Long-term follow-up of four patients with Langer-Giedion syndrome: clinical course and complications.

Long-term observations of individuals with the so-called Langer-Giedion (LGS) or tricho-rhino-phalangeal type II (TRPS2) are scarce. We report here a on follow-up of four LGS individuals, including one first described by Andres Giedion in 1969, and review the sparse publications on adults with this syndrome which comprises ectodermal dysplasia, multiple cone-shaped epiphyses prior to puberty, multiple cartilaginous exostoses, and mostly mild intellectual impairment. LGS is caused by deletion of the chromosomal segment 8q24.11-q24.13 containing among others the genes EXT1 and TRPS1. Most patients with TRPS2 are only borderline or mildly cognitively delayed, and few are of normal intelligence. Their practical skills are better than their intellectual capability, and, for this reason and because of their low self-esteem, they are often underestimated. Some patients develop seizures at variable age. Osteomas on processes of cervical vertebrae may cause pressure on cervical nerves or dissection of cerebral arteries. Joint stiffness is observed during childhood and changes later to joint laxity causing instability and proneness to trauma. Perthes disease is not rare. Almost all males become bald at or soon after puberty, and some develop (pseudo) gynecomastia. Growth hormone deficiency was found in a few patients, TSH deficiency so far only in one. Puberty and fertility are diminished, and no instance of transmission of the deletion from a non-mosaic parent to a child has been observed so far. Several affected females had vaginal atresia with consequent hydrometrocolpos.

A longitudinal study on delirium in nursing homes.

OBJECTIVE: To investigate the evolution of delirium of nursing home (NH) residents and their possible predictors. DESIGN: Post-hoc analysis of a prospective cohort assessment. SETTING: Ninety NHs in Switzerland. PARTICIPANTS: Included 14,771 NH residents. MEASUREMENTS: The Resident Assessment Instrument Minimum Data Set and the Nursing Home Confusion Assessment Method were used to determine follow-up of subsyndromal or full delirium in NH residents using discrete Markov chain modeling to describe long-term trajectories and multiple logistic regression analyses to determine predictors of the trajectories. RESULTS: We identified four major types of delirium time courses in NH. Increasing severity of cognitive impairment and of depressive symptoms at the initial assessment predicted the different delirium time courses. CONCLUSION: More pronounced cognitive impairment and depressive symptoms at the initial assessment are associated with different subsequent evolutions of delirium. The presence and evolution of delirium in the first year after NH admission predicted the subsequent course of delirium until death.

Rapidly fatal poisoning with an insecticide containing rotenone.

Introduction: Rotenone is a botanical pesticide derived from extracts of Derris roots, which is traditionally used as piscicide, but also as an industrial insecticide for home gardens. Its mechanism of action is potent inhibition of mitochondrial respiratory chain by uncoupling oxidative phosphorylation by blocking electron transport at complex-I. Despite its classification as mild to moderately toxic to humans (estimated LD50, 300-500 mg/kg), there is a striking variety of acute toxicity of rotenone depending on the formulation (solvents). Human fatalities with rotenone-containing insecticides have been rarely reported, and a rapid deterioration within a few hours of the ingestion has been described previously in one case. Case report: A 49-year-old Tamil man with a history of asthma, ingested 250 mL of an insecticide containing 1.24% of rotenone (3.125 g, 52.1-62.5 mg/kg) in a suicide attempt at home. The product was not labeled as toxic. One hour later, he vomited repeatedly and emergency services were alerted. He was found unconscious with irregular respiration and was intubated. On arrival at the emergency department, he was comatose (GCS 3) with fixed and dilated pupils, and absent corneal reflexes. Physical examination revealed hemodynamic instability with hypotension (55/30 mmHg) and bradycardia (52 bpm). Significant laboratory findings were lactic acidosis (pH 6.97, lactate 17 mmol/L) and hypokalemia (2 mmol/L). Cranial computed tomography (CT) showed early cerebral edema. A single dose of activated charcoal was given. Intravenous hydration, ephedrine, repeated boli of dobutamine, and a perfusor with 90 micrograms/h norepinephine stabilized blood pressure temporarily. Atropine had a minimal effect on heart rate (58 bpm). Intravenous lipid emulsion was considered (log Pow 4.1), but there was a rapid deterioration with refractory hypotension and acute circulatory failure. The patient died 5h after ingestion of the insecticide. No autopsy was performed. Quantitative analysis of serum performed by high-resolution/accurate mass-mass spectrometry and liquid chromatography (LC-HR/AM-MS): 560 ng/mL rotenone. Other substances were excluded by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS/MS). Conclusion: The clinical course was characterized by early severe symptoms and a rapidly fatal evolution, compatible with inhibition of mitochondrial energy supply. Although rotenone is classified as mild to moderately toxic, physicians must be aware that suicidal ingestion of emulsified concentrates may be rapidly fatal. (n=3): stridor, cyanosis, cough (one each). Local swelling after chewing or swallowing soap developed at the earliest after 20 minutes and persisted beyond 24 hours in some cases. Treatment with antihistamines and/or steroids relieved the symptoms in 9 cases. Conclusion: Bar soap ingestion by seniors carries a risk of severe local reactions. Half the patients developed symptoms, predominantly swellings of tongue and/or lips (38%). Cognitive impairment, particularly in the cases of dementia (37%), may increase the risk of unintentional ingestion. Chewing and intraoral retention of soap leads to prolonged contact with the mucosal membranes. Age-associated physiological changes of oral mucosa probably promote the irritant effects of the surfactants. Medical treatment with antihistamines and corticosteroids usually leads to rapid decline of symptoms. Without treatment, there may be a risk of airway obstruction.

DETERMINE Working document #4 'Economic arguments for addressing social determinants of health inequalities'

The Institute of Public Health in Ireland (IPH) is a partner in the European project DETERMINE, building on its previous involvement in the Closing the Gap project in 2004-2006. In Year 2 the DETERMINE project  focused on identifying and exploring economic arguments to support action on social determinants of health inequalities.  Working document #4 'Economic arguments for addressing social determinants of health inequalities' presents the findings.

DETERMINE Working Document #1 'Policies and actions addressing the social determinants of health inequalities: examples of activity at EU member state level in Europe'

The Institute of Public Health in Ireland (IPH) is a partner in the European project DETERMINE, building on its previous involvement in the Closing the Gap project in 2004-2006. In the first year of the project (2007-2008) 15 DETERMINE partners identified policies and actions that have taken place within countries, and at the EU level, to address Social Determinants of Health Inequalities. These policies and actions were identified via a questionnaire, which also identified structures and tools/mechanisms being used in the country to support a 'health in all policy' approach.

A non-circadian role for clock-genes in sleep homeostasis: a strain comparison.

BACKGROUND: We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in three inbred strains of mice for which the homeostatic sleep rebound following SD differs. We reasoned that if clock genes are functionally implicated in sleep homeostasis then the SD-induced changes in gene expression should vary according to the genotypic differences in the sleep rebound. RESULTS: In all three strains per expression was increased when animals were kept awake but the rate of increase during the SD as well as the relative increase in per after 6 h SD were highest in the strain for which the sleep rebound was smallest; i.e., DBA/2J (D2). Moreover, whereas in the other two strains per1 and per2 reverted to control levels with recovery sleep, per2 expression specifically, remained elevated in D2 mice. dbp expression increased during the light period both during baseline and during SD although levels were reduced during the latter condition compared to baseline. In contrast to per2, dbp expression reverted to control levels with recovery sleep in D2 only, whereas in the two other strains expression remained decreased. CONCLUSION: These findings support and extend our previous findings that clock genes in the forebrain are implicated in the homeostatic regulation of sleep and suggest that sustained, high levels of per2 expression may negatively impact recovery sleep.

Working Arrangements For The Welfare & Safeguarding of Child Victims of Human Trafficking - February 2011 (PDF 2.91MB)

Guidance issued by The Department of Health, Social Services & Public Safety & The Police Service for Northern Ireland

Best Practice Guidance on Joint Working between the HSC and the Pharmaceutical Industry and other relevant organisations (PDF 260KB)

HSS (GEN) 1) 1/95 update. It is intended to replace the guidance previously provided by former HSSBs and Trusts to assist employers and staff in maintaining strict ethical standards in the conduct of HSC business, in this instance, with the pharmaceutical industry

Guide to Flexible Working Options - June 2009 (PDF 578 KB)

This guide aims to outline the Department's position on flexible working.

Änderung des Therapieziels am Lebensende: Effekte einer Klinik-Leitlinie [Changing the treatment goal at the end of life: effects of a guideline at a hospital].

BACKGROUND AND OBJECTIVE: Deciding about treatment goals at the end of life is a frequent and difficult challenge to medical staff. As more health care institutions issue ethico-legal guidelines to their staff the effects of such a guideline should be investigated in a pilot project.¦PARTICIPANTS AND METHODS: Prospective evaluation study using the pre-post method. Physicians and nurses working in ten intensive care units of a university medical center in Germany answered a specially designed questionnaire before and one year after issuance of the guideline.¦RESULTS: 197 analyzable answers were obtained from the first (pre-guideline) and 251 from the second (post-guideline) survey (54 % and 58 % response rate, respectively). Initially the clinicians expressed their need for guidelines, advice on ethical problems, and continuing education. One year after introduction of the guideline one third of the clinicians was familiar with the guideline's content and another third was aware of its existence. 90% of those who knew the document welcomed it. Explanation of the legal aspects was seen as its most useful element. The pre- and post-guideline comparison demonstrated that uncertainty in decision making and fear of legal consequences were reduced, while knowledge of legal aspects and the value given to advance directives increased. The residents had derived the greatest benefit.¦CONCLUSION: By promoting the knowledge of legal aspects and ethical considerations, guidelines given to medical staff can lead to more certainty when making in end of life decision.

Congenital Myasthenic Syndromes with COLQ mutations: Long term follow-up

Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous inherited disorders characterized by impaired neuromuscular transmission. Mutations in the acetylcholinesterase (AChE) collagenlike tail subunit gene (ColQ) cause recessive forms of synaptic CMS with end plate AChE deficiency. We report the time course of clinical manifestations in 15 COLQ-mutated patients followed from 1987 to 2010. All patients suffered from a muscle weakness with onset at birth or in childhood. Ocular and bulbar signs were found in 60% of the patients and delayed pupillary light response in 20% of our patients. EMG study demonstrated a decrement on repetitive nerve stimulation and repetitive compound muscle action potential in all patients. Clinical symptoms strongly fluctuated daily, weekly, monthly or even yearly. Severe relapses were characterized by a general motor weakness associated with pain which resolved spontaneously after a few months whereas the relapses with these symptoms and bulbar signs could last up to several years. Genetic analyses identified 16 different mutations including 9 novel ones. There was no genotype-phenotype correlation. Our study confirms the predominance of oculobulbar signs and the frequency of respiratory distress in COLQrelated CMS. At the end of the follow up of 23 years, interesting findings were (i) the spontaneous reversibility of severe relapses, some of them lasting for up to 5 years (ii) the good prognosis of COLQ-related CMS, since at the end of the follow-up 80% of patients were ambulant and 87% of patients had no respiratory trouble (iii) the efficacy of Ephedrine and, to a lesser extend, of 3-4 DAP. The triggering factors of relapses were esterase inhibitors, effort, puberty, pregnancy and delivery highlighting the importance of hormonal factors in CMS. In conclusion, patients diagnosed with unknown congenital myopathy should undergo an electrophysiological study of neuromuscular junction to identify ColQ-related CMS.

MIMAS 3.0 is a Multiomics Information Management and Annotation System.

BACKGROUND: DNA sequence integrity, mRNA concentrations and protein-DNA interactions have been subject to genome-wide analyses based on microarrays with ever increasing efficiency and reliability over the past fifteen years. However, very recently novel technologies for Ultra High-Throughput DNA Sequencing (UHTS) have been harnessed to study these phenomena with unprecedented precision. As a consequence, the extensive bioinformatics environment available for array data management, analysis, interpretation and publication must be extended to include these novel sequencing data types. DESCRIPTION: MIMAS was originally conceived as a simple, convenient and local Microarray Information Management and Annotation System focused on GeneChips for expression profiling studies. MIMAS 3.0 enables users to manage data from high-density oligonucleotide SNP Chips, expression arrays (both 3'UTR and tiling) and promoter arrays, BeadArrays as well as UHTS data using MIAME-compliant standardized vocabulary. Importantly, researchers can export data in MAGE-TAB format and upload them to the EBI's ArrayExpress certified data repository using a one-step procedure. CONCLUSION: We have vastly extended the capability of the system such that it processes the data output of six types of GeneChips (Affymetrix), two different BeadArrays for mRNA and miRNA (Illumina) and the Genome Analyzer (a popular Ultra-High Throughput DNA Sequencer, Illumina), without compromising on its flexibility and user-friendliness. MIMAS, appropriately renamed into Multiomics Information Management and Annotation System, is currently used by scientists working in approximately 50 academic laboratories and genomics platforms in Switzerland and France. MIMAS 3.0 is freely available via http://multiomics.sourceforge.net/.

Sequential histological changes in Biomphalaria glabrata during the course of Schistosoma mansoni infection

Biomphalaria glabrata, highly susceptible to Schistosoma mansoni, were seen to shed less and less cercariae along the time of infection. Histological examination kept a close correlation with this changing pattern of cercarial shedding, turning an initial picture of no-reaction (tolerance) gradually into one of hemocyte proliferation with formation of focal encapsulating lesions around disintegrating sporocysts and cercariae, a change that became disseminated toward the 142nd day post miracidial exposure. Findings were suggestive of a gradual installation of acquired immunity in snails infected with S. mansoni.