The Effect of Ketoconazole on the Phagocytosis and Intracellular Killing of Candida albicans by Polymorphonuclear Granulocytes

Summary: The synergism between the polymorphonuclear granulocytes and ketoconazole was studied in vitro. The phagocyte index proved to be 87.3 + 8.1. while the Candida killing index was 20.8 + 4.8. Treatment of granulocytes with ketoconazole did not influence their activity. However, the treatment of Candida albicans with ketoconazole led to unchanged phagocytosis, but a significantly higher killer activity. The results indicate that not the immunomodulating effect of the imidazole derivative, but its antimycotic effect, is responsible for the synergism observed between ketoconazole and the host defence mechanisms.
Zusammenfassung: Der Synergismus zwischen polymorphonukleären Granulozyten und Ketoconazol wurde in der vorliegenden Studie in vitro untersucht. Die Bestimmung des Phagozytosenindex ergab einen Wert von 87,3 + 8,1. und beim Candida-Abtötungsindex 20,8 + 4,8. Die Behandlung der Granulozyten mit Ketoconazol ließ die Aktivität dieser Zellen unbeeinflußt. Wird der Candida-Suspension Ketoconazol zugesetzt, beeinflußt es die Phagozytose der Candida-Zellen nicht, sondern erhöht signifikant die candidacide Aktivität. Die Ergebnisse weisen darauf bin, daß der zwischen dem Arzneimittel und dem Abwehrsystem des Wirtes bestehende Synergismus sich nicht aus einem immunomodulierenden Effekt der Imidazol-Derivate erklärt, sondern auf die antimykotische Wirkung von Ketoconazol zurückgeht.     

Über die Furacin-Retinopathie beim Kaninchen

Zusammenfassung Eine neue Substanz zur Erzeugung einer experimentellen Retinopathie beim Kaninchen konnte gefunden werden. Die Veränderungen der Pigmentschicht sowie die im ERG beobachteten Anomalien werden näher beschrieben. Der Vorteil der Methode liegt in ihrer leichten Handhabung, verbunden mit einer konstanten Reproduzierbarkeit innerhalb eines relativ kurzen Zeitraumes.

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On the furacin-retinopathy in rabbits1. Communication

Summary A new substance for provocation of an experimental retinopathy in rabbits could be found. The changes of the pigment layer and the anomalies of the ERG are described in detail. The advantage of the method are the easy application, and a constant reproductivness, within a relatively short time.

     

Effectiveness of resistance training in combination with botulinum toxin-A on hand and arm use in children with cerebral palsy: A pre-post intervention study

ABSTRACT: BACKGROUND: The aim of this study was to investigate effects of additional strength training after use of Botulinum Toxin-A (BoNT-A) in the upper limbs of children with cerebral palsy (CP). METHODS: Ten children with CP (range 9 - 17 years, Manual Ability Classification System II) with unilaterally affected upper limbs were assigned to two intervention groups. One group received BoNT-A treatment (group B), the other BoNT-A plus 8 weeks strength training (group BT). Hand activity was measured with Melbourne assessment of unilateral upper limb function (Melbourne) and Assisting Hand Assessment (AHA). Measures of muscle strength, muscle tone, and active range of motion were used to assess neuromuscular body function. Measurements were performed before and two and five months after intervention start. Change scores and differences between the groups in change scores were statistically tested in SPSS version 18, using Mann-Whitney U test and Wilcoxon Signed Rank test, respectively. RESULTS: Both groups had very small improvements in AHA and Melbourne two months after BoNT-A injections, without differences between groups. There were significant, or close to significant, short-term treatment effects in favour of group BT for muscle strength in injected (elbow flexion strength, p=0.08) and non-injected muscles (elbow extension and supination strength, both p=0.05), without concomitant increases in muscle tone. Active supination range improved in both groups but more so in group BT (p= 0.09). There were no differences between the groups three months after training ended. CONCLUSIONS: Strength training strengthens non-injected muscles temporarily and may reduce short term strength loss that results from BoNT-A injections without increasing muscle tone. Moreover, additional strength training may increase active range of motion to a larger extent than BoNT-A alone. None of the improvements in neuromuscular body functions further improved hand activity. Larger clinical trials are needed to further investigate whether strength training can counteract strength loss caused by BoNT-A, whether the combination of BoNT-A and strength training is superior to BoNT-A or strength training alone in improving active range of motion, and whether more task-related strength training is a more effective approach to improve hand activity.     

White matter alterations in social anxiety disorder

White matter architecture in patients with social anxiety disorder (SAD) has rarely been investigated, but may yield insights with respect to altered structural brain connectivity. Initial evidence points to alterations in the uncinate fasciculus (UF). We applied diffusion tensor imaging in 25 patients with SAD and 25 matched healthy subjects. Whole-brain fractional anisotropy (FA) maps were used for group comparison and voxel-wise correlation with psychometric and clinical measures. Additionally, a region-of-interest analysis of the UF was performed. Patients with SAD had reduced FA compared to healthy subjects in or near the left UF and the left superior longitudinal fasciculus. There were no regions with increased FA in SAD. In the region-of-interest analysis, a negative correlation between FA and trait anxiety was identified in the left and right UF in patients, but not in healthy subjects. No correlations with social anxiety scores were observed. The present study partially confirms previous results pointing to frontal WM alterations in or near the UF in patients with SAD. SAD-specific dimensional associations of FA with trait anxiety might reflect general pathological and/or compensatory mechanisms as a function of symptom severity in patients. Future studies should disentangle in which way the identified WM alterations match functional alterations.     

Everolimus for the treatment of uveitis refractory to cyclosporine A: a pilot study

Background

This study investigated the efficacy of everolimus, a potent inhibitor of T lymphocyte proliferation, for treating noninfectious uveitis. The study design was an open-label prospective trial.

Methods

Twelve patients with severe chronic uveitis (anterior and intermediate n?=?9, panuveitis n?=?3) refractive to cyclosporine A (CsA) received additional everolimus. Main outcome measure: the primary outcome measure was uveitis inactivity at 3 months. Secondary outcome measures were uveitis recurrence, visual acuity (BCVA), laser flare photometry values, cystoid macular edema, and tapering of concomitant corticosteroids and/or immunosuppressive drugs in 12 months with the addition of everolimus and after withdrawing everolimus. Percentages of peripheral blood CD3⁺CD4⁺CD25⁺Foxp3⁺ cells were studied.

Results

At month 3 with everolimus, uveitis was inactive in all patients. By 12 months, uveitis had recurred in four patients after tapering (n?=?2) or withdrawing (n?=?2) CsA. BCVA remained stable in all patients, mean foveal thickness (OCT) was slightly reduced from 308 μm at baseline to 255 μm (p?=?0.1), and mean flare values were slightly reduced from 27.8 to 19.3 photons/msec (p?=?0.1). It was possible to achieve a 50 % dose reduction of systemic prednisone (n?=?8) or CsA (n?=?8). After withdrawing everolimus, uveitis recurred in 50 % within 1 month; by 6 months, BCVA dropped ≥2 lines in five patients, and prednisone use increased ≥50 % in four patients. The percentage of peripheral blood CD3⁺CD4⁺CD25⁺FoxP3⁺ T cells increased during the everolimus treatment, and dropped after withdrawal.

Conclusions

Uveitis inactivity was achieved with the addition of everolimus in patients with chronic, CsA-refractive anterior and intermediate uveitis, or panuveitis.     

Microarray analysis reveals similarity between CD8+CD28- T cells from young and elderly persons, but not of CD8+CD28+ T cells

We isolated highly purified CD8⁺CD28⁺ and CD8⁺CD28⁻ T cell populations from healthy young and elderly persons for gene expression profiling using Affymetrix oligonucleotide microarrays. We demonstrate that the gene expression profile of CD8⁺CD28⁻ T cells is very similar in young and elderly persons. In contrast, CD8⁺CD28⁺ in elderly differ from CD8⁺CD28⁺ in young persons. Hierarchical clustering revealed that CD8⁺CD28⁺ in elderly are located between CD8⁺CD28⁺ in young and CD8⁺CD28⁻ (young and old) T cells regarding their differentiation state. Our study demonstrates a dichotomy of gene expression levels between CD8⁺CD28⁺ T cells in young and elderly persons but a similarity between CD8⁺CD28⁻ T cells in young and elderly persons. As CD8⁺CD28⁺ T cells from elderly and young persons are distinct due to a different composition of the population, these results suggest that the gene expression profile does not depend on chronological age but depends on the differentiation state of the individual cell types.     

Alloimmune and autoimmune background in recurrent pregnancy loss - successful immunotherapy by intravenous immunoglobulin

PROBLEM: Immunotherapies [leukocyte immunization, intravenous immunoglobulin (IVIG)] introduced to treat women with recurrent spontaneous abortions (RSA) have still controversial results in most clinical trials. A selection of these patients would be advantageous for higher efficacy. METHOD OF STUDY: A complex immunological panel assay was offered to patients with reproductive failure without any other known cause. We focused here on the cellular immunological parameters. RESULTS: High cytotoxic T lymphocyte precursor frequency and cell-mediated cytotoxic activity and a rather high natural killer cell activity were found in alloimmune RSA patients. Thirty-two patients were investigated by immunological assays and in 78% of the women an alloimmune background could be defined. The efficacy of IVIG treatment was 96% in this group. CONCLUSIONS: The novel cellular immunological assays proved to be favourable for the indication of RSA patients and showed the usefulness of this selection process for effective immunotherapy.     

Development of thalassaemic iron overload cardiomyopathy despite low liver iron levels and meticulous compliance to desferrioxamine

It is believed that myocardial iron deposition and the resultant cardiomyopathy only occur in the presence of severe liver iron overload. Using cardiovascular magnetic resonance, it is now possible to assess myocardial and liver iron levels as well as cardiac function in the same scan, allowing this supposition to be examined. We describe a patient with progressive myocardial iron deposition and the development of early iron overload cardiomyopathy despite excellent compliance to standard subcutaneous desferrioxamine, minimal liver iron and well-controlled serum ferritin levels. These indirect markers remained far below the thresholds conventionally believed to be associated with increased cardiac risk.     

Effects of a single-lung recruitment maneuver on the systemic release of inflammatory mediators

Objective To study the hypothesis, that systemic levels of pro-inflammatory and anti-inflammatory cytokines may be affected by a single recruitment maneuver in mechanically ventilated patients.Design Prospective, interventional clinical trial.Setting Intensive care unit of a university hospital.Patients Sixteen mechanically ventilated patients with clinical and radiological signs of atelectasis.Interventions A single recruitment maneuver (RM) was performed by elevating the airway pressure to 40 cmH₂O for 7 s.Measurements and main results Plasmatic concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70 and tumor necrosis factor (TNF-α), arterial blood gases and hemodynamic parameters were measured immediately before and 5–360 min after the RM. The RM caused a minor, nevertheless significant improvement of oxygenation (p = 0.02) and carbon dioxide elimination (p = 0.006) as well as a moderate drop of the mean arterial pressure (p = 0.025). In contrast, plasma concentrations remained unaffected by the RM in all six mediators measured.Conclusion A single inflation with an airway pressure of 40 cmH₂O for 7 s improved gas exchange only slightly and did not modify systemic levels of inflammatory mediators in mechanically ventilated patients with radiological evidence of atelectasis.This study was supported by departmental funds