Reference and target region modeling of [11C]-(R)-PK11195 brain studies.

PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo imaging of microglial activation in the human brain. In this work we devised a supervised clustering procedure and a new quantification methodology capable of producing binding potential (BP) estimates quantitatively comparable with those derived from plasma input with robust quantitative implementation at the pixel level. METHODS: The new methodology uses predefined kinetic classes to extract a gray matter reference tissue without specific tracer binding and devoid of spurious signals (in particular, blood pool and muscle). Kinetic classes were derived from an historical database of 12 healthy control subjects and from 3 patients with Huntington's disease. BP estimates were obtained using rank-shaping exponential spectral analysis (RS-ESA) (both plasma and reference input) and the simplified reference tissue model (SRTM). Comparison between plasma- derived BPs and those produced with the new reference methodology was performed using 6 additional healthy control subjects. Reliability of the new methodology was performed on 4 test-retest studies of patients with Alzheimer's disease. RESULTS: The new algorithm selected reference voxels in gray matter tissue avoiding regions with specific binding located, in particular, in the venous and arterial circulation. Using the new reference, BP values obtained using a plasma input and a reference input were in excellent agreement and highly correlated (r = 0.811, P < 10(-5)) when calculated with RS-ESA and less so (r = 0.507, P < 0.005) when SRTM was used. In the production of parametric maps, SRTM was used with the new reference extraction, resulting in test-retest variability (10.6%; mean ICC = 0.878) that was superior to that obtained using the previous unsupervised clustering approach (mean ICC = 0.596). CONCLUSION: Reference region modeling combined with supervised reference tissue extraction produces a robust and reproducible quantitative assessment of [(11)C]-(R)-PK11195 studies in the human brain.     

Differences in CMV-Specific T-Cell Levels and Long-Term Susceptibility to CMV Infection after Kidney, Heart and Lung Transplantation

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T-cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV-specific T-cell frequencies in long-term renal (1.48%; range 0.06-17.26%) and heart transplant recipients (0.90%; 0.13-12.49%) did not differ from controls (1.82%; 0.26-21.00%). In contrast, CMV-specific T-cell levels were significantly lower in lung transplant recipients (0.50%; <0.05-4.98%) and showed a significant correlation with the frequency of infectious episodes (r =-0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T-cell reactivity in vitro. In conclusion, monitoring CMV-specific CD4 T cells may serve as a measure for long-term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.     

Cardinal points and image–object magnification with an accommodative lens implant (1 CU)

A simple mathematical method for the determination of the cardinal points of pseudophakic eyes after implantation of an accommodative intraocular lens [posterior chamber intraocular lenses (PCIOL)] is presented. The purpose of this study was to explore the changes during pseudophakic accommodation (PAC) in (1). the positions of the cardinal points, (2). the distance of the object conjugate with the retina, and (3). the image-object magnification. These theoretical accommodation data are compared with clinical measurements. METHODS AND PATIENTS: Using biometrical measurements of the axial length, equivalent power of the cornea and the anterior chamber depth (ACD) in the non-accommodated state we used linear geometric optics for determination of the cardinal points and object distance as well as lateral magnification (the ratio of image to object size). With the measurement of ACD decrease (following pharmacological stimulation of the ciliary muscle with 2% pilocarpine eye drops) we determined the changes of the cardinal points and magnification to assess PAC amplitude from the shortening of the object distance. Calculated values of PAC amplitude were compared with the respective measured values derived from amplitude measures by accommodometer, defocusing and streak retinoscopy. We analysed the results of a prospective study on 35 eyes of 28 patients after cataract surgery (target refraction: -0.2 D) and accommodative PCIOL implantation (1 CU, Human Optics AG, Erlangen, Germany) 3 months after surgery. RESULTS: After pilocarpine eye drops, ACD (mean +/- S.D., range; median) decreased by 0.88 +/- 0.48 mm (0.51-1.91; 0.66). Distance of the in-focus object decreased from the non-accommodated state (-5.62 +/- 1.83 m, -25 to -1.1; -4.83 m) to the accommodated state (ACD decrease) (-0.81 +/- 0.21, -2.11 to -0.65; -0.79 m). For a theoretical ACD decrease of 1.0 mm (the intrinsic limitation of the PCIOL design) it was -0.59 +/- 0.28, -1.31 to -0.51; -0.63 m and resulted in an objective accommodative response of 1.49 +/- 0.16, 1.21-1.81; 1.46 D, depending on the actual geometry of the individual eye. On average, magnification as induced by PAC in contrast to that induced by adequate spectacle addition differed by only about 1%. Accommodation measured with defocusing and the accommodometer correlated significantly with the theoretical value based on IOLMaster measurement of ACD decrease (r = 0.752, p = 0.005 and r = 0.676, p = 0.02). Likewise, accommodation measured with streak retinoscopy correlated weakly with the theoretical value based on IOLMaster ACD decrease (r = 0.465, p = 0.05). CONCLUSIONS: Using geometrical optics, PAC can be derived from the biometric data of the eye and the measured ACD decrease. This approach may be an additional indicator for the accommodative response in pseudophakic patients and may allow a subdivision of the measured accommodation into true PAC and pseudoaccommodation, for example, because of increased depth of focus induced by pupillary constriction.     

Über die Bedeutung der Leber in der Pathogenese der trophallergischen Ernährungsstörungen im Säuglingsalter

Zusammenfassung Nach einleitenden Beobachtungen über die trophallergischen Ernährungsstörungen im Säuglingsalter wird eingehend die Rolle der Leber, die eine Zentralstellung in der Pathogenese der zur Diskussion stehenden Krankheitsgruppe einnimmt, berücksichtigt. Eigene Untersuchungen und Beobachtungen sowie Berücksichtigung der einschlägigen Literatur führen zur Kenntnis des Schutzmechanismus, den die Leber im trophallergischen Geschehen ausübt. Widals hämoklasische Krise gewinnt dabei eine neue Bedeutung; ihr positiver Ausfall ist im Säuglings- und Kleinkindesalter identisch mit der erwähnten Schutzfunktion der Leber. Aus diesen Erkenntnissen wird eine Arbeitshypothese entwickelt, die geeignet ist, das bisher rätselhafte sogenannte Abgleiten des Säuglings in die Intoxikation bzw. in den totalen trophallergischen Schock während einer klinisch bedeutungslosen Grundkrankheit zu erklären: Durch einen pathologischen Sympathikotonus während der Grundkrankheit wird die schützende Lebervenensperre durchbrochen und damit sowohl den Schockgiften als auch dem Allergen der Weg in den gesamten Organismus geöffnet, wo diese Substanzen ihre verheeernde Wirkung auszuüben imstande sind. Auf therapeutische Folgerungen, die sich auf dieser Hypothese aufbauen könnten, wird nicht eingegangen. Die Anregung zu therapeutischen Versuchen sei hiermit gegeben.Mit Einverständnis des Chefarztes der Städt. Kinderklinik Bayreuth: Dr. K. Beck.     

Effect of a 0.5% Dilution of Propofol on Pain on Injection during Induction of Anesthesia in Children

Background: Pain on injection of propofol in children has been reported to be as high as 30-80%. The reason for the pain is assumed to be the aqueous phase of the propofol emulsion. Therefore, for the first time, this study tested the hypothesis that dilution of propofol to a 0.5% emulsion might reduce the incidence of pain during propofol injection.

Methods: The study design was prospective, monocenter, double-blind, and randomized. Sixty-four children aged 2-6 yr were scheduled to receive 0.5% or 1.0% propofol in a medium-chain-triglyceride/long-chain-triglyceride emulsion. Incidence and intensity of pain were assessed by spontaneous expressions of pain and withdrawal of the arm. In a subgroup of 21 children, serum triglyceride levels were measured before and 3 and 20 min after induction. Adverse events were recorded.

Results: Amounts of propofol required until loss of eyelash reflex were 4.40 +/- 1.01 mg/kg for 0.5% propofol and 4.31 +/- 0.86 mg/kg for 1.0% propofol. Percentages of children who showed at least one pain reaction were 23.3% in the 0.5% propofol group and 70.0% in the 1.0% propofol group (P < 0.001). Serum triglycerides were higher in the 0.5% propofol group 3 and 20 min after injection (251.7 vs. 148.8 mg/dl; P = 0.001 and 135.5 vs. 75.5 mg/dl; P = 0.03). Adverse events or complications did not occur.     

18F-FDG PET for mediastinal staging of lung cancer: which SUV threshold makes sense?

(18)F-FDG PET is the most accurate noninvasive modality for staging mediastinal lymph nodes in lung cancer. Besides using visual image interpretation, some institutions use standardized uptake value (SUV) measurements in lymph nodes. Mostly, an SUV of 2.5 is used as the cutoff, but this choice was never deduced from respective studies. Receiver operating characteristic (ROC) analyses demonstrated that SUV thresholds of more than 4 resulted in the highest accuracy. But these high cutoffs imply high false-negative rates (FNRs). The aim of our evaluation was to determine an optimal SUV threshold and to compare its diagnostic performance with the results of visual interpretation. METHODS: This retrospective study included 95 patients with suspected lung cancer who underwent mediastinoscopy/mediastinal lymphadenectomy after (18)F-FDG PET (90-150 min after 250 MBq of (18)F-FDG). Maximum SUV was measured in 371 lymph node regions biopsied afterward and visually interpreted using a 6-level score (- - - through + + +). Diagnostic performance was assessed by ROC analysis. FNR and false-positive rate (FPR), the sum of both error rates (FNR + FPR), and diagnostic accuracy were plotted against a hypothetical SUV threshold to determine the optimum SUV threshold. RESULTS: SUVs in metastatic lymph nodes were higher (mean +/- SD, 7.1 +/- 4.5; range, 1.4-26.9; n = 70) than in tumor-free lymph node stations (2.4 +/- 1.7; range, 0.6-14.9; n = 301; P < 0.01). Inflammatory lymph nodes exhibited slightly increased SUVs (2.7 +/- 2.0; range, 0.8-14.9; n = 146). The plot of error rates featured a minimum of the sum FNR + FPR for an SUV of 2.5. With increasing SUV threshold, the FPR decreased most prominently up to that value whereas a continuous rise of FNR was noticed. Highest diagnostic accuracy was achieved with an SUV of 4.5. The areas under the ROC curves demonstrated that visual interpretation tends to be more accurate than SUV quantification (visual, 0.930 +/- 0.022; SUV, 0.899 +/- 0.025; P = 0.241). Using an SUV of 2.5 as the threshold, the resulting sensitivity, specificity, and negative predictive value were 89%, 84%, and 96%, respectively. CONCLUSION: For mediastinal staging, the choice of an SUV of 2.5 as the threshold is justified because FNR + FPR is minimized. The resulting high negative predictive value of 96% allows the omission of mediastinoscopy in patients with negative mediastinal findings on (18)F-FDG PET images. For the experienced observer, visual analysis should be relied on primarily, with calculation of the SUV used, at most, as a secondary aid. For the less experienced observer, the SUV may be of greater value.     

Chronische Diarrh?en unter NSAR

Ohne Zusammenfassung     

Juristische Praxis in den Life Sciences.

Ohne Zusammenfassung     

Expressed-emotion development and course of schizophrenic illness: considerations based on results of a CFI replication

This study examines the correlation between development of expressed emotion (EE) in relatives and course of illness of 99 DSM-III schizophrenic patients. Patients whose relatives were high EE at baseline and at the 2nd CFI approximately 20 months later had a poor prognosis at the very outset of the study and an unfavourable course of illness. They had a higher rehospitalisation rate, more symptoms, lower psychosocial assessment, and a poorer 2-year and even 8-year outcome. Patients from families with a fluctuating EE or a consistently low EE had better courses. Expessed emotion is therefore a valid predictor not only of symptomatic relapses, but also of other important aspects of schizophrenia. The connection between EE index and course of illness seerns not to be simply reactive or causal, but complex and non-uniform.