Correction to: Influence of oral anticoagulation on success rates and risk of bleeding events after iStent inject implantation combined with phacoemulsification

Graefe's Archive for Clinical and Experimental Ophthalmology - The published online version contains mistake as the author's first name and last name have been interchanged as "Hild...     

DSM-III symptom disorders (Axis I) and personality disorders (Axis II) in an outpatient population

Type and prevalence of Axis I and Axis II disorders (DSM-III) were assessed in a sample of 298 consecutive psychiatric outpatients. The instruments used were SCID and SIDP. About half of the Axis I diagnoses consisted of different subgroups of depression. Most patients had more than one diagnosis, anxiety being the second most common disorder. Eighty one percent of the subjects met the criteria for a personality disorder diagnosis; half of them obtained more than one Axis II diagnosis. Personality disorder was more common among men than among women. Avoidant and dependent personality disorders constituted the most frequent diagnoses.     

Mutation of the surface-exposed amino acid Trp to Ala in the FVIII C2 domain results in defective secretion of the otherwise functional protein

The C2 domain of factor VIII (FVIII) is important for FVIII-phospholipid (PL) and FVIII-von Willebrand factor (VWF) interactions. A FVIII structural model, derived by electron crystallography, suggests four hydrophobic loops at the FVIII C2 domain-PL interface. Within loop four, the solvent-exposed amino acid, Trp(2313), is believed to contribute to FVIII-PL binding. To analyse this interaction, the amino-acid exchange Trp(2313) to Ala (W2313A) was introduced into the C2 domain of B-domain-deleted FVIII (dBFVIII). Both proteins, dBFVIII and W2313A, were expressed in a mammalian expression system. Labelling experiments showed that the mutation W2313A resulted in reduced secretion but did not affect intracellular synthesis of the protein. Specific activity, kinetic parameters, binding to VWF and haemostatic potential in a murine model of haemophilia A were found to be similar for both proteins. Binding studies to synthetic 4% phosphatidyl-l-serine vesicles showed, however, a 28-fold higher K(D) for W2313A, indicating the important role of Trp(2313) in the FVIII-PL interaction. In conclusion, the C2-domain-surface-exposed residue Trp(2313), is critical for secretion of the protein. The W2313A mutation weakens binding to phosphatidyl-l-serine vesicles but the mutant protein has the same effector function as dBFVIII in vitro and in vivo.     

Different inflammatory responses induced by three LDL‐lowering apheresis columns

Low‐density lipoprotein (LDL) apheresis is well‐established in selected patients with uncontrolled LDL levels. As such treatment affects biomarkers important in atherosclerosis and acute coronary syndromes, we systematically compared the inflammatory response induced by three LDL apheresis columns. Three patients with heterozygous familial hypercholesterolemia participated in a cross‐over study with six consecutive treatments with three different LDL apheresis columns: DL‐75 (whole blood adsorption), LA‐15 (plasma adsorption), and EC‐50W (plasma filtration). Biochemical parameters and inflammatory biomarkers, including complement activation products and 27 cytokines, chemokines, and growth factors were measured before and after treatment. Complement was activated through the alternative pathway. The final end product sC5b‐9 increased significantly (P < 0.01) and equally with all devices, whereas the anaphylatoxins C3a and C5a were lower by use of the adsorption columns. Hs‐CRP was reduced by 77% (DL‐75), 72% (LA‐15), and 43% (EC‐50W). The cytokines were consistently either increased (IL‐1ra, IP‐10, MCP‐1), decreased (IFN‐γ, TNF‐α, RANTES, PDGF, VEGF), or hardly changed (including IL‐6, IL8, MIP‐1αβ) during treatment. The changes were in general less pronounced with the adsorption columns. All columns reduced LDL significantly and to the same extent. In conclusion, three LDL‐apheresis devices with equal cholesterol‐lowering effect differed significantly with respect to the inflammatory response. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Current- and voltage-clamp recordings and computer simulations of Kenyon cells in the honeybee

The mushroom body of the insect brain is an important locus for olfactory information processing and associative learning. The present study investigated the biophysical properties of Kenyon cells, which form the mushroom body. Current- and voltage-clamp analyses were performed on cultured Kenyon cells from honeybees. Current-clamp analyses indicated that Kenyon cells did not spike spontaneously in vitro. However, spikes could be elicited by current injection in approximately 85% of the cells. Of the cells that produced spikes during a 1-s depolarizing current pulse, approximately 60% exhibited repetitive spiking, whereas the remaining approximately 40% fired a single spike. Cells that spiked repetitively showed little frequency adaptation. However, spikes consistently became broader and smaller during repetitive activity. Voltage-clamp analyses characterized a fast transient Na+ current (INa), a delayed rectifier K+ current (IK,V), and a fast transient K+ current (IK,A). Using the neurosimulator SNNAP, a Hodgkin-Huxley-type model was developed and used to investigate the roles of the different currents during spiking. The model led to the prediction of a slow transient outward current (IK,ST) that was subsequently identified by reevaluating the voltage-clamp data. Simulations indicated that the primary currents that underlie spiking are INa and IK,V, whereas IK,A and IK,ST primarily determined the responsiveness of the model to stimuli such as constant or oscillatory injections of current.     

Dye-labeled benzodiazepines: development of small ligands for receptor binding studies using fluorescence correlation spectroscopy

To investigate benzodiazepine receptor binding studies by fluorescence correlation spectroscopy (FCS), the four fluorophores fluorescein, tetramethylrhodamine, Oregon Green 488, and Alexa 532 were coupled to the benzodiazepine Ro 07-1986/602 (Ro). Binding assays to polyclonal antibodies to benzodiazepines and at the native benzodiazepine receptor on the membrane of rat hippocampal neurons were established to examine the dye-labeled ligands for their benzodiazepine character and their binding behavior. Both the fluorescein and the Oregon Green488 moiety led to a loss of the benzodiazepine receptor binding of the corresponding Ro derivatives. Antibody recognition and interactions to the receptor were observed for the tetramethylrhodamine derivative (K(D) = 96.0 +/- 9.5 nM) but with a high amount of nonspecific binding at the cell membrane of about 50%. In saturation experiments a K(D) value of 97.2 +/- 8.5 nM was found for the Alexa Fluor 532 derivative-antibody interaction. Investigation of the binding of this ligand to the benzodiazepine receptor in FCS cell measurements led to confirmation of high specific binding behavior with a K(D) value of 9.9 +/- 1.9 nM. A nonspecific binding of <10% was observed after coincubation with 1 microM of midazolam. The different properties of the labeled benzodiazepine derivatives and the requirements of the fluorophore in small dye-labeled ligands in FCS binding studies, at the membrane of living cells, are discussed.     

How does the blood leave the brain? A systematic ultrasound analysis of cerebral venous drainage patterns

The internal jugular veins are considered to be the main pathways of cerebral blood drainage. However, angiographic and anatomical studies show a wide anatomical variability and varying degrees of jugular and non-jugular venous drainage. The study systematically analyses the types and prevalence of human cerebral venous outflow patterns by ultrasound and MRI. Fifty healthy volunteers (21 females; 29 males; mean age 27±7 years) were studied by color-coded duplex sonography. Venous blood volume flow was measured in both internal jugular and vertebral veins in the supine position. Furthermore, the global arterial cerebral blood volume flow was calculated as the sum of volume flows in both internal carotid and vertebral arteries. Three types of venous drainage patterns were defined: a total jugular volume flow of more than 2/3 (type 1), between 1/3 and 2/3 (type 2) and less than 1/3 (type 3) of the global arterial blood flow. 2D TOF MR-venography was performed exemplarily in one subject with type-1 and in two subjects with type-3 drainage. Type-1 drainage was present in 36 subjects (72%), type 2 in 11 subjects (22%) and type 3 in 3 subjects (6%). In the majority of subjects in our study population, the internal jugular veins were indeed the main drainage vessels in the supine body position. However, a predominantly non-jugular drainage pattern was found in approximately 6% of subjects.This study was presented in part as an oral presentation at the 8th Meeting of Neurosonology and Hemodynamics, Alicante, Spain, 18–21 May 2003.