[Late recognition of anti-NMDA receptor encephalitis: the effect of a one-track mind in multiple specialties]. / Laattijdige herkenning van anti-NMDA-receptorencefalitis: interdisciplinaire tunnelvisie?

Anti-NMDA receptor encephalitis is an auto-immune disorder often presenting with non-specific and heterogeneous neuropsychiatric symptoms at onset. This complicates a quick and accurate diagnosis. However, a tardy diagnosis has a negative impact on morbidity and mortality. We report about a patient with the clinical presentation of a psychotic depression, who was diagnosed with anti-NMDA receptor encephalitis only after a thorough diagnostic work-up. Neurological symptoms were wrongly attributed to the psychiatric syndrome or considered as side-effects of its treatment. We present an overview of clinical aspects of the disorder, distinctive psychiatric symptoms, diagnostic tools, treatment and prognosis.

[Euthanasia: opinions and experiences of Flemish psychiatrists working at a university]. / Euthanasie: opvattingen en ervaringen van universitair werkzame Vlaamse psychiaters.

BACKGROUND: Little is known about the attitude of Belgian psychiatrists and psychiatrists in training towards euthanasia for psychiatric reasons. AIM: To analyse opinions about and experiences with euthanasia in physicians from a university psychiatric hospital. METHOD: A mail with a questionnaire was sent to the 111 psychiatrists and psychiatrists in training from University Psychiatric Centre KU Leuven to assess their profile, opinions towards euthanasia in different cases and own experiences with requests for euthanasia in the last five years. RESULTS: The response rate was 45%. The majority of psychiatrists were accepting towards euthanasia, also in the case of psychiatric disorders (64%) or a combination of non-terminal somatic and psychosocial illness (60%). Religious psychiatrists were less accepting towards euthanasia than non-religious colleagues. Older psychiatrists (more than 20 years of working experience) were more open towards euthanasia than their younger colleagues, but less so than psychiatrists in training. Encounters with euthanasia were limited. CONCLUSION: The common attitude towards euthanasia in doctors from a tertiary psychiatric centre is accepting. More research in a broader population is recommended.

Measurements of the energy distribution of a high brightness rubidium ion beam.

The energy distribution of a high brightness rubidium ion beam, which is intended to be used as the source for a focused ion beam instrument, is measured with a retarding field analyzer. The ions are created from a laser-cooled and compressed atomic beam by two-step photoionization in which the ionization laser power is enhanced in a build-up cavity. Particle tracing simulations are performed to ensure the analyzer is able to resolve the distribution. The lowest achieved full width 50% energy spread is (0.205 ±â€¯0.006) eV, which is measured at a beam current of 9 pA. The energy spread originates from the variation in the ionization position of the ions which are created inside an extraction electric field. This extraction field is essential to limit disorder-induced heating which can decrease the ion beam brightness. The ionization position distribution is limited by a tightly focused excitation laser beam. Energy distributions are measured for various ionization and excitation laser intensities and compared with calculations based on numerical solutions of the optical Bloch equations including ionization. A good agreement is found between measurements and calculations.

Acceptable health and priority weighting: Discussing a reference-level approach using sufficientarian reasoning.

Health care systems are challenged in allocating scarce health care resources, which are typically insufficient to fulfil all health care wants and needs. One criterion for priority setting may be the 'acceptable health' approach, which suggests that society may want to assign higher priority to health benefits in people with "unacceptable" than in people with "acceptable" health. A level of acceptable health then serves as a reference point for priority setting. Empirical research has indicated that people may be able and willing to define health states as "unacceptable" or "acceptable", but little attention has been given to the normative implications of evaluating health benefits in relation to a reference level of acceptable health. The current paper aims to address this gap by relating insights from the distributive justice literature, i.e. the sufficientarian literature, to the acceptable health approach, as we argue that these approaches are related. We specifically focus on the implications of an 'acceptability' approach for priority weighting of health benefits, derived from sufficientarian reasoning and debates, and assess the moral implications of such weighting.

Are all health gains equally important? An exploration of acceptable health as a reference point in health care priority setting.

BACKGROUND: Accumulating evidence suggests that members of society prefer some QALY gains over others. In this paper, we explore the notion of acceptable health as a reference point in assessing the value of health gains. The value of health benefits may be assessed in terms of their position relative to this reference level, benefits above the level of acceptable health being valued differently from benefits below this level. In this paper we focus on assessing the level of acceptable health at different ages and associations with background variables. METHODS: We recruited a sample of the adult population from the Netherlands (n = 1067) to investigate which level of health problems they consider to be acceptable for people aged 40 to 90, using 10-year intervals. We constructed acceptable health curves and associated acceptable health with background characteristics using linear regressions. RESULTS: The results of this study indicate that the level of health problems considered acceptable increases with age. This level was associated with respondents' age, age of death of next of kin, health and health behaviour. CONCLUSIONS: Our results suggest that people are capable of indicating acceptable levels of health at different ages, implying that a reference point of acceptable health may exist. While more investigation into the measurement of acceptable health remains necessary, future studies may also focus on how health gains may be valued relative to this reference level. Gains below the reference point may receive higher weight than those above this level since the former improve unacceptable health states while the latter improve acceptable health states.

Do people desire to be healthier than other people? A short note on positional concerns for health.

Contrary to traditional economic postulates, people do not only care about their absolute position but also about their relative position. However, empirical evidence on positional concerns in the context of health is scarce, despite its relevance for health care policy. This paper presents a first explorative study on positional concerns in the context of health. Using a 'two-world' survey method, a convenience sample of 143 people chose between two options (having more in absolute terms or having more in relative terms) in several health and non-health domains. Our results for the non-health domains compare reasonably well to previous studies, with 22-47% of respondents preferring the positional option. In the health domain, these percentages were significantly lower, indicating a stronger focus on absolute positions. The finding that positional concerns are less prominent in the health domain has important implications for health policy, for instance in balancing reduction of socio-economic inequalities and absolute health improvements.

Patient-specific instruments for surgical resection of painful tarsal coalition in adolescents.

INTRODUCTION: Congenital tarsal coalition resection in adolescents may be hindered by the complex three-dimensional anatomy of the talocalcaneal joint. Peroperative fluoroscopy is not greatly contributive, especially for talocalcaneal coalition. HYPOTHESIS: 3D planning and patient-specific instruments facilitate the procedure. MATERIALS AND METHODS: A made-to-measure surgical guide (patient-specific instrument) was used in 9 consecutive patients for tarsal coalition resection (7 talocalcaneal and 2 calcaneonavicular coalitions). The guide was created by 3D modeling from the CT scan of the foot. Placed on the bone surface, it oriented the saw blade to resect the bone bridge at the appropriate depth. A fascia lata allograft was interposed. Complete resection and absence of recurrence were checked on postoperative CT in talocalcaneal and on radiography in calcaneonavicular coalitions. RESULTS: Resection was complete in all cases, with no recurrence at last follow-up. DISCUSSION: This technique makes tarsal coalition resection easier and more reliable and may be recommended to improve precision. LEVEL OF EVIDENCE: Level IV, prospective study of a new surgical technique.

Tuning organic magnetoresistance in polymer-fullerene blends by controlling spin reaction pathways.

Harnessing the spin degree of freedom in semiconductors is generally a challenging, yet rewarding task. In recent years, the large effect of a small magnetic field on the current in organic semiconductors has puzzled the young field of organic spintronics. Although the microscopic interaction mechanisms between spin-carrying particles in organic materials are well understood nowadays, there is no consensus as to which pairs of spin-carrying particles are actually influencing the current in such a drastic manner. Here we demonstrate that the spin-based particle reactions can be tuned in a blend of organic materials, and microscopic mechanisms are identified using magnetoresistance lineshapes and voltage dependencies as fingerprints. We find that different mechanisms can dominate, depending on the exact materials choice, morphology and operating conditions. Our improved understanding will contribute to the future control of magnetic field effects in organic semiconductors.

Recombinant human microplasmin: production and potential therapeutic properties.

The effect of recombinant human microplasmin was studied in ischemic stroke models in mice and in an extracorporeal loop thrombosis model in rabbits. Human microplasminogen ( micro Plg), which lacks the five 'kringle' domains of plasminogen was expressed with high yield in Pichia pastoris. It was purified, converted to microplasmin ( micro Pli) and equilibrated with 5 mmol L(-1) citrate, pH 3.1, yielding a stable preparation. In mice with middle cerebral artery (MCA) ligation, an intravenous (i.v.) bolus of 5.0 mg kg(-1) micro Pli reduced infarct size at 24 h from 27 (26-30) to 25 (21-28) mm3 (median and range, n= 16 each, P= 0.0001), whereas 4.0 mg kg(-1) rt-PA and 40 mg kg(-1) micro Plg had no effect. Infarct reduction was observed with administration at 4 h after occlusion. In mice with MCA, infarct size at 24 h was reduced from 20 (14-30) to 9.1 (3.1-25) mm3 with 5.0 mg kg(-1) micro Pli (n = 15 each, P < 0.002) and to 11 (5.2-27) mm3 with 4.0 mg kg(-1) rt-PA (n = 6; P= 0.02). Infarct reduction was still observed at 10 h after occlusion with micro Pli but not with t-PA. In rabbits with radiolabeled clots in an extracorporeal arteriovenous loop, local infusion of 2.5 mg kg(-1) micro Pli over 2 h, induced 51 +/- 15% lysis (mean +/- SD, n= 11) vs. a control value of 23 +/- 5.5%. micro Pli did not prolong template bleeding times, whereas equipotent doses of rt-PA were associated with extensive rebleeding. The potency of micro Pli in both models was similar to that of intact plasmin. These findings indicate that recombinant micro Pli may be useful for treatment of ischemic stroke and arterial thrombosis.

Is the apparent cardioprotective effect of recent alcohol consumption due to confounding by prodromal symptoms?

Previous research has reported a protective association between alcohol drinking and acute coronary heart disease in the 24-hour period after drinking. This study investigated whether this apparent protective association resulted from confounding due to the effect of prodromal symptoms on drinking behavior. In 1992, the authors conducted a case-control study that measured recent alcohol consumption and reasons for recent abstention from alcohol among patients with acute coronary heart disease identified from a community-based disease register and a representative control sample from the same community (Auckland, New Zealand). Cases were significantly more likely than controls to report recent abstention from drinking because they felt unwell. In unadjusted analyses, a protective association was observed between recent alcohol consumption and acute coronary heart disease; however, this association was weakened considerably after adjustment for the effect of prodromal symptoms on drinking behavior. The previously reported protective association between recent alcohol consumption and acute coronary heart disease appears to be largely due to the confounding effect of prodromal symptoms on drinking.

A case-crossover analysis of a case-control study of alcohol consumption and coronary events: the effects of exposure definition and the use of control data.

BACKGROUND: Case-crossover studies can be used to assess the effects of transient exposures in acute events by comparing cases' exposures at the time of the event against their usual exposure. Cases from a case-control study can also be analysed by this method if appropriate information is obtained. METHODS: We apply the case-crossover method to data collected in a case-control study of acute coronary events, to estimate the risk of alcohol consumption in the 24 h before a coronary event. Two questions, concerning the usual frequency of consuming alcohol and how much was consumed, were used in the analysis. The sensitivity of effect estimates to the two questions and to different ways of eliciting probabilities from them, are examined. The cases and controls were both analysed in the same way, assigning controls a 'pseudo-event' time at random. It is suggested that controls may provide a benchmark to establish whether bias exists in the case-series analysis. RESULTS: We find that the case-crossover analysis is sensitive to how exposure probabilities are assigned. Adopting a Poisson model for exposures leads to inflated risk estimates. The bias is removed if the control series is used to adjust estimates. There appears to be a small protective effect from alcohol consumption. CONCLUSION: Case-crossover designs have considerable potential, but reliable information on usual exposure limits their applicability. More research is required on how best to elicit exposure probabilities.

Occurrence of an HIV-1 gp160 endoproteolytic activity in low-density vesicles and evidence for a distinct density distribution from endogenously expressed furin and PC7/LPC convertases.

Human immunodeficiency virus (HIV) glycoprotein (gp) 160 processing by host cell proteinases is an essential step for viral fusion and infectivity. We have identified a rat liver subcellular fraction which specifically processes gp160 into gp120 and gp41. Using equilibration of microsomes in sucrose gradients, the gp160 cleavage activity was associated with particles equilibrating at low densities, well-separated from the endoplasmic reticulum, cis-Golgi network, Golgi stacks, lysosomes and plasma membrane. Its density distribution was compatible with light secretory vesicles derived from the trans-Golgi network (TGN) or to endosomes, but association with endosomes was not supported by free flow electrophoresis. Although furin and pro-protein convertase (PC) 7/LPC have been proposed as the major gp160 processing convertases, the rat liver microsomal gp160 processing activity was essentially resolved from furin and only partially overlapped PC7/LPC. These data suggest that proteinase(s) other than furin and PC7/LPC, presumably located in TGN-derived vesicles, may participate in the gp160 processing into gp120 and gp41.

Furin and proprotein convertase 7 (PC7)/lymphoma PC endogenously expressed in rat liver can be resolved into distinct post-Golgi compartments.

The intracellular compartmentalization in rat liver of the membrane-associated convertases furin and proprotein convertase 7 (PC7)/lymphoma PC (LPC) was investigated by analytical subcellular fractionation. In control animals, both enzymes were found to localize in fractions depleted of endoplasmic reticulum, cis-Golgi and lysosomal markers, but to co-distribute with the Golgi marker galactosyltransferase and the trans-Golgi network (TGN) marker TGN38. After overloading Golgi-derived vesicles with very-low-density lipoproteins (VLDL) by feeding rats with ethanol, the distribution of PC7/LPC was shifted markedly towards lower densities, in contrast with those of furin and the TGN marker. This provides support for the TGN localization of endogenously expressed furin and indicates that, at steady state, a considerable proportion of PC7/LPC may be associated with vesicles derived from the TGN.

Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell lines.

The human immunodeficiency virus HIV envelope glycoprotein gp160 is synthesized as an inactive precursor, which is processed into its fusiogenic form gp120/gp41 by host cell proteinases during its intracellular trafficking. Kexin/subtilisin-related endoproteases have been proposed to be enzyme candidates for this maturation process. In the present study, 1) we examined the ability of partially purified precursor convertases and their isoforms to cleave gp160 in vitro. The data demonstrate that all the convertases tested specifically cleave the HIV envelope glycoprotein into gp120 and gp41. 2) We demonstrated that a 19-amino acid model peptide spanning the gp120/gp41 junction is cleaved by all convertases at the same gp160 site as that recognized in HIV-infected cells. 3) In an effort to evaluate specific convertase inhibitors, we showed that the alpha1-antitrypsin variant, alpha1-PDX, inhibits equally well the ability of the tested convertases to cleave gp160 in vitro. 4) Three lymphocyte cell lines were screened by reverse transcription polymerase chain reaction in an effort to identify which are the convertases expressed in the most common HIV target, the CD4(+) lymphocytes. The data demonstrate that furin, PC5/6, and the newly cloned PC7 are the main transcribed convertases, suggesting that these proteinases are the major gp160-converting enzymes in T4 lymphocytes.

Penetrating injuries of the iliac arteries: a South African experience.

BACKGROUND: We did a retrospective study of 62 patients with penetrating injuries of the iliac arteries. METHODS: The cause of injury was gunshot wound in 85.5% and stabbing in 14.5%. The arterial repair was achieved by various means: lateral arteriorrhaphy, end-to-end anastomosis, and polytetrafluoroethylene interposition grafts. RESULTS: There was a 42% mortality rate from exsanguination or secondary coagulopathy directly related to the arterial injury. Persistent shock, resuscitative thoracotomy, free intraperitoneal hemorrhage, and the number of vascular injuries were directly related to mortality. CONCLUSIONS: A high index of suspicion, aggressive resuscitation, and prompt surgery are necessary to improve the chances of surviving this ominous injury.

An epidemiologic survey of periodontal disease in Dutch adults.

An epidemiologic survey was carried out to assess the prevalence and severity of periodontal disease in randomly selected samples of employed populations in the Netherlands. Of the 1,337 persons examined by five examiners, 19.8% were edentulous; 61% of dentate persons had intense gingivitis in an average of 2.4 segments of their mouths; 53% had pockets of 3-6 mm and a further 10.1% had pockets of greater than 6 mm. The prevalence of gingivitis and pocketing increased with increasing age and decreasing levels of education. As no measures of predicting compliance were used and because treatment philosophies differ, no reasonable assessment of treatment needs could be made.