Complications associated with maxillary nerve block anaesthesia via the greater palatine canal

This paper documents the type, frequency and duration of complications associated with regional anaesthesia of the maxillary nerve via the greater palatine canal in a series of 101 patients treated in the Oral Surgery Department, United Dental Hospital of Sydney.     

The different contributions of local luminance decreases and increases to the pattern electroretinogram (PERG).

The typical pattern-onset-offset stimulus (stimulus A) consisting of local luminance increases and decreases was broken down into stimuli presenting only local luminance increases (stimulus B) or only local luminance decreases (stimulus C). With stimulus B the onset ERGs are luminance responses. With stimulus C the onset ERGs are pattern-related responses showing a spatial band-pass function. With stimulus A the response is a linear addition of responses to stimuli B and C. The simultaneously recorded VEP is a pattern-related response with all three stimuli (A-C).     

Combined NGS Approaches Identify Mutations in the Intraflagellar Transport Gene IFT140 in Skeletal Ciliopathies with Early Progressive Kidney Disease

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib‐polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer‐Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer‐Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end‐stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono‐renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy.     

Therapeutic Drug Monitoring of Venlafaxine in an Everyday Clinical Setting: Analysis of Age,Sex and Dose Concentration Relationships

Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of venlafaxine, by patient age and sex. From a therapeutic drug monitoring (TDM) database located at Odense University Hospital, Denmark, we identified all adults for whom the treating physician had requested clinical advice on the TDM result for venlafaxine between 2002 and 2012. We identified 1077 TDM samples of venlafaxine from 334 males and 743 females (median age 45 years), and the median daily dose was 225 mg. Median plasma concentration of venlafaxine and o‐desmethylvenlafaxine (ODV) was 306 nmol/L and 861 nmol/L, respectively. The median dose‐corrected serum level for venlafaxine was 1.49 nmol/L/mg., while the dose‐corrected serum level of men and women were 1.21 nmol/L/mg and 1.60 nmol/L/mg, respectively. The dose‐corrected sum of venlafaxine and ODV was 8.91 nmol/L/mg (IQR 6.56–12.26) versus 5.52 nmol/L/mg (IQR 4.16–7.52) for patients above 64 years and below the age of 65 years, respectively. Dose‐corrected plasma concentrations of venlafaxine and ODV are increased to a clinically significant degree in patients above the age of 64, and initiation of venlafaxine therapy in the elderly should be made cautiously and supported by drug measurements.     

The effect of activated protein C on plasma cytokine levels in a porcine model of acute endotoxemia

Objective To assess the anti-inflammatory effects of recombinant human activated protein C (rhAPC) in a porcine model of acute endotoxemia. Design and setting Animal randomized controlled study at the Laboratory of Clinical Institute, Aarhus University Hospital. Subjects Eighteen female landrace pigs (30 kg). Interventions By pairwise randomization, pigs were given either LPS or LPS and rhAPC. Both groups received a stepwise increasing LPS infusion for 30 min; whereafter the infusion continued at a lower rate (300 min LPS in both groups). The LPS+rhAPC group received rhAPC (100 μg/kg per hour) 15 min before the LPS infusion began and throughout the trial period. Results While rhAPC showed no modifying effects on peak plasma levels of pro- or anti-inflammatory cytokines (TNF-α, IL-6, IL-8, IL-10), TNF-α and IL-10 peaked significantly later in the rhAPC-treated animals. The profibrinolytic effects of rhAPC were confirmed by decreased plasminogen activator inhibitor 1 levels, while no differences were found in other coagulation markers, hemodynamic, metabolic, or leukocyte data between the two groups. Conclusions We found no significant effect of rhAPC on plasma levels of either pro- or anti-inflammatory cytokines in this porcine model of acute endotoxemia. However, TNF-α and IL-10 peaked significantly later in the rhAPC-treated animals.     

Target spectrum of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib

Following the initial success of imatinib as frontline therapy for chronic myeloid leukemia (CML), several second-generation therapeutics have been developed with increased potency and the ability to inhibit the majority of imatinib-resistant mutations. Here, we review the current knowledge about the target specificity of the two new inhibitors nilotinib and dasatinib in comparison to imatinib, including the recent large-scale chemical proteomics screens.