Outcomes of surgical management of familial intrahepatic cholestasis 1 and bile salt export protein deficiencies.

Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants).

"I Felt Like I Was Being Abused All Over Again": How Survivors of Child Sexual Abuse Make Sense of the Perinatal Period Through Their Narratives.

Sequelae following child sexual abuse pervade the lives of adult survivors, significantly impacting on pregnancy and childbirth. Symptoms of this distress are recognized, but meanings for women are less understood. This research aimed to examine the meaning for women themselves of the impact of child sexual abuse on experiences of pregnancy, childbirth, and the postnatal period.

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries.

Background: In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.

Methods: We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population.

Apathy and impulse control disorders in Parkinson's disease: a direct comparison.

Background: Apathy and impulse control disorders (ICDs) in Parkinson's disease (PD) are clinically important complications and may exist on a common behavioral spectrum of disorders of reward and motivation.

Objective: To directly compare PD participants with apathy those with ICDs on range of demographic, neurologic and psychiatric measures.

Methods: Ninety-nine non-demented PD participants (ICD, n = 35; apathy, n = 26; and controls, n = 38) were assessed in the study.

Behavioural disorders, disability and quality of life in Parkinson's disease.

Background: although non-motor symptoms of Parkinson's disease (PD) are known to adversely affect disability and health-related quality of life, the impact that specific disorders of reward and motivation have remains unclear. Impulse control disorders are more likely in those with a younger disease onset although there is no strong evidence to date that apathy is related to age of onset or correlated with a longer duration of disease.

Objective: to examine the effects of apathy and impulse controls disorders on disability and health-related quality of life.

Carer burden in apathy and impulse control disorders in Parkinson's disease.

Background: The neuropsychiatric complications of Parkinson's disease (PD), which include behaviour disturbances such as apathy and the impulse control disorders (ICDs), may have a significant effect on patients with PD and their carers. The contribution of these behaviour disorders to carer burden is less understood. Therefore, the aim of this study was to explore the relationship that apathy and ICDs have with carer burden.

The conversational mini-mental state examination: Estimating cognitive impairment.

Formal cognitive testing is an integral part of the mental state examination, and we aimed to test whether clinicians were able to predict the score on the mini-mental state examination (MMSE) by watching a conversation between a person and the interviewer about their memory. A total of 41 professionals rated 30 patients-generally the scores on the MMSE were underestimated and experienced professionals did worse than less experienced practitioners. The results underscore the need for formal cognitive assessment and the requirements for training in the administration of cognitive tests.

Differences in presentation and progression between severe FIC1 and BSEP deficiencies.

Background & Aims: Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations.

A pilot randomized controlled trial of sleep therapy in Parkinson's disease: effect on patients and caregivers.

Objective: By means of a controlled trial, to investigate the efficacy, tolerability and feasibility of a multi-component sleep therapy intervention versus basic sleep hygiene education in PD patients with sleep disturbances and their live-in carers.

Methods: Patient-carer dyads were randomised to either of the two interventions. Quantitative measures of sleep, psychiatric and overall functioning were administered at baseline and two weeks after the intervention to patients and carers.

Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation.

Ischemic preconditioning (IP) is an effective method for protecting organs from ischemia/reperfusion (IR) injury; however, the molecular basis of this protective effect is poorly understood. This study assessed the gene expression profile in liver allografts during transplantation and evaluated the impact of IP. Prereperfusion and postreperfusion biopsy specimens from livers subjected to IP (n = 19) or no preconditioning (the IR group; n = 16) were obtained.

Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN).

Background: Thorough knowledge of the regulatory requirements is a challenging prerequisite for conducting multinational clinical studies in Europe given their complexity and heterogeneity in regulation and perception across the EU member states.

Methods: In order to summarise the current situation in relation to the wide spectrum of clinical research, the European Clinical Research Infrastructures Network (ECRIN) developed a multinational survey in ten European countries. However a lack of common classification framework for major categories of clinical research was identified, and therefore reaching an agreement on a common classification was the initial step in the development of the survey.

Randomized controlled trial of memantine in dementia associated with Parkinson's disease.

The objective of this study is to investigate the safety and tolerability of memantine, a glutamatergic modulator, in patients suffering from dementia associated with Parkinson's disease (PDD), an increasingly common complication of PD. This was a 22-week trial of 25 participants with a DSM-IV diagnosis of PDD who were randomized to either placebo or 20 mg/day of memantine. Memantine was well tolerated by participants at 20 mg/day dosing.

Bright light therapy for agitation in dementia: a randomized controlled trial.

Background: Agitation is common in people with dementia, is distressing to patients and stressful to their carers. Drugs used to treat the condition have the potential to cause particularly severe side effects in older people with dementia and have been associated with an increased death rate. Alternatives to drug treatment for agitation should be sought.

Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing.

Unlabelled: The gene encoding the human bile salt export pump (BSEP), ABCB11, is mutated in several forms of intrahepatic cholestasis. Here we classified the majority (63) of known ABCB11 missense mutations and 21 single-nucleotide polymorphisms (SNPs) to determine whether they caused abnormal ABCB11 pre-messenger RNA splicing, abnormal processing of BSEP protein, or alterations in BSEP protein function. Using an in vitro minigene system to analyze splicing events, we found reduced wild-type splicing for 20 mutations/SNPs, with normal mRNA levels reduced to 5% or less in eight cases.

Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.

Background & Aims: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy.

Methods: Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11.

Lack of hepatocellular CD10 along bile canaliculi is physiologic in early childhood and persistent in Alagille syndrome.

Many tissues, including hepatobiliary cells, express neutral endopeptidase (CD10), encoded by MME. Serum neutral endopeptidase activity (NEA) has been recommended as a marker of cholestasis in adults but not in children with Alagille syndrome (AGS). We investigated ontogenic and disease-related differences in the expression of CD10.

Orofacial dyskinesia, frontal lobe dysfunction, and coping in older people with psychosis.

Objective: To investigate whether orofacial tardive dyskinesia (OTD) is associated with frontal lobe dysfunction and whether either are related to the coping abilities independent of psychiatric symptoms in older people with psychotic disorders.

Methods: A total of 52 patients, aged over 65 years or over, who satisfied International Classification of Diseases, Tenth Revision criteria for psychotic disorders (F20-F29) were recruited into the study. OTD was measured using the Abnormal Involuntary Movements Scale and Waddington et al.

Asymptomatic spontaneous cerebral emboli predict cognitive and functional decline in dementia.

Background: Spontaneous cerebral emboli (SCE) are frequent in Alzheimer's disease (AD) and vascular dementia (VaD). We investigated the effect of SCE on the rates of cognitive and functional decline in AD and VaD.

Methods: One hundred thirty-two patients with dementia (74 AD, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association [NINCDS/ADRDA] criteria; 58 VaD, National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences [NINDS/AIREN] criteria) underwent 1-hour transcranial Doppler for detection of SCE (mean [SD] age 75.

Carbodiimide-mediated cross-linking of RNA to nylon membranes improves the detection of siRNA, miRNA and piRNA by northern blot.

The northern blot, or RNA gel blot, is a widely used method for the discovery, validation and expression analysis of small regulatory RNA such as small interfering RNA (siRNA), microRNA (miRNA) and piwi-interacting RNA (piRNA). Although it is straightforward and quantitative, the main disadvantage of a northern blot is that it detects such RNA less sensitively than most other approaches. We found that the standard dose of UV used in northern blots was not the most efficient at immobilizing small RNA of 20-40 nt on nylon membranes.

The role of vascular risk factors in late onset bipolar disorder.

Background: The association between late life depression and cerebro-vascular risk and cerebro-vascular disease is well established. Do similar links exist with late onset bipolar disorder?

Aims And Objectives: Patients with early onset (less than 60 years of age) bipolar disorder were compared with those of late onset (aged 60 and above) in relation to cognitive function, physical health and vascular risk factors.

Method: Cross-sectional survey of elderly bipolar disorder patients (above 65 years) involved with secondary care mental health services.

Deletion/insertion polymorphism of the angiotensin-converting enzyme gene and white matter hyperintensities in dementia: A pilot study.

Objectives: To examine the association between the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism and white matter hyperintensities (WMHs) in patients with dementia.

Design: Observational pilot study with adjustment for potential confounders using analysis of covariance.

Setting: Secondary care old-age psychiatry services in greater Manchester, United Kingdom.

Cerebral emboli and depressive symptoms in dementia.

Background: The vascular depression hypothesis and our recent findings of increased frequency of spontaneous cerebral emboli in dementia suggest that such emboli may be involved in the causation of depressive symptoms in dementia.

Aims: To evaluate the association between spontaneous cerebral emboli and depressive symptoms in Alzheimer's disease and vascular dementia.

Method: In a cohort of 142 patients with dementia (72 with Alzheimer's disease and 70 with vascular dementia), the association between spontaneous cerebral emboli and clinically relevant depressive symptoms was examined using multiple logistic regression analyses.

Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency.

Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational-analysis studies could demonstrate that deficiency of the canalicular bile acid transporter bile salt export pump (BSEP) and mutation in ABCB11, encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC)--or "neonatal hepatitis" suggesting PFIC--that was associated with HCC in young children. We studied 11 cases of pediatric HCC in the setting of PFIC or "neonatal hepatitis" suggesting PFIC.