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Memory Loss (memory + loss)
Selected AbstractsTenuifolin, an extract derived from tenuigenin, inhibits amyloid-, secretion in vitroACTA PHYSIOLOGICA, Issue 4 2009J. Lv Abstract Aim:, Previous studies have shown that tenuigenin, a crude extract of Polygala tenuifolia Willd. that is commonly used in traditional Chinese herbal medicine for memory loss, can reduce the secretion of A, from cultured cells. However, the mechanism underlying this effect and the active compound derived from tenuigenin is unknown. In this study, a purified component of tenuigenin, tenuifolin, was examined and revealed to be an effective compound in vitro. Methods:, A, secretion from three sets of COS-7 cells, each carrying a plasmid expressing a different form of APP was examined following the treatment with tenuifolin. Initially, tenuifolin was determined to have no inherent toxicity to either the transfected or wild type cells at the effective concentrations. Cells were then treated with 0.5,2.0 ,g mL,1 tenuifolin for 12 h and their media were examined via an ELISA for A,1-40 and A,-42. Results:, We found that treatment with 2.0 ,g mL,1 tenuifolin significantly decreased A, secretion from COS-7 cells without altering the ratio of A,1-40 and A,-42. This effect is most probably due to inhibition of the ,-site APP cleaving enzyme as A, secretion was not inhibited from cells expressing the C99 fragment. Conclusion:, Tenuifolin is an effective compound from tenuigenin. We believe that this finding should lead the way for future experiments to determine the exact mechanism for tenuifolin's effect on A, secretion. [source] Functional MRI Predicts Memory Performance after Right Mesiotemporal Epilepsy SurgeryEPILEPSIA, Issue 2 2005Jozsef Janszky Summary:,Purpose: Anterior temporal lobe resection (ATR) is a treatment option in drug-resistant epilepsy. An important risk of ATR is loss of memory because mesiotemporal structures contribute substantially to memory function. We investigated whether memory-activated functional MRI (fMRI) can predict postoperative memory loss after anterior temporal lobectomy in right-sided medial temporal lobe epilepsy (MTLE). Methods: We included 16 patients (10 women) aged 16,54 years. The mean age at epilepsy onset was 12.5 years (range, 1,26 years). The patients' mean Wechsler IQ score was 95.2 (range, 62,125). The activation condition of fMRI consisted of retrieval from long-term memory induced by self-paced performance of an imaginative walk. All but one patient had left-sided speech dominance according to speech-activated fMRI. Outside the scanner, we evaluated the pre- and postoperative visual memory retention by using Rey Visual Design Learning Test. Results: We found a correlation between the preoperative asymmetry index of memory- fMRI and the change between pre- and postsurgical measures of memory retention. Reduced activation of the mesiotemporal region ipsilateral to the epileptogenic region correlated with a favorable memory outcome after right-sided ATR. Conclusions: In light of the postoperative results, the theoretical implication of our study is that fMRI based on a simple introspective retrieval task measures memory functions. The main clinical implication of our study is that memory- fMRI might replace the invasive Wada test in MTLE by using a simple fMRI paradigm. Predictive power, however, will be studied in larger patient samples. Other studies are required for left-sided MTLE and neocortical epilepsies to assess the clinical usefulness of memory- fMRI. [source] A novel mutation in the PSEN1 gene (L286P) associated with familial early-onset dementia of Alzheimer type and lobar haematomasEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2007R. Sánchez-Valle The aim of this study was to describe a novel mutation in exon 8 of the presenilin gene (L286P) associated with early-onset autosomal dominant Alzheimer's disease (AD) and lobar haematomas. The proband was a woman who developed cognitive decline with predominant memory loss at the age of 35 years. The patient died at the age of 54 years and the neuropathological examination confirmed the diagnosis of AD. Three of her four siblings, one parent and one sibling of her parent had suffered from cognitive decline at ages between 35 and 42 years. Three of them also presented lobar haematomas. The neuropathological examination, available in one of them, disclosed the presence of severe amyloid angiopathy as the cause of the haematoma. The study of PSEN1 gene with single strand conformation polymorphism technique failed to show abnormalities suggestive of mutations. Direct sequencing disclosed the presence of a missense mutation in codon 286 (L286P) in the proband and her already affected descendent, which was absent in the healthy sibling. L286P is a novel mutation in PSEN1 that causes familial early-onset AD and brain haematomas related to amyloid angiopathy. [source] Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Coleen M. Atkins Abstract Traumatic brain injury (TBI) results in significant hippocampal pathology and hippocampal-dependent memory loss, both of which are alleviated by hypothermia treatment. To elucidate the molecular mechanisms regulated by hypothermia after TBI, rats underwent moderate parasagittal fluid-percussion brain injury. Brain temperature was maintained at normothermic or hypothermic temperatures for 30 min prior and up to 4 h after TBI. The ipsilateral hippocampus was assayed with Western blotting. We found that hypothermia potentiated extracellular signal-regulated kinase 1/2 (ERK1/2) activation and its downstream effectors, p90 ribosomal S6 kinase (p90RSK) and the transcription factor cAMP response element-binding protein. Phosphorylation of another p90RSK substrate, Bad, also increased with hypothermia after TBI. ERK1/2 regulates mRNA translation through phosphorylation of mitogen-activated protein kinase-interacting kinase 1 (Mnk1) and the translation factor eukaryotic initiation factor 4E (eIF4E). Hypothermia also potentiated the phosphorylation of both Mnk1 and eIF4E. Augmentation of ERK1/2 activation and its downstream signalling components may be one molecular mechanism that hypothermia treatment elicits to improve functional outcome after TBI. [source] APP is required during an early phase of memory formationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2000R. Mileusnic Abstract The amyloid ,/A4 protein precursor (APP) has been shown to be implicated in age-associated plastic changes at synapses that might contribute to memory loss in Alzheimer's disease. As APP has previously been reported to have multiple functions during normal development, we have employed a one-trial passive avoidance task in day-old chicks to study its role in the process of memory formation. Administration of anti-APP antibodies, injected 30 min pretraining, prevented memory for a one-trial passive avoidance task in day-old chicks without effects on general behaviour or initial acquisition. Amnesia was apparent by 30 min post-training and lasted for at least 24 h. The same result was obtained by down-regulation of APP expression by APP-antisense, injected 8,12 h pretraining. However, injections of anti-APP antibodies or APP antisense at later post-training time did not cause amnesia for the task. Unlike antibodies and antisense, injection of the APP328,332 pentapeptide, in either orientation, 30 min pretraining, rescued the memory and prevented antisense-induced amnesia. The post-training time within which the antibody- and antisense-induced amnesia, and within which the APP peptides prevent amnesia, correspond to that during which memory formation is vulnerable to disruption of the putative signal transduction functions of APP. These results suggest that: (i) APP is required during an early phase of memory formation, and (ii) the memory enhancing effect of secretory APP is localized within a 5-mer sequence of growth-promoting domain. [source] Dimensions of Ambiguous Loss in Couples Coping With Mild Cognitive Impairment,FAMILY RELATIONS, Issue 2 2007Rosemary Blieszner Abstract: We applied the theory of ambiguous loss to couples with mild cognitive impairment (MCI), an age-related decline in memory and other cognitive processes assumed not to interfere with daily activities or the maintenance of personal relationships. Face-to-face interviews with 67 older married couples revealed that lack of understanding about the behavioral manifestations of MCI resulted in much ambiguity in their lives. Fluctuations in the elders' functioning required spouses to alter their daily activities and responsibilities. As a result, couples often experienced distress that affected their emotional involvement with one another. Findings advance theoretical implications of ambiguous loss and provide educators and practitioners with suggestions for working with couples experiencing mild memory loss. [source] Health profiles and quality of life of 518 survivors of thyroid cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2003Pamela N. Schultz RN Abstract Background. Available literature describes the long-term outcome of thyroid cancer survivors with respect to thyroid cancer but not their overall medical and social well-being. Methods. Five hundred eighteen thyroid cancer survivors responded to a survey regarding medical and social impacts of their cancer experience. Results. All had surgery, and 417 (80.5%) also had some radiation. Two thirds (64.5%) reported that cancer created health effects varying by gender and passage of time; neurologic, musculoskeletal, and psychologic problems seemed most prominent. They reported more memory loss and psychologic problems than other cancer survivors and more migraine headaches than both other cancer survivors and the general population. Regarding family and work, they integrated well in society overall. However, unsolicited comments by 24.5% of responders disclosed symptoms reminiscent of thyroid hormone imbalance. Conclusion. Thyroid cancer survivors generally report good health long term but describe distinct, lasting medical problems including symptoms of thyroid dysregulation. The extent and manner in which cancer therapy contributes to the health profile of the group merits further inquiry. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000,000, 2003 [source] Using duration of memory loss to improve differentiation of mild cognitive impairment from normal cognitionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 2 2006Anthony L. Kupferschmidt No abstract is available for this article. [source] No association between subjective memory complaints and apolipoprotein E genotype in cognitively intact elderlyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 12 2004Dylan G. Harwood Abstract Objective This cross-sectional study examined the relationship between subjective memory complaints and the apolipoprotein epsilon 4 allele (,4), a genetic risk factor for Alzheimer's disease (AD), among cognitively normal subjects identified from a community memory screening. Design The sample comprised 232 consecutive white non-Hispanic older adults who presented to a free community-based memory-screening program at a University affiliated memory disorders center. Participants were classified as cognitively normal based on scores on the age and educated adjusted Folstein Mini-Mental Status Exam (MMSAdj) and a brief Delayed Verbal Recall Test (DRT). Subjects were assessed for APOE genotype, subjective memory complaints (Memory Questionnaire, MQ), depressive symptoms (Hamilton Depression Rating Scale, HDRS), and history of four major medical conditions that have been associated with memory loss (stroke/transient ischemic attack [TIA], atherosclerotic heart disease, hypertension, and diabetes). A hierarchical regression analysis was performed to examine the association between APOE genotype and memory complaints after controlling for a host of potential confounding factors. Results The APOE ,4 allele frequency for cognitively normal subjects was 0.13. Subjective memory complaints were predicted by depressive symptoms and a history of stroke/TIA. They were not associated with APOE genotype, MMSAdj score, DRT score, age, education, gender, and reported history of atherosclerotic heart disease, hypertension, or diabetes. Conclusion The results did not suggest an association between subjective memory complaints and the APOE ,4 allele in this sample of cognitively intact subjects. This indicates that memory complaints may confer risk for future dementia through pathways independent of APOE genotype. The results also show that older adults with memory complaints are at increased risk for underlying depression. Copyright © 2004 John Wiley & Sons, Ltd. [source] Are cognitively intact seniors with subjective memory loss more likely to develop dementia?INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 9 2002Philip St John Abstract Background Subjective memory loss (SML) is common in elderly persons. It is not clear if SML predicts the development of dementia. Objectives (1) to determine if SML in those with normal cognition predicts dementia or cognitive impairment without dementia (CIND); (2) to determine if an association is independent of the effect of age, gender and depressive symptoms. Methods Secondary analysis of the Manitoba Study of Health and Aging (MSHA), a population-based prospective study. Data were collected in 1991, and follow-up was done 5 years later. Community-dwelling seniors sampled randomly from a population-based registry in the Canadian province of Manitoba, stratified on age and region. Only those scoring in the normal range of the Modified mini-mental state examination (3MS) were included. Predictor variables were self-reported memory loss, 3MS, Center for epidemiological studies,depression scale (CES-D), age, gender, and education. Outcomes were mortality and cognitive impairment five years later. Results In bivariate analyses, SML was associated with both death and dementia. In multivariate models, SML did not predict mortality. After adjusting for age, gender, and depressive symptoms, SML predicted dementia. However, after adjusting for baseline 3MS score, SML did not predict dementia. Conclusions Memory complaints predict the development of dementia over five years, and clinicians should monitor these persons closely. However, the proportion of persons developing dementia was small, and SML alone is unlikely to be a useful clinical predictor of dementia. Copyright © 2002 John Wiley & Sons, Ltd. [source] Long-term effect of the ICU-diary concept on quality of life after critical illnessACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2010C. G. BÄCKMAN Background: Critically ill patients often spend time in the intensive care unit (ICU) either unconscious or sedated. On recovery, they are often in a state of confusion with memory loss that may be associated with a longstanding reduction in health-related quality of life (QoL). We hypothesised that the ICU-diary concept could improve their QoL by filling in their memory gaps. Methods: A non-randomised, prospective study in a non-academic eight-bedded general ICU. A group of patients (n=38) were selected to receive the ICU-diary concept (keeping a diary with photos while on the ICU plus a follow-up meeting) when a long and complicated course was expected. Health-related QoL at 6, 12, 24 and 36 months was compared with a group that did not receive the ICU-diary (n=224). The Medical Outcomes Study 36-Item Short-Form (SF-36) was used to measure health-related QoL. Multiple regression models adjusted for age, sex, illness severity, pre-existing disease and diagnostic category was used to analyse the effects of the ICU-diary concept at 6 months, and changes over time were analysed using repeated measures MANOVA. Results: Crude and adjusted scores for two dimensions of SF-36 (general health and vitality) and the physical component summary score were significantly higher at 6 months in the ICU-diary group (P<0.05) and some of the effects remained during the 3-year follow-up period (P<0.05). Conclusion: The ICU-diary concept was associated with improved health-related QoL during the 3-year follow-up period after a critical illness. The effect of this intervention needs to be confirmed in a larger randomised study. [source] Persecutory symptoms and perceptual disturbance in a community sample of older people: the Islington studyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2001G. Livingston Abstract Background While there are extensive studies of paranoid symptoms and perceptual disturbance (PPD) in younger adults, relatively little is known about older adults with similar symptoms. Method This study took place in Islington, an inner London borough. Enumeration Districts were randomised to provide a sampling frame. Residents aged 65 or over were interviewed at home. The Short-CARE was used to elicit psychiatric symptoms and diagnosis. Sociodemographic particulars were elicited using the Client Sociodemographic and Service Receipt Inventory. Questions were asked regarding sight and hearing. We used subsections of the geriatric mental scale to identify people who had PPD symptoms. Medications taken were recorded. We asked ,Do you have any health problems?' as a screening question for subjective health problems. Results We interviewed 720 people. Twenty-eight (3.9%) participants scored positively on the PPD sub-scales of the GMS. A forward logistic regression analysis for independent predictors of PPD found the significant independent predictors were dementia (p,=,0.0000; odds ratio 6.8), drinking alcohol in last 6 months (p,<,0.03; odds ratio 0.3), drinking alcohol to help sleep (p,<,0.005; odds ratio 9.6), subjective memory loss (p,<,0.007; odds ratio 3.3) and uncorrected visual impairment (p,<,0.02; odds ratio 2.8). Conclusion There is a relatively high prevalence of PPD in older people living in the community. This is not associated with higher use of services despite the increased needs. Further studies should consider interventions to meet this unmet need. Copyright © 2001 John Wiley & Sons, Ltd [source] Primary CNS angiitis presenting as short-term memory loss: a case report and literature reviewINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2008Bradley DUHON Abstract Primary angiitis of the central nervous system (PACNS) is an idiopathic vasculitis of the small to medium vessels that often eludes diagnosis because of its variable signs and symptoms. A 36-year-old woman presented with a 4-week history of progressive memory loss. Neurological examination revealed only severe cognitive deficits including anterograde amnesia. Magnetic resonance imaging demonstrated multiple ring-enhancing lesions involving the left frontal lobe and uncus and bilateral thalami. Stereotactic biopsy showed findings consistent with CNS angiitis. Further workup revealed no evidence of systemic disease. We report the first case of biopsy-proven PACNS presenting as profound isolated anterograde amnesia. [source] A literature review of spirituality in coping with early-stage Alzheimer's diseaseJOURNAL OF CLINICAL NURSING, Issue 5a 2008Linda Beuscher PhD Aims., This paper presents a literature review focusing on the use of spirituality in coping by older persons with early-stage Alzheimer's disease from their perspectives. The purpose of this literature review is to examine the existing body of knowledge about spirituality in coping with Alzheimer's disease and to apply a spiritual framework of coping in organizing the literature to identify themes and gaps in knowledge. Background., Despite the abundance of Alzheimer's disease research, little is known about how older persons with this devastating disease cope with the consequential losses. Maintaining a sense of normalcy and preserving self-worth are coping strategies reported by older persons with early-stage Alzheimer's disease. As spirituality is an effective coping resource for older persons with numerous psychological and personal losses in their lives, it may be an important coping resource for person with Alzheimer's disease. Method., A literature search was conducted to find research published between 1990,2006 aimed at understanding spirituality in coping with early-stage Alzheimer's disease. Conclusions., Six research studies were reviewed. Findings suggest that persons with early-stage Alzheimer's disease draw from their spirituality and faith to find meaning and courage in facing the challenges of cognitive losses. Furthermore, they are able to provide rich information about their spirituality and the psychosocial aspects of living with Alzheimer's disease. Limited empirical knowledge compels the need for future research to explore how spirituality is utilized in coping with early-stage Alzheimer's disease. Relevance to clinical practice., Enhancing persons' abilities to cope effectively with their diseases is an important goal of nursing care. Understanding how older persons with Alzheimer's disease cope with their memory loss is critical to the development of evidence-based interventions to minimize the stress of living with this disease. [source] Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature deathAGING CELL, Issue 2 2010Mariana Pehar Summary The longevity-assurance activity of the tumor suppressor p53 depends on the levels of ,40p53 (p44), a short and naturally occurring isoform of the p53 gene. As such, increased dosage of p44 in the mouse leads to accelerated aging and short lifespan. Here we show that mice homozygous for a transgene encoding p44 (p44+/+) display cognitive decline and synaptic impairment early in life. The synaptic deficits are attributed to hyperactivation of insulin-like growth factor 1 receptor (IGF-1R) signaling and altered metabolism of the microtubule-binding protein tau. In fact, they were rescued by either Igf1r or Mapt haploinsufficiency. When expressing a human or a ,humanized' form of the amyloid precursor protein (APP), p44+/+ animals developed a selective degeneration of memory-forming and -retrieving areas of the brain, and died prematurely. Mechanistically, the neurodegeneration was caused by both paraptosis- and autophagy-like cell deaths. These results indicate that altered longevity-assurance activity of p53:p44 causes memory loss and neurodegeneration by affecting IGF-1R signaling. Importantly, Igf1r haploinsufficiency was also able to correct the synaptic deficits of APP695/swe mice, a model of Alzheimer's disease. [source] The Association of Alcohol-Induced Blackouts and Grayouts to Blood Alcohol ConcentrationsJOURNAL OF FORENSIC SCIENCES, Issue 4 2006Paul J. Perry Ph.D. ABSTRACT: The primary aim of this study was to investigate the association between measured blood alcohol concentration (BAC) and the presence and degree of amnesia (no amnesia, grayout, or blackout) in actively drinking subjects. A secondary aim was to determine potential factors other than BAC that contribute to the alcohol-induced memory loss. An interview questionnaire was administered to subjects regarding a recent alcohol associated arrest with a documented BAC greater than 0.08 g/dL for either public intoxication, driving under the influence, or under age drinking was administered. Demographic variables collected included drinking history, family history of alcoholism, presence of previous alcohol-related memory loss during a drinking episode, and drinking behavior during the episode. Memory of the drinking episode was evaluated to determine if either an alcohol-induced grayout (partial anterograde amnesia) or blackout (complete anterograde amnesia) occurred. Differences in (1) mean total number of drinks ingested before arrest, (2) gulping of drinks, and (3) BAC at arrest were found for those having blackouts compared with no amnesia; while differences in drinking more than planned were found between the no amnesia and grayout groups. A strong linear relationship between BAC and predicted probability of memory loss, particularly for blackouts was obvious. This finding clinically concludes that subjects with BAC of 310 g/dL or greater have a 0.50 or greater probability of having an alcoholic blackout. [source] Relevant activities of extracts and constituents of animals used in traditional Chinese medicine for central nervous system effects associated with Alzheimer's diseaseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2006Yuhao Ren The centipede Scolopendra subspinipes mutilans L. Koch (,Wugong'), the beetle Mylabris phalerata Pallas (,Ban mao') and the earthworm Pheretima aspergillum Chen (,DiLong') have a reputation in traditional Chinese medicine for reducing symptoms of central nervous system decline, including memory loss. A series of extracts of all three organisms was tested for acetylcholinesterase (AChE) inhibition and copper ion binding effects, the latter likely to reduce oxidative damage caused by excess copper. The beetle and centipede chloroform extracts showed the strongest AChE inhibitory effects (30.6% inhibition at 105 ,g mL,1 and 32.3% inhibition at 167 ,g mL,1, respectively) and, in the case of the centipede, this was traced to the unsaturated fatty acids present using bioassay-guided fractionation. Cantharidin from the beetle was shown to have AChE activity (31% inhibition at 1 ,M, 0.196,g mL,1), making it a major contributor to the activity of the beetle extract. The earthworm showed no AChE inhibitory activity. Since unsaturated fatty acids have not been previously reported to have AChE inhibitory activity, a series of related compounds was tested to determine structure-activity relationships. It was found that activity existed where there was a chain length of more than 16 C atoms with at least one unsaturated bond in the chain. The carboxylic acid group was also necessary for activity. The fatty acids present in the centipede also showed the ability to bind copper ions when tested using a novel thin layer chromatography method designed to detect copper-binding compounds. The activities reported give some support to the use of the beetle and centipede in traditional Chinese medicine for improving cognitive function. [source] AUTOMIC FAILURE AND NORMAL PRESSURE HYDROCEPHALUS IN A PATIENT WITH CHRONIC DEMYELINATING INFLAMMATORY NEUROPATHYJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002M. Laurà A 75-year-old man with HCV hepatitis developed at the age of 70 presented with rest and action tremor localized at both hands and progressive cognitive impairment with memory loss. Four years later he begun to complain of progressive fatigue, occasional falls, numbness at the extremities and orthostatic hypotension. One month after admission, he rapidly worsened with inability to walk, mainly because of autonomic failure. Neurological examination revealed gait disturbances, including a wide base of support and short stride, slurred speech, reduction of upward gaze, rest and action tremor at both hands, intrinsic hand muscle and anterior tibialis muscle wasting and weakness on both sides, absent deep tendon reflexes, loss of vibration sense at lower limbs, and bilateral pes cavus. Routine laboratory studies, autoantibodies, thyroid function, neoplastic markers and immunoelectrophoresis were normal. Cryoglobulins were absent, whereas CSF protein content was increased (142 mg/dl). Autonomic nervous system investigation detected severe orthostatic hypotension. Nerve conduction studies showed absent sensory potentials and a marked reduction of compound motor action potential amplitudes and of motor conduction velocities. A sural nerve biopsy revealed remarkable onion bulb-like changes, endoneurial and perivascular infiltrations of inflammatory cells. Psychometric tests showed mild cognitive impairment. Brain MRI was consistent with normotensive hydrocephalus. The findings indicated the presence of chronic inflammatory demyelinating polyneuropathy, autonomic nervous system involvement and normal pressure hydrocephalus. A condition of multiple system atrophy (MSA) might be taken into account, even if somatic peripheral nerve involvement may rarely occur in MSA. Moreover the normal pressure hydrocephalus could be due to the high protein content in CSF (Fukatsu R et al., 1997). [source] Tea drinking prevents memory loss?NUTRITION BULLETIN, Issue 1 2005C. Williamson [source] (635) The Advantages and Adverse Effects of Long-Term Intrathecal Delivery of Opioid and Clonidine HCL AdmixturePAIN MEDICINE, Issue 2 2000Article first published online: 25 DEC 200 Introduction: Intrathecal clonidine may be effective in neuropathic pain situations where large doses of opioids and local anesthetics or baclofen result in side effects and inadequate pain control. Addition of clonidine activates K (ATP) channels via a-2 receptors. Clonidine administered intrathecally provides fourfold better pain control with lower side effects than systemic clonidine. Because clonidine does not interact with opioid receptors, it fails to cause opioid-like side effects. Clonidine and opioids may have a synergistic efficacy. Materials & Methods: We performed a retrospective analysis of 23 patients, 10 male and 13 female, with a mean age of 55.4 years. Seventeen patients had neuropathic pain and 6 patients had mixed (neuropathic-nociceptive) nonmalignant pain. They had failed to achieve satisfactory analgesia despite preclinical infusion of high dose morphine sulfate, hydromorphone HCL, or combinations of bupivacaine HCL/opioid or baclofen. The range of initiating daily dose of clonidine was 25 ,g to 50 ,g, to a maximum of 900 ,g/day. The clonidine doses were titrated upwards to the end point of either efficacy or adverse effects. Clinical parameters studied were patient vital signs, pain intensity, pain relief, quality of sleep, drug intake, and side effects. Results: The preclonidine VAPS scores were on average 7.67 and the postclonidine VAPS scores were 5.82. Sleep improved for 50% of patients having poor to fair sleep. Length of therapy ranges from 1 month to 35 months with an average of 14.7 months of therapy. Of the 23 patients studied, 8 patients have been satisfied, coping with any side effects, and are still receiving mixed clonidine/opioid therapy. The side effects noted were nausea (9), sleepiness (8), dry mouth (7), dizziness (7), orthostatic hypotension (2), short term memory loss (2), headache (2), edema (2), depression (2), tinnitus (1), lethargy (1), nausea with vomiting (1), decreased energy (1), decreased libido (1), impotence (1), fine tremor (1), and anxiety (1). Conclusions: Intraspinal infusion of clonidine plus opioid may provide safer and better synergistic control of intractable neuropathic or mixed nonmalignant pain than pure intraspinal infusions of u-opioid with local anesthetic. [source] Latest news and product developmentsPRESCRIBER, Issue 4 2008Article first published online: 20 MAR 200 Suicide warning for all antidepressants All antidepressants are to include a warning of the risk of suicide in their product information, the MHRA says. The requirement formerly applied only to SSRIs but, following a US review of safety data, the Agency says the risk is similar for all classes of antidepressants. Patients at increased risk include young people with psychiatric morbidity and those with a history of suicidal ideation. Patients are at increased risk of suicide until remission occurs, and clinical experience shows that the risk is increased during the early stages of recovery. Confusion over type 2 diabetes management Contradictory findings have been reported from two studies of intensive management of type 2 diabetes. The STENO-2 study (N Engl J Med 2008;358:580-91) found that tight control of blood glucose, blood pressure and lipids plus low-dose aspirin in 160 patients with type 2 diabetes and microalbuminuria significantly reduced all-cause mortality, cardiovascular events, cardiovascular death and microvascular complications by 40-60 per cent. The US National Heart, Blood and Lung Institute has announced the end of the intensive treatment arm of the ACCORD study (unpublished). This study was comparing intensive lowering of blood glucose below currently recommended levels (target HbA1C <6 per cent) with conventional management in adults with type 2 diabetes at especially high risk for heart attack and stroke. Although mortality was reduced in both arms compared with other populations, intensive treatment was associated with increased mortality equivalent to three deaths per 1000 patients per year over four years. Another antibiotics campaign The Government has launched another campaign to promote public awareness that antibiotics are not appropriate for viral infections causing coughs, colds and sore throats. Get Well Soon , Without Antibiotics is supported by a national advertising campaign and leaflets and posters encouraging the public to ask advice rather than demand a prescription. Details are available at www.dh.gov.uk. Episenta: once-daily sodium valproate Following a launch to specialists last year, a new once-daily modified-release formulation of sodium valproate is being promoted more widely to GPs. Episenta is licensed for the treatment of all forms of epilepsy and is formulated as modified-release capsules of 150mg and 300mg and sachets of modified-release granules of 500mg and 1000mg. The dose may be administered once or twice daily. Patients may be switched from enteric-coated tablets of valproate to the same dose given as Episenta. Episenta costs £5.70 or £10.90 for 100 × 150mg or 300mg capsules, and £18 or £35.50 for 100 × 500mg or 1000mg sachets. Latest NICE agenda The Department of Health has referred a new batch of topics for appraisal by NICE. Six of seven technology appraisals are for cancer drugs; the last is for dabigatran etexilate for venous thromboembolism. There will be four new clinical guidelines: autism spectrum disorders, hypertension in pregnancy, bed-wetting in children and severe mental illness with substance abuse. Two combined public health and clinical guidelines will address alcohol misuse. Varenicline vs NRT Varenicline (Champix) offers slightly greater smoking cessation rates than nicotine replacement therapy (NRT) in the long term and better symptom improvement, an international study has shown (Thorax 2008; published online:10.1136/ thx.2007.090647). A total of 746 smokers were randomised to treatment with varenicline 1mg twice daily for 12 weeks or transdermal NRT (21mg reducing to 7mg per day) for 10 weeks. Continuous abstinence rates for the last four weeks of treatment were 56 vs 43 per cent. The corresponding rates for one year were 26 and 20 per cent. Varenicline was associated with greater reductions in cravings, withdrawal symptoms and smoking satisfaction, but more nausea (37 vs 10 per cent). Adverse reactions class effect of statins The MHRA has identified several adverse effects that it says are class effects of the statins (Drug Safety Update 2008;1:Issue 7). Following a review of clinical trials and spontaneous reports, it is now apparent that any statin may be associated with sleep disturbance, depression, memory loss and sexual dysfunction; interstitial lung disease has been reported rarely. Product information is being updated to include the new information. Depression, including suicidal ideation, has also been associated with varenicline (Champix), the MHRA says; affected patients should stop treatment immediately. The combination of transdermal nicotine replacement therapy (NRT) and varenicline appears to be associated with a higher incidence of nausea, headache, vomiting, dizziness, dyspepsia and fatigue than NRT alone. The MHRA has also announced that, following the suspension of marketing authorisation for carisoprodol (Carisoma), it is considering a phased withdrawal of the closely-related meprobamate , the main active metabolite of carisoprodol. Following a successful pilot study, the public are being encouraged to report adverse reactions on yellow cards; the MHRA notes that health professionals provide more complete reports but patients include more information about quality of life. The scheme will be promoted via community pharmacies throughout the UK from February 2008. Cochrane: evidence on back pain interventions The latest release of Cochrane reviews includes three meta-analyses assessing interventions for back pain. Overall, NSAIDs were found to be effective as short-term treatment for acute or chronic back pain but the effect size was small. They were comparable with paracetamol but associated with more adverse effects; COX-2 selective NSAIDs were similarly effective, with slightly fewer adverse effects. There was no evidence that antidepressants reduced back pain but intensive individual patient education (lasting 2.5 hours) was effective for acute and subacute back pain and comparable with manipulation and physiotherapy; its effects on chronic pain were unclear. Copyright © 2008 Wiley Interface Ltd [source] BUREAUCRACIES REMEMBER, POST-BUREAUCRATIC ORGANIZATIONS FORGET?PUBLIC ADMINISTRATION, Issue 2 2009CHRISTOPHER POLLITT The paper examines the hypothesis that post-bureaucratic forms of organization perform less well than traditional bureaucracies with respect both to organizational memory and learning from experience. First, the paper discusses the meanings of the main terms and concepts to be used in the argument, and delimits its domain. Second, it identifies a series of mechanisms that are likely to bring about memory loss. Third, it examines the empirical literature in search of evidence to confirm or disconfirm the existence and effects of these mechanisms. Fourth, it reflects on its own limitations. Finally, it sets out some broad conclusions concerning the state of organizational memories in the public sector. The aim is to develop new theory, identify relevant generative mechanisms, set this model alongside such evidence as is available, and suggest lines for further research. The new men of the Empire are the ones who believe in fresh starts, new chapters, clean pages; I struggle on with the old story, hoping that, before it is finished, it will reveal to me why it was that I thought it worth the trouble. (J. M. Coetzee, Waiting for the Barbarians, 1980, p. 26) [source] Lies in a Time of Threat: Betrayal Blindness and the 2004 U.S. Presidential ElectionANALYSES OF SOCIAL ISSUES & PUBLIC POLICY, Issue 1 2005Eileen L. Zurbriggen Exit polls from the 2004 U.S. presidential election indicated overwhelming support for President Bush among voters who said they valued honesty, even though the Bush administration had been sharply criticized for deceiving the public, especially concerning the reasons for invading Iraq. A psychological theory recently developed to help explain memory loss in trauma survivors sheds light on this paradox. Betrayal Trauma Theory (Freyd, 1996) states that memory impairment is greatest when a victim is dependent on the perpetrator. The theory also predicts who will be "blind" to signs of deception,those who are emotionally or financially dependent on the person who is lying. Although every American is dependent on the U.S. President to some extent, religious conservatives may be more psychologically dependent than others. Because they believe their core values are under attack, they depend on powerful leaders such as President Bush to defend these values. This psychological dependence may make it difficult for them to notice the administration's deceptions. [source] Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuationBIOFACTORS, Issue 1-4 2005Peter H. Langsjoen Abstract Fifty consecutive new cardiology clinic patients who were on statin drug therapy (for an average of 28 months) on their initial visit were evaluated for possible adverse statin effects (myalgia, fatigue, dyspnea, memory loss, and peripheral neuropathy). All patients discontinued statin therapy due to side effects and began supplemental CoQ10 at an average of 240 mg/day upon initial visit. Patients have been followed for an average of 22 months with 84% of the patients followed now for more than 12 months. The prevalence of patient symptoms on initial visit and on most recent follow-up demonstrated a decrease in fatigue from 84% to 16%, myalgia from 64% to 6%, dyspnea from 58% to 12%, memory loss from 8% to 4% and peripheral neuropathy from 10% to 2%. There were two deaths from lung cancer and one death from aortic stenosis with no strokes or myocardial infarctions. Measurements of heart function either improved or remained stable in the majority of patients. We conclude that statin-related side effects, including statin cardiomyopathy, are far more common than previously published and are reversible with the combination of statin discontinuation and supplemental CoQ10. We saw no adverse consequences from statin discontinuation. [source] Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicusBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2006C Tohda Background and purpose: Neurons with atrophic neurites may remain alive and therefore may have the potential to regenerate even when neuronal death has occurred in some parts of the brain. This study aimed to explore effects of drugs that can facilitate the regeneration of neurites and the reconstruction of synapses even in severely damaged neurons. Experimental approach: We investigated the effects of extracts of Astragalus mongholicus on the cognitive defect in mice caused by injection with the amyloid peptide A,(25-35). We also examined the effect of the extract on the regeneration of neurites and the reconstruction of synapses in cultured neurons damaged by A,(25-35). Key results: A. mongholicus extract (1 g kg,1 day,1 for 15 days, p.o.) reversed A,(25-35)-induced memory loss and prevented the loss of axons and synapses in the cerebral cortex and hippocampus in mice. Treatment with A,(25-35) (10 ,M) induced axonal atrophy and synaptic loss in cultured rat cortical neurons. Subsequent treatment with A. mongholicus extract (100 ,g/ml) resulted in significant axonal regeneration, reconstruction of neuronal synapses, and prevention of A,(25-35)-induced neuronal death. Similar extracts of A. membranaceus had no effect on axonal atrophy, synaptic loss, or neuronal death. The major known components of the extracts (astragalosides I, II, and IV) reduced neurodegeneration, but the activity of the extracts did not correlate with their content of these three astragalosides. Conclusion and implications: A. mongholicus is an important candidate for the treatment of memory disorders and the main active constituents may not be the known astragalosides. British Journal of Pharmacology (2006) 149, 532,541. doi:10.1038/sj.bjp.0706865 [source] | ||||||||||||||||