Intranasal orexin A modulates sympathetic vascular tone: a pilot study in healthy male humans.

Previous research suggests that the neuropeptide orexin A contributes to sympathetic blood pressure (BP) control inasmuch as hypothalamic injection of orexin A increases sympathetic vasomotor tone and arterial BP in rodents. In humans with narcolepsy, a disorder associated with loss of orexin-producing neurons, vasoconstrictive muscle sympathetic nerve activity (MSNA) is reduced. Since intranasally administered oligopeptides like orexin are known to modulate brain function, we investigated the effect of intranasal orexin A on vascular sympathetic baroreflex function in healthy humans. In a balanced, double-blind crossover study, orexin A (500 nmol) and placebo, respectively, were intranasally administered to 10 lean healthy males (age 25.8 ± 4.6 yr). MSNA was assessed microneurographically before and 30-45 min after either substance administration. Additionally, baroreflex was challenged via graded infusions of vasoactive drugs before and after substance administration. Baroreflex function was defined as the correlation of BP with MSNA and heart rate. Intranasal orexin A compared with placebo induced a significant increase in resting MSNA from pre-to postadministration [Δburst rate, orexin A vs. placebo: +5.8 ± 0.8 vs. +2.1 ± 0.6 bursts/min, P = 0.007; total activity 169 ± 11.5% vs. 115 ± 5.0%; P = 0.002]. BP, heart rate, and sympathovagal balance to the heart, as represented by heart rate variability (HRV), as well as baroreflex sensitivity during the vasoactive challenge were not altered. Intranasally administered orexin A acutely induced vasoconstrictory sympathoactivation in healthy male humans. This result suggests that orexin A mediates upward resetting of the vascular baroreflex set point at centers superordinate to the mere baroreflex feedback loop.NEW & NOTEWORTHY Our pilot study adds another important part to the complex network of neuroendocrine-sympathetic interaction. Our results demonstrate that intranasal orexin A elicits an excitatory effect on sympathetic vascular tone superordinate to mere baroreflex feedback regulation. This resetting of the baroreflex set point suggests an activation of hypothalamic core centers such as the paraventricular nucleus (PVN). The role of the orexinergic system in the development of neurogenic arterial hypertension warrants further investigations.

Intranasal oxytocin has sympathoexcitatory effects on vascular tone in healthy males.

Oxytocin appears to be involved in the neuroendocrine regulation of sympathetic blood pressure (BP) homeostasis. In animals, intracerebral administration of oxytocin induces BP-relevant sympathetic activation. In humans, central nervous effects of oxytocin on BP regulation remain unclear. Intranasal administration supposedly delivers oligopeptides such as oxytocin directly to the brain. We investigated the effects of intranasal oxytocin on sympathetic vascular baroreflex function in humans using microneurographic techniques. In a balanced, double-blind crossover design, oxytocin or placebo was administered intranasally to 12 lean, healthy males (age 25 ± 4 yr). Muscle sympathetic nerve activity (MSNA) was assessed microneurographically before (presubstance), 30-45 min (postsubstance I), and 105-120 min (postsubstance II) after oxytocin administration. Baroreflex was challenged via graded infusions of vasoactive drugs, and correlation of BP with MSNA and heart rate (HR) defined baroreflex function. Experiments were conducted in the afternoon after a 5-h fasting period. After oxytocin, resting MSNA (burst rate and total activity) showed significant net increases from pre to postsubstance II compared with placebo [Δincrease = +4.3 ± 1.2 (oxytocin) vs. +2.2 ± 1.4 bursts/min (placebo), ANOVA; P < 0.05; total activity = 184 ± 11.5% (oxytocin) vs. 121 ± 14.3% (placebo), ANOVA; P = 0.01). This was combined with a small but significant net increase in resting diastolic BP, whereas systolic and mean arterial BP or HR as well as baroreflex sensitivity at vasoactive drug challenge were not altered. Intranasally administered oxytocin induced vasoconstrictory sympathoactivation in healthy male humans. The concomitant increase of diastolic BP was most likely attributable to increased vascular tone. This suggests oxytocin-mediated upward resetting of the vascular baroreflex set point at centers superordinate to the mere baroreflex-feedback loop.

An economic analysis of preimplantation genetic testing for aneuploidy by polar body biopsy in advanced maternal age.

OBJECTIVE: What are the cost per live birth and the incremental cost of preventing a miscarriage with preimplantation genetic testing for aneuploidy (PGT-A) by polar body biopsy and array-based comprehensive genome hybridisation (aCGH) versus regular IVF/ICSI without PGT-A for infertility treatment in women 36-40 years of age? DESIGN: Decision tree model. POPULATION: A randomised clinical trial on PGT-A (ESTEEM study). METHODS: Two treatment strategies were compared: one cycle of IVF/ICSI with or without PGT-A. Costs and effects were analysed with this model for four different cost scenarios: high-, higher medium, lower medium and low-cost. Base case, sensitivity, threshold, and probabilistic sensitivity analyses were used to examine the cost-effectiveness implications of PGT-A. RESULTS: PGT-A increased the cost per live birth by approximately 15% in the high-cost scenario to approximately 285% in the low-cost scenario. Threshold analysis revealed that PGT-A would need to be associated with an absolute increase in pregnancy rate by 6% to >39% or, alternatively, would need to be US$2,969 (high-cost scenario) to US$4,888 (low-cost scenario) cheaper. The incremental cost to prevent one miscarriage by PGT-A using the base case assumptions was calculated to be US$34,427 (high-cost scenario) to US$51,146 (low-cost scenario). A probabilistic sensitivity analysis showed cost-effectiveness for PGT-A from 1.9% (high-cost scenario) to 0.0% (low-cost scenario) of calculated samples. CONCLUSIONS: While avoiding unnecessary embryo transfers and miscarriages are important goals, patients and doctors need to be aware of the high-cost implications of applying PGT-A using aCGH on polar bodies. TWEETABLE ABSTRACT: PGT-A by polar body biopsy and comprehensive genome hybridisation increases cost per live birth and requires high financial spending per miscarriage averted.

Decline of lactate in tumor tissue after ketogenic diet: in vivo microdialysis study in patients with head and neck cancer.

In head and neck squamous cell carcinoma (HNSCC) aerobic glycolysis is the key feature for energy supply of the tumor. Quantitative microdialysis (µD) offers an online method to measure parameters of the carbohydrate metabolism in vivo. The aim was to standardize a quantitative µD-study in patients with HNSCC and to prove if a ketogenic diet would differently influence the carbohydrate metabolism of the tumor tissue. Commercially available 100 kDa-CMA71-µD- catheters were implanted in tumor-free and in tumor tissue in patients with HNSCC for simultaneous measurements up to 5 days. The metabolic pattern and circadian rhythm of urea, glucose, lactate, and pyruvate was monitored during 24 h of western diet and subsequent up to 4 days of ketogenic diet. After 3 days of ketogenic diet the mean lactate concentration declines to a greater extent in the tumor tissue than in the tumor-free mucosa, whereas the mean glucose and pyruvate concentrations rise. The in vivo glucose metabolism of the tumor tissue is clearly influenced by nutrition. The decline of mean lactate concentration in the tumor tissue after ketogenic diet supports the hypothesis that HNSCC tumor cells might use lactate as fuel for oxidative glucose metabolism.

Treatment of chronic tinnitus with θ burst stimulation: a randomized controlled trial.

OBJECTIVE: To test whether 4 weeks of bilateral repetitive transcranial magnetic stimulation (rTMS) to the temporal or temporoparietal cortex is effective and safe in the treatment of chronic tinnitus. METHODS: In this controlled 3-armed trial, 48 patients with chronic tinnitus were treated with 4 weeks (20 sessions) of bilateral continuous theta burst stimulation (cTBS) at the Tübingen University Hospital. They were randomized to stimulation above the temporal cortex, the temporoparietal cortex, or as sham condition behind the mastoid. Patients were masked for the stimulation condition. Tinnitus severity was assessed after 2 and primarily 4 weeks of treatment and at 3 months follow-up with the tinnitus questionnaire and by a tinnitus change score. Audiologic safety was monitored by pure-tone and speech audiometry after 2 and 4 weeks of cTBS. RESULTS: Tinnitus severity was slightly reduced from baseline by a mean (SD) 2.6 (8.2) after sham, 2.4 (8.0) after temporoparietal, 2.2 (8.3) after temporal treatment of 16 patients each, but there was no significant difference between sham treatments and temporal (confidence interval [CI] -5.4 to +6.7) or temporoparietal cTBS (CI -5.9 to +6.3) or real cTBS (CI -7 to +5.1). Patients' global evaluation of tinnitus change after treatment did not indicate any effects. Audiologic measures were unaffected by treatment. CONCLUSIONS: Treating chronic tinnitus for 4 weeks by applying cTBS to the temporal or temporoparietal cortex of both hemispheres appears to be safe but not more effective than sham stimulation. However, these results are not to be generalized to all forms of rTMS treatments for tinnitus.

[Clinical trials with medical devices: lack of quality illustrated for faecal incontinence]. / Therapiestudien mit Medizinprodukten: Mangelnde Qualität illustriert anhand analer Inkontinenz.

BACKGROUND: Medical devices must be safe and functioning states the law. Treatments with medical devices need not be efficacious to be allowed. We investigated special requirements and problems arising from the law. METHODS: The market for medical devices is contrasted with that for drugs. The requirements of relevant laws are discussed. Finally, published clinical studies on anal incontinence are analysed with respect to their methodological quality. RESULTS: Clinical trials of medical devices for treat-ing anal incontinence are of poor methodological quality thus preventing evaluation of the devices' utility. CONCLUSION: Large, high quality clinical studies of the efficacy of medical devices for treating anal incontinence are urgently needed. Only such studies enable health technology assessment and comprehensible decisions on reimbursement by health insurance.

[Fluorescence diagnosis in patients with non-muscle invasive bladder cancer: results of a metaanalysis]. / Fluoreszenzdiagnostik bei Patienten mit nicht muskelinvasivem Harnblasenkarzinom: Ergebnisse einer Metaanalyse.

PURPOSE: Heterogeneous results of single studies with photodynamic diagnosis (PDD) in bladder cancer have been reported. A metaanalysis of prospective studies has now been performed. MATERIAL AND METHODS: The effect of PDD in addition to WLC on a) the diagnosis and b) the therapeutic outcome of primary or recurrent non-muscle invasive bladder cancer (NMIBC) investigated by cystoscopy or transurethral resection was analysed. An electronic database search was performed. Trials were included if they prospectively compared WLC with PDD in bladder cancer. Primary endpoints were additional detection rate, residual tumour at second resection and recurrence-free survival. RESULTS: Significantly more tumour-positive patients were detected with PDD in all patients with non-muscle invasive tumours (= 20 %) [95 % confidence interval (CI): 8 to 35 %] and in CIS patients (= 39 %) (CI: 23 to 57 %). Residual tumour was significantly less often found after PDD (odds ratio 0.28, CI: 0.15 to 0.52, p < 0.0001). Recurrence-free survival was significantly higher at 12 and 24 months in the PDD groups than in WLC only groups. CONCLUSIONS: More bladder tumour-positive patients are detected by PDD. Best results were found in CIS patients. Diagnosis with PDD results in a more complete resection and a longer recurrence-free survival.

[Relapse rate within 6 months after successful ECT: a naturalistic prospective peer- and self-assessment analysis]. / Rückfallraten innerhalb von 6 Monaten nach erfolgreicher EKT--Eine naturalistische prospektive Fremd- und Selbstbeurteilungsanalyse.

BACKGROUND: Up to 100% relapse rate after successful electroconvulsive therapy (ECT) poses a challenge for patients and psychiatrists. The aim of the study was to evaluate the outcome of patients affected by major depression after the successful course of acute ECT. METHODS: 84 patients recruited in a randomized double blind multicenter study designed to investigate the optimal stimulation placement in acute ECT had a follow up under naturalistic conditions between the 5th and 7th month. Outcome, maintenance therapy and patients; attitude were evaluated with semi structured questionnaires by patients and the study raters. RESULTS: 82.14% (68/84) questionnaires of the patients and 83.3% (70/84) of the rater were returned. 98% of the patients had at least one antidepressant; only in 23% (20/68) lithium was prescribed. 35% (7/20) of the patients with lithium and 57% (16/28) without lithium had a relapse within the first 6 months (OR 0.6) in a median of 2.5 months. Only one institution offered maintenance ECT in 8.3% (7/84) patients. For 52.2% of the patients ECT was a helpful treatment an 49.3% would recommend the therapy to their relatives. The vast majority (59.4%) wishes a better information about the ECT and 21.4% feel frightening about the therapy. CONCLUSIONS: The results show a high relapse rate and highlight the meaning of maintenance medication especially for a lithium combination therapy, as stated before. In regard to the subjective sensation the patients claim a better education about the ECT and anyway one of four patients feel frightening about the therapy.

A mathematical description of nerve fiber bundle trajectories and their variability in the human retina.

We developed a mathematical model wherein retinal nerve fiber trajectories can be described and the corresponding inter-subject variability analyzed. The model was based on traced nerve fiber bundle trajectories extracted from 55 fundus photographs of 55 human subjects. The model resembled the typical retinal nerve fiber layer course within 20 degrees eccentricity. Depending on the location of the visual field test point, the standard deviation of the calculated corresponding angular location at the optic nerve head circumference ranged from less than 1 degrees to 18 degrees , with an average of 8.8 degrees .

Audit of motor weakness and premature catheter dislodgement after epidural analgesia in major abdominal surgery.

In a quality improvement audit on epidural analgesia in 300 patients after major abdominal surgery, we identified postoperative lower leg weakness and premature catheter dislodgement as the most frequent causes of premature discontinuation of postoperative epidural infusion. Lower limb motor weakness occurred in more than half of the patients with lumbar epidural analgesia. In a second period monitoring 177 patients, lumbar catheter insertion was abandoned in favour of exclusive thoracic placement for epidural catheters. Additionally, to prevent outward movement, the catheters were inserted deeper into the epidural space (mean (SD) 5.2 (1.5) cm in Period Two vs 4.6 (1.3) cm in Period One). Lower leg motor weakness declined from 14.7% to 5.1% (odds ratio 0.35; 95% confidence interval 0.16-0.74) between the two periods. Similarly, the frequency of premature catheter dislodgement was reduced from 14.5% to 5.7% (odds ratio 0.35; 95% confidence interval 0.17-0.72). With a stepwise logistic regression model we demonstrated that the odds of premature catheter dislodgement was reduced by 43% for each centimetre of additional catheter advancement in Period Two. We conclude that careful audit of specific complications can usefully guide changes in practice that improve success of epidural analgesia regimens.

IL-6 receptor, IL-8 receptor and TNF-alpha238 (G/A) polymorphisms are not associated with Behçet's disease in patients of German or Turkish origin.

OBJECTIVE: To assess the association of polymorphisms of the IL-6 receptor gene (+24013A/G:Ala31Ala; +48892 A/C:Asp358Ala), the IL-8 receptor gene (+2607G/C:Ser/Thr IL-8RA), and TNF-alpha 238 (G/A) single nucleotide polymorphism (SNP) with Behçet's disease in patients of German or Turkish origin. METHODS: DNA was extracted from blood samples taken from patients in Germany (n=93) and Turkey (n=28), as well as from 51 German and 20 Turkish healthy controls. The polymorphisms were analysed by PCR with the LightCycler system. RESULTS: No significant association was found between TNF-alpha 238, +2607 IL-8RA, +48892 IL-6R or +24013 IL-6R- polymorphisms and nationality or disease. Statistically there was no difference between the patients and controls (TNF-alpha 238: p = 0.86; +2607 IL-8RA: p=0.23; +48892 IL-6R: p=0.087; +24013 IL-6R: p = 0.80) nor between Germans and Turks (TNF-alpha 238: p=0.13; +2607 IL-8RA: p=0.68; +48892 IL-6R: p=0.32; +24013 IL-6R: p=0.65). CONCLUSION: The single nucleotide polymorphisms of the IL-6 and IL-8 receptor genes and the TNF-alpha gene analysed here do not appear to be associated with Behçet's disease.

[Automated pulmonary nodule volumetry with an optimized algorithm. Accuracy at different slice thicknesses compared to unidimensional and bidimensional measurements]. / Lungenrundherdvolumetrie mit optimiertem Segmentierungsalgorithmus. Genauigkeit bei verschiedenen Schichtdicken verglichen mit ein- und zweidimensionalen Messungen.

PURPOSE: This in-vivo study quantifies the accuracy of automated pulmonary nodule volumetry in reconstructions with different slice thicknesses (ST) of clinical routine CT scans. The accuracy of volumetry is compared to that of unidimensional and bidimensional measurements. MATERIALS AND METHODS: 28 patients underwent contrast enhanced 64-row CT scans of the chest and abdomen obtained in the clinical routine. All scans were reconstructed with 1, 3, and 5 mm ST. Volume, maximum axial diameter, and areas following the guidelines of Response Evaluation Criteria in Solid Tumors (RECIST) and the World Health Organization (WHO) were measured in all 101 lesions located in the overlap region of both scans using the new software tool OncoTreat (MeVis, Deutschland). The accuracy of quantifications in both scans was evaluated using the Bland and Altmann method. The reproducibility of measurements in dependence on the ST was compared using the likelihood ratio Chi-squared test. RESULTS: A total of 101 nodules were identified in all patients. Segmentation was considered successful in 88.1% of the cases without local manual correction which was deliberately not employed in this study. For 80 nodules all 6 measurements were successful. These were statistically evaluated. The volumes were in the range 0.1 to 15.6 ml. Of all 80 lesions, 34 (42%) had direct contact to the pleura parietalis oder diaphragmalis and were termed parapleural, 32 (40%) were paravascular, 7 (9%) both parapleural and paravascular, the remaining 21 (27%) were free standing in the lung. The trueness differed significantly (Chi-square 7.22, p value 0.027) and was best with an ST of 3 mm and worst at 5 mm. Differences in precision were not significant (Chi-square 5.20, p value 0.074). The limits of agreement for an ST of 3 mm were +/- 17.5 % of the mean volume for volumetry, for maximum diameters +/- 1.3 mm, and +/- 31.8 % for the calculated areas. CONCLUSION: Automated volumetry of pulmonary nodules using OncoTREAT has a conformable accuracy for an ST of 3 mm and 1 mm and is even more accurate for an ST of 5 mm than unidimensional or bidimensional measurements. A difference of more than +/- 17.5% occurs with a probability of less than 5% at an ST of 3 mm.

The use of semi-automated kinetic perimetry (SKP) to monitor advanced glaucomatous visual field loss.

PURPOSE: (i) To compare visual field (VF) results obtained with semi-automated kinetic perimetry (SKP) and automated static perimetry (ASP) in patients with advanced glaucomatous VF loss, (ii) to evaluate test-retest reliability of SKP and ASP and (iii) to assess patients' preference for SKP and ASP. METHODS: Twenty eyes of 20 patients (11 male, 9 female, aged 38 to 83 years) with advanced glaucomatous VF loss (stage III or IV according to the Aulhorn classification). Each of the 20 patients were examined in 4 sessions every 3 months with SKP (Goldmann stimulus III4e, I4e and at least one additional dimmer stimulus, within the 90 degrees visual field) and ASP within the 30 degrees VF, employing a threshold-related, supra-threshold test strategy with high spatial resolution for the same instrument (Octopus 101 perimeter, Haag-Streit Inc., Koeniz, Switzerland). RESULTS: Visual field areas (VFA) were compared by analyses of covariance (ANCOVA) with co-variable time, patient effect and their interaction. Test-retest reliability was assessed by ratios (R) of intersection and union of VFA: The mean VFA within the 30 degrees of VF at baseline was 2,344 square degrees (deg(2)) with SKP (Goldmann stimulus III4e) and 1,844 deg(2) with ASP. The patients showed stable visual fields for both SKP and ASP. Comparison of SKP with ASP of the same sessions revealed a median ratio of intersection and union of VFA of 0.78 with the III4e stimulus and of 0.79 with the I4e stimulus. When follow-up SKPs were compared with baseline SKPs the median of the ratios was between 0.80 and 0.93 for the different isopters. The corresponding ratio of ASP's follow-up and baseline VFs was 0.81 (with the size III static stimulus). Nineteen of 20 patients preferred kinetic perimetry to static perimetry. CONCLUSIONS: The comparability between SKP and ASP is satisfactory and within the range of the test-retest reliability of ASP. SKP shows slightly better test-retest reliability than ASP. The majority of patients with advanced glaucomatous visual field loss prefer SKP instead of ASP. SKP is a valuable alternative to ASP in monitoring advanced glaucomatous visual field loss.

Hyperattenuating bone marrow abnormalities in myeloma patients using whole-body non-enhanced low-dose MDCT: correlation with haematological parameters.

We aimed to establish the role of hyperattenuating medullary abnormalities detected by whole-body non-enhanced low-dose multidetector CT (WBLD-MDCT) in multiple myeloma (MM) patients referred for primary evaluation. 50 consecutive patients with untreated Stage I (n(I) = 11), Stage II (n(II) = 10) and Stage III (n(III) = 29) MM underwent WBLD-MDCT for staging. The number and size of osteolysis, as well as haematologic parameters including paraprotein and beta2-microglobulin levels, were assessed and related to the number, size and density of medullary abnormalities assumed to represent myeloma involvement. Bone marrow abnormalities were found in 2/11 (18%) Stage I, 6/10 (60%) Stage II and 20/29 (69%) Stage III myeloma patients, and did not parallel the incidence of osteolysis. Patients with medullary lesions had higher levels of immunoglobulin A (median, 4730 mg dl(-1) vs 1520 mg dl(-1)), light-chain proteinuria (median, 690 mg dl(-1) vs 214 mg dl(-1)) and IgG paraprotein (median, 3270 mg dl(-1) vs 2610 mg dl(-1)) compared with patients without medullary lesions. In patients with medullary abnormalities, levels of serum beta2-microglobulin were significantly higher than in patients without detectable marrow infiltrates (median, 4.3 mg dl(-1) vs 2.4 mg dl(-1); p = 0.0015). In conclusion, medullary abnormalities visualized by WBLD-MDCT are encountered in all stages of myeloma, including cases without osteolysis. They are associated with significantly elevated serum levels of paraprotein (reflecting tumour mass) and beta2-microglobulin, a prospective prognostic marker for myeloma. The nature and possible prognostic significance of medullary abnormalities detected by WBLD-MDCT therefore warrants further investigation.

The pupillary light reflex pathway: cytoarchitectonic probabilistic maps in hemianopic patients.

OBJECTIVE: The anatomy of the human pupillary light reflex (PLR) pathway is a matter of debate. The aim of this study was twofold: namely, to investigate the association of a relative afferent pupillary defect (RAPD) in acquired suprageniculate lesions with the location and extent of the cerebral lesions. Further, we suggest a new strategy of lesion analysis by combining established techniques with the stereotaxic probabilistic cytoarchitectonic atlas developed by the Jülich group. METHODS: Twenty-three patients with homonymous visual field defects participated in this study. The RAPD was quantified clinically by two independent examiners with graded neutral density filters (swinging flashlight test). Using MRI in each individual, cerebral regions commonly affected in patients with a RAPD but spared in patients without a RAPD were determined and subsequently assessed by using cytoarchitectonic probabilistic maps. RESULTS: A RAPD was present in 10/23 patients. Comparison of patients showing a RAPD vs those not showing a RAPD revealed that a region including the course of the optic radiation at its early beginning in the temporal white matter is commonly associated with a RAPD. CONCLUSIONS: It was demonstrated that the pupillary light reflex (PLR) depends on the input of suprageniculate neurons, thus supporting the involvement of a cortical pathway also. The site of integration of cortical signals in relation to the PLR into the pupillomotor pathway may be located suprageniculately in the vicinity of the lateral geniculate nucleus. Moreover, the suggested combination of established lesion analysis techniques with the probabilistic cytoarchitectonic atlas turned out to be a very helpful amelioration of stroke data analyses.

Visual field defects in acute optic neuritis--distribution of different types of defect pattern, assessed with threshold-related supraliminal perimetry, ensuring high spatial resolution.

PURPOSE: To assess the pattern and the local spatial frequency distribution of visual field defects (VFDs) in eyes with clinically diagnosed optic neuritis (ON) and their currently unaffected fellow eyes, using threshold-related, slightly supraliminal perimetry, ensuring high spatial resolution. METHODS: Records obtained with the Tübingen Automatic perimeter (TAP, Oculus Inc., Dudenhofen, Germany) and the Octopus 101 perimeter (Haag-Streit Inc, Koeniz, Switzerland), using a standardized grid of 191 static targets within the central 30 degrees visual field, were analysed retrospectively. VFDs were assigned to 15 classes. RESULTS: Visual fields (VF) from 99 patients (26 male and 73 female subjects, aged from 18 to 51 years) with clinically diagnosed, acute ON (52 right eyes, 48 left eyes affected, one bilateral involvement) were evaluated. Central scotomas were the most common finding in associated eyes, covering 41% of all VFDs in affected eyes. Nerve fibre bundle defects were found in 29% and paracentral scotomas in 14% of all VFDs. Fellow eyes were perimetrically normal in 65% of the clinically monocular ONs. Nerve fibre bundle defects were found in 21% and diffuse scotomas in 9% of the fellow eyes. CONCLUSIONS: Central scotomas and retinal nerve fibre bundle defects are the most common VFDs in acute ON. Small central and paracentral scotomas that most probably would have been missed by automated thresholding perimetry with its relatively coarse grid could be detected by threshold-related, slightly supraliminal strategy. Of the fellow eyes in clinically apparent monocular optic neuritis, 35% present with visual field defects.

Intracellular cytokine patterns in Behçet's disease in comparison to ankylosing spondylitis--influence of treatment with interferon-alpha2a.

OBJECTIVE: Treatment of Behçet's disease (BD) with human recombinant interferon-alpha2a (IFN-alpha2a) has proven clinically effective. The mechanism of action is unknown. This is the first study investigating the influence of IFN-alpha2a on intracellular cytokines in T-cells in patients with BD in comparison to healthy controls and to patients with ankylosing spondylitis (AS). METHODS: Cytokine expression of T-cells was investigated in 10 patients with BD before and 4 and 12 weeks after initiation of treatment with IFN-alpha2a. 10 patients with AS and 10 healthy individuals served as controls. Peripheral blood mononuclear cells were assayed by flow cytometry for the cell surface markers CD3, CD8 and CD4 and for the intracellular cytokines interleukin 2 (IL 2), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin 4 (IL 4). RESULTS: The fraction of CD3+ and CD4+ T-cells producing IL 2 was significantly lower in untreated BD and AS patients compared to healthy controls (p = 0.02 and 0.007). However, the number of IFN-g-producing CD3+ T-cells in untreated BD patients was elevated in comparison to both control groups (p = 0.05). T-cell cytokine analysis of BD patients revealed a significant increase of IL 2-production in T-cells during IFN-alpha2a treatment (p < 0.001). CD4+ T-cells producing IFN-gamma and TNF-alpha increased significantly (p = 0.002 and p = 0.01). CONCLUSION: In BD and AS, CD3+ and CD4+ T-cells producing IL 2 are reduced. This may hint at a similarity in the pathogenesis of these HLA-class I-associated disorders. IFN-alpha2a induces restoration of IL 2-production in patients with BD which is likely to be one mechanism of action of IFN-alpha2a.

Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells

To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37) on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 æm ("thin" or "thick" dendrites, respectively). Three cells (4.5 percent) were bistratified, having thick dendrites, and the others (95.5 percent) were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40 percent) and 2 groups with inner (50-100 percent) stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat ß-cells, whereas one group of cells with thick dendrites includes cells that resemble cat a-cells.

Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells.

To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37) on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 microm ("thin" or "thick" dendrites, respectively). Three cells (4.5%) were bistratified, having thick dendrites, and the others (95.5%) were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40%) and 2 groups with inner (50-100%) stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat beta-cells, whereas one group of cells with thick dendrites includes cells that resemble cat alpha-cells.

Inducible HSP70 levels in thoracic wound fluid indicate myocardial damage after open heart surgery.

AIM: Heat shock proteins (HSP) act as chaperones and protect cellular homeostasis. They are induced by multiple forms of cell stress. Nothing is known about their rise in the drainage fluid after cardiac and thoracic operations. METHODS: Forty-five patients undergoing open heart surgery or major lung resections were studied. Levels of inducible HSP70 were measured daily in thoracic wound fluid and blood with ELISA tests in addition to multiple conventional blood and wound fluid parameters. Data were analyzed using analysis of covariance and Spearman's rank-correlation coefficient. RESULTS: Inducible HSP70 was detectable in all thoracic fluid samples. Mean HSP70-level after open heart surgery was 64 ng/mL and 40 ng/mL in patients without extracorporeal circulation (P=0.015). Drainage HSP70 levels were correlated with white blood cell counts in wound fluid (P<0.0001) and blood CK-MB levels (P<0.0001). Correlation coefficients between white blood cells in blood and local HSP-levels were explicitly lower (P=0.0023). There was a steady decrease in HSP levels in drainage fluid from day 1 to day 4 (P<0.0001). CONCLUSIONS: Inducible HSP70 is present in postoperative thoracic drainage fluid. Drainage levels are higher in patients after open heart surgery and are correlated with blood CK-MB levels, indicating cardiomyocyte damage. Our data further suggest that extracellular HSP70 is released also by white blood cells. Additional studies are needed to examine the role of extracellular HSP70 in wound healing processes and myocardial damage.