Contribution of head movement to gaze command coding in monkey frontal cortex and superior colliculus

Most of what we know about the neural control of gaze comes from experiments in head-fixed animals, but several "head-free" studies have suggested that fixing the head dramatically alters the apparent gaze command. We directly investigated this issue by quantitatively comparing head-fixed and head-free gaze trajectories evoked by electrically stimulating 52 sites in the superior colliculus (SC) of two monkeys and 23 sites in the supplementary eye fields (SEF) of two other monkeys. We found that head movements made a significant contribution to gaze shifts evoked from both neural structures. In the majority of the stimulated sites, average gaze amplitude was significantly larger and individual gaze trajectories were significantly less convergent in space with the head free to move. Our results are consistent with the hypothesis that head-fixed stimulation only reveals the oculomotor component of the gaze shift, not the true, planned goal of the movement. One implication of this finding is that when comparing stimulation data against popular gaze control models, freeing the head shifts the apparent coding of gaze away from a "spatial code" toward a simpler visual model in the SC and toward an eye-centered or fixed-vector model representation in the SEF.     

Selective recruitment of Th2-type cells and evasion from a cytotoxic immune response mediated by viral macrophage inhibitory protein-II

The viral CC chemokine macrophage inhibitory protein-II (vMIP-II) encoded by human herpes virus 8 (HHV-8) binds to multiple chemokine receptors, however, its ability to control the initial recruitment of specific leukocyte subtypes from the peripheral circulation has not been fully clarified. Here we show that vMIP-II blocks the firm arrest and transmigration of monocytes or Th1-like T lymphocytes triggered by RANTES immobilized on activated human microvascular endothelium (HMVEC) under flow conditions. The internalization of the receptors CCR1 and CCR5 that mediate arrest and transmigration of these cells in response to RANTES was prevented by vMIP-II, supporting its role as an antagonist of CCR1 and CCR5. In contrast, vMIP-II triggered the firm arrest of eosinophils and Th2-like T cells by engaging CCR3, as confirmed by its down-regulation. Immunohistochemical analysis of HHV-8-associated Kaposi's sarcoma lesions marked by vMIP-II expression and mononuclear cell infiltration revealed a predominance of Th2-type CCR3(+) lymphocytes over Th1-type CXCR3(+)/CCR5(+) leukocytes, indicating that as a CCR3 agonist vMIP-II can drive a Th2-type immune response in vivo. Thus, our data provide evidence for a immunomodulatory role of vMIP-II in directing inflammatory cell recruitment away from a Th1-type towards a Th2-type response and thereby facilitating evasion from cytotoxic reactions.     

Three-dimensional eye-head coordination during gaze saccades in the primate

The purpose of this investigation was to describe the neural constraints on three-dimensional (3-D) orientations of the eye in space (Es), head in space (Hs), and eye in head (Eh) during visual fixations in the monkey and the control strategies used to implement these constraints during head-free gaze saccades. Dual scleral search coil signals were used to compute 3-D orientation quaternions, two-dimensional (2-D) direction vectors, and 3-D angular velocity vectors for both the eye and head in three monkeys during the following visual tasks: radial to/from center, repetitive horizontal, nonrepetitive oblique, random (wide 2-D range), and random with pin-hole goggles. Although 2-D gaze direction (of Es) was controlled more tightly than the contributing 2-D Hs and Eh components, the torsional standard deviation of Es was greater (mean 3.55 degrees ) than Hs (3.10 degrees ), which in turn was greater than Eh (1.87 degrees ) during random fixations. Thus the 3-D Es range appeared to be the byproduct of Hs and Eh constraints, resulting in a pseudoplanar Es range that was twisted (in orthogonal coordinates) like the zero torsion range of Fick coordinates. The Hs fixation range was similarly Fick-like, whereas the Eh fixation range was quasiplanar. The latter Eh range was maintained through exquisite saccade/slow phase coordination, i.e., during each head movement, multiple anticipatory saccades drove the eye torsionally out of the planar range such that subsequent slow phases drove the eye back toward the fixation range. The Fick-like Hs constraint was maintained by the following strategies: first, during purely vertical/horizontal movements, the head rotated about constantly oriented axes that closely resembled physical Fick gimbals, i.e., about head-fixed horizontal axes and space-fixed vertical axes, respectively (although in 1 animal, the latter constraint was relaxed during repetitive horizontal movements, allowing for trajectory optimization). However, during large oblique movements, head orientation made transient but dramatic departures from the zero-torsion Fick surface, taking the shortest path between two torsionally eccentric fixation points on the surface. Moreover, in the pin-hole goggle task, the head-orientation range flattened significantly, suggesting a task-dependent default strategy similar to Listing's law. These and previous observations suggest two quasi-independent brain stem circuits: an oculomotor 2-D to 3-D transformation that coordinates anticipatory saccades with slow phases to uphold Listing's law, and a flexible "Fick operator" that selects head motor error; both nested within a dynamic gaze feedback loop.     

Intraoperative treatment of chronic atrial fibrillation with ultrasound

AIM: The purpose of this retrospective study is to evaluate the efficacy of intraoperative atrial compartmentalization utilizing ultrasound (US) energy in selected patients with chronic atrial fibrillation (CAF). METHODS: From March 1999 to June 2000, 27 patients with ages ranging from 15 to 69 (mean 44.62+/-15.61 years), 15 of whom were female, underwent intraoperative atrial compartmentalization with US. Mitral valve replacement was performed in 22 patients, mitral valve repair in 4 and 1 patient with paroxysmal atrial fibrillation (AF) underwent isolated atrial compartmentalization. The compartmentalization procedure was started using an ultrasonic device (UltraCision) at the level of the right atrium on cardiopulmonary bypass (CPB) and with beating heart, and then, after the mitral valve procedure, the ablation-lines were traced in an inverted U-shape, involving the 4 pulmonary veins. All patients were given verapamil or amiodarone for electrical atrial remodeling for 6 months. RESULTS: Time of surgery was 166 min on average, that is approximately 79 min of CPB, 59 min of aortic crossclamping, 12.5 min for right atrial lesion lines and 14 min for the left ones. After weaning CPB, all the patients maintained adequate cardiac output. Immediate reversion to sinus rhythm was achieved in 24 patients (88.8%). A small intraoperative left atrial wall rupture due to the ablation technique was easily repaired by a direct continuous suture. Another complication observed in 1 patient was a sternal instability, which was fixed successfully. Two patients died because of postoperative respiratory failure due to bilateral pneumonia in 1 case and low cardiac output, complicated by septicemia. The pharmacological anti-arrhythmic treatment was stopped 6 months after surgery. During 29 months of follow-up, 20 patients (74%) were still in sinus rhythm. CONCLUSIONS: The use of US during mitral valve operation in patients with CAF allowed for easy and rapid reestablishment of the sinus rhythm. This technique modifies and makes the Maze procedure easier, decreases surgical time and the incidence of postoperative complications.     

Effect of acetylcholine on the release of pancreatic and gastric somatostatin-like immunoreactivity in normal, chemically sympathectomized and indomethacin-treated dogs

The present study was designed to determine the effects of intravenously infused acetylcholine on the release of pancreatic and gastric somatostatin-like immunoreactivity (SLI), in anesthetized normal, chemically sympathectomized and Indomethacin-treated prostaglandin deficient dogs. In normal dogs acetylcholine infusion (500 micrograms/min) elicited a significant rise in pancreatic vein, inferior vena cava, fundic and antral vein SLI levels. In the sympathectomized animals the rise in pancreatic and antral vein SLI was not different from the controls, while the rise in fundic vein SLI was abolished, and inferior vena cava plasma SLI levels were reduced. During Indomethacin-induced prostaglandin deficiency, basal SLI levels were reduced significantly, and the acetylcholine-induced stimulation was completely abolished from both stomach and pancreas. It is concluded that in anesthetized dogs the intravenous infusion of acetylcholine stimulates pancreatic and gastric SLI release, and this stimulatory effect depends on the presence of prostaglandins and is modulated by adrenergic mechanisms.     

Affective disorders in the aftermath of miscarriage: a comprehensive review

We review the research literature regarding affective symptomatology and disorders following miscarriage, with an emphasis on controlled studies and those that have been published since the last review article in 1996. The current review draws a sharp distinction between controlled and uncontrolled designs and clarifies the proper inferences that may be drawn from each, as only with an appropriate comparison group can it be determined whether the affective reactions following miscarriage are a specific consequence of the reproductive loss or of other life events common in women of reproductive age. In addition to providing an update of the literature on depression in the aftermath of miscarriage and associated risk factors, we also discuss reproductive loss in the context of attachment theory and grief, and present information on topics that were not covered extensively (or at all) by prior reviews, such as issues related to a pregnancy subsequent to miscarriage and the impact of miscarriage on the partners of miscarrying women. In the final section, treatment options relevant to miscarriage are presented.     

Interpersonal psychotherapy adapted for the group setting in the treatment of postpartum depression

Interpersonal psychotherapy (IPT) has demonstrated efficacy in the individual treatment of antepartum and postpartum depression. The current investigation extends prior work by examining the efficacy of a group IPT approach for the treatment of postpartum depression. Depression scores of 17 women diagnosed with postpartum depressive disorder (DSM-IV criteria) decreased significantly from pre- to post-treatment. Follow-up assessments at 6 months revealed continuation of the treatment effect. Results indicate that IPT adapted for a group model has positive implications for the treatment of postpartum depression, demonstrating both short-term and longer-term effects in the reduction of depressive symptomatology. Study limitations include the small sample size, absence of control group, possible bias in therapist's assessments, and lack of monitoring adherence, which may have jeopardized the accuracy of the results.     

Effect of histamine H2-receptor stimulation on postprandial pancreatic and gastric endocrine function in dogs

The effect of histamine H2-receptor stimulation via the infusion of impromidine was assessed with regard to postprandial plasma insulin, pancreatic polypeptide (PP), somatostatin, and gastrin levels. The effect of impromidine was assessed in the postprandial state during a liver extract/sucrose test meal which had a buffer capacity to maintain the intragastric pH at a constant level for the time impromidine was infused. Postprandial plasma insulin and gastrin levels were not changed by impromidine (10 micrograms/kg X h-1). Plasma somatostatin levels rose significantly, whereas the postprandial increase of plasma PP levels was attenuated. The effects on somatostatin and PP were antagonized by the infusion of cimetidine, a specific histamine H2-receptor blocker. In conclusion the present data demonstrate that in the postprandial state activation of H2-receptors stimulates somatostatin and inhibits PP release while insulin and gastrin release are not affected.     

Metastasiertes kastrationsresistentes Prostatakarzinom

Background

At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented.

Objectives

The focus is on the clinical impact of these data.

Materials and methods

A group of German experts in the field of urogenital–oncologic expertise discussed the clinical impact with respect to the current data.

Results

The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC.

Conclusions

Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20?mg/m² cabazitaxel.

     

Storage and release of acetylcholine by a clonal cell line.

The nerve cell line PC12, in its morphologically undifferentiated state, synthesizes, stores, and secretes catecholamines and acetylcholine. At least 60% of the basal level of neurotransmitter release is due to a calcium-dependent mechanism, and the rate of secretion is enhanced by increasing external potassium. A minimum of 80% of the intracellular acetylcholine and catecholamines are stored in particulate structures. The storage site for acetylcholine is dense core vesicles that can be distinguished from those containing catecholamines on the basis of vesicle density on sucrose gradients, vesicle size, and reserpine sensitivity. These results are discussed in relation to what are thought to be the early stages of synapse formation in cell culture.