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We describe theoretical background, development, and piloting of a measure for quality of life in older adults that specifically takes into account the subjective perspective. Although quality of life is usually subjectively assessed, normative thresholds for “the good life” are most often set by a third party. The new tool FLQM asks for respondents to name, rate, and weight those domains in life that are most important for their life-satisfaction solely from their own point of view. Construct validity was pilot-tested in two samples of elders (N 1 = 44; N 2 = 90). Correlations were in the medium range in both studies and support the questionnaire’s validity. There were no age or gender differences on total score. However, in Study 1 as well as in Study 2 older subjects named significantly fewer domains than did younger participants. Further, in Study 1 the overall number of distinct domains generated by the participants diminished with age—the “interindividual pool of domains” shrank. Implications of this age-associated narrowing of domainscope are discussed on a background of adaptation theories. Concluding, the new questionnaire seems apt to assess older peoples’ quality of life even in a physically very ill population, but needs further testing, especially regarding its reliability. This is currently being undertaken in a larger longitudinal sample to assure psychometric properties.

The narrow therapeutic range of tacrolimus requires careful management after liver transplantation (LT). The aim of this study was to investigate the influence of graft function on tacrolimus trough levels during the first post-transplant week. Ninety-three patients receiving deceased-donor LT were observed in a prospective observational study. Graft function was determined by the new LiMAx test (maximal liver function capacity). Significant correlations between LiMAx readouts and consecutive tacrolimus levels, up to r = -0.529 (p0.0001), were determined throughout the observed period of time. Patients with initially poor graft function revealed higher trough levels (n = 24; 20.1 ± 11.6ng/mL) in comparison with fair (n = 40; 13.7 ± 7.8 ng/mL) and good function (n = 29; 9.5 ± 4.4ng/mL; p0.0001) already at the second post-transplant day. Toxic levels could be predicted with an area under receiver operating characteristic analysis AUROC=0.751 (p = 0.001) with high sensitivity and specificity. Insufficient levels could be predicted with AUROC=0.800 (p = 0.003). In conclusion, initial graft function is a major factor influencing the pharmacokinetics of tacrolimus and can be validly determined by the LiMAx test. Thus, recipients with poor functioning grafts are prone of developing toxic levels within the first week after LT, whereas patients with good functioning grafts frequently develop insufficient levels with the current immunosuppressive protocols.

We investigated sex differences and the role of estrogen receptor-β (ERβ) on myocardial hypertrophy in a mouse model of pressure overload. We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERβ knockout (ERβ−/−) mice. All mice were characterized by echocardiography and hemodynamic measurements and were killed 9 wk after surgery. Left ventricular (LV) samples were analyzed by microarray profiling, real-time RT-PCR, and histology. After 9 wk, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. ERβ deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that WT male hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than WT female hearts. ERβ−/− mice exhibited a different transcriptional response. ERβ−/−/TAC mice of both sexes exhibited induction of proapoptotic genes with a stronger expression in ERβ−/− males. Cardiac fibrosis was more pronounced in male WT/TAC than in female mice. This difference was abolished in ERβ−/− mice. The number of apoptotic nuclei was increased in both sexes of ERβ−/−/TAC mice, most prominent in males. Female sex offers protection against ventricular chamber dilation in the TAC model. Both female sex and ERβ attenuate the development of fibrosis and apoptosis, thus slowing the progression to heart failure.

In human cortex it has been suggested that the tissue at risk is indicated by clusters of spreading depolarizations (SDs) with persistent depression of high-frequency electrocorticographic (ECoG) activity. We here characterized this zone in the ET-1 model in rats using direct current (DC)-ECoG recordings. Topical application of the vasoconstrictor endothelin-1 (ET-1) induces focal ischemia in a concentration-dependent manner restricted to a region exposed by a cranial window, while a healthy cortex can be studied at a second naïve window. SDs originate in the ET-1-exposed cortex and invade the surrounding tissue. Necrosis is restricted to the ET-1-exposed cortex. In this study, we discovered that persistent depression occurred in both ET-1-exposed and surrounding cortex during SD clusters. However, the ET-1-exposed cortex showed longer-lasting negative DC shifts and limited high-frequency ECoG recovery after the cluster. DC-ECoG recordings of SD clusters with persistent depression from patients with aneurysmal subarachnoid hemorrhage were then analyzed for comparison. Limited ECoG recovery was associated with significantly longer-lasting negative DC shifts in a similar manner to the experimental model. These preliminary results suggest that the ischemic zone in rat and human cortex is surrounded by a normally perfused belt with persistently reduced synaptic activity during the acute injury phase.

Initial graft function is a major factor influencing the clinical outcome after liver transplantation (LTX), but a reliable method for assessing and predicting graft dysfunction directly after LTX is not available. Ninety-nine patients undergoing deceased-donor LTX were studied in a prospective pilot study to evaluate the LiMAx test, the indocyanine green test, and conventional biochemical parameters with respect to their sensitivity and prognostic power for the diagnosis of initial graft dysfunction. Patients suffering from initial graft dysfunction (defined as technical complications or primary nonfunction (n = 8)) had significantly decreased LiMAx readouts (43 +/- 18 versus 184 +/- 98 mug/kg/hour, P < 0.001) immediately after LTX. Univariate analysis also showed significant differences for serum bilirubin, ammonia, glutamate dehydrogenase, and the international normalized ratio (P < 0.05), but multivariate analysis revealed LiMAx as the single independent predictor of initial dysfunction (P = 0.008) with an area under the receiver operating characteristic curve (AUROC) of 0.960 (95% confidence interval = 0.921-0.998, P < 0.001). In addition, the diagnosis of primary nonfunction (n = 3) was evaluated with LiMAx and aspartate aminotransferase (AST) activity on the first postoperative day. The calculated AUROC values were 0.992 (0.975-1.0, P = 0.004) for LiMAx and 0.967 (0.929-1.0, P = 0.006) for AST. By a combination of test results obtained directly after LTX and on the first day, LiMAx indicated primary nonfunction with a sensitivity of 1.0 (0.31-1.0) and a positive predictive value of 1.0 (0.31-1.0), whereas AST classification showed a sensitivity of 0.67 (0.13-0.98) and a positive predictive value of 0.29 (0.05-0.70). In conclusion, the assessment of initial graft function using the LiMAx test might be effective for identifying critical complications that could threaten graft survival within 24 hours after LTX.

Aims The present study aimed to explore the impact of the angiotensin type 1 receptor blocker valsartan (VAL) on inflammatory-/lipid-/glucose parameters in hypertensive diabetic patients with and without coronary artery disease (CAD). Methods This was a 16-week, randomized, double-blind, placebo-controlled two-center study with VAL 320 mg/d in 109 hypertensive diabetic patients ( n = 56 non-CAD; n = 53 CAD). Results VAL treatment did not significantly affect serum interleukin-6 (IL-6) or tumor necrosis factor α (TNFα) levels in the overall study population but significantly reduced serum IL-6 in the subgroup with high inflammatory load at baseline (IL-6 > median (2.0 ng/L), n = 54: [median, ng/L]): VAL: from 3.5 to 2.4; placebo: from 3.2 to 3.5; p = 0.035). VAL significantly lowered total- and LDL-cholesterol in the whole study population: [median, mg/dL]: total cholesterol: VAL: from 178 to 168; placebo: from 174 to 173, p = 0.039; LDL-cholesterol: VAL: from 96 to 90, placebo: from 102 to 103, p = 0.006, whereas glycemic parameters were not affected. Conclusions The present study demonstrates significant anti-inflammatory efficacy of VAL in hypertensive diabetic patients with enhanced inflammatory burden. High-dose VAL therapy significantly lowered total- and LDL-cholesterol levels. The combined actions of cholesterol and blood pressure lowering by VAL may provide additional clinical benefits for these high-risk patients.

International audience; Epidemiologic data on incidence, prevalence and risk factors for chronic kidney disease (CKD) and its progression to kidney failure in people ≥70 years are scarce. This lack may have two reasons: First, the issue has only recently gained importance by the changing demographics characterized by an aging society. Secondly, a validated method for estimating kidney function in terms of glomerular filtration rate (GFR) in the elderly is still lacking. In this paper we describe the methodology of a combined longitudinal and cross-sectional approach of a population based study which will start in January 2010. The aims of the study are to identify prevalent and incident cases of CKD as well as co-morbidities and associated risk factors for progression of disease in this specific age-group. To assess prevalence, a new GFR estimation equation is to be developed. In a longitudinal approach a population based, age stratified sample of 2,000 subjects ≥70 years will be randomly drawn from a data base of a large health insurance company. Interview, physical examination, and preliminary estimation of GFR, based on serum creatinine will be performed. The entire cohort will be followed over the course of 2 years. In a cross-sectional approach a subsample of 600 subjects will be defined based on preliminary GFR values. Kidney function will be determined by measuring plasma clearance of an exogenous filtration marker (Iohexol). A new GFR-equation will be developed and validated using Iohexol clearance as gold standard to estimate GFR accurately and precisely. Data of 2,000 subjects will be used to estimate prevalence of CKD.

Summary Background High-dose methotrexate is the standard of care for patients with newly diagnosed primary CNS lymphoma. The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a standard of care. We aimed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival. Methods Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May, 2000, and May, 2009. Patients were allocated by computer-generated block randomisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy, with stratification by age ( vs ≥60 years) and institution (Berlin vs Tubingen vs all other sites). The biostatistics centre assigned patients to treatment groups and informed local centres by fax; physicians and patients were not masked to treatment group after assignment. Patients enrolled between May, 2000, and August, 2006, received high-dose methotrexate (4 g/m 2 ) on day 1 of six 14-day cycles; thereafter, patients received high-dose methotrexate plus ifosfamide (1·5 g/m 2 ) on days 3–5 of six 14-day cycles. In those assigned to receive first-line chemotherapy followed by radiotherapy, whole brain radiotherapy was given to a total dose of 45 Gy, in 30 fractions of 1·5 Gy given daily on weekdays. Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine. The primary endpoint was overall survival, and analysis was per protocol. Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival, with a non-inferiority margin of 0·9. This trial is registered with ClinicalTrials.gov, number NCT00153530. Findings 551 patients (median age 63 years, IQR 55–69) were enrolled and randomised, of whom 318 were treated per protocol. In the per-protocol population, median overall survival was 32·4 months (95% CI 25·8–39·0) in patients receiving whole brain radiotherapy (n=154), and 37·1 months (27·5–46·7) in those not receiving whole brain radiotherapy (n=164), hazard ratio 1·06 (95% CI 0·80–1·40; p=0·71). Thus our primary hypothesis was not proven. Median progression-free survival was 18·3 months (95% CI 11·6–25·0) in patients receiving whole brain radiotherapy, and 11·9 months (7·3–16·5; p=0·14) in those not receiving whole brain radiotherapy. Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy (22/45, 49% by clinical assessment; 35/49, 71% by neuroradiology) than in those who did not (9/34, 26%; 16/35, 46%). Interpretation No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma, but our primary hypothesis was not proven. The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors. Funding German Cancer Aid.

PURPOSE: To analyze the association of normal-pressure glaucoma and migraine. METHODS: In a prospective study, 154 patients with glaucoma (56 normal-pressure subgroup and 98 high-pressure glaucoma subgroup), 55 patients with ocular hypertension, and 75 control subjects were analyzed by means of a standardized questionnaire based on International Headache Society criteria. RESULTS: According to the questionnaire, 46 patients (17%) were classified as suffering from migraine and 20 (7%) from tension headache (episodic and chronic). The prevalence of headache, migraine, and tension headache did not vary significantly among control subjects, patients with ocular hypertension, and patients with glaucoma, but migraine was significantly more common in patients with normal-pressure glaucoma (28%) compared with control subjects (12%; P P CONCLUSION: The results suggest an association of normal-pressure glaucoma and migraine and a potential, common vascular etiology of both diseases.

Background The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months. Methods and design 1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up. Discussions The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task. Trial Registration clinicaltrials.gov NCT00715533

The value of a full-field flicker stimulus in glaucoma diagnosis was tested. In 69 normals, 60 ocular hypertension, and 50 manifest primary openangle glaucoma patients, the temporal contrast (flicker) thresholds were tested with a sinusoidally flickering white light of constant mean photopic luminance (10 candela/m) presented in a full-field bowl. A modulatable xenon-arc lamp was used, and only one frequency (37.1 Hz) was tested. Luminances were corrected according to pupil widths. No significant age relationships of flicker thresholds were found in normal eyes. Forty (80%) of glaucoma eyes were recognized as pathologic at a specificity of 93%. In the glaucoma group, significant correlations of flicker thresholds were found with measurements of neuroretinal rim areas of the optic disc (linear r = -0.61, nonparametric r = -0.59, p = 0.001) and with perimetric mean defects (linear r = 0.74, nonparametric r = 0.66, p = 0.0001). Because of its high sensitivity and the significant correlation with perimetric losses and neuroretinal rim areas, the full-field flicker test can be used as a quick (5 min per eye) additional examination in the diagnosis of glaucoma.

To validate the LiMAx test, a new bedside test for the determination of maximal liver function capacity based on C-methacetin kinetics. To investigate the diagnostic performance of different liver function tests and scores including the LiMAx test for the prediction of postoperative outcome after hepatectomy.Liver failure is a major cause of mortality after hepatectomy. Preoperative prediction of residual liver function has been limited so far.Sixty-four patients undergoing hepatectomy were analyzed in a prospective observational study. Volumetric analysis of the liver was carried out using preoperative computed tomography and intraoperative measurements. Perioperative factors associated with morbidity and mortality were analyzed. Cutoff values of the LiMAx test were evaluated by receiver operating characteristic.Residual LiMAx demonstrated an excellent linear correlation with residual liver volume (r = 0.94, P0.001) after hepatectomy. The multivariate analysis revealed LiMAx on postoperative day 1 as the only predictor of liver failure (P = 0.003) and mortality (P = 0.004). AUROC for the prediction of liver failure and liver failure related death by the LiMAx test was both 0.99. Preoperative volume/function analysis combining CT volumetry and LiMAx allowed an accurate calculation of the remnant liver function capacity prior to surgery (r = 0.85, P0.001).Residual liver function is the major factor influencing the outcome of patients after hepatectomy and can be predicted preoperatively by a combination of LiMAx and CT volumetry.

Background Despite recent work hour restrictions, 24-hour calls remain an important part of patient care. The aim of this study was to assess the impact of 24-hour night calls on the psychomotor and cognitive skills of surgeons with a virtual surgery simulator (VSS) and psychometric tests. We hypothesized that sleep loss impairs surgical skills and concentration performance. Methods Seventeen surgery residents (test group) and 13 medical students (reference group) performed a 5-day training program on the VSS. The test group was then assessed during a night call on 4 test points (8 am and 4 pm on the on-call day, 8 am on the postcall day, and 8 am on the recovery day) to assess the effects of sleep loss on these surgery residents. The reference group performed the same tests but without a night call. Results The training resulted in a homogenous performance level for both groups. The average time for the test group was 26 minutes. The analysis between rested and sleep-deprived participants (6.5 ± 0.9 vs 2.9 ± 1.4 hours of night sleep) in the on-call part showed no performance differences. No impairment was found for the VSS and the cognitive tests within the test group between the start of the working day and the start of the postcall day after the night of relative sleep loss. The subgroup analysis showed no significant differences regarding the amount of night sleep and laparoscopic experience. Conclusion No performance impairment was found for surgeons with a VSS and standardized cognitive tests after a night of relative sleep loss. Although there is no doubt that sleep deprivation ultimately impairs human functioning, typical surgical skills do not necessarily deteriorate with a limited amount of sleep loss under clinical conditions.

In multiple sclerosis (MS), diffuse brain parenchymal damage exceeding focal inflammation is increasingly recognized to be present from the very onset of the disease, and, although occult to conventional imaging techniques, may present a major cause of permanent neurological disability. Subtle tissue alterations significantly influence biomechanical properties given by stiffness and internal friction, that--in more accessible organs than the brain--are traditionally assessed by manual palpation during the clinical exam. The brain, however, is protected from our sense of touch, and thus our current knowledge on cerebral viscoelasticity is very limited. We developed a clinically feasible magnetic resonance elastography setup sensitive to subtle alterations of brain parenchymal biomechanical properties. Investigating 45 MS patients revealed a significant decrease (13%, P0.001) of cerebral viscoelasticity compared to matched healthy volunteers, indicating a widespread tissue integrity degradation, while structure-geometry defining parameters remained unchanged. Cerebral viscoelasticity may represent a novel in vivo marker of neuroinflammatory and neurodegenerative pathology.

Gastrointestinal side effects of immunosuppressive drugs have got a high importance in clinical practice. The aim of this basic experimental study was to characterize the direct and immediate influence of seven commonly used immunosuppressive drugs on the small bowel functions. Therefore, the influence of ciclosporin A, tacrolimus, mycophenolate mofetil, enteric coated MPA, sirolimus, everolimus and FTY720 on-glucose absorption (I-GLU), chloride secretion (I-CHL), and barrier function (I-BAR) was investigated.br /Jejunum of Wistar rats was mounted into modified Ussing-chambers and thereafter incubated with a low (therapeutic) or high (toxic) concentration of immunosuppressive drugs for one hour. I-GLU was measured by 3-O-methyl-D-glucopyranose kinetics. I-CHL was assessed through basal, bumetanide inhibited and theophylline + PgE(2 )activated short circuit current difference. I-BAR was assessed by transepithelial resistance and( 3)H-Lactulose-Flux.br /No differences were observed within the analyzed parameters whether immunosuppressive drugs were added from mucosal or serosal intestine side. The glucose absorption was not influenced by any of the analyzed immunosuppressive drugs. The small intestine barrier function was diminished by everolimus in the toxic group only. Only mycophenolate mofetil and EC-MPA decreased chloride secretion in the toxic concentration. None of the analyzed drugs increased chloride secretion.br /In conclusion, the analyzed immunosuppressive drugs had no direct and immediate influence on gastrointestinal function in therapeutic concentrations. However, toxic concentrations of mycophenolate mofetil, enteric coated MPA, and everolimus might be of importance for local effects on small bowel function due to oral application.br /br /br /

Viscoelasticity is a sensitive measure of the microstructural constitution of soft biological tissue and is increasingly used as a diagnostic marker, e.g. in staging liver fibrosis or characterizing breast tumors. In this study, multifrequency magnetic resonance elastography was used to investigate the in vivo viscoelasticity of healthy human brain in 55 volunteers (23 females) ranging in age from 18 to 88 years. The application of four vibration frequencies in an acoustic range from 25 to 62.5 Hz revealed for the first time how physiological aging changes the global viscosity and elasticity of the brain. Using the rheological springpot model, viscosity and elasticity are combined in a parameter mu that describes the solid-fluid behavior of the tissue and a parameter alpha related to the tissue's microstructure. It is shown that the healthy adult brain undergoes steady parenchymal 'liquefaction' characterized by a continuous decline in mu of 0.8% per year (P0.001), whereas alpha remains unchanged. Furthermore, significant sex differences were found with female brains being on average 9% more solid-like than their male counterparts rendering women more than a decade 'younger' than men with respect to brain mechanics (P=0.016). These results set the background for using cerebral multifrequency elastography in diagnosing subtle neurodegenerative processes not detectable by other diagnostic methods.

Skin-prick tests (SPTs) are a standard way to test for sensitizations to allergens, but to date, techniques that allow for high-quality measurements of the resulting weals for research purposes are lacking. In this study, we assessed a new three-dimensional (3D) imaging technology for its accuracy and consistency. We found that this new technology showed very little intraoperator and interoperator variation for repeated measurements of a model of known area by each of two operators. We also found that repeated measurements of the same object over 4 months showed virtually no variation. Finally, 3D imaging was superior to traditional ruler measurements for assessing SPT reactions to histamine and allergen. For high-quality measurements of SPT reactions, 3D imaging is accurate, consistent and reliable.

We developed a public Internet program called SimChip (www.simchip.de). It performs virtual "in silico experiments", which reflect the in vivo situation of gene expression. Our computer model simulates up- and downregulation of genes on the basis of differential equations for linear synthesis and non-linear decay of mRNA. Steady-state concentrations are described as ratios of the respective rate constants: c = S/D. Using physiological synthesis rates of 0 to 50 mRNA molecules per min per cell and decay rates of 0.05 to 25% per min, SimChip helps to understand the right-skewed distribution patterns of gene expression levels and calculates the experimental endpoint of the theoretically infinite time needed to achieve perfect equilibrium.

Background: The current EAACI/GA²LEN/EDF guidelines recommend assessing disease activity in chronic urticaria (CU) by using an established and well-defined symptom score, i.e. the urticaria activity score (UAS), which combines daily wheal numbers and pruritus intensity. However, this UAS has never been formally tested for its suitability in assessing CU activity. Aim: To determine the UAS correlation with quality of life (QoL) in CU patients and to compare the UAS to other symptom scores. Methods: Chronic urticaria symptoms (wheals, erythema, angioedema, pruritus) were assessed on seven consecutive days in 111 CU patients for their numbers, duration, size, and/or intensity. Quality of life was assessed by using the Dermatology Life Quality Index. Both, urticaria activity and QoL were determined before and after a 3-week period, in which the patients followed a pseudoallergen-low diet. Results: Urticaria activity score values correlated positively, albeit weakly, with QoL impairment in CU patients (r2 = 0.31, P

Purpose To evaluate the accuracy of four MR sequences used as part of a whole-body MRI protocol to detect pulmonary lesions in cancer patients. Materials and Methods A total of 31 oncology patients were imaged in a 1.5T MR scanner (Magnetom Avanto; Siemens Medical Solutions, Germany) for whole-body staging. MR chest imaging included: axial and coronal T2-weighted (T2w)–short-tau inversion-recovery (STIR), axial T2w turbo spin-echo (TSE), and contrast-enhanced (CE) three-dimensional (3D) volumetric interpolated breathhold examination (VIBE). Multidetector computed tomography (MDCT) of the thorax served as the reference standard. The MDCT and MR images were evaluated independently by two radiologists. Comparative analysis was performed per lesion, per lobe, and per patient. Sensitivity, specificity, and predictive values were determined. Results Compared to MDCT that detected 268 pulmonary lesions ranging from 2 to 75 mm in diameter, the MR sensitivities were 91.1%, 92.5%, 90.8%, and 87.3% for the coronal STIR, the axial STIR, the axial T2w-TSE, and the axial CE 3D-VIBE, respectively. Undetected pulmonary lesions were either calcified or smaller than 10 mm in the axial diameter. With coronal STIR, six false-positive findings were detected; with axial STIR, 14 were detected; with axial T2w-TSE, 10 were detected; and with 3D-VIBE, seven were detected. Conclusion Pulmonary MRI is feasible as part of a whole-body MRI protocol. In our study, STIR images achieved high accuracy compared to chest MDCT for pulmonary lesions of 3 mm in size or larger. J. Magn. Reson. Imaging 2008. © 2008 Wiley-Liss, Inc.

Background: The impact of meningeal dissemination in primary CNS lymphoma (PCNSL) is debated, and the reported frequency varies. We prospectively evaluated the diagnostic value of PCR in comparison with CSF cytomorphology and MRI for diagnosing meningeal dissemination in PCNSL. Methods: We evaluated 282 patients from a multicenter therapy study for PCNSL for the presence of meningeal dissemination: 205 with CSF cytomorphology, 171 with PCR of the rearranged immunoglobulin heavy-chain genes in CSF, and 217 with cranial MRI. Results: Meningeal dissemination was found in 33 of 205 patients (16%) by cytomorphology, in 19 of 171 (11%) patients evaluated by PCR, and in 8 of 217 patients (4%) by MRI. Considering either of these methods, the relative frequency of meningeal dissemination was 17.4% (49 of 282 patients). PCR was monoclonal in 6 of 19 (32%) samples with positive cytomorphology, 1 of 13 samples (8%) with suspicious cytology, and in 10 of 105 (10%) cytologically negative samples. In 11 samples with positive and 12 with suspicious cytology, PCR showed only a polyclonal pattern. The probability of meningeal dissemination detection was higher in cases with CSF pleocytosis (>5/μL) with an OR of 2.48 (95% CI 1.15–5.34, p = 0.018). CSF protein had no predictive value for meningeal dissemination detection. Conclusions: We found a low rate of meningeal dissemination in primary CNS lymphoma in this large prospective study. The rate of discordant PCR and cytomorphologic results was high. Thus, the methods should be regarded as complementary. CSF pleocytosis had predictive value for meningeal dissemination detection.

Summary Purpose: Different authors suggested the occurrence of a pleomorphic affective syndrome in patients with epilepsy named interictal dysphoric disorder (IDD). We sought to investigate whether IDD occurs only in patients with epilepsy and to validate IDD features against DSM-IV criteria. Methods: Consecutive patients with a diagnosis of epilepsy (E) or migraine (M) have been assessed using the BDI, MDQ, and the Interictal Dysphoric Disorder Inventory (IDDI), a questionnaire specifically created to evaluate IDD symptoms. Diagnosis of current and lifetime DSM-IV Axis I disorders was established using the MINI Plus version 5.0.0. Results: A total of 229 patients (E = 117; M = 112) were evaluated. Females were significantly more represented in the migraine group (E = 46.5% vs. M = 73.3% p = 0.009), but there was no difference in age, duration of the disease, or education level. Patients with epilepsy were more likely to screen positively at MDQ (E = 17% vs. M = 5.3% p = 0.006) and to have a diagnosis of bipolar disorder (E = 14.5% vs. M = 4.5% p = 0.013) as compared to migraine patients. There was no between-groups difference in IDD prevalence (E = 17%; M = 18.7%) and IDDI total scores (E = 4.1 ± 2.0 vs. M = 3.8 ± 2.0). Validation of IDD against DSM-IV categories showed current major depression being the foremost diagnostic category correlated with IDD in both epilepsy (OR = 0.32–0.12–0.88, p = 0.028) and migraine (OR = 0.10, 95% CI = 0.02–0.49, p = 0.004) samples. Current anxiety disorder correlated with IDD only in migraine patients (OR = 0.19, 95% CI = 0.05–0.77, p = 0.02). Conclusion: IDD represents a homogenous construct that can be diagnosed in a relevant proportion of patients but it is not typical only of epilepsy, occurring in other central nervous system disorders such as migraine.

Objective Leucovorin and extracorporeal removal of methotrexate (MTX) have limited efficacy in delayed MTX elimination after high-dose methotrexate (HD-MTX) therapy. Glucarpidase (carboxypeptidase G2) cleaves MTX into nontoxic metabolites, but experience with this enzyme is limited in adult patients. We evaluated the effects of glucarpidase intervention in adult and elderly patients with delayed MTX elimination. Patients and methods Forty-three patients (age, 18-78 years) with MTX serum concentrations (sMTX) of 1-1,187 micromol/l received glucarpidase, leucovorin rescue guided by MTX immunoassay, and standard supportive care. MTX and MTX metabolites were quantified in serum (24 patients) and urine (8 patients) by high-performance liquid chromatography. Contributory risk factors, toxicities, and survival were recorded in all patients. Results Glucarpidase was well tolerated and resulted in an immediate >97% reduction in sMTX, with a 0.2%-35% urinary recovery of the total MTX dose as inactive MTX metabolites. Forty (93%) of 43 patients had normalization (n = 25) or improvement (n = 15) of their serum creatinine. Frequent grade III-IV MTX toxicities were hematological (60%) and mucositis (35%); only eight (19%) patients developed grade III-IV nephrotoxicity. Ten (23%) of 43 patients experienced fatal complications associated with HD-MTX therapy. Patients with three or more contributory risk factors for delayed MTX elimination had a significantly poorer survival than patients with fewer than three risk factors (hazard ratio, 3.64; confidence interval, 1.14-17.54). Conclusions Glucarpidase is well tolerated and produces a rapid inactivation of substantial amounts of MTX. However, overall results are still unsatisfactory in adult and elderly patients, suggesting that earlier recognition of delayed MTX elimination and more rapid intervention are needed.

Aim of this study was to evaluate the long-term reproducibility of frequency doubling technology (FDT) screening procedures.Longitudinal data of 433 eyes of 294 patients with no progression of glaucomatous optic disc atrophy were retrospectively analyzed: 62 control eyes, 184 ocular hypertensive eyes, 104 preperimetric, and 83 perimetric open-angle glaucoma eyes. All subjects had annual tests with the FDT perimeter and a standardized ophthalmologic examination (ie, conventional perimetry, optic disc inspection, tonometry, lens opacity measurement for exclusion of cataract). The present analysis used a published overall screening score with case-wise recalculation of missed localized probability levels. We analyzed long-term variability by correlation analysis, sign tests, and limits of agreement (LoA) as introduced by Altman and Bland. All subjects had at least 2 annual tests. Three hundred twenty-six eyes had 2 annual tests with the C-20 procedure and at least 1 test with the N-30 protocol another year later. One hundred thirty-five eyes had 1 C-20 and 2 annual tests with the N-30 protocol.Analyses of repeated measurements revealed a significant learning effect (P0.001, LoA: -4, 17) between the first and second examination but no significant difference between the second and following tests with the C-20 protocol (P0.6, LoA: +/-9). In addition, there was no significant difference between second C-20 and N-30 tests (P0.5, LoA: -12, 6).The study demonstrates the variability of FDT tests over several years. Longitudinal FDT-results in a clinical study showed a higher reproducibility if the first test was discarded. Reproducibility of screening with the N-30 protocol is comparable to the C-20 procedure if an overall score is considered.

Purpose Expression of the genes ERG (v-ets erythroblastosis virus E26 oncogene homolog) and BAALC (brain and acute leukemia, cytoplasmic) shows similarity during hematopoietic maturation and predicts outcome in acute myeloid leukemia. We hypothesized that like ERG, BAALC expression might be of prognostic significance in acute T-lymphoblastic leukemia (T-ALL) and that ERG and BAALC expression together would better identify the patient's risk profile. Patients and Methods ERG and BAALC mRNA expression were determined by real-time reverse transcriptase polymerase chain reaction in 153 adults with T-ALL. Patients were designated low or high ERG expressers and low or high BAALC expressers. Results High BAALC expression correlated with a higher frequency of early T-ALL (P < .0001), CD34 positivity (P < .0001), coexpression of myeloid markers (P = .0001), and high ERG expression (P = .03). High BAALC compared with low BAALC patients had an inferior relapse-free survival (RFS; P = .0008) and overall survival (OS; P = .0001). In contrast, patients with low expression of both ERG and BAALC (representing 41% of all T-ALL patients) had the most favorable outcome (P < .0001; 4-year RFS: low ERG/low BAALC 81%; P < .0001; 4-year OS: low ERG/low BAALC 69%). On multivariable analysis, low ERG/low BAALC expression was of independent favorable prognostic significance (RFS, P = .001; OS, P = .003). Conclusion Low expression of both ERG and BAALC identifies T-ALL patients with a distinctly favorable long-term outcome.

This study was undertaken to identify and compare the prognostic value of gene expression, chromosomal, and clinico-pathological data for the prediction of subsequent metastases in patients with primary uveal melanoma.For comparison of different sets of predictor variables diagonal linear discriminant analysis was used. Chromosomal events were assessed by comparative genomic hybridization and gene expression profiling by microarray. Twenty-eight patients with a median follow-up of 68 months were analyzed, of whom 12 had developed subsequent metastases.Diagonal linear discriminant analysis with crossvalidation of gene expression data detected 42 genes as differentially expressed in metastasizing vsnon-metastasizing uveal melanomas in all 28 cases. Comparing quantitative scores of discriminant analysis, grouping precision was significant better with gene expression profiling compared to comparative genomic hybridization (P=0.01) and to clinical data (P=0.001). Two published gene lists associated with monosomy 3 and metastatic tumor growth were used as classifier for discriminant analysis and yielded superior classification in patients with and without subsequent metastases than chromosomal or clinico-pathological data.In our patient cohort gene expression profiling of primary uveal melanoma tissue was superior to clinical-pathological and chromosomal analysis to assess for the risk of subsequent metastases.

The purpose of this randomized, clinical, double-blind short-term trial was to evaluate the efficacy of a new lacquer containing a new component (phosphonic acid methacrylate) designed for treating dentine hypersensitivity. Eighty-eight patients participated in this study. At the first visit one tooth was treated with the lacquer (1), while another tooth was treated with a placebo (2). Sensitivity levels were determined before treatment as well as after one week. An air blast stimulus and a visual analogue scale were used for evaluation. At baseline, the mean hypersensitivity score of group 1 (53.2+/-26.3) was comparable to the mean hypersensitivity score of the teeth in group 2 (53.3+/-24.4). After one week, a significant reduction of the mean hypersensitivity scores (p0.001; t-test) was revealed in group 1 (25.8 +/-26.6) as well as in group 2 (26.4+/-25.3). The difference between the two treatment groups was not significant (p = 0.7). There is either no difference between the two treatment modalities or the placebo response and/or the time effect was so strong that the treatment efficacy of the new lacquer was hidden by these effects.

2032 Background: Although potentially curable, primary CNS lymphoma (CNS) is still a therapeutic challenge and only a minority of patients survive longer than 5 years. The factors which define the ...

The purpose of this clinical trial was to evaluate the efficacy of 2 over-the-counter whitening systems: a liquid whitening gel (5.9% hydrogen peroxide, twice a day for 15 minutes), and a sodium chlorite-based whitening gel applied in a tray system (10 minutes twice a day).Sixty volunteers (minimum shade A3 on 1 maxillary tooth) were selected to participate in this single-blind (examiner-blinded), single-center, 2-group trial. The subjects were randomly divided into 2 groups (n = 30 each) and instructed to bleach their teeth for 2 weeks. Efficacy was measured using the Vita Classical shade guide and a spectrophotometer at baseline, as well as after 2 weeks and 6 months.For the subjectively measured tooth shades, improvement for maxillary canines was 2.03 +/- 3.67 tooth shades in group 1 and 1.08 +/- 2.19 tooth shades in group 2 after 2 weeks; the maxillary incisors revealed a tooth shade improvement of 0.83 +/- 1.71 tabs in group 1 and 0.73 +/- 2.22 tabs in group 2 (P.05, except maxillary incisors in group 2; t test). Objectively measured tooth shade scores revealed a change of 0 +/- 0.25 tooth shade tabs (P.05).The bleaching gel containing hydrogen peroxide achieved a slight improvement, and the sodium chlorite-based bleaching gel achieved only a small tooth color improvement. Moreover, subjectively and objectively measured tooth shades revealed considerably different results in the clinical situation.

Purpose In adult T-lymphoblastic leukemia (T-ALL) disease-free survival remains limited to 32% to 46%. The adverse prognosis in T-ALL has not been attributed to cytogenetic or molecular aberrations. We have determined the prognostic impact of the oncogenic transcription factor ERG in T-ALL. Patients and Methods ERG expression was analyzed by real-time polymerase chain reaction (PCR) in 105 adults with newly diagnosed T-ALL treated on the German ALL protocols. Patients were dichotomized at ERG′s median expression into low (n = 52) and high (n = 53) expressers. Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time PCR. Results High ERG expressers compared with low ERG expressers had an inferior overall survival (OS, P = .02; 5-year OS: high ERG 26% v low ERG 58%) and relapse-free survival (RFS, P = .003; 5-year RFS: high ERG 34% v low ERG 72%). On multivariable analysis high ERG expression (P = .005), immunophenotypic subgroups (early v mature v thymic T-ALL; overall P = .04), HOX11L2 positivity (P = .055), and absence of HOX11 (P = .017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n = 57), high ERG (HR, 4.1; P = .02) and presence of HOX11L2 (HR, 6.6; P = .008) were independent adverse factors for RFS. Conclusion High expression of ERG is an adverse risk factor in adult T-ALL. Within thymic T-ALL, otherwise classified as standard-risk, high ERG expression-identified patients that were four times more likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of alternative regimens.

To evaluate the bond strengths of six different luting cements to fiber-reinforced composite (FRC) posts after various pre-treatment procedures.180 FRC posts were divided into three groups (n=60) and received the following surface treatments. Group 1: untreated control; Group 2: silane treatment; Group 3: CoJet treatment. The posts of each group were fixed with six different luting cements. Push-out tests were performed to determine the bond strengths between the cements and the fiber posts.The observed bond strengths (MPa) of the different resin cements to the posts were significantly affected by the type of cement (P0.001), but not by the pre-treatment chosen (P0.05; 2-way-ANOVA). Without consideration of the pre-treatment procedures, Clearfil showed the highest bond strengths, followed by Panavia F and RelyX, whereas Multilink, Variolink and PermaFlo showed significantly lower bond strength values (P0.05; Tukey's B).

SUMMARY Background: This study evaluated the clinical efficacy and duration of effectiveness of a new bleaching lacquer for self-application without the use of mouth guards. It compared two different application times. Methods: Forty-six adult subjects who requested bleaching treatment were selected to participate in this randomized, single-blind (examiner-blinded), single center, two-group trial. The subjects were randomly divided into two groups (n=23 each), each being instructed to bleach (8% carbamide peroxide) their six maxillary anterior teeth for two weeks. Daily contact time in Group 1 was 20 minutes once a day and, in Group 2, the time was 20 minutes twice a day. Efficacy was measured subjectively using the Chromascop Complete shade scores obtained at baseline and after one, two and three weeks, as well as after one, three, six and nine months. Results: After two weeks of treatment, the teeth in the Group 1 subjects exhibited a 2.4 ± 0.2 mean shade scores improvement compared to baseline (p0.05). The observed effects were stable for six months. Conclusions: It can be concluded that the new bleaching lacquer is efficacious; however, a double application does not seem to be obligatory.

PURPOSE: To evaluate whether keratometric readings as a measure of corneal shape are associated with optic disc dimensions and with the degree and rate of perimetric progression of chronic open-angle glaucoma or ocular hypertension. METHODS: The hospital-based observational study included 1826 eyes of 936 patients with ocular hypertension, patients with chronic open-angle glaucoma, or normal individuals. For 733 ocular hypertensive or glaucomatous eyes, follow-up examinations were performed with a mean follow-up time of 58.0+/-34.7 months. Observation procedures were keratometry, morphometric optic disc analysis, tonometry, and perimetry. RESULTS: In the normal study group, area of the neuroretinal rim, alpha zone and beta zone of parapapillary atrophy, and retinal vessel diameter were not significantly associated with keratometric readings. In the entire study population, the optic disc area was significantly (P

We sought to test the platelet inhibitory and anti-inflammatory effects of a higher statin dosage compared with combined treatment with ezetimibe plus a low statin dose.Reducing the level of low-density lipoprotein cholesterol (LDL-C) with statins induces important pleiotropic effects such as platelet inhibition. An insufficient LDL-C reduction often is treated with ezetimibe, an intestinal cholesterol absorption inhibitor, in combination with a low statin dose. It is not known whether this combination therapy has the same pleiotropic effects as a statin monotherapy.Fifty-six patients with coronary artery disease were assigned randomly to receive either 40 mg/day of atorvastatin or 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin for 4 weeks. The levels of LDL-C, platelet activation markers after stimulation, platelet aggregation, and plasma chemokine levels (i.e., regulated on activation normally T-cell expressed and secreted [RANTES]) were measured before and after changing lipid-lowering medication.Platelet activation markers (P-selectin) after stimulation (adenosine diphosphate) were reduced by 40 mg/day of atorvastatin (-5.2 +/- 1.6 arbitrary units) but not by ezetimibe plus low-dose atorvastatin (2.1 +/- 1.8 arbitrary units; p0.005) despite a similar reduction of LDL-C (atorvastatin -1.01 +/- 0.18 mmol/l vs. ezetimibe plus atorvastatin -1.36 +/- 0.22 mmol/l, p = NS). Thrombin receptor-activating peptide-induced platelet aggregation as well as plasma RANTES levels were reduced by 40 mg/day of atorvastatin but not by ezetimibe plus low-dose atorvastatin.Platelet reactivity and a proinflammatory chemokine were reduced more by the higher atorvastatin dose than by ezetimibe plus low-dose atorvastatin. In patients with coronary artery disease, it might be important to combine ezetimibe with higher statin dosages to benefit from cholesterol-independent pleiotropic effects.

Different compositions of tooth-colored posts may influence the bonding capacity of various luting agents to these posts. An appropriate understanding of these interactions is presently unavailable.This study initially evaluated the effects of various pretreatment procedures on bond strengths to zirconium-oxide posts using a phosphate-methacrylate resin luting agent. Following that investigation, the bond strengths of various luting agents to tribochemically coated glass-fiber-reinforced composite (FRC) resin and zirconium-oxide posts were investigated.Two hundred zirconium-oxide posts (CosmoPost) divided into 10 groups (n=20) were luted into artificial post spaces prepared with drills provided by the manufacturer. In 4 groups the posts were luted with phosphate-methacrylate resin agent (Panavia F) after receiving one of the following pretreatment procedures: no treatment (control); airborne-particle abrasion; silica coating and silanization with an intraoral airborne-particle-abrasion device (CoJet); or silica coating and silanization with a laboratory airborne-particle-abrasion device in combination with airborne-particle abrasion (Rocatec). The other zirconium-oxide posts in the 6 remaining groups were silica coated (CoJet), silanated, and luted with 1 of 6 different luting agents (Multilink, Variolink, PermaFlo DC, RelyX Unicem, Clearfil Core, and Ketac Cem). Additionally, 60 FRC posts (FRC Postec) were silica coated (CoJet), silanated, and luted with 1 of the 6 resin luting agents (Panavia F, Multilink, Variolink, PermaFlo DC, RelyX, and Clearfil Core). Push-out tests were performed to evaluate the bond strengths between luting agents and posts. Qualitative scanning electron microscopy (SEM) analyses were performed to evaluate the effects of the pretreatment procedures on the surface of the zirconium-oxide posts. Data were analyzed using analysis of variance (ANOVA) followed by the post hoc Tukey B test (alpha=.05).Bond strengths to the posts were significantly affected by the type of luting agent and the type of post (P.001; 2-way ANOVA). Bond strengths of all luting agents to the FRC posts were significantly higher than to the zirconium-oxide posts (P.01), except for Multilink and PermaFlo DC, which demonstrated higher bond strength values to the zirconium-oxide posts (P.001). Pretreatment procedures significantly increased the bond strength of Panavia F to the zirconium-oxide posts (P.05). SEM analyses revealed distinctive irregularities on the surface of the pretreated zirconium-oxide posts compared to the untreated posts.Bond strengths of luting agents to tooth-colored posts are significantly affected by the type of luting agent and the type of post. All investigated pretreatment procedures of zirconium-oxide posts significantly increased the bond strength of Panavia F.

Background: Standard salvage therapy has not been established for recurrent primary central nervous system lymphoma (PCNSL). We report the final results of a prospective study on topotecan chemotherapy in relapsed or refractory PCNSL. Patients and methods: The study included 27 patients with a median age of 51 years and an ECOG performance status of 2. Fourteen patients were refractory to the last therapy, and 13 relapsed after a median period of 6.0 months. Pretreatment with up to four regimens included chemotherapy in 26 patients and whole brain irradiation in 14. A 30-min daily topotecan infusion of 1.5 mg/m2 for 5 days was repeated every 3 weeks. Results: The response rate was 33% with five complete (CR) and four partial remissions (PR). The median follow-up was 37.7 months. All complete responders had sustained remissions lasting for 9 to 28 months. The median event-free survival (EFS) was 2.0 months (9.1 months in responders), the overall survival (OAS) was 8.4 months. CTC grade 3–4 leukopenia occurred in 26% and thrombocytopenia in 11% of the patients. Eight of 12 patients alive without cerebral lymphoma ≥ six months after topotecan exhibited deficits attributable to late neurotoxicity. Conclusion: Topotecan as monotherapy is active in relapsed and refractory PCNSL with tolerable toxicity.

In this paper we discussed the usefulness and problems concerning the implementation of a multicentre clinical registry for Adamantiades-Behcet’s disease. Of course, this paper was written from the perspective of a statistician. Thus, the concepts described in the paper have to be filled with life by clinical experts of Adamantiades-Behcet’s disease. However, the necessity of such a registry and the benefit obtained from the cooperation of different centres is obvious and may improve patient care and research in this medical field.

Superiority of irinotecan/cisplatin over etoposide/cisplatin was suggested in small-cell lung cancer (SCLC). This trial investigated irinotecan/carboplatin (IP) versus etoposide/carboplatin (EP).The interim analysis at the phase II/phase III transition point of the multicenter trial is reported. Extensive disease SCLC patients were randomized to receive carboplatin AUC 5 mg x min/ml either in combination with 50 mg/m2 of irinotecan on days 1, 8 and 15 (IP) or with etoposide 140 mg/m2 days 1-3 (EP). The primary end point was response rate and the secondary end points were toxicity and progression-free survival.Seventy patients were randomized. Significant differences in grade 3 and 4 thrombopenia (17% IP versus 48% EP, P = 0.01) and neutropenia (26% IP versus 51% PE, P0.01) were found. Grade 3 and 4 diarrhea was more frequent with IP (18%) than with EP (6%) (P = 0.133). Response rates were 67% and 59% (P = 0.24) in the IP versus EP arm, respectively. Median progression-free survival (PFS) was 9 months (95% CI 7.1-10.9) in the IP arm and 6 months (95% CI 4.1-7.9) in the EP arm (P = 0.03).IP is active, less toxic and appears to improve PFS. Based on the phase II results the trial has been extended to phase III to assess the impact on overall survival.

Objective: To evaluate which factors influence maximum gain in best-corrected visual acuity after intravitreal injection of triamcinolone acetonide as treatment for diffuse diabetic macular edema. Methods: This prospective clinical interventional study included 53 eyes with diffuse diabetic macular edema receiving an intravitreal injection of about 20 mg of triamcinolone. The mean±SD follow-up was 10.2±7.6 months. Results: In a multiple linear regression analysis, maximum gain in best-corrected visual acuity after the intravitreal injection of triamcinolone was significantly (P.001) and negatively correlated with an increased degree of macular ischemia and a higher preoperative visual acuity. Improvement in best-corrected visual acuity was significantly and positively correlated with increased degree of macular edema (P=.001). Change in best-corrected visual acuity after the intravitreal triamcinolone injection was statistically independent (P.15) of age, sex, pseudophakia, and macula grid laser treatment before inclusion into the study. The results were comparable for gain in visual acuity at 6 months after the injection. Conclusion: Pronounced macular edema may have a positive impact, and marked macular ischemia and a high preoperative best-corrected visual acuity may have a negative impact, on an increase in best-corrected visual acuity after intravitreal triamcinolone injection in patients with diabetic macular edema. Arch Ophthalmol. 2005;123:1338-1343

The aim of this retrospective single-center study was to analyze the clinical characteristics and outcome of non-Hodgkin lymphoma (NHL) patients with central nervous system (CNS) involvement and to identify prognostic factors for survival. We searched our hospital records for NHL patients diagnosed with CNS involvement from 1982 to 2004, and 43 patients were identified. The median age was 63 years (range 23-88) and the median Karnofsky performance status was 55% (range 10-90). Treatment of CNS lymphoma included intrathecal chemotherapy in 33 patients (77%), systemic chemotherapy in 25 (58%), and radiotherapy in 16 (37%). Twenty-six patients showed a CNS response. The median survival after CNS manifestation was 5 months (range 2 days-82.5+months). Nine patients achieved long-term survival. Low lactate dehydrogenase (LDH) at CNS manifestation and a CNS response to therapy were favorable independent prognostic factors for survival in multivariate analysis (p = 0.051 and p0.0005, respectively), whereas a young age at initial diagnosis, initial CNS involvement, an initially normal LDH, and high-dose chemotherapy for CNS involvement were significant in univariate analysis. In conclusion, long-term survival can be achieved in patients with secondary CNS lymphoma. LDH at CNS manifestation and a CNS response to therapy were significantly associated with survival.

PURPOSE. To evaluate whether the amount of glaucomatous optic nerve damage at presentation of the patient and the rate of progression of glaucoma during follow-up are related to central corneal thickness. METHODS. The prospective observational clinical study included 861 eyes of 454 white subjects (239 normal eyes of 121 subjects, 250 ocular hypertensive eyes of 118 patients, 372 eyes of 215 patients with chronic open-angle glaucoma). For 567 eyes (304 patients) with ocular hypertension or chronic open-angle glaucoma, follow-up examinations were performed, with a mean follow-up time of 62.7 33.2 months (median, 60.8; range, 6.2–124.9). All patients underwent qualitative and morphometric evaluation of color stereo optic disc photographs and white-on-white visual field examination. Central corneal thickness was measured by corneal pachymetry. RESULTS. Central corneal thickness correlated significantly (P 0.001) and positively with the area of the neuroretinal rim and negatively with the loss of visual field. Development or progression of glaucomatous visual field defects detected in 119 (21.0%) eyes was statistically independent of central corneal thickness, in univariate (P 0.99) and multivariate Cox regression analyses (P 0.19). CONCLUSIONS. At the time of patient referral, the amount of glaucomatous optic nerve damage correlated significantly with a thin central cornea. Progression of glaucomatous optic nerve neuropathy was independent of central corneal thickness, suggesting that central corneal thickness may not play a major role in the pathogenesis of progressive glaucomatous optic nerve damage. (Invest Ophthalmol Vis Sci. 2005;46:1269 –1274)

Atherosclerosis is a chronic inflammatory disease accompanied by the expression of endothelial adhesion molecules. Phloretin is a plant-derived phytochemical that is mainly present in apples. Because phloretin is reported to promote antioxidative activities, we investigated the effects of phloretin on cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin) in human umbilical vein endothelial cells (HUVECs). Phloretin prevented TNF-alpha-stimulated upregulation of VCAM-1, ICAM-1, and E-selectin expression in a concentration-dependent manner. To the same extent as for TNF-alpha, phloretin also inhibited IL-1beta-induced upregulation in expression of all 3 adhesion molecules. Inhibition of cytokine-induced adhesion molecule expression for VCAM-1, ICAM-1, and E-selectin was detected already at the level of mRNA. Preincubation with phloretin dose-dependently attenuated TNF-alpha-stimulated adhesion of monocytic THP-1 cells to HUVECs and human aortic endothelial cells. Phloretin did not affect TNF-alpha-stimulated activation of nuclear factor kappaB (NF-kappaB) but inhibited activation of interferon regulatory factor 1, a transcription factor involved in the regulation of endothelial cell adhesion molecule expression. In human platelets, phloretin diminished adenosine diphosphate (ADP) and thrombin receptor-activating peptide-stimulated expression of the activated form of the GPIIb/IIIa complex and reduced platelet aggregation stimulated by ADP. Thus phloretin may have beneficial effects in the onset and progression of cardiovascular diseases.

Aim To evaluate the resin–dentine interface of different adhesive systems and corresponding luting cements proposed for bonding fibre posts to root canal dentine. Methodology Fifty extracted maxillary canines and central incisors were used. After root canal treatment the teeth were randomly divided into five groups of 10 teeth each. Fibre posts were inserted with five different adhesive systems and corresponding luting cements. Group 1: Clearfil Core/New Bond (Kuraray), group 2: Multilink (Vivadent), group 3: Panavia 21/ED Primer (Kuraray), group 4: PermaFlo DC (Ultradent), and group 5: Variolink II/Excite DSC (Vivadent). The primer was labelled in each case with 0.1% Rhodamine B isothiocyanate (RITC). Each root was sectioned into 2 mm thick slices at 1, 4 and 7 mm below the cementoenamel junction. The resin–dentine interface was evaluated using a Confocal Laser Scanning Microscope; the thickness of the hybrid layer and the number of resin tags were measured. The statistical analysis was performed using nonparametrical tests for comparisons between groups; for overall comparisons the Kruskal–Wallis test was used. Intraindividual analysis within teeth was performed using a linear model. Results The thickness (μm) of the hybrid layer of group 1 (5.45; SD 1.21), group 4 (3.36; SD 1.59), and group 5 (4.33; SD 1.19) was significantly higher than in the other groups (P ≤ 0.05). The number of resin tags observed in group 1 was significantly higher than in groups 2–4 (P