD65. Possibly, this could exacerbate the autoimmune assault in the early stages of IDDM, and be of practical importance in attempts to ameliorate the autoimmune response towards the beta-cells in IDDM.


An endoscopic study of antibiotic-associated hemorrhagic colitis. Colonoscopy was performed on acute stage within 72 hours from onset in 48 patients with antibiotic-associated hemorrhagic colitis (AAHC). From our observations we have developed a new endoscopic classification of AAHC and investigated the incidence of each finding in further detail. We have classified in principle the endoscopic findings of the 48 subjects into two groups: major and minor ones respectively. Category of major findings were: 1) diffuse mucosal hemorrhage (100%); 2) spotty mucosal hemorrhage (100%), and 3) linear mucosal hemorrhage (22.9%), while minor findings were: 1) irregular ulcers in 10.4%; 2) aphthoid ulcers in 6.3%, and 3) linear erosions or ulcers in 4%. Minor findings were ulcers or erosions present over the hemorrhagic mucosa associated with the moderate degree of inflammation. A histopathologic study of colon biopsy specimens from 24 patients with AAHC showed hemorrhage and inflammatory cell infiltration in the lamina propria mucosae varying from mild to moderate in extent. It was concluded that AAHC was a colonic mucosal hemorrhagic disease caused by the destruction of mucosal vessels from unknown causes and in this disease mild to moderate inflammation was partially followed by ulceration over the edematous and hemorrhagic mucosa of the colon.


[Changes in spinal evoked potentials caused by spinal blood flow obstruction and acidosis]. The effects of partial obstruction of blood flow and mixed type acidosis on the conduction spinal evoked potentials (C-SEP) were studied in cats anaesthetized with sodium pentobarbitone and immobilized with d-tubocurarine. Following the ligation of some intercostal arteries, changes in the C-SEP occurred: the amplitudes showed either an increase or a decrease, while the latencies were uniformly prolonged. Mixed-type acidosis resulting from a decrease in the respiratory minute volume led to a decrease in the amplitudes and an increase in the latencies. The above findings indicate that not only mechanical (obstruction of the blood flow) but also metabolic (mixed-type) factors lead to changes in the C-SEP. It is therefore important to take these factors into account and the waveform of the C-SEP should be interpreted in terms of amplitude and latency.


Enterovesical fistula caused by inflammatory bowel diseases. Enterovesical fistula caused by inflammatory bowel diseases is a rare disorder. Two male patients with recurrent cystitis had sigmoid colon diverticulitis causing enterovesical fistula. One female patient with Crohn's disease developed enterovesical fistula with abdominal and urinary symptoms. In each patient, a barium enema revealed causative bowel diseases. The precise diagnosis of enterovesical fistula was made either by cystography or cystoscopy. One-stage resection of the inflamed bowel with fistula and affected the bladder wall was proved to be an effective treatment for these three patients, while a long term follow up is specifically necessary in the patient with Crohn's disease.


The P300 wave of the human event-related potential. The P300 wave is a positive deflection in the human event-related potential. It is most commonly elicited in an "oddball" paradigm when a subject detects an occasional "target" stimulus in a regular train of standard stimuli. The P300 wave only occurs if the subject is actively engaged in the task of detecting the targets. Its amplitude varies with the improbability of the targets. Its latency varies with the difficulty of discriminating the target stimulus from the standard stimuli. A typical peak latency when a young adult subject makes a simple discrimination is 300 ms. In patients with decreased cognitive ability, the P300 is smaller and later than in age-matched normal subjects. The intracerebral origin of the P300 wave is not known and its role in cognition not clearly understood. The P300 may have multiple intracerebral generators, with the hippocampus and various association areas of the neocortex all contributing to the scalp-recorded potential. The P300 wave may represent the transfer of information to consciousness, a process that involves many different regions of the brain.


Jerk-locked averaging: technique and application. Jerk-locked averaging (JLA) is used to record the timing and distribution of brain activity preceding brisk involuntary movements such as those observed in patients with myoclonus. JLA is capable of revealing a premyoclonus spike in the absence of paroxysmal activity in the routine EEG. The technique of JLA is described together with a consideration of the way in which the presence or absence of premyoclonus activity and the somatosensory evoked potential (SEP) can help to classify patients with involuntary movement disorders. The relationship between the premyoclonus spike and the N25-P33 complex of the SEP is discussed. Although the most common finding in patients with myoclonus of cortical origin is a large, well-defined positive-negative spike with the positive peak occurring about 20 ms before electromyographic onset, a wide variety of time relationships and topographies has been observed in other disorders of involuntary movement and some of these are described. The lack of correlation between the apparent origin of the premyoclonus spike in motor cortex and pathology in patients with myoclonus is discussed.


Invasive recording of movement-related cortical potentials in humans. Movement-related cortical potentials (MRCPs), especially the premovement components seen only in association with voluntary movements, may represent the higher brain functions related to preparation for voluntary movements. Recent advances in many aspects (single unit and field potential recordings in animals, intracranial recording of MRCPs in epileptic patients, magnetoencephalography, and positron emission tomography) have provided new information about the physiological significance of MRCPs. In contrast to the findings on scalp recordings, in which the early potentials prior to movement onset are seen more widely, the main cortical generators appear to be discretely localized in bilateral primary and supplementary motor areas with a contralateral predominance. This review outlines the findings in scalp-recorded MRCPs and compares them with the results of invasive recordings, paying special attention to their physiological significance.


Evaluation of dementia by event-related potentials. Event-related potentials depend on the context of the target stimulus and relate to the cognitive aspects of discriminating target from nontarget stimuli. For clinical purposes, they are elicited most commonly by auditory stimuli. They are influenced by advancing age and by alterations in mental function. They have been used to distinguish dementia from pseudodementia. More specifically, the P3 component of these potentials has a high sensitivity and specificity to dementia, and a prolongation in P3 latency is therefore helpful in establishing the diagnosis of dementia with confidence. Serial studies can provide a means of following changes in cognitive function over time. It may also be possible to distinguish between different types of dementia by the pattern of electrophysiologic abnormalities and in particular by which components of the event-related potentials are delayed.


The split rib bundle graft in mandibular reconstruction. This article describes a modified technique for the use of free non-vascularized split ribs (bound together in the form of a tight bundle), to reconstruct different types of mandibular defects. Experience gained over the last 4 years in treating 38 patients with different pathological lesions is presented. The procedure, carried out simultaneously with bone resection proved to be highly effective in providing mesio-distal spanning of the defect, adequate mandibular height as well as bucco-lingual thickness. This technique utilizes the different theories of osteogenesis: (a) from the periosteal cells, (b) from the transplanted living osteocytes and from (c) stimulating host mesenchymal cells to form new bone by bone induction. The surgical technique, results and conclusions are presented in this report.


Control of vertical dimension during maxillary orthognathic surgery. A clinical trial comparing internal and external fixed reference points. The accuracy of vertical control during maxillary orthognathic surgery was assessed in 45 patients, comparing the use of traditional internal measurements across the osteotomy lines (15 subjects) with measurements between the incisor teeth and an external reference point consisting of a bone screw placed at nasion (two groups of 15 subjects each). Although use of a fixed external reference point can significantly decrease positioning error (p < 0.001), considerable care is required during application of rigid fixation to maintain the correct vertical dimension.


Ultrasound imaging of the TMJ disc in asymptomatic volunteers. Preliminary report. The position of the TMJ disc in 23 asymptomatic volunteers was determined by ultrasonography imaging. A very low incidence (2.1%) of internal derangements was revealed. The results are discussed in the light of current concepts on the aetiology of TMJ internal derangements. Since ultrasound imaging makes possible noninvasive dynamic investigation of the TMJ arrangements, performance of a prospective long-term study including a sufficiently large group of volunteers is suggested to clarify further the real incidence of TMJ internal derangements.


The treatment of the fractured edentulous maxilla. The results of a follow-up of 13 out of 21 patients treated for fractures of the edentulous maxilla are presented. They were treated alternatively with craniofacial suspension wiring and with miniplate osteosynthesis. Better results are achieved by miniplate osteosynthesis. Depending on the general condition of the patient, a treatment scheme can be recommended.


Surgical versus non-surgical treatment of fractures of the articular process of the mandible. In a clinical, radiographic and angiographic study, we reinvestigated 34 patients with dislocated fractures of the condylar neck. 20 of them had been treated by open reduction, 14 in a conservative-functional way. The clinical results were nearly equal in both groups. The instrumental registration and the X-ray findings showed considerable deviations in the joint physiology in the conservative group. 19 of 20 patients operated on showed near-anatomical reconstruction with good functional results.


Axial 'anchor' screw (lag screw with biconcave washer) or 'slanted-screw' plate for osteosynthesis of fractures of the mandibular condylar process. Almost a quarter of all mandibular fractures are located in the condylar neck region and generally lead to disturbances of occlusion. Because they still possess active growth centres, children and adolescents can take advantage of the joint's remodelling capacity following conservative treatment of these fractures. Fractures with displacement of the condylar head in adults can interfere with function if they are not surgically reduced (Krenkel and Strobl, 1989). In addition, a compensatory overloading of the non-fractured side, which originally goes unnoticed, can bring about disc pathology and chronic pain years later. For this reason, a surgical technique was developed for the management of mandibular condylar neck fractures. A new axial/oblique-axial lag screw (anchor screw) with biconcave washers (anchor washer) makes it possible to carry out standardized osteosynthesis in the region of the thin mandibular condyle neck. Functional exercises can be initiated immediately after the operation. There are three operative procedures using an extraoral approach (1-3) and two using an intraoral approach (4-5), depending on the type and severity of the fracture: 1. Direct anchor screw osteosynthesis with closed gliding hole. 2. Indirect anchor screw osteosynthesis with open gliding groove and safety plates. 3. Osteosynthesis with a 'slanted-screw' plate for longer oblique fractures. 4. Intraoral anchor screw method. 5. Intraoral anchor screw method with intraoral 'slanted-screw' plate. The functional long-term results of conservatively and surgically treated mandibular condylar neck fractures were objectively documented by means of mechanical and electronic axiography. The functional long-term results of the condylar neck fractures treated surgically were significantly better than those treated conservatively.(ABSTRACT TRUNCATED AT 250 WORDS)


Step cannulation system for both articular compartments of the TMJ. Technical note. We have developed a step cannulation system consisting of a set of six obturators with increasing diameters for effective use of the arthroscope in the diagnosis and surgical treatment of disorders of the temporomandibular joint.


Efficacy of cyhalothrin and lambdacyhalothrin against Boophilus microplus (Acari: Ixodidae). A study was conducted to determine the efficacy of cyhalothrin and lambdacyhalothrin as a whole-body spray and lambdacyhalothrin as a pour-on application on cattle infested with Boophilus microplus (Canestrini). A laboratory bioassay was also done with both spray formulations. Cattle were infested with all parasitic life stages of B. microplus, then treated with 0.007 or 0.01% (AI) concentrations of cyhalothrin as a spray; 0.005, 0.007, or 0.01% (AI) concentrations of lambdacyhalothrin as a spray, or 1% (AI) lambdacyhalothrin as a pour-on. As determined by calculations of the index of reproduction (IR), the 0.007 and 0.01% (AI) cyhalothrin provided 92.4 and 97.3% control, respectively; the 0.005, 0.007, and 0.01% (AI) lambdacyhalothrin provided 92.4, 98.2 (average of two treatments) and 99.3% control, respectively; and the lambdacyhalothrin pour-on treatment provided < 50% control. Bioassay results indicated lambdacyhalothrin to be twice as effective as cyhalothrin against B. microplus.


New diets for production of house flies and stable flies (Diptera: Muscidae) in the laboratory. A diet for rearing the house fly, Musca domestica (L.), was developed from feed constituents available on a year-round basis in Gainesville, FL. The diet, called the Gainesville House Fly Diet, performed as well or better than the Chemical Specialties Manufacturers' Association fly larval medium (CSMA) and can be mixed, bagged, and delivered by a local feed mill within 3 d. By adding pelleted peanut hulls 1:1 by volume, the house fly diet becomes suitable for rearing the stable fly, Stomoxys calcitrans (L.). Use of these diets and the economics involved are discussed further.


Evaluation of various parts of the paw paw tree, Asimina triloba (Annonaceae), as commercial sources of the pesticidal annonaceous acetogenins. Various plant parts of the paw paw tree (Asimina triloba Dunal, Annonaceae) were extracted and partitioned to concentrate the mixture of acetogenins into a standardized pesticidal extract (F005). A bioassay with brine shrimp larvae (Artemia salina Leach) was used to determine the relative potencies of the various extracts. The small twigs (0-0.5 cm diameter) yielded the most potent extract (LC50 = 0.04 ppm); the stem wood (LC50 = 4.9 ppm) and leaves (LC50 = 53.7 ppm) yielded the poorest activities. The unripe fruits, seeds, root wood, root bark, and stem bark were notably potent and, generally, yielded > 2% of their dry weight as F005. The smaller diameter stems were more potent than the larger stems. We conclude that, by pollarding the trees, the entire twigs and small branches of paw paw could be processed to produce a potent acetogenin mixture; this biomass could be made available in quantities needed for commercialization of the pesticidal product and could be renewable through regrowth from the parent trunk and larger branches.


Cholinergic and H1-receptor influences of histamine on slowly adapting pulmonary stretch receptor activity in the rabbit. Afferent impulses of slowly adapting pulmonary stretch receptors (SARs) were obtained by dissecting fine slips from the left vagus nerve (LVN) and by leaving the rest of the nerve intact. In the same SAR preparation, changes of the receptor activity in response to right atrial injections of histamine (10 and 60 micrograms/kg) were successively examined before and after atropine (1 mg/kg), partial vagal efferent ablation, and mequitazine (1 mg/kg) in 10 rabbits. Administration of histamine led to an increase in the SAR activity, and this effect became more pronounced by increasing the dose of histamine. Atropine treatment diminished the responses of SARs to histamine at different doses. Partial vagal efferent ablation produced by denervation of the rest of the intact LVN slightly reduced the response of SARs to histamine at 10 micrograms/kg but had no significant effect on the SAR response to 60 micrograms/kg histamine. In the absence of vagal afferent and efferent activities on the left side, mequitazine, a potent H1-receptor blocker, completely blocked low- and high-dose effects of histamine on SARs. We compared the responses of the receptor activity to aerosol histamine (1 and 4%) and to topical application of histamine (0.1 ml, 0.025% and 0.1%) in six SAR preparations. The magnitude and duration of increased SAR activity became more prominent by increasing the concentration of histamine. The firing pattern and discharge rate of SARs following aerosol or intratracheal administration of histamine were similar to those after intra-atrial histamine. In addition, we also examined the excitatory responses of SAR activity to right atrial injections of histamine at 10 and 60 micrograms/kg before and after topical administration of atropine (0.1 ml, 1%, n = 6) or mequitazine (0.1 ml, 1%, n = 6) in 12 SAR preparations. Intratracheal atropine diminished the response of SARs to 10 micrograms/kg of histamine but had no significant effect on the response of SARs to histamine at 60 micrograms/kg. All the responses of SARs to histamine were completely blocked by topical application of mequitazine. These results suggest that the change of SAR activity produced by histamine at 10 micrograms/kg occurs mainly as a result of the release of acethylcholine (ACh) via the vagovagal reflex and that the activation of H1-receptors of the airway smooth muscle contributes importantly to the response of SARs to histamine at 60 micrograms/kg.


Vagal stimulation during muscarinic and beta-adrenergic blockade increases atrial contractility and heart rate. We determined the effects of continuous cardiac vagal nerve stimulation on atrial contractility and on heart rate in mongrel dogs in which we blocked the muscarinic and beta-adrenergic receptors. Each dog received atropine, 0.5 mg/kg and propranolol, 0.5-1 mg/kg. We stimulated the cardiac vagus nerves in each dog for three separate 5-min periods at frequencies of 0 (control), 20, and 40 Hz (5 ms, 15 V) and measured the changes in atrial contractility and heart rate. Vagal nerve stimulation increased right atrial contractility from the control value by 27% at 20 Hz and by 19% during stimulation at 40 Hz (P < 0.001). Vagal nerve stimulation also increased the heart rate from 114 +/- 5 beats/min during the control period to 146 +/- 10 beats/min (P < 0.01) during stimulation at a frequency of 20 Hz and to 140 +/- 11 beats/min (P < 0.05) during stimulation at 40 Hz. Injection of the vasoactive intestinal peptide (VIP) antagonist, [4Cl-D-Phe6,Leu17]VIP, directly into the dog right coronary artery in concentrations of 0 (control), 2, and 4 micrograms/kg did not influence spontaneous atrial contractility or the heart rate. However, 4 micrograms/kg of the VIP antagonist significantly reduced the augmentation in right atrial contractility and the increase in heart rate during vagal nerve stimulation. Our experiments suggest that cardiac vagal nerve stimulation, during muscarinic and beta-adrenergic receptor blockade, releases VIP or a 'VIP-like substance', that significantly augments atrial contractility and increases heart rate.


Differential effects on sympathetic nerve activities elicited by activation of neurons in the pressor areas of dorsal and rostral ventrolateral medulla in cats. Changes of the nerve activity of the sympathetic renal and vertebral nerves were elicited by microinjection of sodium glutamate (50 nmol/100 nl) into the pressor areas of the dorsal (DM) and rostral ventrolateral medulla (RVLM) in cats under urethane-chloralose anesthesia. Animals were bilaterally vagotomized, artificially ventilated, and paralyzed with gallamine triethiodide. The vertebral nerve activity always increased when pressor responses were induced by DM or RVLM stimulation. However, the effects of medullary stimulation on the renal nerve activity were variable. Three types of renal nerve responses concomitant with the pressor responses were observed in either baroreceptor-intact or baroreceptor-denervated cats. They were: (1) augmentation (type I); (2) attenuation (type II); and (3) insignificant change (type III). Type I responses were often elicited by RVLM stimulation whereas type II responses were often elicited by DM stimulation. Findings suggested that neurons integrating these sympathetic nerve activities were not equally distributed in the pressor areas of DM and RVLM. This result supports the notion that neurons located in different pressor areas of the brainstem exert differential effects over different sympathetic nerve activities.


Light enhances sympathetic and suppresses vagal outflows and lesions including the suprachiasmatic nucleus eliminate these changes in rats. Neurons in the suprachiasmatic nucleus (SCN) are suggested to be involved in the mechanism of glucose homeostasis. This mechanism was examined by studies on the effect of illumination on the activity of autonomic efferents to the adrenals, pancreas and liver. Exposure of one eye of anesthetized rats to light enhanced the efferent activity of the adrenal nerve and suppressed that of vagal pancreatic and hepatic nerves. No change in efferent activities of these nerves was observed on light-stimulation of rats with lesions that included the bilateral SCN. These findings indicate that light signals modulate visceral functions including metabolic processes through the retinohypothalamic tract probably via the SCN to autonomic efferent pathways innervating visceral organs.


A novel acetylcholine receptor-related peptide blocks canine cardiac ganglia and inhibits the nicotinic receptor of PC-12 cells. A 13 amino acid peptide from the calf muscle acetylcholine receptor has been previously shown to bind both snake neurotoxins and acetylcholine. In the experiments reported here a modified complementary peptide (cAChR) derived from that acetylcholine receptor peptide was tested for biological activity in a canine heart preparation. It was expected that the modified complementary peptide would exhibit either acetylcholine-like effects or acetylcholine inhibiting effects, since, as a complementary peptide to the receptor, it should resemble acetylcholine. In these studies cAChR was administered via the sinus node artery of dog hearts in intact animals which were anesthetized with pentobarbital, intubated, and prepared with local cardiac electrograms and force gauges. cAChR was also injected directly into thoracic sympathetic ganglia. Both approaches demonstrated cAChR inhibition of neural transmission, cAChR was added to the medium of carbachol stimulated PC-12 cells. In these cells, derived from a rat pheochromocytoma, sodium flux is controlled by neural nicotinic receptors. With or without preincubation cAChR inhibited carbachol stimulation of sodium flux, exhibiting a Ki of approximately 9 x 10(-5) (similar to that of hexamethonium). Thus cAChR appears to be a novel synthetic peptide which interrupts nicotinic cholinergic neural transmission by acting as an antagonist of the neural nicotinic receptor.


Neurons in the caudal ventrolateral medulla mediate the somato-sympathetic inhibitory reflex response via GABA receptors in the rostral ventrolateral medulla. In urethane-anesthetized rabbits, stimulation of the sural nerve, consisting of cutaneous afferents (A-fibers), evoked reflex responses consisting of an early small excitatory component followed by a prolonged inhibitory component in renal sympathetic nerve activity. Bilateral injections of GABA antagonist, bicuculline (4 nmol/site), into the rostral ventrolateral medulla (RVLM), where sympatho-excitatory reticulospinal neurons are located, attenuated the inhibitory component in a dose-dependent manner as well as the inhibition evoked by stimulation of the aortic nerve A-fibers (baroreceptor afferents). Bilateral injections of a neurotoxic agent, kainic acid (4 nmol/site, 3 sites/side), into the caudal ventrolateral medulla (CVLM), where sympatho-inhibitory neurons with axonal projection to the RVLM are located, diminished these sympatho-inhibitory responses. Therefore it is concluded that the sympatho-inhibition evoked by activation of somatic afferents was mediated by neurons in the CVLM and by GABA receptors in the RVLM, as was the sympatho-inhibition associated with the arterial baroreceptor reflex. Bilateral injections of kynurenic acid (4 nmol/site, 3 sites/side) into the CVLM did not affect the somato-sympathetic reflex response, but diminished the sympatho-inhibition produced by activation of the baroreceptor afferents. Sympatho-inhibitory neurons in the CVLM were activated by glutamate when baroreceptor afferents were activated, but another excitatory transmitter may participate in the somato-sympathetic reflex in the CVLM.


Mechanisms involved in aortic baroreceptor excitation during drug-induced aortic pressure elevation in intact rabbits. Aortic baroreceptor activity during drug-induced elevation of arterial pressure in intact animals is determined not only by the magnitudes of arterial pressure elevation but also by other mechanisms such as the direct effects of drugs on aortic wall property and on baroreceptors per se. This study aimed to determine the relative contribution of arterial pressure elevation and other mechanisms on aortic baroreceptor activity during intravenous infusion of norepinephrine (NE), phenylephrine (PE) or angiotensin II (Ang II) in intact anesthetized rabbits, all of which were used to assess arterial baroreflex function in vivo. We simultaneously recorded aortic pressure (AP), afferent aortic nerve activity (ANA) and the aortic diameter (AD) during elevation of AP induced by intra-aortic balloon inflation or intravenous infusions of NE, PE, and Ang II. During Ang II-infusion or balloon inflation, AD progressively increased with increases in AP. The relationships among changes in AP, ANA, and AD were similar during balloon inflation and during Ang II infusion which indicated that increases in ANA during Ang II infusion were caused by increases in AD or strain of baroreceptors. In contrast, during NE or PE infusion, ANA increased with no changes or decreases in AD, respectively. The latter results suggest that in intact rabbits increases in ANA during NE or PE infusion resulted from mechanisms other than an increase in strain of baroreceptors, such as the direct excitatory effect on baroreceptors. Thus, different mechanisms were involved in aortic baroreceptor excitation in intact rabbits during elevation of AP caused by the vasopressor drugs, which are commonly used to assess arterial baroreflex function in vivo.


Elderly care. Automatic implantable cardioverter defibrillators. The automatic implantable cardioverter defibrillators (AICD) is a commonly accepted treatment for an increasing number of elderly clients at high risk for ventricular dysrhythmias and sudden cardiac death. With increasingly successful use of AICDs, a unique group of gerontological patients has emerged with special physical, educational, psychosocial, and emotional needs. Gerontological nurses will encounter these clients in acute care settings as well as in home health care, nursing homes, senior citizen centers, and adult day health-care centers. Nurses need basic information about AICDs to plan for the continued care, teaching, guidance, and reassurance of these clients and their families.


Postmenopausal women. Factors in osteoporosis preventive behaviors. Osteoporosis is a serious health hazard mainly affecting postmenopausal and elderly women. Osteoporotic fractures are one of the leading causes of morbidity and death in the elderly population. Prevention of further loss of bone mass in postmenopausal women can be achieved if women take estrogen replacement therapy, consume adequate levels of calcium, exercise regularly, and practice healthy lifestyle behaviors. Elderly women need to follow the same strategies as postmenopausal women with more emphasis on prevention of falls.


Research considerations: family opinions about elderly relatives in research. As the elderly population expands due to longer life expectancy, clinical investigation will be required to provide optimal care. Family members of the elderly often become involved in the decision to participate in clinical investigation due to moral, ethical, personal, and financial concerns. Establishing rapport with the patient and family members is of great importance for the nurse when conducting clinical investigation. Most relatives interviewed for this study had positive opinions toward research with the elderly.


Intrapreneurial/entrepreneurial roles for nurses in long-term care. Seize the opportunity to be nontraditional. An increasing elderly population with multiple chronic diseases in need of sophisticated nursing care suggests that long-term care needs will continue to escalate. Recent political changes affecting the industry have led to explication of quality care issues and needs of long-term care consumers. Creative, innovative nurses need to seize the opportunity to influence patient care and the long-term care industry positively and cost-consciously. Intrapreneurial and entrepreneurial nursing are nontraditional nursing roles for self-directed, highly motivated nurses. Opportunities exist for gerontological nurses to design, direct, implement, and provide quality patient care; to serve as primary care providers or consultants; and to own and control a nursing practice.


Financing long-term care: a practical mix of public and private. Congress is considering proposals to improve its financing of long-term care. The key issue is whether it should support a social insurance program or a program targeted to a population group defined by income and assets. Social insurance is expensive, costing between $15 and $20 billion. For the most part, it provides benefits--primarily asset protection--to middle- and upper-income individuals. An improved Medicaid program, costing about $8 billion, benefits lower-income individuals but does not protect those with higher incomes. These two options cannot be viewed independently from trends in the private market. Sales of private long-term care policies have grown and between 30 percent and 40 percent of the elderly can be considered potential buyers. If private alternatives are available for those individuals who need asset protection, the case for a more targeted public approach--along with reliance on the private sector--becomes more compelling. Congress should consider a program that enhances Medicaid; improves consumer education; assists states in regulating long-term care policies, so as to enhance consumer protection and confidence; and clarifies taxes on long-term care insurance to encourage workers and the elderly to protect themselves against catastrophic expenses.


Financing universal health insurance: taxes, premiums, and the lessons of social insurance. In a society with strong antitax sentiment and large government deficits, the enactment of universal health insurance is blocked by an impasse over financing. The two chief mechanisms for funding universal health insurance are taxes and insurance premiums. Taxes and premiums are not distinct entities; rather, a spectrum of financing methods exists with varying tax-like and premium-like features. Premium-like financing tends to be voluntary and earmarked for health care, with coverage contingent upon making payments and payments going to private insurance firms. Tax-like financing, in contrast, tends to be mandatory and not earmarked for health care, with coverage not dependent upon making payments and payments going to governments. Over the past century, most industrialized nations have developed highly popular social insurance programs to cover periods of retirement, disability, unemployment, and payment for medical care. Social insurance constitutes a blend of tax-like and premium-like features, offering lessons that might assist in breaking the current impasse over universal health insurance financing.


Physicians' perceptions of the risk of being sued. We explore the deterrent effect of the tort system by assessing physician perceptions of the risk of being sued and the impact of those perceptions on their own practice. The data are from a mailed survey conducted in 1989 of a random sample of physicians who were practicing in New York State in 1984. The survey results were compared to the actual risk of suit using the between-group (Wald) test and logistic regression methods. We also surveyed physicians about practice changes undertaken in the last ten years, factors influencing practice standards, and the costs of being sued and included these in the analysis. On average, physicians estimate that 19.5 out of one hundred of their colleagues will be sued in a given year, approximately three times the actual rate, with significant differences by specialty, location, and suit history. Perceived risk is associated with self-reported changes in test-ordering frequency and reduction in practice scope. The median number of days lost from practice to defend a malpractice suit was three to five, and 6 percent of the physicians surveyed incurred some out-of-pocket expenses. These findings suggest that physicians respond to the messages sent by litigation in a manner consistent with the deterrent theory of tort litigation.


Prospective payment for psychiatric services. The Medicare prospective payment system (PPS) was designed to create financial incentives for providers to contain costs, but it also places them at financial risk. The system includes provisions to mitigate the risk, but, because they may have limited effectiveness in the case of psychiatric services, specialty psychiatric hospitals and eligible psychiatric units of general hospitals are exempt from the system. A variety of payment options have been proposed to integrate these facilities into the PPS. Empirical studies on the financial risk entailed by these options have focused on their impact on risk in the long run. Our study uses a broader framework to evaluate their impact on short-run as well as long-run risk. We use Medicare discharge data for 1985 to simulate alternative PPS payment options under the assumption that treatment patterns remain fixed. Our results suggest that under current PPS payment rules, risk would be high for psychiatric specialty hospitals. However, alternative options exist, which could substantially reduce their exposure to risk, while maintaining incentives to contain costs.


Competition and community mental health agencies. Community mental health agencies (CMHAs) provide most of the institutional outpatient treatment in the United States. A great deal of this care is given to clients at prices below the actual cost of the service. As the number of mental health providers increases, the question of how competition shapes the performance of CMHAs becomes more important. We use a two-stage least-squares model to examine how competition from other outpatient facilities, psychiatrists, and health maintenance organizations (HMOs), coupled with demographic, economic, and organizational factors affects subsidized care in CMHAs. Our analysis shows that competition from psychiatrists and HMOs reduces the number of subsidized visits that CMHAs provide and that agencies in urban areas and those initiated with federal funds provide more subsidized care. By restricting access to outpatient treatment, competition may have adverse long-term consequences for potential clients and for state mental health authorities.


Mental illness and help-seeking behavior among Mariel Cuban and Haitian refugees in south Florida. Differences in psychopathology and use of the mental health system by recent refugee groups are explored in light of competing hypotheses stemming from theories of immigrant adaptation and minority mental health. Results show that would-be Haitian refugees arriving in South Florida during the early 1980s had relatively small needs for mental health care, but whatever needs they had were largely unattended by the health services system. Mariel Cubans had far greater needs that were mostly met satisfactorily by virtue of their familiarity with service facilities prior to departure and their incorporation into a favorable social environment. These contextual factors are added and compared with the individual-level predictor variables suggested by Andersen and others. The results' implications for theories of immigrant mental health and help-seeking and for the implementation of effective delivery programs are discussed.


Factors contributing to the subjective quality of life of the chronic mentally ill. Although the deinstitutionalization of the seriously mentally ill has been severely criticized, the success of some model community programs shows that community care can enhance patients' quality of life. We lack specific knowledge, however, about the components that make these programs effective, and why. A theoretical framework for identifying these critical components is proposed. Services can enhance life satisfaction by increasing individuals' actual power through economic resources or status, thus enhancing their perceptions of mastery. An internal evaluation of a model program provides support for this hypothesis. One hundred and fifty-seven patients were interviewed about services, quality of life, and perceptions of mastery. Results show that services providing economic resources and an empowerment approach to service delivery are significantly related to overall quality of life. Furthermore, perceptions of mastery account for the impact of these components on life satisfaction. These findings suggest interventions that can be adopted by a wide range of mental health programs for the improvement of the quality of life of the chronic mentally ill.


Women and mental health: the interaction of job and family conditions. Current research on the effects of wives' employment on their well-being focuses on the determinants of those effects. Most studies have used a gender model that concentrates on family conditions as mediators. In contrast, studies of the effects of employment on men typically use a job model and focus on work rather than family conditions as determinants. To understand fully the impact of employment on women, these models should be combined. We predict that certain work and family conditions interact, specifically, that the degree of control at work moderates the effects of demands in the family. Using two data sets on community mental health, we have found some support for this hypothesis.


The natural history of cigarette smoking and young adult social roles. The relation between cigarette smoking (in adolescence and adulthood) and the occupancy of conventional adult social roles was investigated in the current study. Two alternative predictions for this relation were examined--"role incompatibility" (which predicts a negative relation between adolescent smoking and adult role occupancy) and "pseudomaturity" (which predicts a positive relation between adolescent smoking and adult role occupancy). Processes of role selection and role socialization were examined using data from a longitudinal study of smoking from adolescence to young adulthood. Both pseudomaturity and role incompatibility predictions found some support in the data, and the two views could be reconciled by considering the student role as the key transition into other adult statuses. Implications for the study of social roles and substance use are discussed.


Gender roles as mediators of sex differences in adolescent alcohol use and abuse. This study tested the hypothesis that internalized gender-role personality attributes and gender-role ideology mediate sex differences in alcohol use and drinking problems in a random sample of 1,077 adolescents aged 13 to 19. Results indicated that gender roles substantially, although not completely, mediated the effects of sex on drinking patterns. The relationships between gender roles and alcohol use were largely consistent with the hypothesis that individuals with conventional gender identities conform more closely to cultural norms that condone drinking among males but not among females. However, effects of the gender-linked attributes of expressivity, emotional control, and instrumentality on drinking also may be interpreted within a framework that views them as functional coping styles. Finally, differences between Black and White teens in the relationships between alcohol use and the masculine attributes of instrumentality and emotional control suggest possible race differences in the functional value of these attributes.


The effect of ambient threats to employment on low birthweight. The hypothesis that ambient threats to employment security are associated with increased rates of low birthweight is tested in two sites. The first test uses interrupted time-series methods to measure the association between a threatened reduction in the number of state workers and the incidence of low birthweight in Sacramento, California. The second test is of the association between unexpectedly low employment and low birthweight in Los Angeles, California. Both tests suggest that White males without Spanish surnames and Spanish-surnamed males are at elevated risk of low birthweight when the community is faced with a perceived threat to employment security. The implications of the findings for economic regulation and the provision of services are discussed.


Socialization to dying: social determinants of death acknowledgement and treatment among terminally ill geriatric patients. Although the vast majority of deaths occur among terminally ill geriatric patients, little is known about the etiology of these patients' death acknowledgement and ultimate type of treatment. Based on interviews with 76 triads composed of physicians, terminally ill patients, and primary caregivers, this study uses the socialization perspective to identify the actors and actions that most strongly affect the patient's death acknowledgment and receipt of exclusively palliative care (i.e., socialization to the dying role). Whereas patient preferences and sociodemographic characteristics do not influence significantly the patient's odds of death acknowledgment, these odds are increased if their primary caregivers accept death, their physicians are not affiliated with a teaching hospital, and the terminal prognosis is disclosed to them and disclosed "matter-of-factly." Patients who acknowledge death, whose agents value pain alleviation over life-prolongation, and whose physicians are not affiliated with a teaching hospital, are substantially more likely to receive exclusively palliative rather than curative terminal treatment.


Diastolic regional wall motion asynchrony in patients with hypertension. Left ventricular regional wall motion was analyzed from angiographic ventriculograms in 51 subjects, 18 of these served as controls, 10 were hypertensive with coronary artery disease, and 23 had a history of hypertension without coronary artery disease. All normal subjects showed normal synchronous wall motion throughout the cardiac cycle. In 10 patients with coronary artery disease and hypertension at the time of catheterization, the major determinant of regional abnormality was coronary artery lesion (sensitivity = 83%, specificity = 95%). Patients who had a history of hypertension and no ischemic disease, were further subdivided into three groups, 4 who were normotensive, 4 with borderline pressures and 15 hypertensive at the time of cardiac catheterization. All normotensive, 3 of the borderline hypertensive, as well as one hypertensive (without coronary artery disease) patients showed normal wall motion. In one patient with borderline pressure and 14 of 15 hypertensive patients diastolic regional asynchrony was detected. Apical region was most commonly affected in these patients. This suggests the importance of treating hypertension in patients and the possible reversibility of abnormal wall motion with treatment.


Analysis of left ventricular function from gated first-pass and multiple gated equilibrium acquisitions. 99mTechnetium-sestamibi is a new myocardial perfusion imaging agent that offers significant physical advantages over 201thallium for myocardial perfusion imaging. One of these advantages is that it can be used in the assessment of ventricular function by means of first-pass radionuclide angiography (FPRNA), acquired during the injection of the tracer. In this study we compared gated list mode first-pass acquisition with 99mTc-sestamibi (FP-MIBI) to multiple gated equilibrium radionuclide ventriculography (MUGA) with 99mTc-labelled red blood cells for the determination of global left ventricular ejection fraction (LVEF). The study population consisted of 20 patients (mean age 54 years) who were submitted to stress-rest perfusion imaging. Resting FPRNA was performed using 99mTc-sestamibi and the reference data were acquired within a week with the MUGA technique. A linear correlation between FP LVEF and MUGA LVEF gave an r = 0.974 (p < 0.01). Diastolic and systolic timing and velocity parameters had lower correlations between these two methods. We conclude that global LVEF can be precisely measured with 99mTc-sestamibi when compared to usually employed MUGA technique with 99mTc-labelled red blood cells.


Detection of aortic dissection by magnetic resonance imaging in adults with Marfan's syndrome. Marfan's syndrome is a connective tissue disorder, which mainly affects the cardiovascular system, together with ocular, skeletal and connective tissue. The cardiovascular manifestations in particular determine the mortality of this disorder. We studied 13 patients, suffering of Marfan's syndrome, with suspected aortic dilatation by means of magnetic resonance imaging (MRI). Aneurysmal dilatation of the aortic root and dissection were the two major findings in our study. Two of the five patients with dissections presented without relevant symptoms in the medical history nor at the time of the MRI examination.


Clinical experience with technetium-99m teboroxime scintigraphy in patients referred for myocardial perfusion evaluation. A series of 30 patients (25 males, 5 females, age = 28-73 years) with a clinical indication of thallium-201 stress/4 hours redistribution scintigraphy has been studied using stress/rest (n = 7) or rest/stress (n = 23) protocols with technetium-99m teboroxime (CARDIOTEC, Squibb Diagnostics) in order to assess the clinical usefulness of this new molecule and to compare it to thallium. In all cases coronary artery disease was known or highly suspected, with a history of myocardial infarction in 18 cases (subacute n = 6, remote n = 12) and/or previous by-pass surgery or PTCA in 5 cases. Medical treatment was not discontinued at the time of stress testing. Coronary angiography was available for 27 patients. Exercise tests for both tracers were carried out on an ergometric bicycle during the same day and the levels of exercise achieved for the thallium studies were very similar to those achieved for teboroxime. Imaging was performed in three planar projections and sudies were evaluated using a model with 4 territories: septal and anterior assumed to correspond to the LAD artery, lateral and latero-posterior (= LCX), inferior and posterior (= RCA) and apex. Classification of results was: normal, ischemic, infarcted and infarcted with ischemia. With reference to the thallium-201 results, agreement was found in 86% (37/43) of normal regions and in 82% (63/77) of abnormal regions. Relative to documented coronary artery lesions (27 patients) sensitivity and specificity of thallium and teboroxime for exact correspondence between arteries and territories were, respectively: thallium, se = 71%, sp = 64%, teboroxime, se = 67%, sp = 75%.(ABSTRACT TRUNCATED AT 250 WORDS)


3D-reconstruction of coronary arteries in view of flow measurement. An angiographic method for measurement of absolute coronary blood flow in patients was developed. It is based on 3D-reconstruction of the left or right coronary tree from digitized biplane coronary cineangiograms. The apparatus is presently composed of a 35 mm cinefilm projector with a video camera and a 512 x 512 x 8 bits image array processor controlled by a VAX-11/750 computer. First, the parameters of the two angiographic projections are determined in form of two 4 x 3 matrices from a pair of cineframes showing a 4 cm cube bearing markers. The cube is filmed after the coronary injection, with unchanged geometric configuration. The coronary arteries of interest are then 3D-reconstructed from a pair of cineframes showing them fully opacified. This allows to compute the intravascular volumes needed for flow determination. In vitro experiments showed that the obtained volume are reasonably accurate. For the measurement of coronary flow, the concentration of contrast medium along the involved arteries is computed (in arbitrary units) from two cineframes taken one (or two) cardiac cycle after onset of the injection. This yields a 'concentration-distance' curve per artery. The volume of fluid (contrast medium mixed with blood) which flows into the arteries during this (or these two) cardiac cycle is determined by applying a concentration threshold to the obtained concentration-distance curves. Measurements performed on a constant flow model were satisfying. Preliminary measurements in 12 patients showed that flow values obtained angiographically into the left anterior descending coronary artery correlate well with the values measured simultaneously by thermodilution in the great cardiac vein (Qangio = 0.83 x Qthermo + 16.1 ml, r = 0.87, n = 29).


An unusual Doppler-echocardiographic finding in case of a Björk-Shiley mitral prosthetic valve thrombosis. We report a patient in whom the commonly accepted Doppler echocardiographic findings failed to suggest prosthetic valve dysfunction. This was diagnosed by M-mode technique. We therefore feel that M-mode echocardiography still has its place in the complete evaluation of patients with suspected prosthetic valve dysfunction.


Technetium-labeled myocardial imaging agents. 99mTc sestamibi and 99mTc teboroxime has unique features that differ from thallium-201 in dosimetry, energy, cellular transport, extraction fraction, retention, washout, and imaging protocols. Sestamibi is ideal for gated and SPECT imaging while SPECT imaging with a multi-head detector system is preferred for teboroxime. Both permit simultaneous assessment of perfusion and function using first-pass radionuclide angiography. This paper discusses the special features and clinical applications of these two technetium agents.