Severe opioid withdrawal precipitated by Vivitrol®.

The risk of severe precipitated opioid withdrawal (POW) is amplified when precipitated by a long-acting opioid antagonist. IM extended release naltrexone (XRNTX;Vivitrol®) is an FDA approved therapy to prevent relapse of opioid and alcohol abuse. Two cases of precipitated opioid withdrawal from XRNTX are presented that illustrate different patient reactions to POW. A 56-year-old woman developed a hypertensive emergency and required continuous intravenous vasodilator, clonidine, and intensive care monitoring after re-initiation of XRNTX following opioid relapse. A 25-year-old man developed agitation and altered mental status after receipt of XRNTX at the conclusion of a twelve-day detoxification program during which he continued surreptitious use of heroin. The patient received benzodiazepines and haloperidol without adequate affect, and required intubation with propofol, lorazepam, and dexmedetomidine infusions. Management of POW from XRNTX is a challenge to emergency providers and protocols to guide management do not exist. Recommended therapies include intravenous fluids, anti-emetics, clonidine, or benzodiazepines as well as therapy tailored to the organ system affected. To minimize risk of POW it is important for providers instituting XRNTX to adhere to the manufacturers warnings and clinic protocols including a naloxone challenge and ensure an adequate opioid free period prior to administration of XRNTX.

The Effect of a Regimen of Antifungal Cream Use on Episodes of Acute Adenolymphangitis (ADL) among Lymphedema Patients: An Application Using Marginal Structural Models.

Episodes of adenolymphangitis (ADL) are a recurrent clinical aspect of lymphatic filariasis (LF) and a risk factor for progression of lymphedema. Inter-digital entry lesions, often found on the web spaces between the toes of those suffering from lymphedema, have been shown to contribute to the occurrence of ADL episodes. Use of antifungal cream on lesions is often promoted as a critical component of lymphedema management. Our objective was to estimate the observed effect of antifungal cream use on ADL episodes according to treatment regimen among a cohort of lymphedema patients enrolled in a morbidity management program. We estimated this effect using marginal structural models for time varying confounding. In this longitudinal study, we estimate that for every one-unit increase in the number of times one was compliant to cream use through 12 months, there was a 23% (RR = 0.77 (0.62, 0.96)) decrease in the number of ADL episodes at 18 months, however the RR's were not statistically significant at other study time points. Traditionally adjusted models produced a non-significant RR closer to the null at all time points. This is the first study to estimate the effect of a regimen of antifungal cream on the frequency of ADL episodes. This study also highlights the importance of the consideration and proper handling of time-varying confounders in longitudinal observational studies.

Postnatal ultrasound reliability in cerebellar vermis assessment.

BACKGROUND: Cerebellar growth in late gestation is impeded by prematurity which may adversely affect neurocognitive development. Assessment of cerebellar growth should be easily attainable, reliable and reproducible. OBJECTIVE: To assess the reliability of linear sonographic cerebellar vermis measurement. METHOD: Cranial ultrasounds of 110 infants ranging from 24 to 41 weeks' gestation were retrospectively reviewed. Cerebellar vermian height, craniocaudal diameter and superior and inferior vermis widths were independently measured on the first midline sagittal image by three neonatal sonologists of varying experience. Interobserver and intraobserver reliability were calculated using the intraclass correlation coefficient (ICC) (2 way mixed model, SPSS V.15.0). RESULTS: 61 images were technically adequate. Interobserver ICCs (95% CI) were: cerebellar vermian height 0.88 (0.82 to 0.92); craniocaudal diameter 0.91 (0.86 to 0.94); superior vermis width 0.84 (0.77 to 0.89); inferior vermis width 0.92 (0.89 to 0.95). Intraobserver ICCs were similar. CONCLUSION: With adequate images, linear ultrasound measurements of cerebellar vermis are reliable.

Predictors of compliance with a mass drug administration programme for lymphatic filariasis in Orissa State, India 2008.

OBJECTIVES: To assess the performance of an educational campaign to increase adherence to a mass-administered DEC regimen against lymphatic filariasis (LF) in Orissa, and to identify factors that could enhance future campaigns. METHOD: Randomized cluster survey, comparing areas that did and did not receive the educational campaign, using a household coverage survey and knowledge, attitudes and practices (KAP) survey. RESULTS: LF MDA coverage for the entire population (n = 3449) was 56% (95% CI: 50.0-61.9). There was no statistical difference between the areas that did and did not receive the educational campaign. The most common barriers to adherence were fear of medication side effects (47.4%) and lack of recognition of one's risk for LF (15.8%). Modifiable, statistically significant, multivariable predictors of adherence were knowing that DEC prevents LF (aOR = 2.6, 95% CI: 1.4-5.1), knowing that mosquitoes transmit LF (aOR = 1.9, 95% CI: 1.1-3.2), and knowing both about the mass drug administration (MDA) in advance and that mosquitoes transmit LF (aOR = 5.4, 95% CI: 2.8-10.4). CONCLUSIONS: India needs to increase compliance with MDA programmes to reach its goal of interrupting LF transmission. Promoting a simple public health message before MDA distribution, which takes into account barriers to and predictors of adherence, could raise compliance with the LF MDA programme.

Adrenocortical secretion of dehydroepiandrosterone in healthy women: highly variable response to adrenocorticotropin.

Excess adrenal androgen (AA) levels are observed in 25--50% of women with the polycystic ovary syndrome (PCOS), and AA excess in PCOS may represent selection bias. Thus, it is possible that AA secretion among the general population is highly variable, and that those women who are predisposed to secreting greater amounts of AA have a greater probability of having PCOS. We now hypothesize that the levels of AAs are highly variable among normal nonhyperandrogenic women, and that this heterogeneity is the result of a variable response of AAs to ACTH stimulation. To test this hypothesis we prospectively studied the response of dehydroepiandrosterone (DHA) and cortisol (F) to a 60-min acute stimulation with ACTH-(1--24) in 56 healthy eumenorrheic nonhirsute healthy women with a mean age of 28.9 yr (range, 20--37 yr.) and a mean body mass index (BMI) of 29.2 kg/m(2) (18.2--46.2 kg/m(2)). Baseline samples and poststimulation samples were assayed for DHA and F. The basal and ACTH-stimulated levels of DHA, but not those of F, were negatively correlated with age, although neither the basal nor ACTH-stimulated responses of DHA and F varied with BMI. After controlling for age, the basal F level was negatively correlated to its net increment (i.e. Delta F; r = -0.54; P < 0.001), whereas there was no significant relationship between basal DHA and Delta DHA. We also compared the intersubject variability (coefficient of variation) for basal and stimulated levels of DHA and F. For basal (DHA(0)), 60 min (DHA(60)), and net increment in (Delta DHA) DHA levels, the coefficients of variation were 67.9%, 61.4%, and 76.0%, respectively; for F(0), F(60), and Delta F, they were 40.4%, 16.9%, and 31.3%, respectively. The variance in Delta DHA was significantly higher, and the variance in F(60) was significantly lower than that in all other variables; DHA(0), DHA(60), F(0), and Delta F had similar variances. In conclusion, in our population of healthy reproductive-aged women we observed that both basal and ACTH-stimulated levels of DHA after ACTH-(1--24) stimulation had significantly greater intersubject variance (approximately 60--70%) compared with the basal and poststimulation levels of F (approximately 15--40%). These data support the hypothesis that among normal women, AA (i.e. DHA) levels are highly variable compared to those of F. In addition, the intersubject variability in DHA levels is at least in part due to a variable response of AAs to ACTH stimulation. Whether the AA excess frequently observed in PCOS is due to the greater risk of those women with higher AA levels, basally and after ACTH stimulation, remains to be confirmed.

A prevalence study of hepatitis A virus infection in a migrant community: Is hepatitis A vaccine indicated?

BACKGROUND: The Advisory Committee on Immunization Practices recommends routine hepatitis A vaccination of children living in communities with high rates of hepatitis A. Rates among children living in migrant farm worker families are unknown. METHODS: Participants recruited from the 1243 migrant children aged 2 to 18 years in Okeechobee County, Florida, were administered a questionnaire. A blood sample was taken for testing for antibodies to hepatitis A virus (anti-HAV), and hepatitis A vaccine was administered. RESULTS: Of 244 (20%) participating children, 125 (51%) were anti-HAV-positive. Seropositivity increased with age from 34% (2- to 5-year-olds) to 81% (>/=14-year-olds) (P <.0001). In multivariate analysis, age (odds ratio [OR] = 1.2/year; 95% CI = 1.1 to 1.3), having a Mexican-born father (OR = 12.2; 95% CI = 2.2 to 227.9), and age on moving to the United States (OR = 1.3/year; 95% CI = 1.0 to 1.6) were independently associated with anti-HAV positivity. Among US-born children aged 2 to 5 years who had never left the United States, 33% were anti-HAV-positive. CONCLUSIONS: Anti-HAV prevalence among migrant children in Okeechobee County, including the youngest US-born children, is high, indicating ongoing transmission of HAV. Children in this and other US migrant communities may benefit from hepatitis A vaccination.

Correlates of total plasma homocysteine: folic acid, copper, and cervical dysplasia.

We examined correlates of total plasma homocysteine (tHcy) in 294 subjects with cervical intraepithelial neoplasia and 170 control subjects. Associations of tHcy with risk factors for cervical intraepithelial neoplasia and 24-h intakes and biochemical indices of nutrients were examined. Plasma and red blood cell folate and plasma B(12) were strong inverse correlates of tHcy (r = -0.35, -0. 31, and -0.27, respectively). Plasma copper and severity of dysplasia were positively correlated with tHcy (r = 0.14 and 0.21, respectively). A stepwise regression model that included red blood cell folate, plasma copper, grade of dysplasia, ethnicity, intake of polyunsaturated fatty acids, plasma vitamin B(12), intake of fat, and oral contraceptive use explained 29% of the variation in tHcy. Two hundred thirty-five subjects with cervical intraepithelial neoplasia were randomized to receive folic acid (10 mg/d) or placebo for 6 mo. After 2, 4, and 6 mo, mean tHcy in the folate-supplemented group (7.2 +/- 1.8, 7.0 +/- 1.9, and 7.0 +/- 2.3 micromol/L, respectively) was significantly lower than baseline and the placebo group at 2, 4, and 6 mo (8.9 +/- 3.1, 8.4 +/- 3.0, and 8.9 +/- 3.1 micromol/L, respectively). Supplementation lowered tHcy even in subjects in the highest quintile of baseline folate. Folate, vitamin B(12), copper, and severity of dysplasia are associated with tHcy. Folate supplementation significantly lowers tHcy even in folate-replete subjects.

Effect of total plasma homocysteine on cervical dysplasia risk.

We investigated whether total plasma homocysteine (tHcy) is associated with risk for cervical intraepithelial neoplasia (CIN). tHcy was evaluated, along with numerous risk factors for CIN and biochemical indexes of nutrients, in a previously reported study population of 294 subjects with CIN and 170 female controls without CIN. tHcy was significantly higher in cases than in controls (9.1 vs. 8.3 mumol/l, p = 0.002). Human papillomavirus type 16 infection [odds ratio (OR) = 6.7], oral contraceptive use (OR = 6.0), parity (OR = 2.2), and cigarette smoking (OR = 1.9) were significantly associated with CIN after adjustment for each other and for age, number of sexual partners, and plasma tHcy, folate, iron, and zinc. Human papillomavirus type 16 positivity increased risk for CIN more when tHcy was > 9.12 mumol/l (OR = 4.7) than when it was < or = 9.12 mumol/l (OR = 3.0). Cigarette use increased risk for CIN when tHcy was > 9.12 mumol/l (OR = 3.9), but not when tHcy was < or = 9.12 mumol/l (OR = 1.5). Parity increased risk for CIN more when tHcy was > 9.12 mumol/l (OR = 4.0) than when tHcy was < or = 9.12 mumol/l (OR = 2.0). These results suggest that elevated plasma tHcy is a risk factor for cervical dysplasia and that it enhances the effects of other risk factors. It is unknown whether tHcy is serving as a marker of folate deficiency or is acting through other mechanisms.

Necessary role for ventral tegmental area adenylate cyclase and protein kinase A in induction of behavioral sensitization to intraventral tegmental area amphetamine.

In the present study, we investigated the effects of selective activation or inhibition of ventral tegmental area (VTA) adenylate cyclase (AC) and protein kinase A (PKA) on long-term sensitization induced by repeated intra-VTA or peripheral amphetamine (AMPH). Selective inhibition of AC by SQ 22,536 (9-(tetrahydro-2-furanyl)-9H-purin-6-amine; 100 nmol/side bilateral into VTA) had no effect on acute basal locomotion but attenuated the locomotor stimulation induced by acute i.p. AMPH (1.5 mg/kg). Coinjection of SQ 22,536 (100 nmol/side) fully blocked the sensitization induced by repeated intra-VTA AMPH (15 nmol/side) but had no detectable effect on the sensitization induced by repeated i. p. AMPH. Persistent activation of AC by intra-VTA cholera toxin (500 ng/side) modestly increased acute locomotion and induced a robust sensitization to i.p. AMPH challenge 10 days after the last of three repeated VTA microinjections. Selective inhibition of PKA by Rp-adenosine-3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPS; 25 nmol/side) had no effect on acute basal or AMPH-stimulated locomotion. Coinjection of Rp-cAMPS (25 nmol/side) fully blocked the sensitization induced by repeated intra-VTA AMPH but had no effect on sensitization induced by repeated i.p. AMPH. Intra-VTA microinjection of the selective PKA activator Sp-adenosine-3',5'-cyclic monophosphothioate triethylamine (Sp-cAMPS; 25-100 nmol/side) dose-dependently stimulated acute locomotion and exerted synergistic effects on locomotor activity when coinfused into the VTA with AMPH but had no detectable effect on acute i.p. AMPH-induced locomotion. Repeated intra-VTA Sp-cAMPS did not induce sensitization to AMPH challenge but potentiated the sensitization induced by repeated i.p. AMPH. These results suggest that VTA cAMP signal transduction is necessary for the induction of persistent sensitization to intra-VTA amphetamine and that peripheral and intra-VTA AMPH may not induce behavioral sensitization by identical mechanisms.

Behavioral and neurochemical effects of the dopamine transporter ligand 4-chlorobenztropine alone and in combination with cocaine in vivo.

The current studies evaluated the novel diphenylmethoxytropane analog 4-chlorobenztropine (4-Cl-BZT), cocaine, and combinations of the two drugs for their abilities to stimulate locomotor activity, produce cocaine-like discriminative stimulus effects, and elevate extracellular dopamine (DA) in the nucleus accumbens (NAc) as measured by in vivo microdialysis. Peripherally administered cocaine was approximately twice as efficacious as 4-Cl-BZT as a locomotor stimulant and was behaviorally active at a lower dose than was 4-Cl-BZT. Cocaine also was more efficacious than 4-Cl-BZT in producing discriminative-stimulus effects in rats trained to discriminate i.p. injections of 10 mg/kg cocaine from saline. The time course of behavioral activation differed markedly between the two drugs, with much shorter onset and duration of locomotor stimulant effects for cocaine relative to 4-Cl-BZT. Similarly, i.p. cocaine (10 and 40 mg/kg) induced a pronounced, rapid, and short-lived increase in DA in the NAc, whereas i.p. 4-Cl-BZT was effective only at the higher dose and produced a more gradual, modest, and sustained (>/=2 h) elevation in accumbens DA. In contrast to i.p. administration, local infusion of 4-Cl-BZT (1-100 microM) into the NAc through the microdialysis probe elevated extracellular DA to a much greater extent than did local cocaine (nearly 2000% of baseline maximally for 4-Cl-BZT versus 400% of baseline for cocaine) and displayed a much longer duration of action than cocaine. However, when microinjected bilaterally into the NAc at 30 or 300 nmol/side, cocaine remained a more efficacious locomotor stimulant than 4-Cl-BZT. Finally, pretreatment with i.p. 4-Cl-BZT dose dependently enhanced the locomotor stimulant, discriminative stimulus effects, and NAc DA response to a subsequent low-dose i.p. cocaine challenge. The diphenylmethoxytropane analog also facilitated the emergence of stereotyped behavior and convulsions induced by high-dose cocaine. The current results demonstrate that DA transporter ligands that do not share the neurochemical and behavioral profiles of cocaine nevertheless may enhance the effects of cocaine in vivo.

Intractable diarrhea from cytomegalovirus enterocolitis in an immunocompetent infant.

Infection with cytomegalovirus (CMV) in infants can be congenital or perinatal. Infected infants may be asymptomatic or present with pneumonia, rash, hepatosplenomegaly, or encephalitis.1 In the presence of an immunodeficiency, severe and sometimes fatal disease may occur. To our knowledge, CMV has not been identified previously as a cause of intractable diarrhea of infancy. We report the case of a 5-week-old immunocompetent infant with intractable diarrhea attributable to CMV-induced enterocolitis. Recognition of this infection and initiation of ganciclovir therapy was associated with a rapid improvement and resolution of the diarrhea.

The effect of a self-monitoring tool on self-efficacy, health beliefs, and adherence in patients receiving hemodialysis.

OBJECTIVE: Assess the effectiveness of a self-monitoring tool on perceptions of self-efficacy, health beliefs, and adherence in patients receiving hemodialysis. DESIGN: A monthly intervention using a pretest, posttest design over a 6-month period. Both the treatment and control groups were randomly selected and received surveys to assess health beliefs, perceptions of self-efficacy for performing specific healthful behaviors, and renal diet knowledge at baseline, before intervention, and 6 months later. The treatment group also received monthly feedback of monthly phosphorus levels and interdialytic weight gains. SETTING: A university hospital-based 43-chair ambulatory dialysis center. SUBJECTS: Forty patients with end-stage renal disease (25 men and 15 women, age 26 to 78 years), on chronic hemodialysis for at least 2 months and with a history of noncompliance with phosphorus and/or fluid restrictions for 1 or more months. MAIN OUTCOME MEASURES: Self-efficacy, health beliefs, knowledge, biochemical, and demographic variables were analyzed. Analysis of variance tests of repeated measures were used to examine relationships between adherence with phosphorus and fluid restrictions to health beliefs and perceptions of self-efficacy after training in self-monitoring. RESULTS: Overall, there were no significant improvements in adherence with phosphorus and fluid restrictions between the two groups, although a comparison within the groups revealed the treatment group had a statistically significant decrease in mean phosphorus levels of 7.14 to 6.22 mg/dL (P = .005) from baseline to month 3. However, because this value was not maintained, it was not statistically significant. No significant differences existed between the two groups for health beliefs and perceptions of self-efficacy. Knowledge scores in the treatment group, however, improved significantly as compared to the control group (P = .008) and was a significant increase from baseline (P = . 002). In the control group, all scores fell slightly but this difference was not significant. CONCLUSIONS: The benefits of patient self-monitoring and behavioral contracting upon adherence in patients on hemodialysis are inconclusive, as serum phosphorus and interdialytic weight gains did not differ between the two groups. The interventional tools also appeared to have little effect on perceptions of self-efficacy and health beliefs. Trends of improvement, however, did exist for phosphorus within the treatment group and subjects in this group had a statistically significant increase in knowledge scores over time. Additional research using repeated measures design is needed to explore the effects of increased frequency and duration of an intervention on the attainment of patient clinical outcome measures.

Androgen response to hypothalamic-pituitary-adrenal stimulation with naloxone in women with myotonic muscular dystrophy.

Myotonic muscular dystrophy (MMD) is a disease of autosomal dominant inheritance characterized by multisystem disease, including myotonia, muscle-wasting and weakness of all muscular tissues, and endocrine abnormalities attributed to a genetic abnormality causing a defective cAMP-dependent kinase. We have previously reported that MMD patients demonstrate ACTH hypersecretion after endogenous CRH release stimulated by naloxone administration while manifesting a normal cortisol (F) response. Additionally, others have reported a reduced adrenal androgen (AA) response to exogenous ACTH administration in MMD patients. As ACTH stimulates the secretion of both AAs and F, it is possible that the discordant relationship of these hormones in MMD patients results from a defect of adrenocortical ACTH receptor function or postreceptor signaling or subsequent biochemical events. Furthermore, the molecular abnormality seen in MMD patients may suggest that the mechanism underlying the frequently observed discordances in the secretion of glucocorticoids and AAs (e.g. adrenarche, surgical trauma, severe burns, or intermittent glucocorticoid administration) are explainable solely via an alteration in the function of the ACTH receptor or postreceptor signaling. To ascertain whether the responses of F and AAs to endogenous ACTH diverged in this disorder, we prospectively studied the responses of these hormones to naloxone-stimulated CRH release in nine premenopausal women with MMD and seven healthy age and weight-matched control women. After naloxone infusion (125 micrograms/kg, i.v.), blood sampling was performed at baseline (i.e. -5 min) and at 30 and 60 min. In addition to the absolute hormone level at each time, we calculated the net increment (i.e. change) at 30 and 60 min and the area under the curve (AUC) for F, ACTH, dehydroepiandrosterone (DHA), and androstenedione (A4). Consistent with our previous study, MMD patients demonstrated higher ACTH levels at all sampling times except [minud]5 min. AUC analysis revealed the ACTHAUC values were significantly higher in MMD than in control women (457 +/- 346 vs. 157 +/- 123 pmol/min.L; P < 0.03), whereas the FAUC response did not differ between MMD and controls (13860 +/- 3473 vs. 13375 +/- 3465 nmol/min.L; P > 0.5). Despite the greater ACTH secretion, the baseline circulating dehydroepiandrosterone sulfate levels were significantly lower in MMD compared with control women (18 +/- 23 vs. 61 +/- 23 mumol/L; P < 0.002). The serum concentrations of A4 at baseline, 30 min, and 60 min and DHA levels at 30 and 60 min were also significantly lower in MMD vs. control women. Additionally, the A4AUC and DHAAUC values were significantly lower in MMD patients than in controls. Furthermore, the net response of DHA at 60 min to the endogenous ACTH increase was also reduced in MMD patients compared with that in control subjects (2.3 +/- 2.1 vs. 5.6 +/- 2.6 nmol/L; P < 0.02). In conclusion, in addition to ACTH hypersecretion to CRH-mediated stimuli, these data suggest that MMD patients have a defect in the adrenocortical response to ACTH, reflected in normal F and reduced DHA and A4 secretion. Whether this defect is inherent to the disease or simply reflects adaptive changes to chronic disease remains to be demonstrated. However, it is possible that further studies of the response of MMD patients to ACTH may reveal a mechanism that explains the frequently observed dichotomy in the secretion of glucocorticoids and AAs.

Adrenal androgen excess in the polycystic ovary syndrome: sensitivity and responsivity of the hypothalamic-pituitary-adrenal axis.

Over 50% of patients with the polycystic ovary syndrome (PCOS) demonstrate excess levels of adrenal androgens (AAs), particularly dehydroepiandrosterone sulfate (DHS). Nonetheless, the mechanism for the AA excess remains unclear. It has been noted that in PCOS the pituitary and ovarian responses to their respective trophic factors (i.e. GnRH and LH, respectively) are exaggerated. Similarly, we have postulated that excess AAs in PCOS arises from dysfunction of the hypothalamic-pituitary-adrenal axis, due to 1) exaggerated pituitary secretion of ACTH in response to hypothalamic CRH, 2) excess sensitivity/responsivity of AAs to ACTH stimulation, or 3) both. To test this hypothesis we studied 12 PCOS patients with AA excess (HI-DHS; DHS, > 8.1 mumol/L or 3000 ng/mL), 12 PCOS patients without AA excess (LO-DHS; DHS, < 7.5 mumol/L or 2750 ng/mL), and 11 controls (normal subjects). Each subject underwent an acute 90-min ovine CRH stimulation test (1 microgram/kg) and an 8-h incremental i.v. stimulation with ACTH-(1-24) at doses ranging from 20-2880 ng/1.5 m2.h) with a final bolus of 0.25 mg. All patient groups had similar mean body mass indexes and ages, and both tests were performed in the morning during the follicular phase (days 3-10) of the same menstrual cycle, separated by 48-96 h. During the acute ovine CRH stimulation test, no significant differences in the net maximal response (i.e. change from baseline to peak level) for ACTH, dehydroepiandrosterone (DHA), androstenedione (A4), or cortisol (F) or for the DHA/ACTH, A4/ACTH, or F/ACTH ratios was observed. Nonetheless, the net response of DHA/F and the areas under the curve (AUCs) for DHA and DHA/F indicated a greater response for HI-DHS vs. LO-DHS or normal subjects. The AUC for A4 and A4/F and the delta A4/delta F ratio (delta = net maximum change) indicated that HI-DHS and LO-DHS had similar responses, which were greater than that of the normal subjects, although the difference between LO-DHS patients and normal subjects reached significance only for the AUC of the A4 response. No difference in the sensitivity (i.e. threshold or minimal stimulatory dose) to ACTH was noted between the groups for any of the steroids measured. Nonetheless, the average dose of ACTH-(1-24) required for a threshold response was higher for DHA than for F and A4 in all groups. No difference in mean responsivity (slope of response to incremental ACTH stimulation) was observed for DHA and F between study groups, whereas the responsivity of A4 was higher in HI-DHS patients than in normal or LO-DHS women. The net maximal and the overall (i.e. AUC) responses of DHA were greater for HI-DHS than for normal or LO-DHS women. The response of A4 and the delta A4/delta F ratio were greater for HI-DHS patients than for LO-DHS patients or normal subjects. Alternatively, HI-DHS and LO-DHS patients had similar overall responses (i.e. AUC) for A4 or A4/F, although both were greater than those of normal subjects. The relative differences in response to incremental ACTH stimulation between steroids was consistent for all subject groups studied, i.e. A4 > F or DHA. In conclusion, our data suggest that AA excess in PCOS patients is related to an exaggerated secretory response of the adrenal cortex for DHA and A4, but not to an altered pituitary responsivity to CRH or to increased sensitivity of these AAs to ACTH stimulation. Whether the increased responsivity to ACTH for these steroids is secondary to increased zonae reticularis mass or to differences in P450c17 alpha activity, particularly of the delta 4 pathway, remains to be determined.

Predictors of stroke complicating carotid artery stenting.

BACKGROUND: The evolving technique of carotid stenting is being evaluated as an alternative to endarterectomy. Identification of the factors that predispose a patient to neurological complications would facilitate further refinement of the technique and optimize patient selection. METHODS AND RESULTS: We analyzed the impact of various clinical, morphological, and procedural determinants on the development of procedural strokes in 231 patients who underwent elective (primary) stenting of 271 extracranial carotid arteries. The mean age of the patients was 68.7+/-10 years, 165 (71%) were males, and 139 (60%) had symptoms attributed to the lesion treated. This series represented a high-risk subset with 164 patients (71%) having significant coronary artery disease, 91 (39%) having bilateral disease, and 28 (12%) having contralateral carotid occlusion. Of the treated vessels, 59 (22%) had prior carotid endarterectomy, 66 (24%) had ulcerated plaques, and 87 (32%) had calcified lesions. Only 37 treated vessels (14%) would have been eligible for inclusion in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). There were 17 (6.2%) minor and 2 (0.7%) major strokes during and within 30 days of the procedure. NASCET-eligible patients had a low (2.7%) risk of procedural strokes after carotid stenting. The results of multivariate analysis revealed advanced age (P=.006) and presence of long or multiple stenoses (P=.006) as independent predictors of procedural strokes. CONCLUSIONS: During this procedural developmental phase of carotid stenting, neurological complications were highly dependent on patient selection. Advanced age and long or multiple stenoses were independent predictors of procedural stroke.

Role of the ovary in the adrenal androgen excess of hyperandrogenic women.

OBJECTIVE: To test the hypothesis that ovarian hormones in women with hyperandrogenism alter adrenocortical steroidogenesis. DESIGN: Combination of two prospective studies. SETTING: Academic medical centers. PATIENT(S): Eighteen hyperandrogenic patients demonstrating hirsutism with either hyperandrogenemia, oligomenorrhea, or both. Eighteen healthy nonhirsute eumenorrheic untreated women served as controls. INTERVENTIONS: Blood sampling basally and after acute adrenal stimulation with ACTH, before and after 20-24 weeks of leuprolide administration. Nine patients also received 0.625 mg/d of oral conjugated esterified estrogens and 10 mg of medroxyprogesterone acetate days 1-12 of the month (i.e., estrogen replacement therapy [ERT]), whereas the remaining nine did not. MAIN OUTCOME MEASURE(S): Before and after the administration of the GnRH agonist (GnRH-a), the basal concentrations of DHEAS; and the levels of androstenedione (A4), DHEA, androstenediol, 11 beta-hydroxyandrostenedione (11-OHA4), and cortisol before and 60 minutes after acute adrenal stimulation, were measured. RESULT(S): Levels of DHEAS, androstenediol, and 11-OHA4 decreased by 15%-30%, regardless of whether patients initially had or did not have DHEAS excess. However, only hyperandrogenic patients with elevated levels of DHEAS showed a significant decrease in basal DHEA levels. No statistically significant difference in the response of either androgen to ACTH (1-24) stimulation was noted with ovarian suppression, regardless of initial DHEAS level or use of ERT. CONCLUSION(S): We found no evidence that ovarian hormone secretion affected adrenal steroidogenesis, and those women with the highest adrenal androgen levels had the least response to GnRH-a suppression. These findings further support the concept of an intrinsic, and possibly primary, abnormality of adrenocortical steroidogenesis in a subset of hyperandrogenic women that is independent of ovarian abnormalities.

Pinealocyte ultrastructure in mutant mice that lack sympathetic innervation to the pineal gland.

Pinealocyte synaptic ribbons (SR) and dense-cored vesicles (DCV) were quantitated in mice that have developmental deficiencies in the sympathetic innervation of the pineal gland due to a null mutation for the p75 low-affinity NGF receptor (NGFR). SR exhibited a significant increase whereas there was a significant decline in the frequency of DCV in mutant mice. These findings support the hypothesis that pinealocyte SR and DCV are regulated by neural mechanisms associated with sympathetic system. Ultrastructural characteristics of pinealocytes in mutants included degenerative changes that culminated in the breakdown of cellular components and the accumulation of flocculent-containing vesicles within the cytoplasm. Ribosomal lamellar complexes were also commonly seen in pinealocytes of mutant rats. Although the mutant pineal gland exhibited signs of metabolic imbalances, the cytoarchitecture of the gland (e.g., vascular compartment) and differentiation of the cells were generally unaffected by developmental deficiencies in the gland's innervation.

Enriched immune-environment of blood-brain barrier deficient areas of normal adult rats.

The circumventricular organs (CVOs) in the brain are without a blood-brain barrier (BBB) and as such directly exposed to blood plasma constituents and blood-borne pathogens. In light of previous studies showing discrepancies regarding the immunocompetence of these organs, we initiated the present study to provide a comprehensive immunohistochemical analysis of the cellular expression of immune-associated antigens within the pineal gland, area postrema and the subfornical organ. In all CVOs, subpopulations of cells morphologically similar to complement receptor type 3 immunoreactive microglial/macrophage cells expressed major histocompatibility complex (MHC) class II antigen, leucocyte common antigen (LCA/CD45), as well as CD4 and ED1 antigen. Based on morphological criteria the MHC class II antigen expressing cells could be grouped into a major population of classical parenchymal and perivascular ramified microglial cells and a minor population presenting itself as scattered or small groups of rounded macrophage-like cells. CD4 and ED1 antigen were expressed by both cell types. CD45 was preferentially expressed by macrophage-like cells. MHC class I antigen was expressed by the vascular endothelium in both BBB-protected and BBB-deficient areas and was additionally present as a lattice-like network throughout the BBB-deficient parenchyma in all CVOs. The results suggest that the BBB-free areas of the brain besides being constantly surveyed by blood-borne macrophages, possess an intrinsic immune surveillance system based on resting and activated microglial cells, which may function as a non-endothelial, cellular barrier against blood-borne pathogens.

Frequency of extra-cardiac activity and its effect on 99Tcm-MIBI cardiac SPET interpretation.

There are limited published data concerning the frequency and relative intensity of abdominal activity on 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) myocardial perfusion scans and its effect on interpretation. We undertook a blinded prospective study to evaluate (1) the frequency and intensity of abdominal activity on single photon emission tomography (SPET) scans, (2) its effect on separate evaluation of rest and stress SPET images, and (3) its effect on clinical interpretation. Patients undergoing one-day rest-stress 99Tcm-MIBI scans were randomized to receive 99Tcm-MIBI obtained from one of two radiopharmacies. The rest plus exercise or rest plus intravenous dipyridamole scans of 303 patients were scored separately by three physicians for (1) intensity of abdominal activity and (2) its effect on scan evaluation. Nuclear reports generated independently of the blinded evaluation were reviewed to assess the effect of abdominal activity on clinical interpretation. There were no statistical differences between pharmacies. Abdominal activity was uncommon on the exercise but common on the rest and dipyridamole scans. The exercise scans differed from the rest and dipyridamole scans in the subgroups: intensity of abdominal activity equal to myocardium, and greater than myocardium (P < 0.001). There was no difference between the rest and dipyridamole scans. The effect on evaluation was moderate in 5% of the exercise, 46% of the dipyridamole and 37% of the rest scans, and severe in 1% of the exercise, 3% of the dipyridamole and 12% of the rest scans. Rest differed from exercise (P < 0.001) and from dipyridamole (P < 0.05). There was no difference between the dipyridamole and exercise scans. Based on the clinical reports, abdominal activity was a limitation to scan interpretation for 20 patients; in 5, the inferior wall could not be evaluated. Although abdominal activity was frequently observed on both the dipyridamole and rest scans, it was a limitation to clinical interpretation in a small fraction of the patients.

A multidimensional evaluation of a nursing information-literacy program.

The goal of an information-literacy program is to develop student skills in locating, evaluating, and applying information for use in critical thinking and problem solving. This paper describes a multidimensional evaluation process for determining nursing students' growth in cognitive and affective domains. Results indicate improvement in student skills as a result of a nursing information-literacy program. Multidimensional evaluation produces a well-rounded picture of student progress based on formal measurement as well as informal feedback. Developing new educational programs can be a time-consuming challenge. It is important, when expending so much effort, to ensure that the goals of the new program are achieved and benefits to students demonstrated. A multidimensional approach to evaluation can help to accomplish those ends. In 1988, The University of Northern Colorado School of Nursing began working with a librarian to integrate an information-literacy component, entitled Pathways to Information Literacy, into the curriculum. This article describes the program and discusses how a multidimensional evaluation process was used to assess program effectiveness. The evaluation process not only helped to measure the effectiveness of the program but also allowed the instructors to use several different approaches to evaluation.