Sociodemographic characteristics of the neighborhood and depressive symptoms in older adults: using multilevel modeling in geriatric psychiatry.

OBJECTIVE: Neighborhood sociodemographic characteristics may be important to the mental health of older adults who have decreased mobility and fewer resources. Our objective was to examine the association between neighborhood context and level of depressive symptomatology in older adults in a diverse geographic region of central North Carolina. METHODS: The sample included 2,998 adults 65 or older residing in 91 census tracts. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression scale (CES-D). Neighborhoods were characterized by five census-based characteristics: socioeconomic disadvantage, socioeconomic advantage, racial/ethnic heterogeneity, residential stability, and age structure. RESULTS: In ecologic level analyses, level of census tract socioeconomic disadvantage was associated with increased depressive symptoms. To determine whether neighborhood context was associated with depressive symptoms independently of individual characteristics, the authors used multilevel modeling. The authors examined the ability of each of five neighborhood (level 2) characteristics to predict a level 1 outcome (CES-D symptoms) controlling for the effects of individual (level 1) characteristics. Younger age, being widowed, lower income, and having some functional limitations were associated with increased depression symptoms conditional on census tract random effects. However, none of the neighborhood characteristics was significantly associated with depression symptoms, conditional on census tract random effects, either unadjusted or adjusted for individual characteristics. CONCLUSION: Any observed association between neighborhood sociodemographic characteristics and individual depressive symptoms in our sample may reflect the characteristics of the individuals who reside in the neighborhood rather than the neighborhood characteristics themselves. The use of multilevel modeling is important to separate these effects.     

Voltage Oscillations in Xenopus Spinal Cord Neurons: Developmental Onset and Dependence on Co-activation of NMDA and 5HT Receptors

The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg²⁺ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT_1a receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT₁, a selective 5HT_1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg²⁺, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg²⁺ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg²⁺ block. When the membrane potential was depolarized by ～20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg²⁺ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg²⁺ through activation of receptors with 5HT_1a-like pharmacology.     

Blood coagulation activation and fibrinolysis during a downhill marathon run.

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.     

Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.     

Case-control study of risk factors for cervical neoplasia in Denmark. II. Role of sexual activity,reproductive factors,and venereal infections

Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n=614) was drawn at random from the female population in the study area by means of the Danish Central Population Register. A structured questionnaire was mailed to cases as well as controls. Increasing number of sexual partners exerted a significant effect on the risk both for carcinoma in situ, and invasive cancer, independently of age at first intercourse and other potential confounders. Conversely, the association with early age at first intercourse became statistically insignificant after allowance for other risk factors, although an increasing risk was still observed with decreasing age at sexual debut. Early age at first episode with genital warts was a significant risk factor for carcinoma in situ, perhaps indicating a possible increased susceptibility of the cervix epithelium during adolescence. A history of genital warts was a good predictor of risk for carcinoma in situ, whereas a history of previous gonorrhea was associated with an increased risk for invasive carcinoma. Women with multiple births had a significantly increased adjusted risk, especially for carcinoma in situ, although some association was also observed with invasive cervical cancer. The study supports the hypothesis of cervical neoplasia being a sexually transmitted disease, and that carcinoma in situ and invasive cervical carcinoma, to a high degree, have similar patterns of risk factors.Drs Kjaer, Engholm, and Lynge are with the Danish Cancer Registry. Dr Dahl is with the Department of Surgery, Slagelse Hospital, Denmark. Dr Bock is with the Department of Gynecology, Rigshospitalet, Copenhagen, Denmark. Dr Jensen, formerly with the Danish Cancer Registry, is deceased. Address correspondence to Dr Kjaer, Danish Cancer Registry, Institute of Cancer Epidemiology, Danish Cancer Society, Rosenvengets Hovedvej 35, Box 839, Copenhagen. Denmark. The Danish Cancer Society supported this study through grants.     

Increased suicide risk among Danish women with non-melanoma skin cancer, 1971-1999.

More suicides than expected (standardized mortality ratio=1.3; 95% confidence interval=1.1-1.6) compared to the population risk were found among Danish women with a diagnosis of non-melanoma skin cancer in the period 1971-1999 but not among men. The increased risk might be associated with a different personality type in this cancer group.     

Spectral analysis of prespeech sounds (spontaneous cries) in infants with unilateral cleft lip and palate (UCLP): a pilot study.

OBJECTIVE: The objectives of the present study were: (1) to analyze the cry features of infants with cleft lip and palate (UCLP) by means of spectral analysis, (2) to describe changes of the acoustic parameters from birth until 9 months of age, and (3) to compare these data with existing cry data of infants without cleft (control group). DESIGN: The study was designed on a interdisciplinary, prospective, and longitudinal basis. SETTING: Interdisciplinary study: (1) Institute of Anthropology at the Humboldt-University, Berlin; (2) Heidelberg University Hospital: Interdisciplinary Cleft Palate and Craniofacial Center. PATIENTS AND METHOD: The cry parameters of five patients with complete unilateral cleft lip, alveolar ridge, and hard and soft palate were analyzed from birth to 9 months of age. The patients were treated with the same protocol. At the age of 24 months, sensomotor development was assessed using the KIPHARD test. Perceptual judgment of speech, performed after 36 months of life, included nasal resonance, nasal emission of air, articulation disorders, and speech intelligibility. MAIN OUTCOME MEASURE: The cry parameters of fundamental frequency (F(0)), pitch period perturbation quotient (PPQ), and cry duration (Tsam) were analyzed. RESULTS: Contrary to the expectation that laryngeal parameters are not affected by vocal tract malformations, differences of cry parameters were found between the patients with UCLP and the non-cleft group. Particularly, the F(0) and its short-time variability (PPQ) were affected. CONCLUSIONS: The preliminary results of this study showed that F(0) and PPQ of spontaneous cries are influenced in patients with UCLP, and a cry analysis might become a noninvasive tool for early detection of an at-risk status for neuromuscular development and prediction of an at-risk status for later speech and language acquisition in infants with cleft lip and palate. Future research strategies are outlined.