Search

OBJECTIVE This study examined relationships between anticholinergic medication burden and brain integrity in people living with HIV (PLWH) and people without HIV (HIV-). METHODS Neuropsychological performance z-scores (learning, retention, executive function, motor/psychomotor speed, language domains, and global cognition), and neuroimaging measures (brain volumetrics and white matter fractional anisotropy) were analyzed in PLWH (n = 209) and HIV- (n = 95) grouped according to the Anticholinergic Cognitive Burden (ACB) scale (0 = no burden, 1-3 = low burden, >3 = high burden). Neuropsychological performance and neuroimaging outcomes were compared between HIV- and PLWH with high anticholinergic burden. Within a cohort of PLWH (n = 90), longitudinal change in ACB score over ∼2 years was correlated to the rate of change per month of study interval in neuropsychological performance and neuroimaging measures. RESULTS A higher number of anticholinergic medications and ACB was observed in PLWH compared with HIV- (P

Background The burden of hepatitis C virus (HCV) is disproportionately borne by persons involved with the justice system. To explore missed opportunities for HCV screening and treatment among a justice-involved population, we examined healthcare utilization and prior opportunities for HCV testing and treatment among persons under community supervision enrolled in an HCV testing and linkage to care study in Rhode Island (RI). Methods Two hundred and fifty individuals under community supervision were recruited from an RI probation and parole office. Participants underwent a rapid HCV antibody test (OraSure Technologies) and a baseline survey, which queried participants on justice involvement, demographics, substance use, healthcare utilization and prior HCV testing. A positive HCV antibody test and no report of previous HCV testing was classified as a missed opportunity for testing. Self-reported prior HCV diagnosis with no history of treatment was classified as a missed opportunities for HCV treatment. Results Forty-five participants (18%) had reactive antibody tests. Of those 45, twenty-five (55%) reported previously being diagnosed with HCV, including thirteen who reported an HCV diagnosis over 10 years ago; none had received HCV treatment. In addition, 135 participants (61.1%) reported previously being tested for HCV; the most common site of prior testing was in jail/prison (n=87). Ten participants had missed opportunities for HCV testing, and 25 had missed opportunities for HCV treatment. Of participants with these missed opportunities, 97% had health insurance, 74% had been to a primary care provider in the past year, and 91% had ≥ 1 identifiable risk factor for HCV. Flowchart of HCV Antibody Test Results and History of HCV Testing Healthcare Utilization among Persons with Missed Opportunities Conclusion Screening for HCV at community supervision sites is an underutilized venue for HCV screening that can identify previously-undiagnosed HCV infections. Many persons under community supervision are aware of their HCV positive status but have never received treatment. Despite involvement in healthcare systems and adequate health insurance coverage, many patients with risk factors for HCV have not been tested for HCV or have only been tested for HCV while incarcerated. Investing in and implementing strategies to increase testing for HCV is necessary to maximize the care continuum in this priority population. Disclosures All Authors: No reported disclosures

Background: While diabetes mellitus (DM) is typically diagnosed in the outpatient setting, 30% of patients in the U.S.A remain undiagnosed, prompting novel approaches to screening. There are 2 million Observation Unit (OU) stays annually in the U.S.A. The OU allows prolonged care for Emergency Department (ED) patients who are not sick enough to be hospitalized. A previous study found 9% of OU patients have undiagnosed DM and therefore our OU practice is to obtain HbA1c on patients without a history of DM. A typical OU stay is 24 hours, allowing adequate time for screening, education and initiation of treatment if warranted. To conserve resources, we developed a screening tool to allow selective HbA1c testing in the OU. Methods: We reviewed OU admissions at a tertiary hospital and included patients with no known history of DM and who had HbA1c assessed during their OU stay. Those with HbA1c ≥ 6.5 were categorized as newly diagnosed DM. Previously validated clinical variables were tested in the model; also included were clinical variables readily available in the OU. A model was developed on 2/3 of the cohort and validated on the remaining 1/3. Results: A total of 2425 patients met inclusion criteria. The final model included: BMI, race, family history of DM, age, serum sodium and potassium, glucose on ED arrival and initial systolic blood pressure. Predictive assessment of the model was strong with a C-statistic of 0.823. The model was validated and findings remained strong with a C-statistic of 0.788. Performance at the optimal cut-point yielded a sensitivity of 0.750 and specificity of 0.771. Conclusions: This screening tool identifies 75% of previously undiagnosed DM patients, while excluding 77% of nondiabetic patients from testing. The model can be used at the bedside or embedded in the electronic medical record to selectively screen for DM. There is potential to identify large numbers of previously undiagnosed DM in the OU and the typical 24-hour stay allows time for education and treatment to be initiated. Disclosure R.M. Noonan: None. W.J. Castillo: None. G.M. Saffran: None. C.B. Montgomery: None. G. Phayal: None. R.H. Seemangal: None. N. Kohn: None. A. Tiberio: None. E. Wolff: None. R. Schulman: None. R. Silverman: None.

Multi-modal neurophysiologic monitoring consisting of triggered and spontaneous electromyography and transcranial motor-evoked potentials may detect and prevent both acute and slow developing mechanical and vascular nerve injuries in lateral lumbar interbody fusion (LLIF) surgery. In case report 1, a marked reduction in the transcranial motor-evoked potentials on the operative side alerted to a 28% decrease in mean arterial blood pressure in a 54-year-old woman during an L3-4, L4-5 LLIF. After hemodynamic stability was regained, transcranial motor-evoked potentials returned to baseline and the patient suffered no postoperative complications. In case report 2, a peroneal nerve train-of-four stimulation threshold of 95 mA portended the potential for a triggered electromyography false negative in a 70-year-old woman with type 2 diabetes, peripheral neuropathy, and body mass index of 30.7 kg/m undergoing an L3-4, L4-5 LLIF. Higher triggered electromyography threshold values were applied to this patient's relatively quiescent triggered electromyography and the patient suffered no postoperative complications. In case report 3, the loss of right quadriceps motor-evoked potentials detected a retractor related nerve injury in a 59-year-old man undergoing an L4-5 LLIF. The surgery was aborted, but the patient suffered persistent postoperative right leg paresthesia and weakness. These reports highlight the sensitivity of peripheral nerve elements to ischemia (particularly in the presence of vascular risk factors) during the LLIF procedure and the need for dynamic multi-modal intraoperative monitoring.

Ventral tegmental area (VTA) GABA neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in alcohol reward. The aim of this study was to examine the role of midbrain connexin-36 (Cx36) gap junctions (GJs) in ethanol's rewarding effects. Using behavioral, molecular and electrophysiological methods we compared the effects of ethanol in mature Cx36 knockout (KO) mice and age-matched wild-type (WT) controls. Cx36 KO mice exhibited significantly more ethanol-induced ataxia in the open field test, but less disruption in motor coordination than their WT controls in the rotarod paradigm. Cx36 KO mice and WT mice treated with the Cx36 antagonist mefloquine (MFQ) consumed significantly less ethanol than their vehicle-treated WT controls in the drink-in-the-dark procedure. The firing rate of VTA GABA neurons in WT mice was inhibited by ethanol with an IC(50) of 0.25 g/kg, while VTA GABA neurons in KO mice were significantly less sensitive to ethanol. Dopamine neuron sIPSC frequency was reduced by ethanol (30 mM) in WT mice, but not affected in KO mice. Cx36 KO mice evinced a significant up-regulation in DAT and D2 receptors in the VTA, as assessed by quantitative RT-PCR. These findings demonstrate the behavioral relevance of Cx36 GJ-mediated electrical coupling between GABA neurons in mature animals, and suggest that loss of coupling between VTA GABA neurons results in disinhibition of DA neurons, a hyper-DAergic state and lowered hedonic valence for ethanol consumption. Synapse, 2010. © 2010 Wiley-Liss, Inc. Language: en

OBJECTIVE: Corticotropin-releasing hormone and gonadotropin-releasing hormone are produced by the human placenta and have been measured in the maternal circulation during pregnancy. Our objective was to determine concentrations of these substances in maternal plasma throughout normal pregnancies and in early pregnancy loss. STUDY DESIGN: Fifty-one pregnant women were followed up prospectively and plasma samples were drawn at 8, 10, 12, 14, 16, 28, and 36 weeks' gestation and during labor. Specific and sensitive radioimmunoassays were used to determine corticotropin-releasing hormone and gonadotropin-releasing hormone concentrations in these samples. RESULTS: Blood samples were drawn at all time points and outcome data were available from 33 women who completed their pregnancies at term without complications. In this normal group circulating corticotropin-releasing hormone concentrations increased from low or undetectable concentrations at 8 weeks (≤23.2 ± 1.3 pg/ml, mean ± SEM) to measurable values at 16 weeks (34.3 ± 2.2 pg/ml). Thereafter there was a significant increase to 1294 ± 113 pg/ml in labor. Gonadotropin-releasing hormone demonstrated a trimodal distribution, increasing significantly from 8 to 14 weeks, decreasing at 16 weeks, and increasing again by term. The ratio of corticotropin-releasing hormone to gonadotropin-releasing hormone in the normal group demonstrated a 30-fold increase from 8 weeks to term. In eight cases of early pregnancy loss corticotropin-releasing hormone and gonadotropin-releasing hormone concentrations were not significantly different from those of the normal group in early pregnancy. In two cases of premature delivery gonadotropin-releasing hormone concentrations and ratios were within the normal range; corticotropin-releasing hormone levels were normal in both cases of premature delivery. CONCLUSION: In this study we determined maternal concentrations of corticotropin-releasing hormone and gonadotropin-releasing hormone in normal pregnancies and in labor at term. Neither maternal concentrations of corticotropin-releasing hormone nor gonadotropin-releasing hormone were useful in identifying pregnant women at risk for early pregnancy loss. (Am J Obstet Gynecol 1996;175:912-6.)

Objective: To determine the frequency by age of ovarian malignancies in women with a pelvic mass and to assess preoperative indicators for ovarian cancer. Methods: Inpatient charts from June 1, 1990, to August 30, 1992, were reviewed with preoperative diagnoses of a pelvic mass. Preoperative evaluation, surgical procedure, and pathologic diagnoses were recorded. Comparisons were made using the Fisher exact test. Results: In patients with ovarian disease, benign masses were found more commonly than malignancies (72 versus 13%, respectively). Ovarian malignancies were more common in patients over age 50 than in patients younger than 50 (25.6 versus 5.1%; p < 0.001). Preoperative platelet count, CA 125, and ultrasound findings did not identify patients with ovarian malignancy. Conclusions: Ovarian malignancies are uncommon in young women, but the risk of malignancy increases with age. Elevated CA 125 levels may prove to be helpful in evaluating pelvic masses in postmenopausal women.

Objective: To determine whether ovarian follicular fluid (FF) stem cell factor concentrations are associated with successful IVF pregnancies. Design: Nested case-control design evaluation of stem cell factor levels from the FF of oocytes fertilized and transferred after controlled ovarian hyperstimulation. Setting: University-based ART program. Patient(s): Infertile women undergoing IVF in a university-based ART program. Intervention(s): Fifty-seven FF samples from a cohort of patients ( n = 13) with tubal factor and unexplained infertility were stored at −80°C and subsequently evaluated for stem cell factor concentration. Patients with endometriosis, polycystic ovary disease, and male factor infertility were excluded. Stem cell factor concentrations were measured using a commercially available ELISA kit according to the manufacturer's specifications. The groups were analyzed using a one-way analysis of variance, and significance was determined using the X 2 analysis of contingency table, the unpaired t-test, or the Mann-Whitney rank-sum test. Main Outcome Measure(s): FF stem cell factor concentration, pregnancy. Result(s): Stem cell factor concentrations were significantly higher in the FF of the patients who achieved successful pregnancies than in those who did not (641.7 ±75.2 pg/mL versus 475.5 ±50.58 pg/mL). Conclusion(s): Elevated FF stem cell factor concentrations are associated with an increased likelihood of IVF success. Therefore, stem cell factor may play a role in human follicular and oocyte development, and increasing infrafollicular stem cell factor concentrations may improve pregnancy rates after oocyte retrieval, fertilization, and ET.

This study evaluates and characterizes the prevalence and nature of physical and sexual abuse among pregnant economically stable middle-class women with access to comprehensive health care. Self-report questionnaires were distributed to 829 pregnant women who attended the prenatal orientation at Wilford Hall Medical Center from October 19 1992 to March 15 1993. Out of the 563 women (68%) who completed the surveys 100 women (18%) reported a history of physical and sexual abuse. The lifetime prevalence of physical abuse was 12% (n = 68) and the lifetime prevalence of sexual abuse was 9% (n = 51). Women who experienced physical abuse often cited an intimate partner as the assailant (5.5%) and reported more than one abusive episode. Injuries are most commonly inflicted to the head and body. Only 1% (n = 7) of the respondents claimed of being physically abused during pregnancy. Majority of these women reported being more physically (46%) rather than sexually (13%) abused by their partner. The findings indicate that health care practitioners may provide resources for counseling and support to women who are victims of physical or sexual abuse in order to reduce the long-term emotional psychological and physical sequelae of the abuse.

Male mice ( C57BL 6J ) were injected once ip with 0.1, 1, 100, 200, 400, 600, 800, or 1000 mg/kg of 2-methylnaphthalene dissolved in corn oil. After 24 hr, the animals were killed and the lungs, livers, and kidneys were prepared for light microscopy. In addition, some lungs were subjected to scanning and transmission electron microscopy. A dose of 200 mg/kg produced a bronchiolar necrosis which affected the nonciliated bronchiolar (Clara) cell; the parenchymal cells remained unaffected. At higher doses of 2-methylnaphthalene (800 mg/kg), in addition to the damaged Clara cell, severe damage to the upper respiratory tract was noted. No liver or kidney pathology was detected by light microscopy in animals treated with the highest dose. No cellular damage was noted in any organ at doses less than 200 mg/kg. Forty-eight hours after a dose of 200–1000 mg/kg of 2-methylnaphthalene, less pulmonary damage was detected by light microscopy. The metabolism of 2-methylnaphthalene was investigated in hepatic, pulmonary, and renal microsomes from C57BL 6J mice. Lung and liver microsomes produced three isomeric dihydrodiols of 2-methylnaphthalene as well as other monohydroxylated metabolites. Only trace amounts of these metabolites were produced by the kidney.

PURPOSE: The aim of our work is to evaluate the added diagnostic value of respiratory gated (4-D) positron emission tomography/computed tomography (PET/CT) in lung lesion detection/characterization in a large patient population of a multicentre retrospective study. METHODS: The data of 155 patients (89 men, 66 women, mean age 63.9 ± 11.1 years) from 5 European centres and submitted to standard (3-D) and 4-D PET/CT were retrospectively analysed. Overall, 206 lung lesions were considered for the analysis (mean ± SD lesions dimension 14.7 ± 11.8 mm). Maximum standardized uptake values (SUV(max)) and lesion detectability were assessed for both 3-D and 4-D PET/CT studies; 3-D and 4-D PET/CT findings were compared to clinical follow-up as standard reference. RESULTS: Mean ± SD 3-D and 4-D SUV(max) values were 5.2 ± 5.1 and 6.8 ± 6.1 (p < 0.0001), respectively, with an average percentage increase of 30.8 %. In 3-D PET/CT, 86 of 206 (41.7 %) lesions were considered positive, 70 of 206 (34 %) negative and 50 of 206 (24.3 %) equivocal, while in 4-D PET/CT 117 of 206 (56.8 %) lesions were defined as positive, 80 of 206 (38.8 %) negative and 9 of 206 (4.4 %) equivocal. In 34 of 50 (68 %) 3-D equivocal lesions follow-up data were available and the presence of malignancy was confirmed in 21 of 34 (61.8 %) lesions, while in 13 of 34 (38.2 %) was excluded. In 31 of these 34 controlled lesions, 20 of 34 (58.8 %) and 11 of 34 (32.4 %) were correctly classified by 4-D PET/CT as positive and negative, respectively; 3 of 34 (8.8 %) remained equivocal. With equivocal lesions classified as positive, the overall accuracy of 3-D and 4-D was 85.7 and 92.8 %, respectively, while the same figures were 80.5 and 94.2 % when equivocal lesions were classified as negative. CONCLUSION: The respiratory gated PET/CT technique is a valuable clinical tool in diagnosing lung lesions, improving quantification and confidence in reporting, reducing 3-D undetermined findings and increasing the overall accuracy in lung lesion detection and characterization.