"My mind goes dead I cannot speak": an expression of DPD.

INTRODUCTION: Here we present a case of Depersonalisation-Derealisation Disorder which involves an unusual environmental trigger and profile of symptoms in a patient with an underlying left frontal encephalomalacia. METHODS: The clinical information has been collected from multiple neurological, psychiatric, neuropsychological examinations and from the patient's medical records. RESULTS: The neuropsychiatric assessment showed depersonalisation, derealisation, de-somatisation and de-affectualisation, along with a good response to SSRI + Lamotrigine; all typical features of DPD. The neuropsychological assessment showed language problems, and other mild cognitive difficulties that may provide a neuropsychological foundation contributing to the DPD episodes. DISCUSSION AND CONCLUSION: Given Mr R's underlying neuropsychological deficit, hearing voices without speech-associated gestures might place excessive demands on his ability to process the information, exacerbating his feelings of threat. This sets up the pattern of suppressed insula activation, and possibly the suppression of the auditory cortex leading to the presented unusual DPD symptoms.

Imagine that: cholinesterase inhibitor treatment of complex visual hallucinations of unknown aetiology.

Introduction: Our objective is to highlight the value of the neurophenomenological classification of complex visual hallucinations (VHs). This approach enabled the authors to successfully treat VHs of uncertain aetiology with cholinesterase inhibitors because the content of the hallucinations suggested dysfunction in cholinergic modulated networks.Methods: We utilise the single case report to describe the nature and content of chronic VHs experienced by a 49-year-old woman following a prolonged admission to ITU. Despite extensive investigation, no clear cause was identified for these hallucinations and the patient did not respond to rationalisation of medications or trials of antipsychotics. We therefore adopted the neurophenomenological approach to classifying and treating her VHs.Results: After several years of distressing visual hallucinations, a course of Rivastigmine was trialed despite no evidence suggestive of a Parkinsonian syndrome. Nevertheless, the patient reported a dose-effect response with significant reduction in the frequency and intensity of her hallucinations, almost to complete resolution.Conclusions: At present there is limited evidence about the medical management of visual hallucinations. This case report suggests that cholinesterase inhibitors may be of benefit, even in the absence of clear parkinsonsian features, if the form and content of the VHs suggest dysfunction in cholinergic modulated attentional networks.

Treatment outcomes in mild traumatic brain injury: a systematic review of randomized controlled trials.

OBJECTIVES: Mild traumatic brain injury (mTBI) is a controversial and under-researched area, despite most traumatic brain injuries being classed as mild. Our objective was to review the evidence underpinning these approaches to treat mTBI including educational, psychological, rehabilitative and pharmacological approaches and discuss their efficacy. METHODS: A systematic review of literature was carried out using Web of science, Scopus, Medline, Pubmed, Cinahl, and PsychInfo databases. Randomized Controlled Trials (RCTs) looking at treatment outcome in mTBI for adults were included, published between 1980 and 2019. Methodological quality of the studies was reviewed using the Scottish Intercollegiate Guideline Network (SIGN) checklist for RCTs. RESULTS: Searches identified 3993 studies, of which 25 met inclusion criteria, and a total number of participants of 3213. Mean age was 35, and 59% male. Ten studies had <100 participants, 15 studies 100-395. Studies were grouped into education and early intervention, rehabilitation (8), psychological interventions (4), and pharmacotherapy (4). Inconsistency of definitions and outcome measures used precluded meta-analysis. CONCLUSIONS: Traditional education and reassurance can no longer be recommended as having the best evidence base for efficacy as compared to psychological and rehabilitative approaches, and guidelines should begin to reflect this.

Knowledge, attitudes, beliefs and practices related to chronic suppurative otitis media and hearing impairment in Pokhara, Nepal.

BACKGROUND: Nepal has a high prevalence of chronic suppurative otitis media and hearing impairment. An improved understanding of patients' knowledge, attitudes, beliefs and practices is therefore important for effective healthcare planning and intervention. METHOD: Questionnaires designed to explore their current knowledge, attitudes, beliefs and practices were completed by 153 participants: 71 were affected by a known ear disease and 82 were unaffected. RESULTS: In the unaffected group, 31.7 per cent considered breast milk to be a risk factor for ear infection. Home remedies (e.g. leaf paste, oils, and urine and/or bodily fluids) had been used by 42.3 per cent of the affected group. Most participants (71.9 per cent) believed that society discriminates against those with hearing impairment. CONCLUSION: Knowledge deficits and false beliefs were found in both groups, along with a significant use of home remedies and a perception of discrimination against people with hearing impairment. These findings are relevant for healthcare providers and may aid the development of policy, interventions and public education initiatives.

Reduced brain N-acetylaspartate suggests neuronal loss in cognitively impaired human immunodeficiency virus-seropositive individuals: in vivo 1H magnetic resonance spectroscopic imaging.

We used magnetic resonance imaging (MRI) and water-suppressed proton magnetic resonance spectroscopic imaging to study the effects of human immunodeficiency virus (HIV) infection on the brains of 10 individuals with cognitive impairment due to HIV and seven normal controls. 1H spectra from nine 2.5-ml volumes in the centrum semiovale and the mesial cortex showed significantly reduced N-acetylaspartate (NAA) relative to choline and creatine in the cognitively impaired HIV-infected subjects. This reduction was due to a nonlocalized decrease of NAA in these patients, only two of whom had moderate atrophy and white matter signal hyperintensities on MRI. Since NAA is a putative neuronal marker, the findings suggest neuronal damage in early stages of HIV infection that is not evident on standard MRI and are consistent with the neuropathologically known neuronal loss.

N-acetylaspartate reductions measured by 1H MRSI in cognitively impaired HIV-seropositive individuals.

We used magnetic resonance imaging (MRI) and water-suppressed proton MR spectroscopic imaging (1H MRSI) to study the effects of human immunodeficiency virus (HIV) infection on the brain. Our recent in vivo finding of lower N-acetylaspartate (NAA), a putative marker of neurons, in the supraventricular brain of cognitively impaired HIV-seropositive patients (CISP) compared to noninfected controls was replicated in a new cohort of 13 CISP patients and extended to include 10 high-risk homosexual HIV-seronegative controls. Throughout the supraventricular brain the ratio of NAA to choline-containing metabolites (NAA/Cho) was lower in CISP subjects than in high-risk controls (1.98 +/- 0.36 vs. 2.35 +/- 0.29, p = 0.016), and the ratio of NAA to creatine-containing metabolites (NAA/Cr) was also lower in CISP subjects than in high-risk controls (3.02 +/- 0.44 vs. 3.56 +/- 0.39, p = 0.007) with Cho/Cr unchanged in both groups. These findings indicate a NAA reduction which suggests neuron loss and/or dendritic and axonal damage. Homosexual high-risk HIV-seronegative controls had metabolite measures similar to previously studied heterosexual HIV-seronegative controls. NAA measures in six cognitively normal HIV-seropositive subjects (CNSP) (NAA/Cho = 2.34 +/- 0.39, NAA/Cr = 3.42 +/- 0.69) were similar to those of controls and tended to be increased relative to those in cognitively impaired HIV-seropositive subjects. This study demonstrates that reduced NAA in the supraventricular brain is associated with the development of severe cognitive impairments secondary to HIV infection and that 1H MRSI methodology reliably detects HIV effects on the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

What happens when doctors stop prescribing temazepam? Use of alternative therapies.

We investigated the withdrawal of temazepam in a single general practice using two alternative prescribing policies: an alternative benzodiazepine; or an alternative group of drugs recommended for short-term management of insomnia, including sedative antihistamines and chloral hydrate. The study showed that temazepam prescribing in general practice can be reduced or stopped by using a simple intervention. An alternative benzodiazepine is useful in helping patients to stop their use of hypnotic agents. The use of antihistamines as substitute hypnotics is not advocated on the basis of our findings.

Estriol: a potent regulator of TNF and IL-6 expression in a murine model of endotoxemia.

The increased incidence of autoimmune disease in premenopausal women suggests the involvement of sex steroids in the pathogenesis of these disease processes. The effects of estrogen on autoimmunity and inflammation may involve changes in the secretion of inflammatory mediators by mononuclear phagocytes. Estradiol, for example, has been reported to regulate TNF, IL-6, IL-1 and JE expression. In the present study the effects of the estrogen agonist, estriol, on cytokine expression have been investigated in mice administered a sublethal lipopolysaccharide, LPS, challenge. Pretreatment of mice with pharmacologic doses of estriol, 0.4-2 mg/kg, resulted in a significant increase in serum TNF levels in both control and autoimmune MRL/lpr mice, following LPS challenge. This increase in TNF over the placebo group was blocked by the estrogen antagonist tamoxifen. Estriol treated mice also exhibited a rapid elevation in serum IL-6 levels following LPS challenge with the peak increase occurring 1 hr post LPS. This contrasted with the placebo group in which maximal serum IL-6 levels were detected at 3 hrs post challenge. This shift in the kinetics of IL-6 increase by estriol was inhibited by tamoxifen. The estriol mediated effects of TNF and IL-6 serum levels were consistent with the changes in TNF and IL-6 mRNA observed ex vivo in elicited peritoneal macrophages. Macrophage cultures from estriol treated animals however, did not demonstrate significant differences from the placebo group for TNF or NO secretion following in vitro LPS challenge. These results suggest that the estrogen agonist estriol can have significant quantitative, TNF, and kinetic, IL-6, effects on inflammatory monokines produced in response to an endotoxin challenge.

The treatment of acute myocardial infarction.

A questionnaire on the management of acute myocardial infarction was sent to 100 randomly selected general practitioners. From the replies received, only 42 provided worthwhile information. The approach to the care and treatment of actual patients and their common complications is discussed and recommendations relating to future audits are made.

Role of p53 assessment in management of Barrett's esophagus.

The risk of developing gastroesophageal adenocarcinoma is increased in patients with Barrett's esophagus. The management of dysplasia in Barrett's esophagus remains controversial. Understanding of the sequence of events preceding malignancy is essential before screening protocols for early diagnosis and preventive measures can be implemented. The aim of this review is to examine the published data on the role p53 assessment may play in the management of Barrett's esophagus. Relevant papers were identified by an extensive text word search of the Medline database and a review of quoted articles. The p53 abnormality occurs more frequently in highly dysplastic epithelium than in nondysplastic epithelium. However, the retrospective nature of most of the available data could be a significant confounding factor. Our current knowledge suggests that p53 protein overexpression does not seem to predict future progression to cancer or determine disease outcome. The p53 abnormality alone can not be reliably used to predict progression of Barrett's esophagus to cancer. We must await long-term evaluation of patients to determine the percentage of patients with p53 gene abnormality, and nondysplastic Barrett's who will progress to dysplasia or carcinoma. Large randomized controlled long-term follow-up studies are much needed.

The involvement of European industry in developing regulations.

In the belief that the release of genetically engineered organisms will provide significant benefits to our society, European industry is taking an active role in the development of regulations which make both economic and scientific sense. Such regulations will have public support and enable industry to predict the cost of satisfying the requirements for risk assessment and hence be more confident in funding research and development programmes.

Delayed P3A in abstinent elderly male chronic alcoholics.

Significant central nervous system toxicity in frontal brain regions has been demonstrated with chronic alcohol consumption both on autopsy and using neuropsychological testing. This study examined the latency of an objective and reproducible brain event-related potential measure of frontal cortex function in chronic elderly male alcoholics who were abstinent 3 months-2 years, a patient group in whom the central nervous system effects of chronic alcohol abuse are thought to be largest and most persistent. We examined the latency of the P3A event-related potential component, which reflects a frontal maximum orienting response to novel stimuli. Twelve elderly abstinent chronic alcoholic males and 11 elderly male controls were studied in an auditory and a visual paradigm, each of which included target, nontarget, and novel rare nontarget conditions. In both modalities, the P3A response to the novel rare nontarget stimuli was significantly delayed in the chronic alcoholics. P3B delays to the target stimuli were also present in the alcoholics, with the P3A and P3B effects being independent of each other. For both P3A and P3B, the effects were larger and more consistent in the visual compared with the auditory modality. Our conclusions are as follows: (1) both P3A and P3B latency delays are evident in elderly abstinent chronic alcoholics; (2) separate mechanisms are responsible for these effects; (3) these effects are more sensitively detected in the visual versus the auditory modality; and (4) delayed P3A latency may be an objective and reproducible index of the frontal cortex effects of chronic alcohol abuse.

Estrogen-induced alterations in lipoprotein metabolism in autoimmune MRL/lpr mice.

Estrogen replacement therapy has been demonstrated to shift the lipoprotein profile toward a less atherogenic one with concomitant increases in HDL and reductions in LDL cholesterol and serum triglycerides. Estrogen, however, has also been implicated in playing a significant role in autoimmune disease and may be involved with disease incidence and progression. The MRL/lpr mouse strain represents an autoimmune disease model with features resembling systemic lupus erythematosus including high-titer autoantibodies, glomerulonephritis, and vasculitis. In the present study, the effects of estrogen treatment on serum lipoprotein profiles were investigated by fast protein liquid chromatography in female MRL/lpr mice, in the MRL/++ strain with a milder form of disease, and in control Balb/c mice. Treatment of MRL/lpr mice for periods of 1 week or longer with pharmacologic doses of estrogen resulted in a significant increase in the amount of cholesterol carried on LDL particles. The up to eightfold increase in LDL cholesterol was less significant in the MRL/++ or Balb/c mice. Maximal increases were observed at 1 to 2 mg/kg of estrogen agonists, and the effect on LDL cholesterol increases was inhibited by tamoxifen. The HDL-to-LDL shift in cholesterol observed in estrogen-treated autoimmune mice correlated with an increase in apolipoprotein E, primarily on larger HDL particles. In addition to the increase in LDL cholesterol, hormonal treatment also resulted in a shift in triglycerides from the VLDL to the LDL fraction in both normal and autoimmune mice. These results suggest that pharmacologic doses of estrogen may contribute to cardiovascular disease progression by shifting the relative distribution of cholesterol from HDL to LDL in this murine model of lupus.

In vivo modulation of murine serum tumour necrosis factor and interleukin-6 levels during endotoxemia by oestrogen agonists and antagonists.

Oestrogen has been reported to modulate tumour necrosis factor (TNF), interleukin (IL)-1 and IL-6 cytokine levels in human mononuclear cell cultures. In the present study, the effects of exogenous oestrogen administration on the cytokine response to an endotoxin challenge was investigated in a murine model of endotoxemia. Animals pretreated for 4 days with 17 alpha ethinyl oestradiol exhibited divergent regulation of TNF and IL-6 levels in sera from endotoxin-stimulated mice. Oestrogen treatment resulted in a significant increase in serum TNF while serum IL-6 levels, relative to the placebo group, decreased in response to an endotoxin challenge. These oestrogenic effects were dose dependent with maximal elevations observed in TNF at 1 mg/kg and maximal reduction in IL-6 at 0.1 mg/kg of 17 alpha ethinyl oestradiol. The increase in TNF levels by ethinyl oestradiol was blocked by co-administration of the oestrogen receptor antagonist tamoxifen. Oestrogen-mediated modulation of the TNF and IL-6 response to endotoxin was also apparent in animals implanted with 17 beta oestradiol pellets. The oestrogen-mediated effects on serum IL-6 were consistent with a reduction in IL-6 mRNA in peritoneal macrophages from oestrogen-treated mice. The effects of oestrogen on TNF and IL-6 production were also investigated in vitro. Oestradiol-treated macrophage cultures produced three- to fourfold lower amounts of IL-6 without any significant modulatory effects on TNF secretion. The combined in vivo and in vitro results demonstrate the modulation of IL-6 and TNF during endotoxemia by oestrogen analogues through an oestrogen receptor-dependent mechanism.