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.

[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.

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.

[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.

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.

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.

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.

Differentiation between malignant and benign solitary pulmonary nodules with proton density weighted and ECG-gated magnetic resonance imaging.

OBJECTIVE: To estimate performance of MRI for differentiating malignant from benign solitary pulmonary nodules (SPN) using morphological characteristics. MATERIAL AND METHODS: MRI in 46 patients with SPN (mean diameter: 19 mm) was carried out on 1.0 Tesla scanner using ECG-gated, gradient echo sequence. Morphological signs of SPN were determined and compared with previously performed helical-CT, where final diagnosis served as reference with 52% frequency of malignancy. Furthermore, three observers evaluated all images. RESULTS: Significant differences between the two groups were found for nodules shape, margin, inhomogeneity and the vessel-sign in MRI, nodules shape, margin, the vessel-sign, and presence of spicules in CT. Using these signs, AUC were 0.746 for MRI and 0.765 for CT. The mean sensitivity, specificity, and accuracy of observers for MRI/CT were 89%/95%, 42%/41%, 66%/68%, respectively. CONCLUSIONS: Despite discrepancies in morphologic appearance, no significant difference of accuracy between MRI and CT was determined. Further investigations are necessary to demonstrate the clinical use in combination with functional parameters, establishing MRI as a comprehensive diagnostic modality for SPN.

Does visual restitution training change absolute homonymous visual field defects? A fundus controlled study.

AIM: To examine whether visual restitution training (VRT) is able to change absolute homonymous field defect, assessed with fundus controlled microperimetry, in patients with hemianopia. METHODS: 17 patients with stable homonymous visual field defects before and after a 6 month VRT period were investigated with a specialised microperimetric method using a scanning laser ophthalmoscope (SLO). Fixation was controlled by SLO fundus monitoring. The size of the field defect was quantified by calculating the ratio of the number of absolute defects and the number of test points; the training effect E was defined as the difference between these two ratios before and after training. A shift of the entire vertical visual field border by 1 degrees would result in an E value of 0.14. RESULTS: The mean training effect of all right eyes was E = 0.025 (SD 0.052) and all left eyes E = 0.008 (SD 0.034). In one eye, a slight non-homonymous improvement along the horizontal meridian occurred. CONCLUSIONS: In one patient, a slight improvement along the horizontal meridian was found in one eye. In none of the patients was an explicit homonymous change of the absolute field defect border observed after training.

Cytokines, cytokine antagonists and soluble adhesion molecules in patients with ocular Behçet's disease treated with human recombinant interferon-alpha2a. Results of an open study and review of the literature.

OBJECTIVE: To elucidate the influence that interferon-alpha exerts on the cytokine network in active ocular Behçet's disease (BD). METHODS: Fifty patients with active ocular BD were treated with human recombinant interferon-alpha2a (rhIFN-alpha2a). Serum was analysed for the presence of IL-10, TNF-alpha, IL-8, IL-6, sIL-2R, IFN-gamma, IFN-alpha, IL-12, IL-4, sTNFRI (p55), sTNFRII (p75), IL-1RA, G-CSF, sE-selectin, sVCAM-1, sICAM-1 and neopterin before initiation of and at several time points during IFN treatment and compared to 21 healthy controls. RESULTS: The levels of IFN-alpha IL1-RA and sTNFRII were significantly increased in the patients at baseline in comparison to healthy controls. During treatment with rhIFN-alpha2a, when remission was achieved as defined by the scoring system used, a significant increase in levels of IFN-alpha, IL-2R, TNF-alpha, sTNF-RII, sICAM-1, sVCAM-1, neopterin in the serum was observed, with a tendency towards increased IL-1RA as well. In contrast, leuko- and thrombocyte counts and sE-selectin serum levels significantly decreased. Positive correlations were found between IFN dosage or serum levels and sVCAM-I, neopterin, sTNF-RII and sIL-2R, between sVCAM-1, sIL-2R, TNF-alpha, sTNF-RII and neopterin, sICAM-I and sVCAM-1, sIL2-R and sTNF-RII, and, finally, between sIL2-R and sICAM-I. CONCLUSIONS: IFN-alpha exerts diverse influences mainly on cytokine antagonists and soluble adhesion molecules. Because sTNF-RII and IL-1RA were increased by IFN-alpha treatment, these might be interesting alternative treatment options in refractory BD. Some of the side-effects of IFN-alpha may be caused by activation of monocytes, which is reflected by an increase in neopterin serum levels.

Olivocochlear activity and temporary threshold shift-susceptibility in humans.

STUDY OBJECTIVES: Animal studies (guinea pig, cat, chinchilla) have shown that activity of the medial olivocochlear efferents can exert noise-protective effects on the cochlea. It is not yet known whether such effects are also existent in humans. Olivocochlear activity can be estimated indirectly by contralateral suppression (CS) of otoacoustic emissions (OAE). MATERIAL AND METHODS: We measured Input/Output functions of distortion products of OAE (DPOAE), with and without contralateral acoustic stimulation by white noise, in 94 normal hearing young male subjects. Seven stimuli with L2 between 20 and 60 dB SPL and L1 = 39 dB + 0.4 L2 ("scissor paradigm") were used at f2 = 2, 3, 4, 5, and 6 kHz. The measurement was repeated 2 weeks later. In 83 subjects of the same group, pure tone audiometry was registered before and 6 minutes after shooting exercises to evaluate individual susceptibility to develop a temporary threshold shift (TTS). RESULTS: Test-retest repeatability of CS was generally good. CS averaged 0.98 dB SPL (SD 1.19 dB, median 0.56 dB). As expected, CS was greatest at low stimulus levels (median 1.06 dB at L2 = 20 dB, as compared with 0.33 dB at L2 = 60 dB). The smallest average CS was found at 4 kHz, and the greatest CS appeared at 2 kHz. A TTS occurred in 7 of 83 (8.5%) subjects. Statistical analysis did not reveal any correlation between the amount of CS and individual TTS susceptibility. CONCLUSIONS AND OUTLOOK: 1) Measurement of CS of DPOAE using an extensive measurement paradigm revealed good test-retest repeatability, confirming the reliability of this audiologic tool. 2) CS of DPOAE does not predict individual susceptibility to mild TTS induced by impulse noise in humans. Possible explanations for the missing association are discussed. Future perspectives include longitudinal studies to further elucidate the association between medial olivocochlear bundle-activity and permanent threshold shift in humans. The goal is to develop a diagnostic tool for the prediction of individual noise vulnerability in humans, thereby preventing noise-induced hearing loss.

Invasive pulmonary aspergillosis: frequency and meaning of the "hypodense sign" on unenhanced CT.

The purpose of this study was to establish the diagnostic value of central hypointensity ("hypodense sign") in lung consolidations or nodules, in severely immunocompromised or neutropenic patients, suspected of having invasive pulmonary aspergillosis (IPA), and to assess its recognition on unenhanced CT scans. Serial CT scans of the lung were retrospectively reviewed in 43 consecutive immunosuppressed patients with IPA, and assessed for the presence of the hypodense sign using standard mediastinal and lung windowing settings, as well as a special, narrower window setting (width 110-140 HU; level 15-40 HU). The temporal relationship between the occurrence of the first CT-finding suspicious of IPA and the appearance of the hypodense sign, as well as between this and the occurrence of the crescent sign, cavitation or reduction in lesion size, was evaluated. Additionally, CT-scans from 89 immunocompromised patients with viral (n=45) or bacterial (n=44) pneumonia, investigated in the same time period at our institution were reviewed, with respect to the presence of the "hypodense" sign. Unenhanced CT scans revealed the hypodense sign in 11 neutropenic patients and 2 severely immunocompromised patients, out of a total of 43 patients with IPA evaluated in this study (30.2%). The mean time between the appearance of the first CT-findings of IPA (large nodule or consolidation +/- positive halo sign) and the hypodense sign was 7.8 days, while the time interval between the hypodense sign and the occurrence of crescent sign, cavitation, or decrease of the lesion's size was 8.3 days. The hypodense sign did not occur in any of the patients with viral or bacterial pneumonia, in the control series. We consider the hypodense sign to be a supplementary tool in the diagnosis of IPA. Its sensitivity was low in our series, but the high specificity makes it valuable in predicting IPA, anticipating the occurrence of cavitation or crescent sign, which are considered specific, but late findings of IPA. The hypodense sign is recognizable also on unenhanced CT, when a narrower lung window setting is used.

[Comparison of conventional full spine radiographs and fluoroscopic scanning method in young patients with idiopathic scoliosis]. / Vergleich von konventioneller Wirbelsäulenganzaufnahme und fluoroskopischer Scan-Methode bei jungen Patienten mit idiopathischer Skoliose.

PURPOSE: Evaluation of low-dose full spine radiographs using fluoroscopic images for the assessment of the Cobb angle measurement in patients with scoliosis. MATERIAL AND METHODS: Twenty-one consecutive patients (aged 10 - 27 years, mean age 14 years) with a conventional full spine examination (film speed class 800) underwent a follow-up exam using digital pulsed fluoroscopy (Multi Diagnost 4, Philips Medical Systems, Eindhoven, The Netherlands). The mean follow-up was 9 months. During a synchronized scan with a C-arm speed of 4 cm/sec fluoroscopic images were stored with a pulsed frequency of 3 images per second. The single images were merged and reconstructed to one image with the software Easy Spine (Philips medical Systems, Eindhoven, The Netherlands). The corresponding dose-area product values (DAP) of both methods were compared. Three independent observers assessed Cobb angles and image quality for each technique. RESULTS: The mean DAP values for conventional imaging was 94.9 cGy x cm (2) and for fluoroscopy 7.8 cGy x cm (2), respectively. A significant dose reduction of 91.8 % (CI 91 % to 95 %) was calculated. The average absolute angle difference between the observers was found to be 2.7 degrees for conventional imaging and 2.4 degrees for the fluoroscopic method. Interobserver standard deviation of 2.9 degrees was lower than the 5.3 degrees for conventional images. Image quality was better in the conventional images. CONCLUSION: Using the scanning method, we could achieve a mean reduction of the radiation dose of 92 %, while the accuracy of the Cobb angle measurements was comparable for both techniques despite of reduced image quality of digital fluoroscopy.

L- and M-cone-driven electroretinograms in Stargardt's macular dystrophy-fundus flavimaculatus.

PURPOSE: To study the dynamics of the long (L)- and middle (M)-wavelength-sensitive cone-driven pathways and their interactions in patients with Stargardt's macular dystrophy-fundus flavimaculatus (SMD-FF) and to correlate them with other clinical parameters and individual genotypes. METHODS: Forty-seven patients with SMD-FF participated in the study. In addition to standard 30-Hz flicker electroretinograms (30-Hz fERG), ERG responses were measured to stimuli that modulated exclusively the L or the M cones (L/M cones) or the two simultaneously. Blood samples were screened for mutations in the 50 exons of the ABCA4 gene. RESULTS: Patients with SMD-FF did not show a decrease in the mean L/M-cone-driven ERG sensitivity, but there was a significant increase in the interindividual variability. The mean L-/M-cone weighting ratio was normal. However, the L-cone-driven ERG was significantly phase delayed, whereas the M-cone-driven ERG was significantly phase advanced. These phase changes were significantly correlated with disease duration. The amplitude and implicit time of the standard 30-Hz fERG both correlated significantly with the L/M-cone-driven ERG sensitivity and with the phase difference between the L/M-cone-driven ERGs, indicating the complex origin of the standard 30-Hz fERG. Probable disease-associated mutations in the ABCA4 gene were found in 40 of 45 patients, suggesting that they form a genetically fairly uniform SMD-FF study group. There was no correlation between the genotype and the L/M-cone-driven ERGS: CONCLUSIONS: The changes in L/M-cone-driven ERG sensitivity and phase possibly represent two independent disease processes. The phase changes are similar to those found in patients with retinitis pigmentosa and possibly are a general feature of retinal dystrophies.

Reaction time in automated kinetic perimetry: effects of stimulus luminance, eccentricity, and movement direction.

PURPOSE: To determine the effects of stimulus eccentricity and luminance level on the reaction time (RT) of young normal volunteers during automated kinetic campimetry. METHODS: We used a specially designed video-campimetric device equipped with a continuous infrared (IR) pupillographic fixation control (Tübingen Computer Campimeter) and recorded reaction times upon presenting horizontally moving small circular stimuli (size 26'; constant angular velocity 2 degrees /s) starting at 16 locations within the central 30 degrees -radius of the visual field. Two different levels of stimulus luminance were used (41.6 cd/m(2) and 110 cd/m(2)), while background luminance was 10 cd/m(2). Each stimulus was presented a total of six times in a randomized order. Subjects were 12 healthy young individuals (aged 21-30 years) with normal ophthalmic examinations. An analysis of variance (ANOVA) was performed on the data. RESULTS: RTs showed considerable inter- and intra-individual variation with individual least squares means (LSM, fitted values of a linear model) ranging from 305 to 454 ms, and residual standard deviation (R.S.D.) 66 ms. Reaction times did not differ significantly as a function of stimulus direction (P>0.6). Higher luminance levels produced significantly reduced reaction times for all stimulus locations and directions (mean reduction: 16 ms; P<0.0001). Reaction times increased with increasing eccentricity, in the mean by 1.8 ms per degree of visual angle, from 365+/-4 ms (S.E.M.) foveally, to 407+/-2 ms at 30 degrees eccentricity; (P<0.0001). CONCLUSIONS: Automated kinetic perimetry should be designed to cope with significant, variable interindividual response characteristics. Other stimulus related factors, such as eccentricity or luminance level, have a significant but comparatively small effect on reaction time within the central 30 degrees -radius visual field in healthy young individuals.

Human recombinant interferon alfa-2a for the treatment of Behçet's disease with sight threatening posterior or panuveitis.

BACKGROUND: Behçet's disease is a multisystem vasculitis of unknown origin. Standard treatment mainly comprises systemic immunosuppressive agents. Ocular involvement, mostly posterior uveitis with retinal vasculitis, leads to blindness in 20-50% of the involved eyes within 5 years. The efficacy of interferon alfa-2a was studied in patients with sight threatening posterior uveitis or retinal vasculitis. METHODS: 50 patients were included in this open, non-randomised, uncontrolled prospective study. Recombinant human interferon alfa-2a (rhIFNalpha-2a) was applied at a dose of 6 million units subcutaneously daily. Dose reduction was performed according to a decision tree until discontinuation. Disease activity was evaluated every 2 weeks by the Behçet's disease activity scoring system and the uveitis scoring system. RESULTS: Response rate of the ocular manifestations was 92% (three non-responder, one incomplete response). Mean visual acuity rose significantly from 0.56 to 0.84 at week 24 (p<0.0001). Posterior uveitis score of the affected eyes fell by 46% every week (p<0.001). Remission of retinal inflammation was achieved by week 24. Mean Behçet's disease activity score fell from 5.8 to 3.3 at week 24 and further to 2.8 at week 52. After a mean observation period of 36.4 months (range 12-72), 20 patients (40%) are off treatment and disease free for 7-58 months (mean 29.5). In the other patients maintenance IFN dosage is three million units three times weekly. CONCLUSIONS: rhIFNalpha-2a is effective in ocular Behçet's disease, leading to significant improvement of vision and complete remission of ocular vasculitis in the majority of the patients.

Chlamydia pneumoniae IgA seropositivity is associated with increased risk for atherosclerotic vascular disease, myocardial infarction and stroke in dialysis patients.

BACKGROUND: Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with chronic renal failure undergoing dialysis therapy. Aim of the study was to evaluate whether there is a correlation between a past infection with Chlamydia pneumoniae inducing antibody production and the manifestation of symptomatic atherosclerotic disease in patients with chronic renal failure on hemodialysis. METHODS: A retrospective study was designed including 151 dialysis patients with a clinical apparent atherosclerotic disease (case subjects) and 116 dialysis patients without any symptomatic atherosclerotic manifestation (control group). An ELISA was used to measure seropositivity for IgA and IgG titers. RESULTS: Elevated IgA titers against Chlamydia pneumoniae were found in 67% of the case subjects, but only in 29% of the controls (OR 5.34, CI 2.98-9.56). Forty-five patients of the case subjects had a history of myocardial infarction (OR 5.14, CI 2.38-11.09). Prior stroke was found in 30 patients in case subjects (OR 4.37, CI 1.73-11.01). The follow-up after 3 years showed that only 20 patients died from cardiovascular disease in the control group in comparison to 57 patients in the case group (OR 2.51). IgG seropositivity revealed an OR of 1.02 (CI 1.0-2.1). CONCLUSION: These results indicate that IgA seropositivity is associated with an increased frequency of symptomatic atherosclerotic manifestations. Especially an increased number of patients was found with prior myocardial infarction or stroke when elevated IgA titers were detected. IgA positivity seems to be a separate prospective risk factor in patients with chronic renal failure and hemodialysis for premature cardiovascular death.