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Regine Kluge

Publications and source records attributed to Regine Kluge.

16 recordsLinked to original sources
PubMed2006

Effect of drug-induced cytotoxicity on glucose uptake in Hodgkin's lymphoma cells.

BACKGROUND: In Hodgkin's lymphoma, F-18-fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) is used for staging and response evaluation after chemotherapy. However, drug-mediated downregulation of glucose uptake in viable Hodgkin's lymphoma cells might limit the use of FDG-PET. METHODS: We analyzed the effect of etoposide on cell viability and uptake of F-18-fluoro-deoxy-D-glucose or the glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) in vitro. RESULTS: Etoposide induced a dose-dependent cytotoxicity in HDLM-2 cells which was significantly correlated with reduced FDG uptake. However, it also significantly increased the portion of viable cells which did not take up 2-NBDG. Interestingly, etoposide-induced cytotoxicity was mainly mediated via caspase-dependent mechanisms, whereas the cell death induced by deprivation of glucose was mediated via caspase-independent mechanisms. CONCLUSION: Etoposide-mediated reduction of glucose uptake by Hodgkin's lymphoma cells is mainly caused by cell death. In a small fraction of viable cells, etoposide might downregulate glucose transporters and/or hexokinase activity and by that inhibit glucose uptake. This, however, might not lead to false-negative results of response evaluation in Hodgkin's lymphoma patients after chemotherapy, because inhibition of glucose uptake itself seems to be a strong inducer of cell death. Altogether, this study provides important in vitro evidence to clarify the mechanisms by which FDG-PET monitors the effect of anti-cancer treatment in Hodgkin's lymphoma patients.

4-Chloro-7-nitrobenzofurazan↗
PubMed2006

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery.

BACKGROUND: ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. CASE PRESENTATION: A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. CONCLUSION: This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using (111)In-pentetreotide and a gamma probe.

Adrenocorticotropic Hormone↗
PubMed2006

[Efficient diagnosis of pathological fractures].

Pathological fractures are defined as fractures, which appear at diseased and mechanically weakened bones due to systemic or local processes. Their frequency is below 5%. This study demonstrates typical results and diagnostic criteria of pathological fractures. It will be shown, how diagnostic analysis is supposed to be performed to recognize pathological fractures. Based just on the X-ray image, diagnostic algorithms should provide all tools required for the radiologist to create a final diagnosis or to refer to other appropriate imaging modalities followed by a correct diagnosis and, if necessary, to allow interdisciplinary causal therapies.

Diagnosis, Differential↗
PubMed2006

Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy?

Neuroendocrine tumors are very heterogeneous, develop from a variety of tissues, and can be difficult to diagnose. Without the clinical manifestation of metastases, it is often difficult to characterize them as malignant. Even so-called completely (R0) resected tumors can spread clinically visible metastases within a few months after initial surgery. Treatment options for neuroendocrine tumors including pheochromocytoma are limited. Molecular targeted therapies using tyrosine kinase inhibitors might prove to be helpful in patients with these tumors. In an immunohistochemical study, we examined KIT in 26 pheochromocytomas, 8 of which were malignant (3 adrenal pheochromocytomas, 5 paragangliomas). KIT expression was found in one of these 8 malignant tumors. This 2.5-cm-large adrenal pheochromocytoma originated from a woman with neurofibromatosis type 1 and spread into spine, skull, and lung. KIT expression could be demonstrated in 5% of tumor cells. On the basis of KIT expression immunohistochemically, we treated patients with neuroendocrine (i.e., medullary thyroid cancer) and other tumors with imatinib 400 mg per day, but without efficacy after 2 months of therapy. Similar results were shown by other investigators. Therefore, monotherapy with imatinib may not be efficacious in patients with neuroendocrine tumors that express KIT. Tyrosine kinase inhibitors such as sorafenib that targets several receptors in addition to KIT may be more efficacious in treating patients with neuroendocrine tumors.

Humans↗
PubMed2005

Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study.

Transplantation of blood-derived circulating progenitor cells (CPC) has been shown to improve myocardial regeneration after myocardial infarction. It remains unclear whether CPC transplantation exerts beneficial effects also in patients with chronic myocardial ischemia. We initiated a randomized, double-blind, placebo-controlled study evaluating the impact of intracoronary infusion of CPCs on coronary vasomotion and left ventricular (LV) function in patients after recanalization of chronic coronary total occlusion (CTO). After recanalization of CTO, 26 patients (age, 63+/-2 years; LV ejection fraction, 53+/-2%) were randomly assigned to the treatment (intracoronary transplantation of CPCs) or control group. Coronary flow reserve in response to adenosine (2.4 mg/min) was measured in the target vessel at the beginning of the study and after 3 months. LV function and infarct size were assessed by MRI and metabolism by 18F deoxyglucose positron emission tomography. CPC application resulted in an increase in coronary flow reserve by 43% from 2.3+/-0.3 to 3.3+/-0.5 (P<0.05 versus beginning and control). At 3 months, the number of hibernating segments in the target region (from 2.9+/-0.6 to 2.0+/-0.6 segments, P<0.05 versus beginning and control) had declined in the treatment group, whereas no significant changes were observed in the control group. MRI revealed a reduction in infarct size by 16% and an increase in LV ejection fraction by 14% in the treatment group (from 51.7+/-3.7 to 58.9+/-3.2%; P<0.05 versus beginning and control) because of an augmented wall motion in the target region. Hence, intracoronary transplantation of CPCs after recanalization of CTO results in an improvement of macro- and microvascular function and contributes to the recruitment of hibernating myocardium.

Angioplasty, Balloon, Coronary↗
PubMed2005

Changes in myocardial perfusion due to physical exercise in patients with stable coronary artery disease.

PURPOSE: Percutaneous transluminal coronary angioplasty (PTCA) is one of the main therapy options for patients with coronary artery disease (CAD), resulting in an improvement in myocardial perfusion and exercise capacity. Nevertheless, studies have also demonstrated a positive effect of regular exercise training on myocardial perfusion and maximum exercise capacity. The aim of this study was to evaluate changes in myocardial stress perfusion after 1 year of exercise training in comparison with the effects of PTCA in patients with CAD. METHODS: In 66 male patients with angiographically confirmed significant coronary artery stenosis in one target vessel, myocardial perfusion scintigraphy was performed at baseline and 12 months after randomisation into either a physical exercise group or a PTCA group. Circumferential count rate profiles in 16 wall segments were classified according to their relative count rate and localisation within or outside the area supplied by the stenosed vessel. RESULTS: Ischaemic segments showed a significant improvement in myocardial count rate within the target area after 12 months in both the PTCA and the training group (PTCA group: from 76.8+/-4.9% to 86.6+/-10.9%, p=0.03; training group: from 74.0+/-7.3% to 83.7+/-10.8%, p<0.01). Outside the target area only the training group showed a significant improvement (from 77.7+/-4.4% to 91.7+/-4.8%, p<0.01). CONCLUSION: Our data indicate a significant improvement in stress myocardial perfusion in the training group after 12 months. The ischaemia is reduced not only in the target region of the leading stenosis but also in other ischaemic myocardial areas. In contrast, after PTCA stress perfusion improves only in the initially ischaemic parts of the target area.

Adult↗
PubMed2005

Different mechanisms for changes in glucose uptake of the right and left ventricular myocardium in pulmonary hypertension.

UNLABELLED: In patients with pulmonary hypertension (PH) the right ventricular (RV)-to-left ventricular (LV) ratio of fatty acid uptake is reduced. In animal studies, such a finding was combined with an increased glucose uptake in RV myocardium. The aim of this study was to measure the metabolic rates of glucose uptake for the RV and LV myocardium in patients in relationship to parameters of RV and LV function. METHODS: Thirty patients with PH underwent PET with (18)F-FDG and SPECT with (99m)Tc-tetrofosmine. The metabolic rate of glucose uptake was determined for RV and LV myocardium using the method of Patlak. A right heart catheter, thermodilution, and Doppler sonography were used to characterize RV and LV function. From these methods, the stroke work of both ventricles and the RV Tei index were calculated. RESULTS: RV-to-LV ratios of (18)F-FDG-uptake increased with rising pulmonary arteriolar resistance (PAR). With increasing PAR, the metabolic rate of glucose uptake of the left ventricle decreased (r = -0.547; P < 0.01) together with LV stroke work (r = -0.838; P < 0.001). The metabolic rate of glucose uptake of the right ventricle, however, correlated neither with RV stroke work (r = 0.124) nor with PAR (r = 0.189) but with the Tei index (r = 0.78; P < 0.001). CONCLUSION: Increasing right-to-left ratios of glucose uptake with an increasing pressure load in the right ventricle in PH are caused mainly by a significant reduction in the LV metabolic rate of glucose uptake. This is obviously due to a reduced energy demand of the LV myocardium caused by reduced stroke work. An increased metabolic rate of glucose uptake in the right ventricle presumably indicates RV impairment, correlating with the Tei index, which is an established prognostic parameter for cardiac dysfunction and poor survival.

Female↗
PubMed2004

Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease: a randomized trial.

BACKGROUND: Regular exercise in patients with stable coronary artery disease has been shown to improve myocardial perfusion and to retard disease progression. We therefore conducted a randomized study to compare the effects of exercise training versus standard percutaneous coronary intervention (PCI) with stenting on clinical symptoms, angina-free exercise capacity, myocardial perfusion, cost-effectiveness, and frequency of a combined clinical end point (death of cardiac cause, stroke, CABG, angioplasty, acute myocardial infarction, and worsening angina with objective evidence resulting in hospitalization). METHODS AND RESULTS: A total of 101 male patients aged < or =70 years were recruited after routine coronary angiography and randomized to 12 months of exercise training (20 minutes of bicycle ergometry per day) or to PCI. Cost efficiency was calculated as the average expense (in US dollars) needed to improve the Canadian Cardiovascular Society class by 1 class. Exercise training was associated with a higher event-free survival (88% versus 70% in the PCI group, P=0.023) and increased maximal oxygen uptake (+16%, from 22.7+/-0.7 to 26.2+/-0.8 mL O2/kg, P<0.001 versus baseline, P<0.001 versus PCI group after 12 months). To gain 1 Canadian Cardiovascular Society class, 6956 dollars was spent in the PCI group versus 3429 dollars in the training group (P<0.001). CONCLUSIONS: Compared with PCI, a 12-month program of regular physical exercise in selected patients with stable coronary artery disease resulted in superior event-free survival and exercise capacity at lower costs, notably owing to reduced rehospitalizations and repeat revascularizations.

Aged↗
PubMed2004

Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production upon second recurrence.

We present a 54-yr-old woman with ectopic corticotropin syndrome caused by a neuroendocrine tumor of the pancreas. At initial presentation, the patient suffered from diarrhea, heartburn, and nonspecific abdominal pain. There was no evidence of Cushing's syndrome. A neuroendocrine tumor in the head of the pancreas with metastases into peripancreatic lymph nodes was diagnosed and completely resected. Fourteen months later, abdominal computed tomography and scintigraphy with (111)In-labeled octreotide suggested relapse of the tumor. The patient again had no evidence of Cushing's syndrome. A second in toto tumor resection was performed. Another 8 months later, the patient developed forgetfulness, depressive episodes, muscle weakness, new-onset hypertension, hypokalemia, plethora, diabetes mellitus, polyuria, and weight loss. Endocrine testing suggested a source of ectopic ACTH production. An octreotide scan showed an intense uptake ventromedial of the left kidney, an area that showed a mass lateral of the superior mesenteric artery on abdominal magnetic resonance imaging. A complete pancreatectomy with splenectomy and left-sided adrenalectomy were performed. At this second relapse, this neuroendocrine tumor clinically had changed its hormonal profile. Immunohistochemically, in contrast to primary tumor and first relapse, we found strong immunostaining for ACTH in tumor cells of the second relapse and a MIB-1 index greater than 20%. To our knowledge, this is the first report describing a pancreatic neuroendocrine tumor that started to secrete ACTH de novo at the time of the second relapse after two former complete tumor resections. This case underscores the pluripotency of neuroendocrine tumor cells and the importance of keeping in mind a possible shift in hormone production during tumor evolution and progression.

ACTH Syndrome, Ectopic↗
PubMed2003

Is correction for age necessary in neuroimaging studies of the central serotonin transporter?

The central neurotransmitter serotonin plays a major role in a number of neuropsychiatric disorders. However, results from post-mortem and in vivo neuroimaging studies of the influence of age on the number of presynaptic serotonin transporters (SERT) are controversial. To provide further evidence of relevance for this ongoing discussion, SERT were imaged in 22 persons without neuropsychiatric impairment using [(123)I]2beta-carbomethoxy-3beta-(iodophenyl)tropane ([(123)I]beta-CIT) and high-resolution single-photon emission tomography (SPET). The SPET analysis method was based on magnetic resonance image co-registration in order to quantify SERT with acceptable inter- and intra-observer variability. Using this technique, we found a significant age-related decline in the thalamic/hypothalamic and midbrain/upper brainstem SERT density, which was more pronounced than that previously reported in the literature. From these results we conclude that age-related changes in SERT density need to be considered in future clinical studies.

Adolescent↗
PubMed2003

[18F]Fluoroazomycinarabinofuranoside (18FAZA) and [18F]Fluoromisonidazole (18FMISO): a comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors.

The present study compares the uptake of [(18)F]Fluoroazomycinarabinofuranoside ((18)FAZA), a recently developed hypoxia tracer for PET imaging of tissue hypoxia, with an established tracer [(18)F]Fluoromisonidazole ((18)FMISO) both in vitro, using Walker 256 rat carcinosarcoma cells, and in vivo in experimental rat tumors eleven to twelve days after tumor cell implantation. In vitro studies indicated that hypoxia-selective uptake of both (18)FAZA and (18)FMISO in tumor cells, 20 and 100 minutes post-incubation was of the same magnitude (20 min: 1.24 +/- 0.4% ((18)FAZA); 1.19 +/- 0.7% ((18)FMISO); 100 min: 3.6 +/- 1.6% ((18)FAZA); 3.3 +/- 1.7% ((18)FMISO)). PET imaging reflected a similar radiotracer distribution in rat tumors for (18)FAZA and (18)FMISO one h after radiotracer injection. The concentration of (18)FAZA in the tumors as measured by PET, however, was lower in comparison to (18)FMISO (SUV(FAZA) = 0.61 +/- 0.2 vs. SUV(FMISO) = 0.92 +/- 0.3, p < 0.05) although the tumor to muscle ratios for (18)FAZA and (18)FMISO did not differ in the PET images that were obtained after one h (SUV(FAZA) = 2.5 +/- 0.5 vs. SUV(FMISO) = 2.9 +/- 0.7). A comparison of PET data three h post-injection (SUV(FAZA) = 3.0 +/- 0.5 vs. SUV(FMISO) = 4.6 +/- 1.8, p < 0.05) demonstrated a lower (18)FAZA uptake that indicates a lower sensitivity of (18)FAZA in comparison to (18)FMISO in detecting hypoxic regions at a longer time in this animal model. However, these data also show a faster elimination of (18)FAZA from blood, viscera and muscle tissue, via the renal system. This advantage of a faster reduction of unspecific binding, in light of similar or marginally lower tumor uptake, warrants further investigation of (18)FAZA as a marker of regional hypoxia in tumors.

Animals↗
PubMed2003

Concordant pre- and postsynaptic deficits of dopaminergic neurotransmission in neurologic Wilson disease.

BACKGROUND AND PURPOSE: Although previous brain imaging studies of Wilson disease (WD) focused on the dopaminergic system, correlational data on the integrity of the pre- and postsynaptic compartments are lacking. The present study was initiated to intra-individually determine the integrity of these compartments in patients with WD. METHODS: A total of 46 patients with WD and 10 matched control subjects underwent [(123)I]2beta-carbomethoxy-3beta-(4[(123)I]iodophenyl)tropane ([(123)I]beta-CIT) and [(123)I]iodobenzamide ([(123)I]IBZM) single photon emission CT (SPECT). For both radiotracers, specific striatal binding ratios (with the cerebellum as the reference region) were calculated after a standardized region-of-interest technique was applied. In addition, the severity of putative neurologic symptoms was evaluated by using a linear scoring system. RESULTS: In patients without neurologic symptoms, striatal binding ratios of both radiotracers did not differ from those of the control group (13.8 +/- 3.1 vs 12.0 +/- 3.4 and 2.00 +/- 0.19 vs 1.90 +/- 0.27; n.s.). In symptomatic patients, however, striatal binding ratios for both [(123)I]beta-CIT and [(123)I]IBZM were significantly reduced (9.1 +/- 2.3 and 1.64 +/- 0.18; P <.001). In all patients with WD, the [(123)I]beta-CIT and [(123)I]IBZM binding ratios were significantly correlated (r = 0.65, P <.001), as were SPECT parameters and the severity of the neurologic symptoms (r = -0.60 and -0.62; P <.001). CONCLUSION: These findings of a concordant bicompartmental dopaminergic deficit in neurologic WD provide in vivo evidence for assigning WD to the group of secondary Parkinsonian syndromes. These results could be relevant in therapeutic decision making in patients with this copper deposition disorder.

Adult↗
PubMedDate not supplied

Management and outcome in patients with Klatskin-mimicking lesions of the biliary tree.

The preoperative and even intraoperative differentiation between benign and malignant strictures at the hepatic hilum remains difficult. The aim of this study was to assess clinical, radiologic, intraoperative, and histopathologic findings; surgical treatment; and outcome of patients with Klatskin mimicking benign lesions. Of 49 consecutive patients who were operated on the initial preoperative radiologic diagnosis of hilar adenocarcinoma (Klatskin tumor), 7 (14%) had benign conditions after final histopathologic diagnosis. Pretreatment work-up, therapy, and outcome of these patients were analyzed. Based on preoperative clinical symptoms, imaging assessment, and CA19-9 values, all seven patients were classified as having malignant neoplasms. At laparotomy, the tumors of six patients were judged to be malignant. Five patients underwent hilar resection and concomitant liver resection, and two patients underwent hilar resection alone. There were no operative deaths. The definitive histopathologic examination showed severe cholangitis with extensive periductal fibrosis in all patients. After a median follow-up of 32 months, all patients are well. Clinical presentation and imaging assessment were similar for Klatskin tumors and benign fibrosing disease; therefore, an aggressive resectional approach is justified in any patient with suspicious obstruction of the liver hilum.

Adult↗