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Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening sideeffect that can occur in response to treatment with antipsychotic drugs. Symptoms commonly include hyperpyrexia, muscle rigidity, autonomic dysfunction and altered mental status. In the current review we provide an overview on past and current developments in understanding the causes and treatment of NMS. Studies on the epidemiological incidence of NMS are evaluated, and we provide new data from the Canada Vigilance Adverse Reaction Online database to elaborate on drug-specific and antipsychotic drug polypharmacy instances of NMS reported between 1965 and 2012. Established risk factors are summarized with an emphasis on pharmacological and environmental causes. Leading theories about the etiopathology of NMS are discussed, including the potential contribution of the impact of dopamine receptor blockade and musculoskeletal fiber toxicity. A clinical perspective is provided whereby the clinical presentation and phenomenology of NMS is detailed, while the diagnosis of NMS and its differential is expounded. Current therapeutic strategies are outlined and the role for both pharmacological and non-pharmacological treatment strategies in alleviating the symptoms of NMS are discussed.

Purpose: The objective of this review is to evaluate the literature on medications associated with delirium after cardiac surgery and potential prophylactic agents for preventing it. Source: Articles were searched in MEDLINE, Cumulative Index to Nursing and Allied Health, and EMBASE with the MeSH headings: delirium, cardiac surgical procedures, and risk factors, and the keywords: delirium, cardiac surgery, risk factors, and drugs. Principle inclusion criteria include having patient samples receiving cardiac procedures on cardiopulmonary bypass, and using DSM-IV-TR criteria or a standardized tool for the diagnosis of delirium. Principal Findings: Fifteen studies were reviewed. Two single drugs (intraoperative fentanyl and ketamine), and two classes of drugs (preoperative antipsychotics and postoperative inotropes) were identified in the literature as being independently associated with delirium after cardiac surgery. Another seven classes of drugs (preoperative antihypertensives, anticholinergics, antidepressants, benzodiazepines, opioids, and statins, and postoperative opioids) and three single drugs (intraoperative diazepam, and postoperative dexmedetomidine and rivastigmine) have mixed findings. One drug (risperidone) has been shown to prevent delirium when taken immediately upon awakening from cardiac surgery. None of these findings was replicated in the studies reviewed. Conclusion: These studies have shown that drugs taken perioperatively by cardiac surgery patients need to be considered in delirium risk management strategies. While medications with direct neurological actions are clearly important, this review has shown that specific cardiovascular drugs may also require attention. Future studies that are methodologically consistent are required to further validate these findings and improve their utility.

Caenorhabditis elegans is a powerful model to study the molecular basis of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is caused by mutations in the polycystic kidney disease (PKD)1 or PKD2 gene, encoding polycystin (PC)-1 or PC-2, respectively. The C. elegans polycystins LOV-1 and PKD-2 are required for male mating behaviors and are localized to sensory cilia. The function of the evolutionarily conserved polycystin/lipoxygenase/alpha-toxin (PLAT) domain found in all PC-1 family members remains an enigma. Here, we report that ATP-2, the beta subunit of the ATP synthase, physically associates with the LOV-1 PLAT domain and that this interaction is evolutionarily conserved. In addition to the expected mitochondria localization, ATP-2 and other ATP synthase components colocalize with LOV-1 and PKD-2 in cilia. Disrupting the function of the ATP synthase or overexpression of atp-2 results in a male mating behavior defect. We further show that atp-2, lov-1, and pkd-2 act in the same molecular pathway. We propose that the ciliary localized ATP synthase may play a previously unsuspected role in polycystin signaling.

Model organisms have been used over a century to understand basic, conserved biological processes. The study of these experimental systems began with genetics and development, moved into molecular and cellular biology, and most recently propelled into functional genomics and proteomics. The goal of this review is simple: to discuss the place of model organisms in "The Age of the Ome": the genome, the transcriptome, and the proteome. This review will address the following questions. What exactly is a model organism? What characteristics make an excellent model system? Using the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans as examples, this review will discuss these issues with the aim of demonstrating how model organisms remain indispensable scientific tools for understanding complex biological pathways and human disease.

The use of trifluoroperazine in a well washed rat brain membrane preparation revealed [(3)H]ifenprodil binding to a single high affinity state with the pharmacology of N-methyl-D-aspartate (NMDA) receptors containing NR2B subunits. Inhibition of [(3)H]ifenprodil binding in the presence of trifluoroperazine by 10 NR1a/NR2B selective agents was highly correlated with their inhibition at rat NR1a/NR2B receptors expressed in Xenopus ooctyes and [(3)H]TCP binding to rat brain NR2B subunit containing NMDA receptors but not with their inhibition of [(3)H]DTG binding. Allosteric interactions with polyamines, Mg(2+), Zn(2+), glutamate, glycine, and their antagonists were consistent with NMDA receptors with NR2B subtype pharmacology. The rank order of polyamine inhibition was spermine > spermidine > 1,5-(diethylamino)piperidine > arcaine > agmatine > putrescine. Both spermidine and MgCl(2) shifted the inhibition curve of ifenprodil to the right in a parallel manner, but Mg(2+) did not appear to be additive to spermidine. Glutamate increased and glycine decreased the binding. Conversely, CPP decreased the binding, and MDL 105,519 increased the binding in an agonist reversible manner. The increase with MDL 105,519 and glutamate appeared to be additive as did the decrease with glycine and CPP. Changes in the buffer pH between 6.5 and 8.0 did not affect the affinity of NR2B agents. Cirazoline but not clonidine inhibited the binding. MK-801 and agents from various other pharmacological classes did not significantly inhibit [(3)H]ifenprodil binding. [(3)H]Ifenprodil binding in the presence of trifluoroperazine appears to be selective for the voltage-independent ifenprodil site on NMDA receptors containing the NR2B subunit.

OBJECTIVE: To compare the findings in dizzy elderly people with those in controls of a similar age to identify which investigations differentiate dizzy from non-dizzy patients and to design an investigational algorithm. DESIGN: Community based study of clinical and laboratory findings in dizzy and control elderly people. SETTING: Research outpatient clinic at a teaching hospital. SUBJECTS: 149 dizzy and 97 control subjects aged over 65 years recruited from a community survey and articles in the local press. MAIN OUTCOME MEASURES: Findings on physical examination, blood testing, electrocardiography (at rest and over 24 hours), electronystagmography, posturography, and magnetic resonance imaging of head and neck (125 (84%) dizzy subjects and 86 (89%) controls); hospital anxiety and depression score; responses to hyperventilation, carotid sinus massage, and the Hallpike manoeuvre. RESULTS: Blood profile, electrocardiography, electronystagmography, and magnetic resonance imaging failed to distinguish dizzy from control subjects because of the frequency of asymptomatic abnormalities in controls. Posturography and clinical assessment (physical examination, dizziness provocation, and psychological assessment) showed significant differences between the groups. A cause of the dizziness was identified from clinical diagnostic criteria based on accepted definitions in 143 subjects, with 126 having more than one cause. The most common diagnoses were central vascular disease (105) and cervical spondylosis (98), often accompanied by poor vision and anxiety. CONCLUSION: Expensive investigations are rarely helpful in dizzy elderly people. The cause of the dizziness can be diagnosed in most cases on the basis of a thorough clinical examination without recourse to hospital referral.

Focuses on a novel two-stage injection unit for plastic molding developed by Ferromatik Milacron. Photograph of the equipment; Shot capacity; Rationale for the use of two-stage injection.