Wednesday, December 19, 2007

Proenkephalin expression and enkephalin release are widely observed in non-neuronal tissues.


Proenkephalin expression and enkephalin release are widely observed in non-neuronal tissues.

Denning GM, Ackermann LW, Barna TJ, Armstrong JG, Stoll LL, Weintraub NL, Dickson EW.

Department of Emergency Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, C-43 GH, Iowa City, IA 52242-1009, United States.

Enkephalins are opioid peptides that are found at high levels in the brain and endocrine tissues. Studies have shown that enkephalins play an important role in behavior, pain, cardiac function, cellular growth, immunity, and ischemic tolerance. Our global hypothesis is that enkephalins are released from non-neuronal tissues in response to brief ischemia or exercise, and that this release contributes to cardioprotection. To identify tissues that could serve as potential sources of enkephalins, we used real-time PCR, Western blot analysis, ELISA, immunofluorescence microscopy, and ex vivo models of enkephalin release. We found widespread expression of preproenkephalin (pPENK) mRNA and production of the enkephalin precursor protein proenkephalin (PENK) in rat and mouse tissues, as well as in tissues and cells from humans and pigs. Immunofluorescence microscopy with anti-enkephalin antisera demonstrated immunoreactivity in rat tissues, including heart and skeletal muscle myocytes, intestinal and kidney epithelium, and intestinal smooth muscle cells. Finally, isolated tissue studies showed that heart, skeletal muscle, and intestine released enkephalins ex vivo. Together our studies indicate that multiple non-neuronal tissues produce PENK and release enkephalins. These data support the hypothesis that non-neuronal tissues could play a role in both local and systemic enkephalin-mediated effects.

PMID: 18082911 [PubMed - as supplied by publisher]

Psychiatric Symptoms in Children and Adolescents With Cyclic Vomiting Syndrome and their Parents.


Psychiatric Symptoms in Children and Adolescents With Cyclic Vomiting Syndrome and their Parents.

Tarbell S, Li BU.

Department of Pediatric Gastroenterology and Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Objective.- To conduct a pilot study to evaluate the prevalence of psychiatric symptoms in children and adolescents with cyclic vomiting syndrome and to assess family history of psychiatric disorder. Background.- Little is known about psychiatric comorbidity in youth with cyclic vomiting syndrome, a periodic syndrome. Methods.- Eighty-five parents, of children aged 3-18 years with cyclic vomiting syndrome confirmed in a multidisciplinary clinic, completed the age-appropriate Children's Symptom Inventory, a questionnaire that screens for psychiatric symptoms in pediatric patients. Twenty-one adolescents aged 13-18 years completed the Youth's Report, a self-report form of this questionnaire. Sixty-two parents completed a family psychiatric history checklist. Results.- These children and their parents evidenced a high prevalence of anxiety and mood symptoms compared to norms of the Children's Symptom Inventory and population norms for internalizing psychiatric disorders. On the age-appropriate Children's Symptom Inventory, 47% of subjects (40/85) met diagnostic cut-off for an anxiety disorder, and 14% (12/85) for an affective disorder. Discrepancies were found in parent and adolescent reports for symptoms of panic disorder (chi-square = 4.83, df = 1, P = .028), posttraumatic stress disorder (chi-square = 6.87, df = 1, P = .009), and somatization disorder (chi-square = 6.41, df = 1, P = .01), with parents reporting significantly more symptoms than the adolescents. Internalizing disorders were also prevalent in the parents with 59% (36/62) endorsing either an anxiety and/or an affective disorder. Mothers reported a significantly higher prevalence of anxiety disorders (35%) than did fathers (13%) (chi-square = 8.43, df = 1, P < .004). Conclusion.- Children and adolescents with cyclic vomiting syndrome appear to be at increased risk for internalizing psychiatric disorders, especially anxiety disorders. Further research using standardized psychiatric interviews and a control group are indicated to further assess psychiatric disorders in children and adolescents with cyclic vomiting syndrome.

PMID: 18081819 [PubMed - as supplied by publisher]

Monday, December 17, 2007

Comorbidity of Migraine and Psychiatric Disorders-A National Population-Based Study.

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Comorbidity of Migraine and Psychiatric Disorders-A National Population-Based Study.

Jette N, Patten S, Williams J, Becker W, Wiebe S.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

Background.- Migraine is common, with an estimated lifetime prevalence of 7-17%. Population-based studies have reported an association between various psychiatric conditions and migraine. This is a population-based study exploring the association between migraine and psychiatric disorders in a large cohort and assessing various health-related outcomes. Objective.- (1) Determine the prevalence of various psychiatric conditions in association with migraine; (2) describe the patterns of association of these comorbidities with a variety of health-related outcomes. Methods.- Data from the 2002 Canadian Community Health Survey were used. This is a national health survey which included administration of the World Mental Health Composite International Diagnostic Interview to a sample of 36,984 subjects. Health-related outcomes included 2-week disability, restriction of activities, quality-of-life, and mental health care utilization. Results.- The prevalence of physician-diagnosed migraine (n = 36,984) was 15.2% for females and 6.1% for males. Migraine was most common in those between ages 25 and 44 years and in those of lower income. Migraine was associated with major depressive disorder, bipolar disorder, panic disorder, and social phobia, all occurring more than twice as often in those with migraines compared with those without. Migraine was not associated with drug, alcohol, or substance dependence. The higher prevalence of psychiatric disorders in migraineurs was not related to sociodemographic variables. Psychiatric disorders were less common in those over 65 years, in those who were in a relationship, and in those of higher income whether migraine was present or not. Health-related outcomes were worst in those with both migraines and a psychiatric disorder and intermediate in those with either condition alone. Conclusion.- Migraine is associated with major depressive disorder, bipolar disorder, panic disorder, and social phobia. Migraine in association with various mental health disorders results in poorer health-related outcomes compared with migraine or a psychiatric condition alone. Understanding the psychiatric correlates of migraine is important in order to adequately manage this patient population and to guide public health policies regarding health services utilization and health-care costs.

PMID: 18070059 [PubMed - as supplied by publisher]

Tuesday, December 11, 2007

Electromagnetic millimeter wave induced hypoalgesia: Frequency dependence and involvement of endogenous opioids.

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Electromagnetic millimeter wave induced hypoalgesia: Frequency dependence and involvement of endogenous opioids.

Radzievsky AA, Gordiienko OV, Alekseev S, Szabo I, Cowan A, Ziskin MC.

Center for Biomedical Physics, Temple University Medical School, Philadelphia, Pennsylvania.

Millimeter wave treatment (MMWT) is based on the systemic biological effects that develop following local skin exposure to low power electromagnetic waves in the millimeter range. In the present set of experiments, the hypoalgesic effect of this treatment was analyzed in mice. The murine nose area was exposed to MMW of "therapeutic" frequencies: 42.25, 53.57, and 61.22 GHz. MMWT-induced hypoalgesia was shown to be frequency dependent in two experimental models: (1) the cold water tail-flick test (chronic non-neuropathic pain), and (2) the wire surface test (chronic neuropathic pain following unilateral constriction injury to the sciatic nerve). Maximum hypoalgesic effect was obtained when the frequency was 61.22 GHz. Other exposure parameters were: incident power density = 13.3 mW/cm(2), duration of each exposure = 15 min. Involvement of delta and kappa endogenous opioids in the MMWT-induced hypoalgesia was demonstrated using selective blockers of delta- and kappa-opioid receptors and the direct ELISA measurement of endogenous opioids in CNS tissue. Possible mechanisms of the effect and the perspectives of the clinical application of MMWT are discussed. Bioelectromagnetics. (c) 2007 Wiley-Liss, Inc.

PMID: 18064600 [PubMed - as supplied by publisher]

Monday, December 10, 2007

Psychiatric disorders and family functioning in children and adolescents with functional abdominal pain syndrome.

J Gastroenterol Hepatol. 2007 Nov 14 [Epub ahead of print]Click here to read Links

Psychiatric disorders and family functioning in children and adolescents with functional abdominal pain syndrome.

Department of Psychiatry, Shiraz University of Medical Sciences, Shiraz, Iran.

Background and Aim: Functional abdominal pain syndrome (FAPS) is a functional gastrointestinal disorder. There is a heightened risk when conducting potentially dangerous and unnecessary medical investigations and procedures in children with FAPS. The aim of this study was to survey the rate of the psychiatric disorders and family functioning in children and adolescents with FAPS. Methods: The subjects were a consecutive new sample of 45 children and adolescents with FAPS, 45 with an organic abdominal pain, and 45 pain-free comparison subjects aged 5-18 years that were interviewed using the Farsi version of K-SADS. Family functioning and the severity of pain were also studied. Results: About 51.1% of patients with FAPS suffered from at least one psychiatric disorder. Psychiatric disorders in the FAPS patients studied included general anxiety disorder (8.9%), obsessive-compulsive disorder (11.1%), attention deficit hyperactivity disorder (15.6%), separation anxiety disorder (24.4%), and major depressive disorder (15.6%). Except for generalized anxiety disorder and tic disorder, the other disorders were significantly more common in the FAPS group than in the two other control groups. Family functioning scores were not significantly different between groups. Discussion: There is a high rate of psychiatric disorders in children and adolescents with FAPS in Iran, but our study found fewer incidences of disorders than previous reports have indicated. Family dysfunction difficulties in FAPS children are not more common than those in the control groups.

PMID: 18005012 [PubMed - as supplied by publisher]

Oral naltrexone to enhance analgesia in patients receiving continuous intrathecal morphine for chronic pain: a randomized, double-blind, prospective pilot study.

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Oral naltrexone to enhance analgesia in patients receiving continuous intrathecal morphine for chronic pain: a randomized, double-blind, prospective pilot study.

Hamann S, Sloan P.

Department of Anesthesiology, University of Kentucky Medical Center, Lexington, USA.

BACKGROUND: Years' worth of observations suggest that morphine has both inhibitory and excitatory actions, and that selective blockade of excitatory effects by low doses of opioid antagonists (e.g., naltrexone) may paradoxically enhance morphine analgesia. The purpose of this pilot study was to evaluate and compare the analgesic efficacy and safety of two different low doses of oral naltrexone given in addition to chronic intrathecal morphine infusions in patients with chronic nonmalignant pain (CNMP). METHODS: After institutional review board approval, 15 patients with CNMP receiving continuous intrathecal morphine were admitted into a prospective, randomized, double-blind, placebo-controlled, seven-day pilot study. Patients were randomized into three treatment groups based on oral naltrexone dose: 100 microg (Group A, n = 3), 10 microg (Group B, n = 7), or placebo (Group C, n = 5). All patients continued with their constant intrathecal morphine infusion, and in addition they received one capsule of study medication every 12 hours for seven days. Other analgesics or coanalgesics were kept at a constant dose level throughout the study. Patients rated pain scores (visual analogue score [VAS]; 0 = no pain, 10 = worst pain imaginable) and side effects three times daily throughout the study period. Efficacy measures included pain intensity difference (PID) scores, constructed so that positive scores indicate a reduction in pain intensity and negative scores indicate a worsening of pain. RESULTS: Fifteen patients (six male, nine female) with a mean (SD) age of 55 (10) years and weight of 81 (21) kg completed the study. The mean (SD) baseline VAS pain intensity rating was similar in all three groups (6.8 [1.5]). Baseline pain VAS score minus the lowest daily pain VAS score yielded the peak PID score. The peak PID score from Day 1 was statistically (p < 0.05) highest (median PID score: 5.9) in Group A compared with Group C. There was a trend in PID scores across Days 2 through 7, with median PID scores higher (i.e., greater pain relief p = 0.07) in Group A. In the daily global pain assessments, the pain scores across Days 2 through 7 approached significance (least pain) in Group A compared to Group C (p = 0.07) or B (p = 0.08). Side effects were common (93 percent of patients), minor (headache, nausea, sedation, dry mouth), and similar across treatment groups. No serious adverse events were observed, and no evidence of opioid withdrawal was seen. CONCLUSIONS: 1) Patients with chronic pain who received oral naltrexone 100 microg BID in addition to their chronic intrathecal morphine infusions demonstrated the greatest improvement (p = 0.07) in their daily pain scores. Because of the small sample size, the results did not reach traditional levels of significance. 2) Side effects were common, minor, and similar across treatment groups. 3) No serious adverse events were recorded. 4) No evidence of opioid antagonist toxicity or opioid withdrawal was observed.

Publication Types:
PMID: 18027539 [PubMed - in process]

Leukocyte-derived opioid peptides and inhibition of pain.

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Leukocyte-derived opioid peptides and inhibition of pain.

Machelska H, Stein C.

Klinik für Anaesthesiologie und operative Intensivmedizin, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200, Berlin, Germany. halina.machelska@charite.de

In peripheral inflamed tissue interactions between leukocyte-derived opioid peptides and opioid receptors on sensory neurons lead to potent, clinically relevant inhibition of pain. Opioid receptors are present on peripheral terminals of sensory neurons and are upregulated in inflammation. Their endogenous ligands, opioid peptides, are synthesized in circulating immune cells, which migrate to injured tissues directed by chemokines and adhesion molecules. Under stressful stimuli or in response to releasing agents (e.g., corticotropin-releasing factor, cytokines, catecholamines) leukocytes can secrete opioids. These peptides activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of excitatory neuropeptides. These effects occur without central opioid side effects such as depression of breathing, clouding of consciousness, or addiction. Future research should elucidate the selective targeting of opioid peptide-containing immune cells to sites of painful tissue injury and the augmentation of opioid peptide and receptor synthesis.

Publication Types:
PMID: 18040794 [PubMed - in process]

Depression and panic disorder as predictors of health outcomes for patients with asthma in primary care.

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Depression and panic disorder as predictors of health outcomes for patients with asthma in primary care.

Schneider A, Löwe B, Meyer FJ, Biessecker K, Joos S, Szecsenyi J.

Department of General Practice and Health Services Research, University Hospital, University of Heidelberg, Vossstrasse 2, 69115 Heidelberg, Germany.

INTRODUCTION: Depression and panic disorder are widely acknowledged as complicating factors in asthma patients. However, their impact on health outcomes in primary care patients is less well examined. This study prospectively evaluated the impact of depression and panic disorder on outcomes of primary care patients with asthma over 1 year. METHODS: At baseline, 256 asthma patients from 43 primary care practices completed self-report questionnaires including the Patient Health Questionnaire (PHQ), the Asthma Quality of Life Questionnaire (AQLQ), and a structured questionnaire evaluating asthma severity, hospitalisation and emergency visits. One year later, 185 (72.3%) patients completed the same questionnaire. RESULTS: At baseline, 3.9% of patients suffered from major depressive disorder, 22.7% from minor depressive disorder, and 7.8% from panic disorder. In the year under evaluation, 17 patients (9.2%) received emergency home visits and 10 patients (5.4%) were admitted to a hospital. Depression at baseline predicted hospitalisation within the subsequent year (OR 6.1; 95% CI 1.5-24.6) and panic disorder predicted unscheduled emergency home visits (OR 4.8; 95% CI 1.3-17.7). Depression but not panic disorder predicted the AQLQ scales activity (p=0.001), symptoms (p=0.001), emotions (p=0.001) and environment (p=0.001) at follow-up. CONCLUSIONS: Although rates of hospitalisation and emergency visits in primary care are low, the impact of psychiatric comorbidity on health outcomes for patients with asthma is substantial. It might be helpful to identify patients with psychiatric comorbidity by analysing reasons for hospitalisation and emergency visits. For these patients, intensifying care with psychiatric interventions might help to reduce inappropriate healthcare utilisation and avoid adverse outcomes.

PMID: 18061424 [PubMed - as supplied by publisher]

Wednesday, December 5, 2007

History of childhood maltreatment is associated with comorbid depression in women with migraine.

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History of childhood maltreatment is associated with comorbid depression in women with migraine.

Tietjen GE, Brandes JL, Digre KB, Baggaley S, Martin VT, Recober A, Geweke LO, Hafeez F, Aurora SK, Herial NA, Utley C, Khuder SA.

Department of Neurology, College of Medicine, The University of Toledo-Health Science Campus, Toledo, OH 43614, USA. gretchen.tietjen@utoledo.edu

BACKGROUND: A bidirectional relationship between migraine and depression suggests a neurobiological link. Adverse experiences, particularly childhood maltreatment, may alter neurobiological systems, and predispose to a multiplicity of adult chronic disorders. Our objective is to determine, within a headache clinic population of women, if depression moderates the abuse-migraine relationship. METHODS: At six headache specialty clinics, women with migraine were diagnosed using ICHD-II criteria, and frequency was recorded. A questionnaire regarding maltreatment history, headache characteristics, current depression, and somatic symptoms was completed. RESULTS: A total of 949 women with migraine completed the survey: 40% had chronic headache (> or =15 headache days/month) and 72% had "very severe" headache-related disability. Major depression was recorded in 18%. Physical or sexual abuse was reported in 38%, and 12% reported both physical and sexual abuse in the past. Migraineurs with current major depression reported physical (p < 0.001) and sexual (p < 0.001) abuse in higher frequencies compared to those without depression. Women with major depression were more likely to report sexual abuse occurring before age 12 years (OR = 2.30, 95% CI: 1.14 to 4.77), and the relationship was stronger when abuse occurred both before and after age 12 years (OR = 5.08, 95% CI: 2.15 to 11.99). Women with major depression were also twice as likely to report multiple types of maltreatment (OR = 2.07, 95% CI: 1.27 to 3.35) compared to those without depression. CONCLUSIONS: Childhood maltreatment was more common in women with migraine and concomitant major depression than in those with migraine alone. The association of childhood sexual abuse with migraine and depression is amplified if abuse also occurs at a later age.

Publication Types:
PMID: 17785664 [PubMed - indexed for MEDLINE]

Tuesday, December 4, 2007

Gender-specific associations of short sleep duration with prevalent and incident hypertension: the Whitehall II Study.

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Erratum in:
  • Hypertension. 2007 Nov;50(5):e170.

Gender-specific associations of short sleep duration with prevalent and incident hypertension: the Whitehall II Study.

Cappuccio FP, Stranges S, Kandala NB, Miller MA, Taggart FM, Kumari M, Ferrie JE, Shipley MJ, Brunner EJ, Marmot MG.

Clinical Sciences Research Institute, Warwick Medical School, Coventry, United Kingdom. sleepresearch@warwick.ac.uk

Sleep deprivation (<or=5 hour per night) was associated with a higher risk of hypertension in middle-aged American adults but not among older individuals. However, the outcome was based on self-reported diagnosis of incident hypertension, and no gender-specific analyses were included. We examined cross-sectional and prospective associations of sleep duration with prevalent and incident hypertension in a cohort of 10,308 British civil servants aged 35 to 55 years at baseline (phase 1: 1985-1988). Data were gathered from phase 5 (1997-1999) and phase 7 (2003-2004). Sleep duration and other covariates were assessed at phase 5. At both examinations, hypertension was defined as blood pressure >or=140/90 mm Hg or regular use of antihypertensive medications. In cross-sectional analyses at phase 5 (n=5766), short duration of sleep (<or=5 hour per night) was associated with higher risk of hypertension compared with the group sleeping 7 hours, among women (odds ratio: 1.72[corrected]; 95% CI: 1.07[corrected] to 2.75[corrected]), independent of confounders, with an inverse linear trend across decreasing hours of sleep (P=0.037[corrected]). No association was detected in men. In prospective analyses (mean follow-up: 5 years), the cumulative incidence of hypertension was 20.0% (n=740) among 3691 normotensive individuals at phase 5. In women, short duration of sleep was associated with a higher risk of hypertension in a reduced model (age and employment) (6 hours per night: odds ratio: 1.56 [95% CI: 1.07 to 2.27]; <or=5 hour per night: odds ratio: 1.94 [95% CI: 1.08 to 3.50] versus 7 hours). The associations were attenuated after accounting for cardiovascular risk factors and psychiatric comorbidities (odds ratio: 1.42 [95% CI: 0.94 to 2.16]; odds ratio: 1.31 [95% CI: 0.65 to 2.63], respectively). Sleep deprivation may produce detrimental cardiovascular effects among women.

Publication Types:
PMID: 17785629 [PubMed - indexed for MEDLINE]