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Purpose This phase I study was performed to evaluate coagulation alterations during extracorporeal circulation (ECC) induced whole body hyperthermia (WBHT) in 12 patients with advanced soft tissue sarcomas.Methods To distinguish between effects of normothermic ECC and ECC-WBHT, blood samples were drawn at different time points: at baseline, after 30 min on normothermic ECC, at the end of the heating period, and 24 h and 7 days thereafter. Standard coagulation tests, coagulation factors, thrombelastography, platelets and reticulated platelets, liver enzymes, and scintigraphic platelet imaging were performed.Results Normothermic ECC resulted in coagulation alterations most likely due to systemic anticoagulation. Induction of hyperthermia caused thrombocytopenia, increased fibrin degradation products, prolonged clotting times, alteration in coagulation factors, and increased liver enzymes. The majority of these effects was most pronounced 24 h after ECC-WBHT. In addition, late liver sequestration of platelets was demonstrated in scintigraphic imaging at that time point.Conclusions Temporal correlation between hemostatic alterations and elevation in liver enzymes leads to the assumption that liver impairment might play a crucial role in coagulation disturbances observed during ECC-WBHT and thereafter, thus strongly supported by liver sequestration of platelets. Therefore a close monitoring of hepatic derived coagulation alterations in patients undergoing extracorporeal whole body hypothermia is warranted.

11C-acetate PET is used in the assessment of various cardiologic and oncologic diseases. This article describes the physiologic uptake of 11C-acetate and presents the common benign findings in different anatomic parts of the body. Salivary glands, tonsils, thyroid, meningeal tuberculoma, meningiomas, and macroadenomas of pituitary gland are sites of mild to moderate tracer uptake in the head and neck region. Parenchymal diseases of the lung and reactive and/or inflammatory mediastinal lymphadenopathies cause benign 11C-acetate uptake in the thorax. Liver, spleen, pancreas, and rectum show an increased uptake. Urinary tract and prostate gland show faint tracer uptake.

ABSTRACTThe present study was performed to evaluate the ability of fosfomycin, a broad-spectrum antibiotic, to penetrate into abscess fluid. Twelve patients scheduled for surgical or computer tomography-guided abscess drainage received a single intravenous dose of 8 g of fosfomycin. The fosfomycin concentrations in plasma over time and in pus upon drainage were determined. A pharmacokinetic model was developed to estimate the concentration-time profile of fosfomycin in pus. Individual fosfomycin concentrations in abscess fluid at drainage varied substantially, ranging from below the limit of detection up to 168 mg/liter. The fosfomycin concentrations in pus of the study population correlated neither with plasma levels nor with the individual ratios of abscess surface area to volume. This finding was attributed to highly variable abscess permeability. The average concentration in pus was calculated to be 182 ± 64 mg/liter at steady state, exceeding the MIC50/90s of several bacterial species which are commonly involved in abscess formation, such as streptococci, staphylococci, and Escherichia coli. Hereby, the exceptionally long mean half-life of fosfomycin of 32 ± 39 h in abscess fluid may favor its antimicrobial effect because fosfomycin exerts time-dependent killing. After an initial loading dose of 10 to 12 g, fosfomycin should be administered at doses of 8 g three times per day to reach sufficient concentrations in abscess fluid and plasma. Applying this dosing regimen, fosfomycin levels in abscess fluid are expected to be effective after multiple doses in most patients.

The influence of thyroid hormones on the immune system is controversial. We analyzed the cytokine expression pattern of T lymphocytes in patients with severe nonimmune hypothyroidism in order to establish the role of thyroid hormones on the immune system. The study comprised 7 patients (1 male and 6 females) 20 to 76 years of age (mean age, 53 years), without signs of chronic thyroiditis, verified by histology and laboratory data. The patients were studied 5 weeks after total thyroidectomy. Peripheral blood mononuclear cell (PBMC) cultures and intracellular cytokine detection by flow cytometry before and after thyroid hormone replacement therapy were performed (free thyroxine [FT4] 0.030 ± 0.034 ng/dL, versus FT4: 2.16 ± 0.68 ng/dL). The control group consisted of 7 healthy subjects (FT4: 1.20 ± 0.21 ng/dL). We found no significant differences in the cytokine pattern (interferon [IFN]-γ, IL-2, interleukin [IL]-4, IL-5, IL-6, IL-10, IL-13, tumor necrosis factor [TNF]-α, TNF-β) of CD4+and CD8+between the matched groups (hypothyroid subjects versus controls, levothyroxine treated subjects versus controls). Our data show no change in the type 1/type 2 balance of peripheral CD4+and CD8+T lymphocytes from patients with nonimmune hypothyroidism. According to our results, the hypothyreotic state does not contribute to the reported changes in cytokine production patterns in Hashimoto's thyroiditis.

An increased uptake of bone-seeking radiopharmaceuticals into malignant bone lesions could further improve the diagnostic accuracy of routine bone scanning. The tracers used in clinical routine for bone scanning are methylene-diphosphonate (MDP), dicarboxypropane-diphosphonate (DPD) and ethylenediaminetetramethylene-phosphonate (EDTMP). MDP and DPD are usually labelled with 99mTc for diagnostic use, whereas EDTMP is labelled with 153Sm for therapeutic purposes. This study aimed to compare, for the first time, bone scanning with an improved preparation of 99mTc-EDTMP (by the addition of rhenium) (carrier-added) with 99mTc-DPD. Twenty malignant bone lesions were investigated in 10 patients. The ratios of bone lesion to soft tissue (BLST) and of bone lesion to normal bone (BLNB) were compared 3 h after the injection of either compound. Quantitative analysis demonstrated a significant (P<0.05) difference in BLST ratio in favour of 99mTc-DPD. The BLNB ratio was not significantly different. Visual image analysis resulted in a clinically comparable interpretation of imaging studies with the use of 99mTc-DPD and carrier-added 99mTc-EDTMP. These preliminary data support the concept of carrier addition to increase bone uptake by the modification of the complex structure of 99mTc-EDTMP. However, any advantage over conventional 99mTc-based tracers for bone scintigraphy in clinical use needs to be demonstrated in controlled trials.

Aim:To investigate the possible changes in the renal tubular function in severe short-term hypothyroidism using 99mTc-MAG3 renography. Methods:27 consecutive thyroidectomized patients (7 males and 20 females) aged 19–79 (mean 53) years were included in the present study. 99mTc-MAG3 renography was performed in all patients before and after thyroid hormone replacement therapy. In addition, 51Cr-EDTA clearance and serum creatinine concentrations were determined. Results:The serum creatinine concentrations were significantly increased in hypothyroidism as compared with the concentrations after thyroxine substitution (1.30 ± 0.44 vs. 1.04 ± 0.32 mg/dl, p < 0.05). According to the 51Cr-EDTA clearance, the glomerular filtration rate was significantly lower in hypothyroidism than after treatment (61 ± 18 vs. 75 ± 23 ml/min). In contrast, we did not find any significant change in the renographic parameters for 99mTc-MAG3 before and after treatment (total excreted activity 20 min after administration 51 ± 12 vs. 54 ± 14%; Tmax left:right 4.2 ± 1.77 : 3.91 ± 1.06 min vs. 4.1 ± 1.66 : 4.4 ± 1.96 min). Conclusions:We did not find any influence of thyroid hormones on the outcome of 99m Tc-MAG3 renography. As 99mTc-MAG3 reflects the tubular function, it seems that the renal hemodynamic changes in severe hypothyroidism mainly affect the glomerular function. In general, the glomerular filtration rate reduction seems to be reversible after hormone substitution therapy; however, care has to be taken in patients with renal insufficiency.

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for followup.

Abstract.: About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with 123I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%±3.63% after 1 h, i.e. a concentration gradient of 10, in a thermo-independent manner within a concentration range from 1.5 to 1500 µM. This indicates an unsaturable uptake process in the tested concentrations. Pre-incubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism.

Background.99m-Tc-tetrofosmin holds significant interest among medical oncologists because of its high positive predictive value (>90%) in pilot trials, exceeding sensitivity and specificity rates of mammography.

Ga -labeled platelets could be useful for positron emission tomographic (PET) studies. In order to identify the optimal chelate for radiolabeling of platelets with Ga , we investigated the platelet uptake of Ga -oxine, -tropolone and -MPO. The platelet uptake of Ga -oxine and -tropolone is very low (&lt;5%). The platelet uptake of Ga -MPO, in contrast, increases with platelet density (highest at 10 platelets/ml) up to 18%. Our data provide evidence that only Ga -MPO could be useful for PET-studies.

Although active smoking is known to enhance platelet thromboxane production, no data on passive smoking are available yet. In an 18 m3 room, the influence of single and repeated exposure to passive smoke for 60 minutes was assessed in nonsmokers and smokers. Smokers and nonsmokers were matched for sex and age. All the evaluated parameters (plasma TXB2, serum TXB2, malondialdehyde, 11-dehydro-TXB2, conversion of exogenous arachidonic acid to hydroxy-5,8,10-heptadecatrienoic acid, and TXB2) were higher in smokers than nonsmokers at baseline conditions, immediately and 6 hours after passive exposure to cigarette smoke. Repeated exposure of nonsmokers rendered their platelets more activated, so they became closer to the behavior of smokers. Contributing to the development of hemostatic imbalance, these results indicate that passive smoking may enhance thromboxane A2 release from the platelets.