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M Schwaiger

Publications and source records attributed to M Schwaiger.

At least 37 records · Page 2Linked to original sources

Cardiac magnetic resonance imaging: long term reproducibility of the late enhancement signal in patients with chronic coronary artery disease.

OBJECTIVE: To determine long term reproducibility of the late enhancement (LE) signal in contrast enhanced magnetic resonance imaging (MRI) and potential changes of the signal after revascularisation. METHODS: 33 patients (29 men, mean (SD) 61 (11) years) with coronary artery disease (CAD) and left ventricular dysfunction (ejection fraction 30 (7)%) underwent two contrast enhanced MRI procedures within 9 (3) months. Fifteen patients (group A: 14 men, 59 (12) years) had no interventions between the two studies. Eighteen patients underwent revascularisation after MRI 1 (group B: 15 men, 62 (9) years). Changes in the LE signal between the first and second MRIs were investigated in both groups as well as intraobserver and interobserver variabilities for delineation of the signal. RESULTS: The LE signal was highly reproducible in groups A and B for segmental analysis (concordance 86% v 82%, respectively; kappa = 0.70 v 0.67) and summed scores (group A: r = 0.97, p < 0.001; group B: r = 0.93, p < 0.001). The LE signal was quantified as 27 (27) cm3 in group A versus 30 (16) cm3 in group B in the first MRI and 26 (25) cm3 versus 30 (15) cm3, respectively, for the second MRI (both not significant). Moreover, low intraobserver and interobserver variabilities were observed in segmental analysis (kappa = 0.86 and 0.74, respectively, for group A, and kappa = 0.87 and 0.82, respectively, for group B). CONCLUSION: In patients with chronic CAD, the LE signal in contrast enhanced MRI is very stable over an extended time period. These results further characterise contrast enhanced MRI as a useful tool for myocardial viability assessment. Low intraobserver and interobserver variabilities promise robustness of the method for clinical application.

Aged↗

Nuclear cardiology in acute coronary syndromes.

Acute coronary syndromes are a frequent manifestation of coronary artery disease, usually being associated with chest pain and presenting as a medical emergency. Since a considerable number of patients with chest pain, however, have a non cardiac etiology of their pain, properly triaging these patients represents a diagnostic challenge for physicians in the emergency department. As the available diagnostic procedures have limited accuracy, many different diagnostic strategies have been evaluated. Among these, radionuclide myocardial perfusion imaging (MPI) at rest or in combination with stress procedures has been investigated in many trials. MPI has been proven to be useful, especially in a patient population with a low to intermediate probability of an ischemic event. Perfusion scintigraphy has a high sensitivity in the detection of myocardial infarction and reveals an excellent negative predictive value, allowing a safe discharge strategy of patients with a negative scan result. Moreover, it enables risk stratification and provides incremental and independent prognostic information regarding short to long term future cardiac adverse events. Several cost effectiveness studies have shown that perfusion imaging leads to lower overall direct costs, mainly by a reduction of unnecessary hospital admissions and diagnostic angiograms, without worsening of the clinical outcome of these patients. As a possible study endpoint, myocardial perfusion imaging in the acute setting enables the quantification of salvaged myocardium and therefore the evaluation of treatment efficacy. Besides perfusion agents, several infarct avid radiopharmaceuticals have been developed, which in part show promising results. However, larger randomized trials evaluating these tracers in clinical settings are needed to warrant routine clinical application.

Angina, Unstable↗

FDG PET and CT in locally advanced adenocarcinomas of the distal oesophagus. Clinical relevance of a discordant PET finding.

AIM: The incidence of adenocarcinomas of the distal oesophagus (ADE) has dramatically increased in Western countries. The clinical importance of a FDG PET finding discordant with CT was determined in patients with locally advanced ADE. In addition, tumour standardized uptake values (SUV) were correlated with patient survival. PATIENTS, METHODS: 40 consecutive patients were analyzed retrospectively. All patients underwent an attenuation corrected FDG PET scan (neck, chest, abdomen) and contrast enhanced helical CT of the chest and abdomen. PET and CT scans were reviewed independently and concomitantly with respect to metastases in predefined lymph node sites and organs. Any discordance between PET and CT was assessed for clinical relevance. Clinical relevance was defined as a change in the overall therapeutic concept (curative vs. palliative). Follow-up imaging and histological evaluation served as the gold standard. Mean tumour SUVs were determined by 1.5 cm regions of interest placed over the tumour's maximum. RESULTS: When read independently from the CT scan FDG PET indicated a clinically relevant change in tumour stage in 9/40 patients (23%) and a non-relevant change in 11/40 patients (28%). PET was correct in 5/9 patients (56%) with clinically relevant discordances. In 4/9 patients PET was incorrect (3 false positive due to suspicion of M1-lymph nodes or lung metastases, 1 false negative in disseminated liver metastases). With concomitant reading, PET indicated a clinically relevant change in tumour stage in 6/40 patients (15%) and a non-relevant change in 5/40 patients (13%). PET was correct in 5/6 patients (83%) with clinically relevant discordances. The patient with disseminated liver disease remained the single false negative. Overall, the benefit from PET was based on its higher diagnostic accuracy at organ sites. Tumour SUV did not correlate with patient survival. CONCLUSION: About half of discordances between FDG PET and CT are clinically relevant. Concomitant reading of PET and CT is advisable as it reduces the overall rate of discordances and enhances the accuracy of PET in clinical relevant discordances (from 56% to 83%).

Adenocarcinoma↗

Proof of principle for the use of 11C-labelled peptides in tumour diagnosis with PET.

PURPOSE: The future significance of peptide radiopharmaceuticals in diagnostic imaging with PET will be dependent on methodological aspects, as well as other requirements such as availability of the radionuclide and cost-effectiveness of its production. The aim of this study was to evaluate whether recent improvements in the modification of peptide pharmacokinetics by carbohydration may open a niche for the use of 11C-labelled peptide receptor binding tracers. METHODS: A carbohydrated analogue of Tyr3-octreotate was used as a clinically relevant peptide. Oxime-mediated coupling between 4-[11C]methoxy-benzaldehyde and an aminooxy-conjugated peptide precursor provided the 11C-labelled peptide in 21+/-5% decay-corrected yield (n=4) in a synthesis time of about 1 h. RESULTS: In rat pancreas carcinoma xenografted mice, the compound displayed predominant and fast renal clearance combined with high tumour uptake (18.5+/-2.8% ID/g) at 30 min post injection. Corresponding values for kidney, liver and intestine were 18.5+/-2.4% ID/g, 3.2+/-0.5% ID/g and 2.1+/-0.3% ID/g, respectively. In a PET study with xenografted mice, the tumour (0.2-0.3 g) was clearly delineated as early as 20 min after injection. Somatostatin receptor (sstr)-specific uptake was demonstrated by reduction of tumour uptake to 20% of control by co-injection of TOC (0.4 mg/kg; 30 min p.i.). CONCLUSION: A 11C-labelled octreotate derivative has been prepared which shows suitable pharmacokinetics for in vivo imaging of sstr-overexpressing tumours and thus represents the first proof of principle for the potential of 11C-labelled peptides in tumour imaging.

Animals↗

Comparison of different SUV-based methods for monitoring cytotoxic therapy with FDG PET.

PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is a promising tool for monitoring cytotoxic therapy in tumours. Due to the limited data available, a standard imaging protocol for the prediction of tumour response has not yet been approved. The aim of this study was to compare commonly applied imaging protocols and calculations of the standardised uptake value (SUV) for the early prediction of histopathological response to chemotherapy. METHODS: Serial FDG PET scans of 43 patients with gastric carcinomas were retrospectively analysed. All patients received two consecutive scans (one bed position at 40 min p.i. and four bed positions at 90 min p.i.) at baseline and during the first cycle of cisplatinum-based chemotherapy. Reconstruction of the images was performed by filtered back-projection (FBP) and using an iterative algorithm (OSEM). SUVs were calculated with and without correction for the blood glucose level using normalisation by body weight, body surface area and lean body mass. Relative percentage changes between SUVs at baseline and follow-up were calculated and analysed for their potential to predict histopathological response to chemotherapy (ROC analysis). Response was defined as less than 10% viable tumour cells in the tumour specimen obtained by surgery 3-4 weeks after the completion of chemotherapy. RESULTS: Eight of 43 patients were histopathological responders to chemotherapy. The percentage changes in SUV(body weight) for responders and non-responders were -52.2 (+/-13.2) and -25.2 (+/-15.2), -54.7 (+/-18.2) and -24.5 (+/-16.1), -53.9 (+/-24.2) and -22.7 (+/-21.3), and -56.7 (+/-21.6) and -26.1 (+/-18.9) for serial scans at 40-min FBP, 40-min OSEM, 90-min FBP and 90-min OSEM, respectively (responders versus non-responders: p<0.01 in each case). According to ROC analysis, neither the scan protocol nor correction for blood glucose significantly influenced the accuracy (approx. 80%) or the cut-off value (approx. -40% change in tumour SUV) for the prediction of response. Normalisation of SUVs by body surface area or lean body mass instead of body weight yielded essentially identical results. CONCLUSION: In gastric carcinomas the prediction of response to chemotherapy on the basis of relative tumour SUV changes is not essentially influenced by any of the methodological variations investigated (time delay after FDG administration, acquisition protocol, reconstruction algorithm, normalisation of SUV). This demonstrates the robustness of FDG PET for therapeutic monitoring and facilitates the comparability of studies obtained at different institutions and with different protocols. However, whichever method is used for therapy monitoring with FDG PET, a highly standardised protocol must be observed to take the dynamics of tumour FDG uptake into account.

Algorithms↗

Preserved visual-vestibular interaction in patients with bilateral vestibular failure.

BACKGROUND: During caloric vestibular stimulation, subjects showed bilateral activation of the vestibular cortex in the posterior insula and retroinsular region as well as concurrent deactivation of visual cortex areas bilaterally. This finding was the basis for the concept of a reciprocal inhibitory interaction between the vestibular and the visual systems. OBJECTIVE: To analyze the modulations of this activation and deactivation pattern in patients with loss of vestibular input, that is, in patients with bilateral vestibular failure (BVF). METHODS: Modulations of regional cerebral blood flow (rCBF) in PET were measured in nine patients with BVF and compared with those in healthy volunteers using statistical group as well as single-subject analyses (Statistical Parametric Mapping 96b). RESULTS: The group analysis of the BVF patients showed only one small region of activation in the posterior insula contralateral to the stimulated ear, whereas the other areas correlating with vestibular, autonomic, and ocular motor function were not activated. Furthermore, the concurrent rCBF decreases of the primary visual cortex seen in healthy volunteers were not found in the patients. These decreases seem to be dependent on an intact vestibular input with concurrent vestibular nystagmus. CONCLUSIONS: The results are compatible with the concept of a reciprocal inhibitory sensorisensory interaction between the vestibular and visual systems that normally act together for orientation in space and perception of motion. This interaction appears to be preserved in the patients at a significantly lower level, that is, with less activation and less deactivation.

Adult↗

[PET/CT for colorectal and hepatic tumors].

This contribution presents clinical and technical aspects of combining positron emission tomography (PET) and computed tomography (CT) for patients with colorectal tumors and characterization of unclear liver foci. In which manner and for which patients combined PET/CT is superior to PET or CT alone is also discussed. PET/CT can fulfil most prerequisites for imaging in pre- and postoperative management of patients with colorectal tumors and best meets the desire for optimal imaging procedures. Some of the disadvantages encountered in frequently employed CT can be overcome by the combination of PET and CT while increasing both sensitivity in detecting lesions and specificity in their characterization. Questions regarding treatment response offer an opportunity for devising novel study concepts and initiating research on new PET tracers. Although few publications are available, we are of the opinion that the combination of functional and anatomical imaging provided by PET/CT can improve both preoperative management and aftercare. To this end, however, optimum cooperation between practitioners of nuclear medicine and radiology is imperative.

Adult↗

Targeting of gelatinase activity with a radiolabeled cyclic HWGF peptide.

Matrix metalloproteinases (MMPs) are a family of proteinases that play an important role in cancer as well as in numerous diseases. In this article, we describe the labeling of a phage display selected cyclic decapeptide containing the HWGF (histidine-tryptophane-glycine-phenylalanine) sequence to target MMP-2 and MMP-9. To evaluate the ability of this labeled peptide to monitor non invasively MMP-2 and MMP-9 activity, in vitro studies, biodistribution, competition studies and plasma metabolites analyses in Lewis Lung cancer tumor bearing mice were performed.

Animals↗

Synthesis and preclinical evaluation of the choline transport tracer deshydroxy-[18F]fluorocholine ([18F]dOC).

11C-labeled choline ([11C]CHO) and 18F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[18F]fluorocholine, ([18F]dOC), a non-metabolizable [18F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [18F]dOC was compared with that of [11C]choline ([11C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [18F]dOC and [11C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC50 [18F]dOC= 11 microM; IC50 [11C]CHO=13 microM. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [18F]dOC after 5 min incubation time is comparable to that of [11C]CHO, whereas the uptake of [11C]CHO was superior after 20 min incubation time. As for [11C]CHO, kidney and liver were also the primary sites of uptake for [18F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [18F]dOC at 10 min post-injection, whereas [11C]CHO uptake was higher at later time points. In conclusion, [18F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [18F]dOC and [11C]CHO result in comparable cellular uptake levels at early time points. In contrast to [18F]dOC, which is transported but not intracellularly trapped, the choline kinase substrate [11C]CHO is transported into tumor cells and retained. Thus, the signal obtained by imaging early after injection is mainly reflecting transport, whereas a valid quantification of choline kinase activity needs imaging at later time points. Further studies have to clarify whether quantification of the transport capacity or the choline kinase activity result in a better pathophysiological correlate and thus is the more useful process for tumor characterization.

Animals↗

Modeling of esophageal bolus flow by functional data analysis of scintigrams.

Peristaltic forces cause a topographic, time-dependent distribution of bolus mass during its esophageal transport. A two-dimensional spatial-temporal pattern (profile) of local transit times is constructed by computer-based double compression of scintigraphic images sampled from whole swallows. Reconstruction by Gaussian bands and modeling this pattern discloses transient ellipsoidal bolus structures. The structures studied in 10 healthy volunteers present highly reproducible quantitative parameters for marking a region-specificity of transit times, which is related to the known region-selectivity of esophageal functions. Correlation of bolus flow with the dynamics of peristalsis is essential for understanding the complex mechanisms of esophageal transport as well as for diagnostic discrimination of disturbances of bolus flow.

Adult↗

Synthesis and biological evaluation of a (99m)Tc-labelled cyclic RGD peptide for imaging the alphavbeta3 expression.

AIM: The alphavbeta3 integrin is involved in tumour induced angiogenesis and tumour metastasis. We describe the synthesis and evaluation of a (99m)Tc-labelled RGD analogue for the visualisation of alphavbeta3 integrin expression. METHODS: The linear peptides were assembled on a solid support. Cyclisation was performed under high dilution conditions. For conjugation with the chelator peptide, a water soluble carbodiimide was used. Radiolabelling was carried out due to standard procedures with high radiochemical yield and radiochemical purity. For in vivo evaluation, nude mice bearing alphavbeta3-positive human melanoma M21 and alphav-negative human melanoma M21-L or Balb/c mice bearing alphav-positive murine osteosarcoma were used. RESULTS: Activity accumulation of (99m)Tc-DKCK-RGD 240 min p. i. was 1.1% ID/g in the alphavbeta3-positive melanoma and 0.3% ID/g in the negative control tumour. In the osteosarcoma model 2.2% ID/g was found 240 min p. i. Planar gamma camera images allowed contrasting visualisation of alphavbeta3-positive tumours 240 min p. i. Blocking of the tumour using the alphavbeta3-selective pentapeptide cyclo(-Arg-Gly-Asp-D-Phe-Val-) reduces activity accumulation in the tumour to background level. However, 240 min p. i. highest activity concentration was found in kidneys resulting in low tumour/kidney ratios. Metabolite analysis 240 min p. i. showed approximately 60% intact tracer in kidneys and 80% in the tumour. Only 24% intact tracer was found in blood 30 min p. i. CONCLUSION: (99m)Tc-DKCK-RGD allows imaging of alphavbeta3-positive tumours in mice. However, pharmacokinetics as well as metabolic stability of the tracer have to be improved for potential clinical application.

Amino Acid Sequence↗

Myocardial blood flow and coronary flow reserve in children with "normal" epicardial coronary arteries after the onset of Kawasaki disease assessed by positron emission tomography.

Myocardial blood flow (MBF) was investigated in children (14.2 +/- 5.01 years) with "resolved" coronary involvement after the onset of Kawasaki disease and angiographically normal epicardial coronary arteries. Ten asymptomatic children with a history of Kawasaki disease had electrocardiography, echocardiography, and positron emission tomography (PET) 10.3 +/- 6.01 years after onset of the acute illness. Myocardial perfusion was assessed by NH(3)- PET at rest and after vasodilatation and compared with that of 10 healthy volunteers (26.1 +/- 6.3 years). No patient had signs of myocardial ischemia; on echocardiography ventricular function was normal without dyskinetic areas or signs of enlargement or stenosis of the proximal coronary arteries. There was no statistical significant difference between patients and volunteers in MBF at rest (0.86 +/- 0.27 vs 0.77 +/- 0.17 ml/g/min), whereas MBF after vasodilatation (2.42 +/- 0.81 vs 3.10 +/- 0.8 ml/g/min) and coronary flow reserve (CFR) (2.89 +/- 0.26 vs 4.09 +/- 1.01 mmHg/ml/g/min) were significantly attenuated in the Kawasaki group. No stress-induced perfusion defects could be detected. In children with a history of Kawasaki disease and angiographically normal epicardial coronary arteries, there is a significant attenuation of MBF after vasodilatation and a significant reduction of CFR. Impairment of vasoreactive ability may indicate residual damage of the coronary arteries and may be a risk factor for atherosclerosis in adulthood.

Adenosine↗

Inter-crystal scatter in a dual layer, high resolution LSO-APD positron emission tomograph.

Improving system efficiency without jeopardizing spatial resolution is one of the main problems of small animal PET scanners. In pursuit of this goal, the future LSO-APD-PET prototype MADPET-II will combine highly granulated detector modules with a dual layer structure. The individual readout of the LSO crystals allows separately handling multiple signals related to those photons scattering between different crystal units (inter-crystal scatter, ICS). The contribution of ICS events can significantly increase the system efficiency. Such coincidences are not characterized by a unique LOR. However, in order to minimize resolution degradation, it would be desirable to identify the primary path of the ICS events. Since ICS is geometry dependent, this work was aimed at investigating the effects of ICS in the performance of the dual layer prototype. Different recovery algorithms to select the primary crystal were implemented and developed, and applied to Monte Carlo simulated data. Some of these algorithms were based on the properties of Compton kinematics. For a centred point source and a 100 keV lower energy threshold, the absolute system efficiency was found to increase by 35% when including ICS events: from 1.8% without ICS events to 2.8% with ICS. Similarly, for a threshold of 200 keV, the contribution of ICS coincidences still represented approximately 20% of the total detected coincidences, leading to an absolute system efficiency of almost 2%. The mispositioning introduced by processing ICS coincidences only led to a moderate broadening of the axial line spread function (LSF), especially at the tails of the profile (FWTM). This effect was also noticeable in the transaxial plane. In presence of scattering media (water-filled cylinder), the resolution degradation was dominated by the contribution of object scatter. The reconstructed images from a simulated homogeneous cylinder filled with activity with a non-active rod at its centre were employed to estimate the impact of ICS on the image quality. In general, the use of ICS coincidences increased the signal-to-noise ratio (SNR) but worsened contrast. The effects of ICS on resolution could be reduced by employing a new identification scheme based on the maximum signal and the Compton kinematics. This method yielded the highest identification rate for the correct photon trajectory, even for a finite energy resolution of 15% (511 keV). This technique also increased the SNR by 17% to 30% and preserved the image contrast. In conclusion, by combining individual crystal readout, a low energy threshold and an appropriate recovery scheme, the processing of ICS coincidences significantly increases the system efficiency without any substantial deterioration of the image quality.

Algorithms↗

Myocardial perfusion and coronary flow reserve assessed by positron emission tomography in patients after Fontan-like operations.

Ventricular dysfunction in patients after Fontan-like operations (FLOs) is a serious complication that might contribute to poor long-term results. Ischemic heart disease will have debilitating consequences on a Fontan heart. Ten patients (15.8 +/- 5.01 years) after FLO had transesophageal echocardiography and cardiac catheterization 9.3 +/- 4.2 years after surgery. Myocardial perfusion was assessed by NH3-positron emission tomography (rest/adenosine) and compared with that of 10 healthy adults (26.1 +/- 6.3 years). Ventricular function was normal in 4 and reduced in 6 patients; end systolic and end diastolic meridional wall stress was significantly elevated in the FLO group. Coronary angiography revealed no stenosis of the coronaries. Compared to normals, myocardial blood flow (MBF) at rest was higher in the FLO group (0.99 +/- 0.25 vs 0.77 +/- 0.17 ml/g/min, p <0.05), whereas MBF after vasodilatation (2.12 +/- 0.78 vs 3.10 +/- 0.85 ml/g/min, p <0.05) and coronary flow reserve (CFR) was reduced (2.5 +/- 0.88 vs 4.1 +/- 1.01, p <0.05), especially in those with impaired ventricular function. Coronary vascular resistance after vasodilatation was elevated in the FLO group (38.2 +/- 17.4 vs 24.5 +/- 8.3 mmHg/ml/g/min, p <0.05). Altered MBF, increased meridional wall stress, and impaired CFR are common findings in FLO. Attenuated CFR and reduced ventricular function are significantly correlated and may be risk factors for the long-term outcome.

Adolescent↗

Differential modulation of subcortical target and cortex during deep brain stimulation.

The combination of electrical deep brain stimulation (DBS) with functional imaging offers a unique model for tracing brain circuitry and for testing the modulatory potential of electrical stimulation on a neuronal network in vivo. We therefore applied parametric positron emission tomography (PET) analyses that allow characterization of rCBF responses as linear and nonlinear functions of the experimentally modulated stimulus (variable stimulator setting). In patients with electrodes in the thalamic ventrointermediate nucleus (VIM) for the treatment of essential tremor (ET) here we show that variations in voltage and frequency of thalamic stimulation have differential effects in a thalamo-cortical circuitry. Increasing stimulation amplitude was associated with a linear raise in rCBF at the thalamic stimulation site, but with a nonlinear rCBF response in the primary sensorimotor cortex (M1/S1). The reverse pattern in rCBF changes was observed with increasing stimulation frequency. These results indicate close connectivity between the stimulated nucleus (VIM) and primary sensorimotor cortex. Likewise, stimulation parameter-specific modulation occurs at this simple interface between an electrical and a cerebral system and suggests that the scope of DBS extends beyond an ablation-like on-off effect: DBS could rather allow a gradual tuning of activity within a neuronal circuit.

Aged↗

Cardiac autonomic dysinnervation and myocardial blood flow in long-term Type 1 diabetic patients.

AIMS: The aim of the study was to assess scintigraphically the relationship between myocardial blood flow response and sympathetic dysinnervation in long-term Type 1 diabetic patients. Effects of the iron chelator deferoxamine on myocardial blood flow were studied and they were investigated according to the presence of cardiac sympathetic dysfunction. METHODS: Myocardial blood flow (MBF) was assessed with N-13 ammonia positron emission tomography in 13 long-term Type 1 diabetic patients and 13 control subjects at rest and in response to sympathetic stimulation (cold pressor test (CPT)). In diabetic patients, the study was repeated after preinfusion with deferoxamine. Furthermore, 123I metaiodobenzylguanidine (MIBG) scintigraphy was applied to assess regional cardiac sympathetic dysinnervation (uptake score 1 = normal, homogeneous uptake em leader 6 = no uptake). RESULTS: In diabetic patients, MBF increased in response to CPT from 78 +/- 18 ml/100 g/min to 84 +/- 26 ml/100 g (8%, P < 0.001). Control subjects demonstrated an increase from 63 +/- 17 ml/100 g to 84 +/- 26 ml/100 g (33%, P < 0.001), respectively. Resting MBF was higher in diabetic patients than in control subjects (P < 0.001). In diabetic patients, increase in MBF in response to CPT was significant in regions with a MIBG uptake score of 3 did not exhibit a significant increase in MBF in response to CPT. After administration of deferoxamine, the increase in MBF in response to CPT was 23% and the magnitude of increase was related to the MIBG uptake score (r = 0.40, P < 0.0001). CONCLUSIONS: Myocardial blood flow response to sympathetic stimulation is significantly impaired in long-term Type 1 diabetes. After preinfusion with deferoxamine the impairment is partially reversed and a relationship between myocardial blood flow and the extent of cardiac sympathetic dysfunction is observed.

3-Iodobenzylguanidine↗

[Incidence, pathoetiology and treatment of interferon-alpha induced neuro-psychiatric side effects].

Interferon alpha (IFN-alpha), an immunomodulatory cytokine, is used for the treatment of several disorders including chronic hepatitis or malignant melanoma. During the therapy IFN-alpha may cause severe neuropsychiatric syndromes including depression with suicidal ideation, paranoid psychoses or confusional states. The reasons and management of these side effects are widely unknown. The underlying pathogenetic mechanisms include various effects on neuroendocrine, cytokine and neurotransmitter systems. This review summarizes therapeutic strategies against IFN-alpha associated psychiatric syndromes. Zolpidem or Zopiclon can be used for the treatment of sleeping disturbances. Serotonin-reuptake-inhibitors including citalopram or paroxetine were shown to be effective for acute treatment of IFN-alpha associated depression. The efficacy of prophylactic treatment for prevention of IFN-alpha induced depression has to be proven in future trials. In an interdisciplinary setting, psychiatric disorders and drug addiction should not prevent patients from interferon-alpha treatment. Furthermore, interdisciplinary care should improve quality of life, adherence and therapeutic outcome of interferon-alpha treated patients.

Humans↗