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Septic shock (SS) is associated with an increase in total and free cortisol along with a disproportionate increase in percent free cortisol, due in part to decreased serum concentrations of cortisol-binding globulin (CBG) and albumin. Relative adrenal insufficiency (RAI) is often seen in septic shock and is biochemically defined by a cortisol increment Objective Keenan et al proposed a set of three differential equations describing a dynamic model for free cortisol secretion and clearance rates, which incorporates the reactions of free cortisol with CBG and albumin, under non-steady-state conditions. We sought to assess maximal cortisol secretion rates in SS and in control subjects using numerical techniques to solve for cortisol equilibrium in the serum compartment and for cortisol secretion and clearance rates. Methods Plasma total and free cortisol, serum CBG, and albumin were measured in subjects with SS (n = 45), subjects with sepsis (S, n = 19), and in healthy controls (HC, n = 10) at 0, 30, and 60 minutes after 250 μg cosyntropin. Numerical solution for cortisol secretion rates used group-specific KA determined by least squares solution and assumed a uniform, maximal cortisol secretion rate to provide a least squares solution for secretion and clearance to fit observed data points. Results The group-specific KA was significantly higher in SS versus S and HC (148, 99, and 78 μM, p Conclusions SS and RAI are associated with a reversible increase in KA, contributing to an increase in percent free cortisol. Maximal cortisol secretion rates are elevated in SS, including RAI subjects. The distribution of the normal range of maximal secretion rates (CV = 48%) suggests that application of numerical solution to non-steady-state conditions, such as the cosyntropin stimulation test, may be useful in distinguishing absolute and relative adrenal insufficiency.

This study was designed to investigate the efficacy of the antidepressant drug bupropion in the treatment of posttraumatic stress disorder (PTSD). Seventeen male combat veterans with chronic PTSD were treated with bupropion in an open-label fashion for 6 weeks. Patients were evaluated with the Clinical Global Impressions Scale for Improvement (CGI-I) at follow-up and rated blindly at baseline and posttreatment with the Clinician Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton Rating Scale for Anxiety. Three patients discontinued bupropion prematurely because of side effects. Of the remaining 14 patients, 10 were classified as treatment responders by the CGI-I. HAM-D scores decreased significantly from baseline to follow-up. The improvement seen in hyperarousal symptoms was significant but was less significant than the change in depressive symptoms. There was no significant change in Intrusion, Avoidance, or total CAPS scores. It was concluded that bupropion was well tolerated. Patients who had experienced sexual dysfunction with selective serotonin reuptake inhibitors reported no complaints during bupropion treatment. Bupropion decreased depressive symptoms and most patients reported global improvement, although PTSD symptoms remained mostly unchanged. Controlled trials should further clarify the role of bupropion in the treatment of PTSD.

Objectives. The purpose of this study was to determine whether persons with developmental dyspraxia and apraxia make similar errors during the performance of four types of tasks. Method. Three groups of subjects with dyspraxia or apraxia (i.e., children with learning disabilities and dyspraxia, young adults with learning disabilities and dyspraxia, older adults with left-hemisphere brain damage with apraxia) and three groups of age-matched control subjects (i.e., children, young adults, older adults) were observed performing transitive, intransitive, verbal command and imitation tasks. Performance was scored on the basis of the types of errors made. Errors were classified as conceptual (nonrelated, unrecognizable, sequencing) or production (omission, perseveration, related, internal configuration, external configuration, incorrect movement, body part as object). Results. No significant difference was found between conceptual and production error patterns for any group. In addition, there was no significant difference between the dyspraxia and apraxia groups or among the control groups on the specific types of production errors made. However, the dyspraxia and apraxia groups differed in the type of conceptual error made on the intransitive task. The body-part-as-object error was the most frequently made error on the transitive, verbal command, and imitation tasks, whereas the movement error was the most frequently made error on the intransitive task. Conclusion. Subjects with dyspraxia or apraxia make similar errors, suggesting that the praxis behaviors are similar.

The objectives of this study were to: (1) assess differences in goal attainment of self-described goals after treatment of symptomatic pelvic organ prolapse (POP) for women who chose surgery compared to women who chose pessary; and (2) compare patient global improvement between groups.Women who had symptomatic stage ≥II prolapse presenting for care of POP to the urogynecology clinic at the University of New Mexico were recruited. Patients listed up to 3 goals they had for their treatment. In addition, they completed the short forms of the Pelvic Floor Distress Inventory (PFDI-20), the POP/Urinary Incontinence Sexual Questionnaire, and the Body Image Scale. Goals listed by patients were then categorized into 10 categories. Each of the listed goals was categorized based on a consensus of 5 providers. At 3 months' follow-up patients listed if they had met their self-described goals on a scale of 0-10 and also answered the Patient Global Improvement Index (PGI-I).There were no significant differences between the 2 groups' baseline characteristics. Surgery patients ranked their goal attainment higher than pessary patients for all the 3 goals listed. Similarly, PGI-I scores were also higher in the surgical (2.4 ± 1.1) than the pessary (1.93 ± 0.8) treatment groups (P.04). Patients in the surgery group also had better symptom improvement as measured by the PFDI-20 (P.02).Patients who chose surgery had better global improvement and met their goals better compared to patients who chose pessary.

OBJECTIVE: Our purpose was to investigate the safety and efficacy of a synthetic intracervical hygroscopic dilator, Dilapan (Gynotech, Inc., Middlesex, N.J.), on ripening the cervix before medically indicated induction of labor. STUDY DESIGN: Two hundred forty patients with a Bishop score of ≤4 were prospectively randomized to receive either preinduction synthetic hygroscopic dilators ( n = 112) or no pretreatment ( n = 128) before oxytocin induction. RESULTS: Compared with controls, the dilator group exhibited a significant change in median Bishop score, but there was no significant difference in length of labor (dilator 18.8 ± 12.8 hours vs control 21.7 ± 14.8 hours) or in the cesarean section rate (dilator 41/112 [36.6%] vs control 49/128 [38.3%]). Relative proportions of nulliparous and multiparous patients, infant weights, and cervical dilation at the time of cesarean section were not significantly different between groups. No adverse maternal or fetal effects could be attributed to use of the device. CONCLUSIONS: Preinduction cervical ripening with hygroscopic dilators does not shorten the length of labor or lower the cesarean section rate in patients undergoing induction of labor. (Am J Obstet Gynecol 1996;175:145-9.)

Laparoscopy has been considered a relative contraindication in pregnant patients because the CO2 pneumoperitoneum may cause maternal and/or fetal hypotension, acidosis, hypercarbia, hypoxia, changes in cardiac output, or uterine artery blood flow. These potential changes were studied in an established animal pregnancy model. Twelve gravid ewes (116-120 days gestation) underwent catheterization of maternal femoral artery and vein, fetal hindlimb artery and vein, insertion of a uterine artery flow probe, and pulmonary artery catheter. Six animals underwent creation of a CO2 pneumoperitoneum (10 mm Hg for 30 min; 15 mm Hg for 30 min). Six control animals were studied without a pneumoperitoneum. The following parameters were recorded at baseline and at preset time points: cardiac output (CO), uterine blood flow (UtBF), amniotic cavity pressure (ACP), end-tidal CO, (Et CO2), maternal and fetal heart rate (HR), blood pressure (BP), and lactate, glucose, and arterial blood gasses. Percent change at each time point compared to baseline was determined for each variable. Statistical significance was determined by repeated measures analysis of variance. No changes were found between study and control animals in maternal BP; CO; lactate, glucose, oxygenation, or fetal HR; oxygenation, lactate, or glucose. Statistically significant differences (P < 0.01) between study and control animals were noted in ACP, Et CO2, MHR, UtBF, FBP, and Maternal/fetal pH, PCO2. All ewes delivered healthy lambs at full gestation. A CO2 pneumoperitoneum up to 15 mm Hg pressure in gravid ewes causes increased intrauterine pressure, decreased UtBF, and induces maternal and fetal acidosis. Despite these intraoperative deleterious effects, long-term fetal well being was not effected.

Tolerance of the behavioral effects of the short-acting, endogenous hallucinogen, N,N-dimethyltryptamine (DMT) is seen inconsistently in animals, and has not been produced in humans. The nature and time course of responses to repetitive, closely spaced administrations of an hallucinogenic dose of DMT were characterized. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate, or saline placebo, four times, at 30 min intervals, on 2 separate days, in a randomized, double-blind, design. Tolerance to "psychedelic" subjective effects did not occur according to either clinical interview or Hallucinogen Rating Scale scores. Adrenocorticotropic hormone (ACTH), prolactin, cortisol, and heart rate responses decreased with repeated DMT administration, although blood pressure did not. These data demonstrate the unique properties of DMT relative to other hallucinogens and underscore the differential regulation of the multiple processes mediating the effects of DMT.

This study investigates the effects of perceived family environment on clinical outcome among patients in Spain who suffer from schizophrenia. Forty-five consecutively admitted DSM-III-R schizophrenic patients were assessed monthly with the Brief Psychiatric Rating Scale during a 9-month period. Patients and parents rated the family environment through the Family Environment Scale (FES). FES factors were considered separately for each family member, since parents' and patient's perceptions of the family environment were weakly correlated. Stepwise multiple regression analysis showed that patients' perceptions of family control and intellectual-cultural orientation predicted rehospitalization. Patients' and mothers' ratings of family control and fathers' scores of conflict and moral religious emphasis predicted psychotic relapse. However, fathers' scores of family cohesion predicted higher negative symptoms. Prior admissions, age of onset and use of depot medication tended to predict outcome in conjunction with the family variables.

We tested the hypothesis that time series analysis can provide accurate predictions of future poison center telephone call volume by a prospective stochastic time series modeling of calls to a university-based regional poison center. All callers evaluated and managed during two sequential years had the time and date of the call recorded in a computer database. Time series variables were formed for poison center calls per hour. Prediction models were developed from the 1992 data and included four types: raw observations, moving average, means with moving average smoothing, and autoregressive integrated moving average. Forecasts from each model were tested against observations from the first 26 weeks of 1993. Each model's adequacy was tested on residuals by autocorrelation functions, integrated periodograms, linear regression, and differences among the variances. A total of 44,584 calls were received in 1992 and 24,781 in the first half of 1993. Large periodic variations in call volume with time of day were found (p < 0.001). The model based on arithmetic means of each hour of the week with three-point moving average smoothing yielded the most accurate forecasts and explained 58.5% of the variation observed in the 1993 test series (p < 0.001). Time series analysis can provide powerful, accurate short range forecasts of future poison center telephone call volume. Simpler, less expensive models performed best in this study.

1558 Background: Polymorphisms in the aromatase (CYP19A1) gene result in differences in the risk for breast cancer and response to treatment. We hypothesize that allele frequencies in the CYP19A1 gene vary according to race and may result in differences in progression of breast cancer among women from different racial backgrounds. The objectives of this study are: 1) to determine the allele/genotype frequencies in the CYP19A1 gene among women with breast cancer from different racial backgrounds, and, 2) to determine the association between disease progression and CYP19A1 gene variants. Methods: Clinical data and stored DNA from 327 patients participating in the Expanded Breast Cancer Registry (EBCR) program at the University of New Mexico were analyzed. These patients were followed-up for a period of 1 to 6 years. Comprehensive genotyping for CYP19A1 gene single nucleotide polymorphisms (SNPs) was performed using microarray (Illumina). Results: Data from 164 non-Hispanic white and 119 Hispanic women were analyzed. Four SNPs (rs1259269, rs17703883, rs16964211, rs28757101) were associated with differences in genotype/allele frequencies between the 2 racial groups. Furthermore, 3 SNPs (rs4646, rs17647478, and rs6493486) were associated with differences in disease progression. The rare allele (G) for the rs17647478 (G/T) is associated with poor progression compared those without the allele (41.7% vs. 17.1%, p=0.04). Similarly the minor (A) allele for the rs4646 (A/C) and the rs6493486 (A/G) is also associated with a greater chance of worsening disease (23.2% vs. 12.4%, p=0.02 and 23.4% vs. 12.4%, p=0.02, respectively). A significant percentage of women carrying the A allele for both rs4646 and rs6493486 and the T allele for the rs17647478 have more advanced disease at the time of presentation. None of the SNPs analyzed result in racial differences in breast cancer progression. Conclusions: Polymorphisms in the CYP19A1 gene influence overall disease progression in breast cancer patients but have no impact on the racial differences of disease behavior. Women carrying the risk alleles present at a more advanced stage and are also at greater risk of progression.

Brain glucose metabolism is impaired during hypoglycemia, but, if sustained, brain metabolism reverts to normal in animal models--data in man are lacking. We tested the hypothesis that adaptations occur to allow maintenance of normal rates of brain glucose uptake (BGU) following recurrent hypoglycemia in man. Twelve normal humans were studied over 4 days. On the initial day, arterial plasma glucose concentrations were decreased from 4.72 to 2.50 mmol/liter in five 0.56 mmol/liter steps. Cerebral blood flow, brain arteriovenous glucose difference, BGU, and cognitive function were quantitated at each step. BGU was initially impaired at the 3.61 mmol/liter glucose step (P = 0.04) and was antedated by increments in epinephrine that began at 4.16 mmol/liter (P = 0.03). The onset of hypoglycemic symptoms occurred during the 3.61 mmol/liter glucose step (P = 0.02), whereas tests of cognitive function generally deteriorated at the 3.05 mmol/liter step (P < 0.05). During the next 56 hr, mean glucose concentrations were kept at 2.9 +/- 0.1 mmol/liter and reached normal only during meals. The stepped clamp protocol was repeated beginning at 4.16 mmol/liter on the last day. No decrement in BGU was observed at any step; cognitive function was preserved until significantly lower glucose concentrations on the final day relative to the first (P = 0.04). Subjects remained asymptomatic of hypoglycemia until they reached a glucose concentration of 2.50 mmol/liter (P < 0.001 vs. day 1), while initial increments in all counterregulatory hormones were forestalled to lower glucose steps than on day 1. Therefore, adaptations occur that allow normal BGU and cerebral function to be maintained during recurrent systemic hypoglycemia. Counterregulatory events that should result in symptoms of hypoglycemia and increments in endogenous glucose production are prevented until extremely subnormal glucose concentrations.

Background: Steroid receptor coactivator (SRC-1 to 3) proteins drive nuclear receptor transcriptional activity by modulating transcriptional processes such as chromatin modification, transcription initiation, chain elongation, and RNA splicing. In patients who display resistance to endocrine treatment, SRC-1 has been implicated in the conversion of tamoxifen anti-agonist activity to its agonist profile. SRC-1 expression is a prognostic of DFS in breast cancer, but its role in inflammatory breast cancer (IBC) remains unknown. Materials and Methods: SRC-1 protein levels were measured by immunohistochemistry in 103 IBC and 11 normal, non-cancer related samples, diagnosed at the Centre Pierre & Marie Curie (Algiers, Algeria). Staining results were correlated with protein levels of ER, PR, and HER2, and clinico-pathological variables, breast cancer-specific (BCSS) and disease-free survival (DFS), and response to tamoxifen treatment. Results: SRC-1 was positive in all normal breast tissue, as well as in 66% of IBC samples. SRC-1 positivity was associated with worse OS (P Discussion: Determining prognosis and predicting response to endocrine treatment is of paramount importance in the search for personalized treatment. SRC-1 expression predicts worse OS, DFS, and, similar to non-IBC, predicts DFS independently of endocrine therapy. This study highlights the importance of SRC-1 expression as a strong prognosticator of BCSS and disease recurrence in IBC patients. *Supported by an UICC ICRET Fellowship (ICR/09/043 to Dr. Chaher) and by New Mexico State IBC funding (New Mexico Senate Bill 532). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-01-19.

Histochemical, immunohistochemical and neurochemical techniques were used to examine the innervation of epineurial nerve sheaths and fascicular nerve bundles of human sural and optic nerves from controls and patients with peripheral neuropathy due to diabetes or alcoholism. The normal distribution of autonomic nerves in both nerve trunk sheaths consisted of a dense innervation by noradrenaline (NA)-containing nerves of the vasa nervorum, together with some fibres in the nervi nervorum. Intrafascicular NA-containing nerves were only present in the sural nerve. Vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-containing nerves also innervated the vasa nervorum and nervi nervorum of the nerve sheaths, although their density was considerably less. Substance P (SP)-containing nerves were sparse and primarily intrafascicular. Neurochemical assays for NA, VIP, NPY and SP in fascicular and epineurial preparations from the sural and optic nerves confirmed the light microscopical observations. Post mortem delay significantly affected the NA levels in the sural nerve but not in the optic nerve while the NA fascicular/epineurial ratio for the sural nerve was independent of this factor. Age, sex and the presence of alcohol at time of death had no effect on transmitter levels in normal sural nerves. In the optic nerve fascicles NA levels were higher in females than in males. In patients with peripheral neuropathy there was a significant reduction in the SP fascicular/epineurial ratio in both the optic nerve, which was histologically normal, and in the sural nerve, where there was evidence of neuropathy. The NA fascicular/epineurial ratio was also significantly reduced in the sural nerve from patients with peripheral neuropathy with a possible greater effect in diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Trace metal analyses in hair are used in archeological, forensic and toxicological investigations as proxies for metabolic processes. We show metallophilic bacteria mediating the deposition of gold (Au), used as tracer for microbial activity in hair post mortem after burial, affecting results of such analyses. Methodology/Principal Findings Human hair was incubated for up to six months in auriferous soils, in natural soil columns (Experiment 1), soils amended with mobile Au(III)-complexes (Experiment 2) and the Au-precipitating bacterium Cupriavidus metallidurans (Experiment 3), in peptone-meat-extract (PME) medium in a culture of C. metallidurans amended with Au(III)-complexes (Experiment 4), and in non-auriferous soil (Experiment 5). Hair samples were analyzed using scanning electron microscopy, confocal microscopy and inductively coupled plasma-mass spectrometry. In Experiments 1–4 the Au content increased with time (P = 0.038). The largest increase was observed in Experiment 4 vs. Experiment 1 (mean = 1188 vs. 161 µg Kg−1, Fisher's least significance 0.001). The sulfur content, a proxy for hair metabolism, remained unchanged. Notably, the ratios of Au-to-S increased with time (linear trend P = 0.02) and with added Au and bacteria (linear trend, P = 0.005), demonstrating that larger populations of Au-precipitating bacteria and increased availability of Au increased the deposition of Au on the hair. Conclusion/Significance Interactions of soil biota with hair post mortem may distort results of hair analyses, implying that metal content, microbial activities and the duration of burial must be considered in the interpretation of results of archeological, forensic and toxicological hair analyses, which have hitherto been proxies for pre-mortem metabolic processes.

To compare the effects of D5LR and invert sugar administered intrapartum on neonatal blood glucose concentrations.This is a prospective, randomized, double-blind study. A total of 32 insulin-requiring diabetic patients were randomized to receive either intravenous 10% invert sugar or lactated Ringer's solution with 5% dextrose (D5LR). Regular insulin was given intravenously with an infusion pump to maintain the plasma glucose concentration between 60 and 90 mg/dl. Neonatal blood glucoses were measured at 30 minutes after birth, four times every hour, and thereafter as indicated. Student's t-test was used for continuous variables and Fisher's exact test was used for categorical data.There were no differences in neonatal blood glucose levels, incidence of neonatal hypoglycemia, or length of neonatal hospital stay between the two groups.Intrapartum administration of invert sugar is not associated with better neonatal homeostasis of glucose compared with using D5LR. Thus, given the expense of invert sugar, D5LR appears to be preferable for intrapartum control of maternal blood glucose.

Melatonin affects gonadal function in nonprimate mammals. Confirmatory data in man are not available. We assessed melatonin's acute effects on luteinizing hormone secretion in 17 normal men. We studied these men in conditions of sleep in the dark, and sleep deprivation in bright light, dim light, and bright light combined with a physiologically relevant infusion of melatonin, while measuring blood levels of immunoreactive LH every 20 min for 7 h. We compared overnight LH secretion, and LH pulse frequency, amplitude, length, interval and area under the curve using a modification of the PULSAR peak identification program, among the four treatments. Areas under the curve for peaks in all three conditions of sleep deprivation were lower than in normal sleep. The presence or absence of melatonin had no additional effect. We conclude that acute suppression of melatonin does not affect LH pulse parameters in normal man, but that sleep deprivation may reduce the amount of LH secreted per pulse.

To assess the reliability of early biometric measurements in pregnancy, transvaginal sonography was performed in 92 pregnancies in the first trimester in a cross-sectional fashion. Measurements included crown-to-rump length (CRL), biparietal diameter (BPD), head and abdominal circumference (HC and AC), and femur length (FL). Stepwise regression analysis of the gestational age was performed. CRL maintained the highest correlation with gestational age (r = 0.99, p less than 0.001). BPD, HC, AC also correlated well. FL showed a less strong correlation with gestational age (r = 0.76, p less than 0.001). CRL remains the standard for early sonography measurements.

To develop guidelines that might help predict prospectively which infants with severe intraventricular hemorrhage (IVH) would require intervention, we obtained serial cranial sonograms to measure the rate of growth of cerebral ventricular volumes in 48 preterm infants with and without IVH. The infants were divided into three groups: (1) those with no IVH (22 infants), (2) those with IVH with acute ventricular dilation (13 infants), and (3) those with IVH with progressive ventricular dilation requiring intervention (13 infants). The decision to intervene because of progressive ventricular dilation was based on clinical criteria and the subjective assessment of increasing ventricular size on weekly cranial sonograms. The rate of cerebral ventricular volume growth in infants with IVH who needed intervention was greater (4.2 +/- 3.3 ml/day) than that in infants without IVH (0.0 +/- 0.1 ml/day; p less than 0.001) and in infants with IVH and acute ventricular dilation (0.0 +/- 0.2 ml/day; p less than 0.001). Using these data, we generated guidelines for predicting prospectively which infants with IVH and ventricular dilation will need intervention for posthemorrhagic hydrocephalus. The guidelines were then confirmed prospectively in 10 infants.

Biologic rhythms give insight into normal physiology and disease. They can be used as biomarkers for neuronal degenerations. We present a diverse data set to show that hair and teeth contain an extended record of biologic rhythms, and that analysis of these tissues could yield signals of neurodegenerations. We examined hair from mummified humans from South America, extinct mammals and modern animals and people, both healthy and diseased, and teeth of hominins. We also monitored heart-rate variability, a measure of a biologic rhythm, in some living subjects and analyzed it using power spectra. The samples were examined to determine variations in stable isotope ratios along the length of the hair and across growth-lines of the enamel in teeth. We found recurring circa-annual periods of slow and fast rhythms in hydrogen isotope ratios in hair and carbon and oxygen isotope ratios in teeth. The power spectra contained slow and fast frequency power, matching, in terms of normalized frequency, the spectra of heart rate variability found in our living subjects. Analysis of the power spectra of hydrogen isotope ratios in hair from a patient with neurodegeneration revealed the same spectral features seen in the patient's heart-rate variability. Our study shows that spectral analysis of stable isotope ratios in readily available tissues such as hair could become a powerful diagnostic tool when effective treatments and neuroprotective drugs for neurodegenerative diseases become available. It also suggests that similar analyses of archaeological specimens could give insight into the physiology of ancient people and animals.

Purpose Free cortisol is released into the serum compartment where it is in equilibrium with serum binding proteins, corticosteroid-binding globulin (CBG), and albumin. The distribution of serum cortisol among free, CBG-bound, and albumin-bound compartments is influenced by association and disassociation rate constants for CBG and albumin, the number of unoccupied protein binding sites, and concentrations of CBG and albumin. Free cortisol in serum or plasma is difficult to assay; thus, salivary cortisol has been proposed as an alternative measure of free cortisol. In this study, we sought to assess and compare numerical methods, using both quadratic (Coolens et al, 1987) and cubic (Keenan et al, 2004) equations to calculate serum free cortisol and compare these findings with salivary cortisol in healthy elderly subjects. Methods Serum and saliva samples were collected from 45 healthy, elderly subjects at 0700 h as part of the New Mexico Aging study (UNM HRRC 01-023). The salivary cortisol and total cortisol were measured using radioimmunoassay and ultrasensitive chemiluminescence, respectively. Serum CBG was measured by radioimmunoassay and serum albumin was measured using a bromcresol green method (UNM RAC 51). The cubic equation implied by Keenan et al and the quadratic equation described by Coolens et al were used to calculate free cortisol using our measured values for total cortisol, total CBG, and total albumin. Calculated free cortisol, total cortisol, and CBG concentration were then compared to salivary cortisol using Pearson9s and Spearman9s correlations. Results There was a significant linear correlation between salivary cortisol and free cortisol calculated using the cubic equation (r = .377, p = .033) and Coolen9s quadratic equation (r = .416, p = .018). In addition, we noted a linear correlation between CBG concentration and total cortisol (r = .441, p = .0049). Conclusion Our data indicate that the free cortisol calculated using either quadratic or cubic equations is correlated significantly with salivary cortisol but that other variables appear to influence measured salivary cortisol concentration. We did not observe the previously reported correlation between total and salivary cortisol, which suggests that aging may influence the relative distribution of cortisol in serum or salivary compartments.

DENCE AND TREATMENT PROGRAM: INCREASED RISK FOR CHOLESTASIS OF PREGNANCY AND PRETERM DELIVERY ELIZA BERKLEY, KIMBERLY LESLIE, SANJEEV ARORA, CLIFFORD QUALLS, JEFFREY DUNKELBERG, University of New Mexico, Obstetrics and Gynecology, Albuquerque, New Mexico, University of New Mexico, Internal Medicine, Albuquerque, New Mexico, University of New Mexico, Clinical Research Center, Albuquerque, New Mexico OBJECTIVE: Hepatitis C is a major problem in high-risk pregnancy clinics but it can be a curable disease in young women who take recommended antiviral regimens in the postnatal period. The purpose of this study was to assess maternal and neonatal outcomes for these patients and to determine whether patients receive postpartum referral. STUDY DESIGN: A historical prospective study was performed in pregnant patients with and without chronic hepatitis C virus (HCV) infection. Multivariate logistic regression statistical analysis was employed to assess the relative contributions of multiple variables to maternal and neonatal outcomes. RESULTS: Three hundred and forty-three women received prenatal care in a drug treatment program between January 2000 and January 2006. One hundred fifty-five (45.2%) were found to be HCV antibody positive, 137 (39.9%) tested negative, and 51 (14.9%) were not evaluated for hepatitis C. Methadone use was highly associated with HCV antibody positivity (AbC) (59.7% vs. 23.4%, p!0.001). The incidence of cholestasis of pregnancy was increased in HCV AbC mothers (10/159, 6.3% vs. 0/141, p=0.002). The risk for preterm delivery was increased nine-fold in HCV AbC women who used methadone compared to HCV negative non-users of methadone (p=0.05, OR 9.27, CI 1-85.95). Neonates born to HCV AbC mothers had lower birth weights (p=0.047) and were more likely to weigh less than 2500 g (p=0.003). Neonates born to HCV AbC mothers had a significantly higher incidence of Neonatal Intensive Care Unit admission (p=0.045). Only 5.7% of HCV AbC mothers and only 1.9% of their neonates were referred postnatally. CONCLUSION: In pregnant women involved in a drug dependence and treatment program, HCV antibody positivity is associated with an increased risk for cholestasis of pregnancy. HCV antibody positivity is highly correlated with methadone use, and neonates born to this subset of women have an increased risk for preterm birth, low birth weight, and NICU admission. Postnatal referral of the mother and infant for evaluation and treatment of hepatitis C appears to be rare.

The purpose of this study was to assess sexual function in women after surgery for stress urinary incontinence and/or pelvic organ prolapse (UI/POP) at 3 and 6 months with the Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire (PISQ).Of 269 eligible women participating in a trial of prophylactic antibiotic use with suprapubic catheters, 102 (37.9%) agreed to participate in a sexual function study. Women underwent a variety of anti-incontinence and reconstructive surgeries. Sexual function and urinary incontinence were assessed preoperatively and at 3 and 6 months postoperatively with the PISQ and Incontinence Impact Questionnaires (IIQ-7). Paired t tests compared changes over time. Logistic regression compared worsening PISQ vs other variables. Generalized McNemar's test compared individual questions pre- and postoperatively. Significance was set at P.05.Mean age was 47.1 (23 to 85) years, and 64% of women were premenopausal. Seventy-five (74%) women completed questionnaires at 3 or 6 months. Sexual function scores declined after surgery despite improvement in IIQ-7 scores (PISQ=86 vs 78, P.001; IIQ-7=52 vs 13, P.001). Behavioral Emotive domain scores worsened at 3 to 6 months compared with preoperative scores, while the Physical domain improved (all P.001). Worsening PISQ scores were independent of age, type of surgery, hysterectomy, complications, or hormonal status (logistic regression, all P.05).Sexual function scores in women after surgery for UI/POP do not improve despite improvement of incontinence at 3 to 6 months after surgery.

Background Valvular heart disease (VHD) is common in patients with rheumatoid arthritis (RA); however, VHD has not been well characterized by transesophageal echocardiography (TEE) and its correlation with clinical features of RA is undefined. Objective To characterize VHD in RA patients by TEE and determine possible correlation with clinical features of RA. Design Cross-sectional controlled study. Participants 33 volunteers with RA; 18 women and 15 men with a mean age of 51 ± 10 years and disease duration of 13 ± 7 years. 33 gender-matched healthy volunteers with a mean age of 41 ± 7 years. Measurements Clinical and laboratory evaluations and multiplane TEE in patients, multiplane TEE in controls. TEE studies were interpreted independent of subjects' clinical data. Results Valve thickening , typically mild and diffuse, was detected in 18 patients (55%) (aortic valve (AV) in 16 (48%), mitral valve (MV) in 11 (33%)(versus 5 controls (15%, p = .002). Valve nodules were detected in 12 patients (36%) (AV in 6 (18%), MV in 6 (18%)(versus 0 controls ( p < .001). Valve nodules were characteristically small with irregular borders and homogeneously echoreflectant without calcification. Nodules were usually located at the basal portion of the leaflets and were always associated with leaflet thickening (p < .001). Valve regurgitation of mild or greater severity was detected in 24 patients (77%) (AV in 3 (10%) and MV in 24 (77%)(versus 20 controls (61%, p = .18). Mitral regurgitation of any and moderate degree was more common in patients than controls (77% and 18% versus 55% and 1%, respectively, p ≤ .05 for both). Significant VHD defined as valve thickening, nodules, or moderate regurgitation was detected in 18 patients (58%) versus 6 controls (18%) (p = .004). Patients with and without VHD had similar age, RA disease duration, peripheral nodular disease, erosive disease, activity and severity of RA, steroid dose and duration, rheumatoid factor, C-reactive protein levels, and erythrosedimentation rate. Limitations Small study and controls were not age matched. Conclusions In patients with RA, (1) VHD is common; (2) valve nodules are a distinctive feature of VHD associated with RA; and (3) VHD may not be related to the clinical features, laboratory variables, or therapy of RA.

Purpose The new allocation policy based on model for end-stage liver disease (MELD) score predicts severity of chronic liver disease. The MELD score is derived from the levels of bilirubin, INR and creatinine but does not account for other manifestations of severe liver disease. Hepatitis C is the most common indication for liver transplant in the US. Our aim was to assess the performance of MELD score in patients with viral hepatitis awaiting transplantation. Methods Data from the Organ Procurement database for liver transplant (LT) candidates were collected from February, 2002 through 2004, representing the first 23 month9s experience with the new plan. Patients with HCV ±HBV±HAV induced PNC were compared to non-HCV ±HBV±HAV PNC for the time on waiting list, numbers of transplants, removals from the waiting list because of death or “too sick”, MELD score values, creatinine, INR and bilirubin. Status 1 and hepatoma patients were excluded. (Table) Conclusions Patients with viral hepatitis have lower levels of bilirubin, INR and creatinine which leads to lower MELD at listing, longer waiting times for transplant and lower rates of LT without an increase in the rate of removal from transplant due to death or “too sick”.

The cosyntropin stimulation test is the initial endocrine evaluation of suspected primary or secondary adrenal insufficiency.To critically review the utility of the cosyntropin stimulation test for evaluating adrenal insufficiency.The MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency.Studies with fewer than 5 persons with primary or secondary adrenal insufficiency or with fewer than 10 persons as normal controls were excluded. For secondary adrenal insufficiency, only studies that stratified participants by integrated tests of adrenal function were included.Summary receiver-operating characteristic (ROC) curves were generated from all studies that provided sensitivity and specificity data for 250-microg and 1-microg cosyntropin tests; these curves were then compared by using area under the curve (AUC) methods. All estimated values are given with 95% CIs.At a specificity of 95%, sensitivities were 97%, 57%, and 61% for summary ROC curves in tests for primary adrenal insufficiency (250-microg cosyntropin test), secondary adrenal insufficiency (250-microg cosyntropin test), and secondary adrenal insufficiency (1-microg cosyntropin test), respectively. The area under the curve for primary adrenal insufficiency was significantly greater than the AUC for secondary adrenal insufficiency for the high-dose cosyntropin test (P0.001), but AUCs for the 250-microg and 1-microg cosyntropin tests did not differ significantly (P0.5) for secondary adrenal insufficiency. At a specificity of 95%, summary ROC analysis for the 250-microg cosyntropin test yielded a positive likelihood ratio of 11.5 (95% CI, 8.7 to 14.2) and a negative likelihood ratio of 0.45 (CI, 0.30 to 0.60) for the diagnosis of secondary adrenal insufficiency.Cortisol response to cosyntropin varies considerably among healthy persons. The cosyntropin test performs well in patients with primary adrenal insufficiency, but the lower sensitivity in patients with secondary adrenal insufficiency necessitates use of tests involving stimulation of the hypothalamus if the pretest probability is sufficiently high. The operating characteristics of the 250-microg and 1-microg cosyntropin tests are similar.

Hypotheses Intoxicated motor vehicle passengers are similar to intoxicated drivers in recurrent health care encounters and risk of death for 5 years after injury. Intoxicated passengers have a greater risk of death than population controls. Design Historical cohort study. Setting University-based level I trauma center. Participants Motor vehicle crash victims admitted to a level I trauma center in 1993. Main Outcome Measures Recurrent hospitalization, emergency department visits, survival analysis, and standardized mortality ratios for 5 years following injury. Results More than one quarter of intoxicated passengers and drivers had recurrent hospitalizations and emergency department visits. Intoxicated occupants were more likely to return to the hospital and the emergency department than nonintoxicated controls (odds ratios, 2.0 and 2.7, respectively). Intoxicated passengers were at increased risk of dying compared with nonintoxicated occupants ( P = .008) and with the general population (standardized mortality ratio = 5.8). Intoxicated occupants were more likely to die an alcohol-related death ( P Conclusions Intoxicated passengers injured in a motor vehicle crash are similar to intoxicated drivers in recurrent hospitalizations and emergency department visits. Intoxicated passengers have an increased mortality rate in the 5 years following injury.

Context.—Retrospective studies have identified oral sulfonylureas, age, and fasting as major risk factors for hypoglycemia in patients with type 2 diabetes. Sulfonylureas may be withheld from elderly patients out of concern for hypoglycemia.Objective.—To evaluate the hypoglycemic effects of maximum doses of once-daily second-generation sulfonylureas administered to fasting elderly patients.Design.—A prospective, randomized, double-blind clinical trial.Setting.—The University of New Mexico General Clinical Research Center.Patients.—Fifty-two sulfonylurea-treated subjects with type 2 diabetes with a mean (SD) age of 65.1 (5.7) years.Interventions.—Subjects were randomly assigned to glyburide or glipizide gastrointestinal therapeutic system (GITS). Each subject participated in three 23-hour fasting studies after the sequential administration of 1 week of placebo and 1 week of 10 mg and 1 week of 20 mg of the assigned sulfonylurea.Main Outcome Measures.—Occurrence of hypoglycemia (defined as plasma glucose level

Objective : To increase lean body mass and improve health status in patients with wasting associated with the acquired immunodeficiency syndrome (AIDS) by treatment with recombinant human growth hormone (rhGH), recombinant human insulin-like growth factor 1 (rhIGF-1), or both. Design : Randomized, double-blind, placebo-controlled clinical trial. Setting : University of New Mexico Clinical Research Center and University of Texas Southwestern Medical Center. Patients : 60 patients with AIDS and wasting as defined by the Centers for Disease Control and Prevention. Patients were divided into four groups of 15 patients each. Intervention : Group 1 received 1.4 mg of rhGH once daily plus placebo twice daily ; group 2 received 5 mg of rhIGF-1 twice daily plus placebo once daily ; group 3 received 5 mg of rhIGF-1 twice daily plus 1.4 mg of rhGH once daily ; and group 4 received placebo three times daily. Measurements : Body weight, body composition, muscle strength, protein catabolism, quality of life, and immune status were assessed at baseline, and changes in these variables were measured at 6 and 12 weeks. Results : At 6 weeks, lean body mass had increased and total fat mass had decreased in the groups receiving rhGH, rhIGF-1, or both. Group 3 had the greatest changes in lean body mass (mean ± SE, 3.2 ± 0.59 kg ; P < 0.001) ; only in this group were changes in body mass maintained at 12 weeks. Only patients in group 1 had improvement in muscular strength of the knees and upper body (P = 0.04) and quality of life (P = 0.01). Immunologic function did not improve in any group. Conclusions : Growth factor therapy had significantly increased lean body mass and decreased fat mass by 6 weeks, but these improvements persisted for 12 weeks only in group 3. Growth factor therapy at the dosages used in this study is not recommended because the magnitude of weight gain was modest and improvements in quality-of-life measures varied.

To determine whether asymptomatic retinal cholesterol embolism is a risk factor for vascular events.Cohort study with retrospectively selected controls.A Veterans Affairs medical center.70 consecutive patients with asymptomatic retinal cholesterol emboli on dilated ocular examination in an eye clinic and 70 controls without retinal emboli. Controls were matched to patients for sex; age; prevalence of hypertension, diabetes mellitus, and ischemic heart disease; serum cholesterol level; and smoking history.Stroke, myocardial infarction, and death.During a mean follow-up of 3.4 years, stroke occurred at an annual rate of 8.5% among patients and 0.8% among controls (adjusted relative risk, 9.9; 95% CI, 2.3 to 43.1; P = 0.002). Nineteen strokes occurred, 17 in patients and 2 in controls; all were nonfatal cerebral infarctions. Twelve of the 17 that occurred in patients were in a carotid artery territory ipsilateral to the qualifying retinal cholesterol embolus and 5 were in another vascular territory. Ocular infarction or hemorrhagic stroke did not occur. Nonfatal myocardial infarction or vascular death occurred at an annual rate of 7.7% among patients and 4.9% among controls (adjusted relative risk, 1.4; 95% CI, 0.7 to 2.9; P = 0.39).Asymptomatic retinal cholesterol embolism is an important risk factor for cerebral infarction independent of commonly recognized vascular risk factors.