The AMPA receptor potentiator LY404187 increases cerebral glucose utilization and c-fos expression in the rat.

AMPA receptor potentiators enhance AMPA receptor-mediated glutamatergic neurotransmission and may have therapeutic potential as cognitive enhancers or antidepressants. The anatomical basis for the action of AMPA receptor potentiators is unknown. The aim of this study was to determine the effects of the biarylpropylsulfonamide AMPA receptor potentiator, LY404187 (0.05 to 5 mg/kg subcutaneously), upon cerebral glucose utilization and c-fos expression using 14C-2-deoxglucose autoradiography and c-fos immunocytochemistry. LY404187 (0.5 mg/kg) produced significant elevations in glucose utilization in 28 of the 52 anatomical regions analyzed, which included rostral neocortical areas and the hippocampus, as well the dorsal raphe nucleus, lateral habenula, and locus coeruleus. No significant decreases in glucose utilization were observed in any region after LY404187 administration. The increases in glucose utilization with LY404187 (0.5 mg/kg) were blocked by pretreatment with the AMPA receptor antagonist LY293558 (25 mg/kg), indicating that LY404187 acts through AMPA receptor-mediated mechanisms. LY404187 (0.5 mg/kg) also produced increases in c-fos immunoreactivity in the cortex, locus coeruleus, and the dorsal raphe nucleus. These studies demonstrate neuronal activation in key brain areas that are associated with memory processes and thus provide an anatomical basis for the cognitive enhancing effects of AMPA receptor potentiators.     

The contribution of optimism and quality of life to depression in an acute coronary syndrome population.

BACKGROUND: Numerous longitudinal studies have revealed that depression following an acute cardiac event poses a risk factor for poor cardiac outcomes. It is therefore important to identify modifiable predictors of depression in order to develop a variety of interventions with this population. AIMS: The aim of the present research was to determine whether the relationship between optimism and depressive symptoms was mediated by self-reported quality of life (QOL) in acute coronary syndrome patients. METHODS: Two weeks following hospital discharge (Time 1) 59 participants completed a self-report questionnaire. Four weeks later (Time 2), 49 of these participants completed the same questionnaire. RESULTS: At Time 1, the relationship between optimism and depressive symptoms was partially mediated by functional QOL and symptom QOL. Furthermore, the relationship between Time 1 optimism and Time 2 depressive symptoms was partially mediated by Time 1 functional QOL. When each of the Time 1 variables were used to predict Time 2 depressive symptoms, only optimism continued to predict depressive symptoms over and above the influence of Time 1 depressive symptoms and other covariates. CONCLUSION: These findings suggest the underlying importance of optimism in influencing depressive symptoms in acute coronary syndrome patients, and indicate that optimism and perceptions of functional QOL may be a possible rehabilitation target for this population.     

Predictors of Partner Notification for C. trachomatis and N. gonorrhoeae: An Examination of Social Cognitive and Psychological Factors

Efforts to control chlamydial and gonococcal infections include notifying eligible sexual partners of possible infection, primarily by asking the diagnosed patient to notify their partners. This approach, known as patient referral, is widely used but poorly understood. The current study examined psychosocial and cognitive factors associated with patient referral among an urban, minority sample of 168 participants recently diagnosed with Chlamydia trachomatis or Neisseria gonorrhoeae. At a follow-up interview 1-month from diagnosis, participants were more likely to have notified all eligible partners if they had greater intention to notify at baseline (OR = 3.72; 95% CI = 1.34, 10.30) and if they had only one partner at baseline (OR = 4.08; 95% CI = 1.61, 10.31). There were also gender differences as well as differences based on type of partner (i.e., regular, casual, one-time). The implications of these findings for the design of programs to promote patient referral for sexually transmitted infections are discussed. Schwartz, Malka, Augenbraun, McCormack, and Wilson are with the State University of New York, Downstate Medical Center, Brooklyn, NY, USA; Rubin is with the New York City Department of Health, Bureau of STD Control, New York, NY, USA; Rubin, Hogben, and Liddon are with the Centers for Disease Control and Prevention, Atlanta, GA, USA; Schwartz is with the Department of Preventive Medicine and Community Health, SUNY Downstate Medical Center, Box 1240, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.     

Upregulation of interleukin-1 receptors in mouse AtT-20 pituitary tumor cells following treatment with corticotropin-releasing factor.

Treatment of AtT-20 cell cultures with increasing concentrations of rat/human corticotropin-releasing factor (r/hCRF) for 24 h resulted in a dose-dependent 2-3 fold increase in specific 125I-labelled recombinant human IL-1 alpha (125I-IL-1 alpha) binding that was paralleled by a 70-80% decrease in 125I-Tyro-ovine CRF binding. Saturation analysis of 125I-IL-1 alpha binding in control and CRF-treated cultures indicated that CRF produced an increase in the density (Bmax) of IL-1 receptors without altering their affinity (KD). The CRF-induced upregulation of IL-1 receptors appears to be mediated through specific membrane receptors for CRF since the CRF receptor antagonist, alpha-helical oCRF (9-41), blocked the CRF-induced upregulation of IL-1 receptors without producing any effect on 125I-IL-1 alpha binding by itself. In summary, these data demonstrate complex interactions between CRF and IL-1 at the pituitary level and identify potential novel mechanisms for cytokines to alter neuroendocrine function.     

Dermal fillers. The next generation.

In today's busy and demanding world, we no longer have the luxury of taking weeks to recover from a surgical procedure and are more frequently seeking quicker alternatives. The use of dermal fillers meets this need but in no way replaces a surgical intervention. Previously, bovine collagen was the only approved dermal filler. However, today there are several options available including a human collagen, a variety of hyaluronic acids, and a permanent injectable product. Each of the products has different uses, indications, and adverse reactions. The experienced injector now has a wider selection of products from which to choose to ensure that the patient receives what is best suited for his or her particular situation. These new products are becoming increasingly popular, due to acceptability and affordability, but are not without potential complications and adverse reactions. This article discusses the use of Cosmoderm/Cosmoplast, Hylaform, Restylane/Perlane, and Artecoll dermal fillers.     

Laparoscopic transhiatal surgery of the esophagus.

OBJECTIVE: Esophagectomy is an operation with high morbidity and mortality. Its adoption as a minimally invasive operation worldwide has been slow, but the potential benefits of reducing the trauma of surgery need to be considered. Our 30-month experience with transhiatal esophagectomy in a district general hospital is presented herein. METHODS: Patients were considered for surgery after radiological staging had excluded inoperable disease. Laparoscopic staging was initially performed. Patients with tumors of the esophagus and high-grade dysplasia in a Barrett's esophagus were included. RESULTS: Twenty-nine patients were referred for consideration for resectional surgery. Nine underwent outpatient laparoscopy only. Twenty patients (age range, 34 to 78, 15 males:5 females) underwent resectional surgery. Seventeen transhiatal resections were completed, 2 were converted to open procedures, and 1 transhiatal resection of a benign tumor was performed. Median time of surgery was 415 minutes (range, 320 to 480) and blood loss was 300 mL (range, 200 to 350). The median length of post-operative ventilation and critical care stay were 1 (range, 1 to 4) and 4 (range, 2 to 8) days. Median duration of hospitalization was 17 days (range, 10 to 28). Thirty-day mortality was 0; 1 patient who was converted to an open procedure died after a cerebrovascular event on day 34. CONCLUSION: A zero mortality rate for laparoscopic resection and a low-morbidity rate compare well with morbidity and mortality in reported series using this method and open surgery. Laparoscopic transhiatal esophagectomy is an advanced, complex procedure that can be performed safely in a district general hospital setting.     

Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy

We describe a method that directly relates tissue neuropathological analysis to medical imaging. Presently, only indirect and often tenuous relationships are made between imaging (such as MRI or x-ray computed tomography) and neuropathology. We present a biochemistry-based, quantitative neuropathological method that can help to precisely quantify information provided by in vivo proton magnetic resonance spectroscopy (¹HMRS), an emerging medical imaging technique. This method, high resolution magic angle spinning (HRMAS) ¹HMRS, is rapid and requires only small amounts of unprocessed samples. Unlike chemical extraction or other forms of tissue processing, this method analyzes tissue directly, thus minimizing artifacts. We demonstrate the utility of this method by assessing neuronal damage using multiple tissue samples from differently affected brain regions in a case of Pick disease, a human neurodegenerative disorder. Among different regions, we found an excellent correlation between neuronal loss shown by traditional neurohistopathology and decrease of the neuronal marker N-acetylaspartate measured by HRMAS ¹HMRS. This result demonstrates for the first time, to our knowledge, a direct, quantitative link between a decrease in N-acetylaspartate and neuronal loss in a human neurodegenerative disease. As a quantitative method, HRMAS ¹HMRS has potential applications in experimental and clinical neuropathologic investigations. It should also provide a rational basis for the interpretation of in vivo ¹HMRS studies of human neurological disorders.     

Exploring the nature of the relationship between child sexual abuse and substance use among women

Aims. This study investigated whether child sexual abuse (CSA) was associated with earlier substance use and greater severity of substance dependence and what aspects of CSA might predict substance abuse. Design. The study compared (a) drug and alcohol treatment clients with and without a history of CSA and (b) CSA survivors outside drug and alcohol treatment who did or did not have current substance abuse. Settings. Semi-structured interviews took place at participants' homes, treatment agencies or the research centre. Participants. Volunteer participants included 100 women recruited from drug and alcohol treatment programmes and 80 CSA survivors recruited through CSA counselling services and media advertising. Measurements. The results focus on data from the Opiate Treatment Index, Severity of Alcohol Dependence Questionnaire, Substance Dependence Scale, Self-Esteem Inventory and self-reported histories of CSA. Findings. There were no differences between CSA survivors and other drug and alcohol treatment clients in their severity of dependence. Women with a history of CSA more frequently identified stimulants as their main problem drug and reported an earlier age of first intoxication and earlier use of inhalants. Among CSA survivors outside drug and alcohol treatment, women with current substance abuse had typically been abused during adolescence by someone outside the family, whereas those without current substance abuse were typically abused by family members before adolescence. Conclusions. The results suggest that adolescence is a crucial time for the influence of CSA experiences on substance abuse.