Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

OBJECTIVE: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). MATERIALS AND METHODS: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. RESULTS: (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. CONCLUSION: The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

Textural features of hypoxia PET predict survival in head and neck cancer during chemoradiotherapy.

PURPOSE: The aim of this study was to investigate whether textural features of tumour hypoxia, assessed with serial [18F]fluoromisonidazole (FMISO)-PET, were able to predict clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC, T1-4, N+, M0) during chemoradiotherapy (CRT). METHODS: In a preliminary evaluation of a prospective trial, tumour hypoxia was evaluated in 29 patients via serial FMISO-PET before and during CRT. All patients received an initial [18F]fluorodeoxyglucose (FDG)-PET before CRT, and tumour regions were defined on this FDG-PET. The first-order metrics tumour-to-background ratio (TBRmean, TBRmax, TBRpeak), coefficient of variation, total lesion uptake and integral non-uniformity were calculated for all scans. Further, 3 second-order (textural) features from two grey-level matrices were calculated, as well as differential non-uniformity (udiff). Prognostic value was examined by median split for group separation (GS) in Kaplan-Meier estimates and correlated with overall survival (OS), quantified via log-rank tests (p ≤ 0.05) and group-relative hazard ratios (HR). RESULTS: Within a median follow-up of 29.6 months (95% CI: 16.8-48.0 months), no first-order metrics predicted OS with a significant GS (all p > 0.05) on any FMISO-PET scan. Only udiff before and in week 2 during CRT (p = 0.03, HR = 10.8 and p = 0.05, HR = 5.2) and non-uniformity from grey-level run length matrix in week 2 separated prognostic groups (p = 0.05, HR = 5.3); lower values were correlated with better OS. Further, the decrease in udiff from before CRT to week 2 was correlated with better OS (p = 0.04, HR = 9.4). FDG-PET before CRT did not predict outcome in any measure. CONCLUSIONS: Textural features on FMISO-PET scans before CRT, in week 2 and, to a limited degree, the change of features during CRT, were able to identify head and neck squamous cell carcinoma patients with better OS, suggesting that a higher homogeneity of the degree of hypoxia in tumours could correlate with a better outcome after CRT.

Influence of localization of PSMA-positive oligo-metastases on efficacy of metastasis-directed external-beam radiotherapy-a multicenter retrospective study.

PURPOSE: Approximately 40-70% of biochemically persistent or recurrent prostate cancer (PCa) patients after radical prostatectomy (RPE) are oligo-metastatic in 68gallium-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET). Those lesions are frequently located outside the prostate bed, and therefore not cured by the current standards of care like external-beam radiotherapy (EBRT) of the prostatic fossa. This retrospective study analyzes the influence of oligo-metastases' site on outcome after metastasis-directed radiotherapy (MDR). METHODS: Retrospectively, 359 patients with PET-positive PCa recurrences after RPE were analyzed. Biochemical recurrence-free survival (BRFS) (prostate-specific antigen (PSA) < post-radiotherapy nadir + 0.2 ng/mL) was assessed using Kaplan-Meier survival and Cox regression analysis. RESULTS: All patients were initially clinically without distant metastases (cM0). Seventy-five patients had local recurrence within the prostatic fossa, 32 patients had pelvic nodal plus local recurrence, 117 patients had pelvic nodal recurrence, 51 patients had paraaortic lymph node metastases with/without locoregional recurrence, and 84 patients had bone or visceral metastases with/without locoregional recurrence. Median PSA before MDR was 1.2 ng/mL (range, 0.04-47.5). Additive androgen deprivation therapy (ADT) was given in 35% (125/359) of patients. Median PSA nadir after MDR was 0.23 ng/mL (range, < 0.03-18.30). After a median follow-up of 16 months (1-57), 239/351 (68%) patients had no biochemical recurrence. Patients with distant lymph node and/or distant metastases, the so-called oligo-body cohort, had an overall in-field control of 90/98 (91%) but at the same time, an ex-field progress of 44/96 (46%). In comparison, an ex-field progress was detected in 28/154 (18%) patients with local and/or pelvic nodal recurrence (oligo-pelvis group). Compared with the oligo-pelvis group, there was a significantly lower BRFS in oligo-body patients at the last follow-up. CONCLUSION: Overall, BRFS was dependent on patterns of metastatic disease. Thus, MDR of PSMA PET-positive oligo-metastases can be offered considering that about one-third of the patients progressed within a median follow-up of 16 months.

Quantification of Tumor Oxygenation Based on FMISO PET: Influence of Location and Oxygen Level of the Well-Oxygenated Reference Region.

Tumor hypoxia may play a fundamental role in determining the radiotherapy outcome for several cancer types. Functional imaging with hypoxia specific radiotracers offers a way to visualize and quantify regions of increased radioresistance, which may benefit from dose escalation strategies. Conversion of the uptake in positron emission tomography (PET) images into oxygenation maps offers a way to quantitatively characterize the microenvironment. However, normalization of the uptake with respect to a well-oxygenated reference volume (WOV), which should be properly selected, is necessary when using conversion functions. This study aims at assessing the sensitivity of quantifying tumor oxygenation based on 18F-fluoromisonidazole (FMISO) PET with respect to the choice of the location and the oxygenation level of the WOV in head and neck cancer patients. WOVs varying not only in shape and location but also with respect to the assigned pO2 level were considered. pO2 values other than the standard 60 mmHg were selected according to the specific tissue type included in the volume. For comparison, the volume which would be considered as hypoxic based on a tissue-to-muscle ratio equal to 1.4 was also delineated, as conventionally done in clinical practice. Hypoxia mapping strategies are found highly sensitive to selection of the location of well-oxygenated region, but also on its assigned oxygenation level, which is crucial for hypoxia-guided adaptive dose escalation strategies.

Influence of experience and qualification on PET-based target volume delineation. When there is no expert--ask your colleague.

BACKGROUND AND PURPOSE: The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. In contrast to automatic contouring, research on visual-manual delineation is scarce. The present study investigates the dependency of manual delineation on experience and qualification. PATIENTS AND METHODS: A total of 44 international interdisciplinary observers each defined a [(18)F]fluorodeoxyglucose (FDG)-PET based gross tumor volume (GTV) using the same PET/CT scan from a patient with lung cancer. The observers were "experts" (E; n = 3), "experienced interdisciplinary pairs" (EP; 9 teams of radiation oncologist (RO) + nuclear medicine physician (NP)), "single field specialists" (SFS; n = 13), and "students" (S; n = 10). Five automatic delineation methods (AM) were also included. Volume sizes and concordance indices within the groups (pCI) and relative to the experts (eCI) were calculated. RESULTS: E (pCI = 0.67) and EP (pCI = 0.53) showed a significantly higher agreement within the groups as compared to SFS (pCI = 0.43, p = 0.03, and p = 0.006). In relation to the experts, EP (eCI = 0.55) showed better concordance compared to SFS (eCI = 0.49) or S (eCI = 0.47). The intermethod variability of the AM (pCI = 0.44) was similar to that of SFS and S, showing poorer agreement with the experts (eCI = 0.35). CONCLUSION: The results suggest that interdisciplinary cooperation could be beneficial for consistent contouring. Joint delineation by a radiation oncologist and a nuclear medicine physician showed remarkable agreement and better concordance with the experts compared to other specialists. The relevant intermethod variability of the automatic algorithms underlines the need for further standardization and optimization in this field.

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity.

BACKGROUND: Stereotactic ablative body radiotherapy (SBRT, SABR) is being increasingly applied because of its high local efficacy, e.g., for small lung tumors. However, the optimum dosage is still under discussion. Here, we report data on 45 lung lesions [non-small cell lung cancer (NSCLC) or metastases] in 39 patients treated between 2009 and 2010 by SABR. PATIENTS AND METHODS: SABR was performed with total doses of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) prescribed to the 60% isodose line encompassing the planning target volume. Three-monthly follow-up CT scans were supplemented by FDG-PET/CT if clinically indicated. RESULTS: The median follow-up was 17 months. Local progression-free survival rates were 90.5% (all patients), 95.0% (NSCLC), and 81.8% (metastases) at 1 year. At 2 years, the respective local progression-free survival rates were 80.5%, 95.0%, and 59.7%. Overall survival rates were 71.1% (all patients), 65.4% (NSCLC), and 83.3% (metastases) at 1 year. Overall survival rates at 2 years were 52.7%, 45.9%, and 66.7%, respectively. Acute side effects were mild. CONCLUSION: With the moderate dose schedule used, well-tolerated SABR led to favorable local tumor control as in other published series. Standardization in reporting the dose prescription for SABR is needed to allow comparison of different series in order to determine optimum dosage.

Comparison of PET/CT and whole-mount histopathology sections of the human prostate: a new strategy for voxel-wise evaluation.

BACKGROUND: Implementation of PET/CT in diagnosis of primary prostate cancer (PCa) requires a profound knowledge about the tracer, preferably from a quantitative evaluation. Direct visual comparison of PET/CT slices to whole prostate sections is hampered by considerable uncertainties from imperfect coregistration and fundamentally different image modalities. In the current study, we present a novel method for advanced voxel-wise comparison of histopathology from excised prostates to pre-surgical PET. Resected prostates from eight patients who underwent PSMA-PET/CT were scanned (ex vivo CT) and thoroughly pathologically prepared. In vivo and ex vivo CT including histopathology were coregistered with three different methods (manual, semi-/automatic). Spatial overlap after CT-based registration was evaluated with dice similarity (DSC). Furthermore, we constructed 3D cancer distribution models from histopathologic information in various slices. Subsequent smoothing reflected the intrinsically limited spatial resolution of PSMA-PET. The resulting histoPET models were used for quantitative analysis of spatial histopathology-PET pattern agreement focusing on p values and coefficients of determination (R 2). We examined additional rigid mutual information (MI) coregistration directly based on PSMA-PET and histoPET. RESULTS: Mean DSC for the three different methods (ManReg, ScalFactReg, and DefReg) were 0.79 ± 0.06, 0.82 ± 0.04, and 0.90 ± 0.02, respectively, while quantification of PET-histopathology pattern agreement after CT-based registration revealed R 2 45.7, 43.2, and 41.3% on average with p < 10-5. Subsequent PET-based MI coregistration yielded R 2 61.3, 55.9, and 55.6%, respectively, while implying anatomically plausible transformations. CONCLUSIONS: Creating 3D histoPET models based on thorough histopathological preparation allowed sophisticated quantitative analyses showing highly significant correlations between histopathology and (PSMA-)PET. We recommend manual CT-based coregistration followed by a PET-based MI algorithm to overcome limitations of purely CT-based coregistrations for meaningful voxel-wise comparisons between PET and histopathology.

Primary Care Providers Knowledge, Attitude and Practices Related to Hepatitis C Screening and Treatment in the Oral Direct Acting Antiviral Agents Era.

BACKGROUND: There are over 3 million Americans infected with hepatitis C virus (HCV). Despite recent advances in HCV treatment, a major barrier to care remains a limited number of treaters. HCV therapy provision by primary care providers (PCPs) could expand access by increasing the pool of HCV treating clinicians. OBJECTIVE: To characterize current HCV care practices, willingness and self-efficacy of PCPs to become HCV treaters. DESIGN PARTICIPANTS AND MAIN MEASURES: Two hundred and seventy one PCPs were identified from community clinics affiliated with a large academic center and 4 large federally qualified health centers in Baltimore, MD. An internet-based survey was administered to assess provider demographics, clinical practice site and willingness to provide HCV care. Factors associated with willingness to provide HCV care were examined using odds ratios (OR). KEY RESULTS: Among 129 (48%) PCPs who responded, the majority (70%) had an MD/DO degree and were white (60%). Only a few PCPs, 12 (10%), had treated at least 1 patient for HCV in the prior year. Although only 22% agreed that HCV treatment should be provided by PCPs, 84% were interested in more HCV training. Willingness to provide treatment was strongly linked to having a high proportion of HCV-infected patients (>20% versus <20%; OR 3.9; 95% confidence interval [CI] 1.5-10) and availability of other services at the primary care site including HIV treatment (OR 6.5; 95% CI 2.5-16.5), substance abuse treatment (OR 3.3; 95% CI 1.3-8.4) and mental health services (OR 4.9; 95% CI 2.0-12.1). CONCLUSION: These data suggest that efforts to expand HCV medical provider capacity will be most impactful if they initially focus HCV training on PCPs with a high prevalence of HCV among their patients and existing systems to support HCV care.

15N tracer techniques for the differential diagnosis of dwarfism and prediction of growth hormone action in children.

[15N]Glycine in a single oral dose was used to study nitrogen turnover in 18 short children, aged 3-14 yr. On the basis of their serum GH responses to insulin-induced hypoglycemia, the patients were divided into 3 groups: complete GH deficiency (GHD; n = 5); partial GH deficiency (pGHD; n = 6), and children with constitutional growth delay and familial short stature (CGD/FSS; n = 7). The mean 48-h renal excretion of 15N by patients with GHD was 66.09 +/- 14.12% (+/- SD) of the tracer dose. This decreased to 27.64 +/- 5.33% after two injections of 10 IU/m2 GH (P less than 0.001). 15N excretion by patients with pGHD was 47.19 +/- 13.42%, and it decreased after GH injection to 22.69 +/- 4.58% (P less than 0.005). Patients with CGD/FSS had 15N excretion of 37.27 +/- 5.68%, and it did not change in response to GH. The mean protein synthesis rate in GHD patients was extremely low, and it increased after GH injection from 0.99 +/- 0.46 to 3.53 +/- 0.43 g/kg X day. In pGHD patients the protein synthesis rate increased from 2.62 +/- 0.84 to 4.50 +/- 1.09 g/kg X day. The CGD/FSS patients had no change in protein synthesis rate after GH. Our results suggest that studies of the metabolism of [15N]glycine might be of value in predicting responsiveness to GH therapy.

Isolated GH deficiency with dominant inheritance: new mutations, new insights.

Autosomal dominantly inherited isolated GH deficiency is caused by mutations of GH-1 that alter the normal structure of GH. We studied 16 familial cases and 1 sporadic case with isolated GH deficiency type II from 1 Dutch and 4 German families by direct sequencing of PCR-amplified genomic DNA and ectopic transcript analysis of lymphocyte mRNA. In addition, the clinical data of the affected individuals were analyzed. Two previously reported mutations and 1 novel splice site mutation in intron III of GH-1 (+1G to C and +1G to A; new, +2T to C) were detected that cause exon 3 skipping. We also discovered a novel G6191 to T missense mutation in exon 4 of GH-1 that changes valine 110, which is highly conserved in mammalian and several nonmammalian GH, to phenylalanine. Splicing of the primary RNA transcript was not affected by this mutation, which is very likely to alter the normal GH structure at the protein level. The onset of growth failure was earlier, and the degree was more severe in affected children with GH-1 splice site mutations compared with those in children with the GH-1 missense mutation. In addition, the severity of the phenotype was variable, even within the same family. The age at diagnosis was between 0.8-9.6 yr (median, 5.1 yr); height at diagnosis was between -2.5 and -8.1 SD score (median, -4.0). Most of the children were lean at diagnosis, with a body mass index ranging from -1.7 to +3.3 SD score (median, -0.5). The 5 affected adults had final heights between -1.8 and -4.5 SD score (median, -3.6), centripetal obesity, and muscular hypotrophy. Before therapy, IGF-I and IGF-binding protein-3 serum levels of all affected children were severely diminished (<<5th percentiles for age). The maximum GH peak in a total of 25 stimulation tests was between 0.1-5.0 microg/liter (median, 0.9), indicating severe GH deficiency. The height of the adenohypophysis studied by magnetic resonance imaging was normal in 2 affected children and mildly decreased in 2 others. Substitution with GH resulted in good catch-up growth in all treated children. Children with severe GH and IGF-I deficiencies, but normal size of the adenohypophysis should be examined for GH-1 splice site and missense mutations. The observed discrepancy between the very homogeneous hormone data proving severe GH and IGF-I deficiencies and the high variability of growth failure even within the same family suggests that the onset and predominance of GH-dependent growth during infancy are individually different and modified by as yet unknown factors.

Variable phenotype associated with Ser505Asn-activating thyrotropin-receptor germline mutation.

Constitutively activating thyrotropin-receptor (TSHR) germline mutations have been identified as a molecular cause of hereditary nonautoimmune hyperthyroidism. To date, seven cases of familial and six cases of sporadic nonautoimmune hyperthyroidism have been described associated with 13 different TSHR germline mutations, with a variable clinical course. We report the case of a 12.3-year-old girl with a history of thyrotoxicosis since the age of 11 months who developed diffuse thyroid hyperplasia at the age of 4.5 years. The patient has required continuous moderate-dose antithyroid medication, to maintain euthyroidism. There were no clinical signs of autoimmune thyroid disease and autoantibodies were negative. An activating germline mutation in the TSHR gene was suspected and was found in TSHR exon 10 (Ser505Asn) but was absent in the girl's mother. This same mutation, was first reported in a patient with severe intrauterine hyperthyroidism with early and progressive goiter development. Our patient had a significantly less severe clinical course with later onset compared to the original patient with the same TSHR germline mutation.

Effects of neoadjuvant radio-chemotherapy on 18F-FDG-PET in esophageal carcinoma.

AIM: To investigate whether results of [F-18]-fluorodeoxy-d-glucose (FDG) positron emission tomography (PET) of esophageal cancer (EC) before and after neoadjuvant radio-chemotherapy correlate with histopathology after esophageal resection. METHODS: Twenty consecutive patients with EC without distant metastases were examined twice with 18F-FDG-PET during primary staging and after neoadjuvant radio-chemotherapy. FDG standardised uptake values (SUV) were correlated with the histopathological findings (percentage of viable tumour cells, tumour regression grade 1-5). RESULTS: Regression analysis revealed a slight (not significant) positive correlation between SUV(pre) (R=0.41, p=0.08) and SUV(post) (R=0.37, p=0.11) and the percentage of viable tumour cells in the resectate. Although all patients showed a significant decrease in SUV after radio-chemotherapy (p < 0.01) the percentual decrease of the SUV after therapy (DeltaSUV%) did not significantly differ between the TRG-groups. In 12 of 20 patients (60%), therapy-induced esophagitis was detected in post-therapeutic PET images. CONCLUSION: In EC, a higher pre-therapeutic SUV might be correlated with a higher fraction of vital tumour cells remaining after radio-chemotherapy. Applying the neoadjuvant therapy protocol and the study design used in this examination, there is no correlation between decrease in SUV and histopathology.

Autosomal dominant nonautoimmune hyperthyroidism. Clinical features-diagnosis-therapy.

Autosomal dominant nonautoimmune hyperthyroidism is a hereditary form of hyperthyroidism caused by constitutively activating germline mutations in the TSH-receptor gene. Clinical features comprise familial prevalence of thyroid autonomy in more than 2 generations and conditions of persisting neonatal hyperthyroidism or nonautoimmune hyperthyroidism of childhood onset with frequent relapses of hyperthyroidism under thyrostatic therapy and after thyroid surgery. Once clinically suspected the diagnosis can be confirmed by mutation analysis of genomic DNA extracted from a routinely obtainable EDTA blood sample. In patients with hereditary nonautoimmune hyperthyroidism a near total thyroidectomy is recommended as the first line treatment to avoid relapses from residual thyroid tissue with the activating TSHR mutation. Furthermore, genetic counselling of the affected patients is advised.

Lymph node staging in extracranial head and neck cancer with FDG PET--appropriate uptake period and size-dependence of the results.

AIM: Identification of a rationale for the appropriate uptake period for static clinical extracranial head and neck PET imaging and evaluation of the diagnostic accuracy of such an optimized FDG PET approach for lymph node staging in the head and neck region. METHODS: In a subset of 5 patients, kinetic tumour studies were performed in order to identify the cellular activity plateau phase of FDG accumulation for head and neck cancer. Seventy-eight consecutive patients (11 women, 67 men; mean age +/- SD: 55 +/- 11 years; range, 36-78 years), presenting with histologically proven squamous cell carcinoma and sonographically detected lymph nodes in 86 neck sides, underwent clinically indicated FDG PET imaging. PET results were compared to those derived from histological examinations and follow-up imaging results after 6 months in order to calculate sensitivity and specificity for lymph node staging. RESULTS: FDG kinetics in head and neck cancer indicate that the cellular activity plateau of FDG accumulation is reached after an uptake period of 90 min. Using this protocol metastatic involvement of neck sides with lymph nodes less than 1 cm in diameter was correctly identified with a sensitivity of 71.4% and a specificity of 92.3%. Sensitivity increased with the lymph node diameter (1.1-1.5 cm 83.3%, 1.6-2.0 cm 100%, > 2 cm 88.9%). CONCLUSION: The appropriate uptake period for static clinical extracranial head and neck PET imaging that allows measurements in the activity plateau phase is about 90 min. FDG PET may add some significant information regarding metastatic spread into regional lymph nodes.

[Appropriate uptake period for myocardial PET imaging with 18F-FDG after oral glucose loading]. / Optimaler Akquisitionszeitpunkt für die Herz-PET mit 18F-FDG nach oraler Glukosebelastung.

AIM: Identification of a rationale for the appropriate uptake period for myocardial (18)F-FDG-PET imaging of patients with and without diabetes mellitus. METHODS: In a subset of 27 patients, static 2D-PET examination was performed of patients with chronic coronary artery disease and known myocardial infarction. The patients fasted (at least 4 h) before examination. (18)F-FDG (330 +/- 20 MBq) was injected intravenously. The image quality was semiquantitativly determined by ROI-analysis and the myocardium-to-blood pool activity ratio (M/B) was calculated. I.) Scans 30, 60, and 90 min p. i. of 10 non-diabetic patients (60 g oral glucose loading one hour before FDG-injection, low-dose intravenous insulin bolus if necessary). II.) Scans 30, 60, and 90 min p. i. of 10 patients with known non-insulin dependent diabetes (20 g glucose, insulin bolus). III.) Scans 90 min p. i. of 7 patients with known non-insulin dependent diabetes and elevated fasting serum glucose level (140-200 mg/dl; insulin bolus, no glucose). RESULTS: I.) The M/B ratio significantly increases in nondiabetic patients with the uptake time (30 min 1.95 +/- 0.20; 60 min 2.96 +/- 0.36; 90 min 3.78 +/- 0.43). II.) In patients with non-insulin dependent diabetes the M/B ratio also significantly increases with uptake time. Compared to non-diabetic patients group II reached smaller M/B values (30 min 1.56 +/- 0.10; 60 min 2.15 +/- 0.14; 90 min 2.71 +/- 0.19). III.) In the group of patients with elevated fasting serum glucose level (who only got insulin but no glucose loading) the M/B activity ratio 90 min p. i. was clearly inferior compared with diabetic patients after oral glucose loading and insulin administration (M/B 2.71 +/- 0.19 versus 2.16 +/- 0.07). CONCLUSIONS: In static myocardial viability PET studies with (18)F-FDG an uptake time of 90 min yields image quality superior to that obtained after shorter uptake time.

Blue rubber-bleb-nevus syndrome with predominant urinary bladder hemangiomatosis.

In a 2-year-old girl a blue rubber-bleb-nevus syndrome is described. Apart from cutaneous hemangiomas, pronounced hemangiomas of the urinary bladder were diagnosed and treated by laser surgery. The features of the disorder are discussed as a special clinical condition within the framework of this syndrome.

Metabolic effects of HAY's diet.

The aim of the study was, to evaluate the metabolic effect of HAY's diet on protein turnover, fat oxidation, respiratory quotient, body fat and weight loss. Twelve healthy adults received an individually regular diet and thereafter a corresponding isocaloric and isonitrogenous 10-day HAY-diet. Protein turnover and 13C-fat oxidation were investigated after administration of [15N]glycine and an [U-13C]algae lipid mixture. The 15N and 13C enrichment in urine and breath were measured by isotope ratio mass spectrometry. The respiratory quotient was measured by indirect calorimetry. Body fat, total body water and lean body mass were estimated by bio-electric impedance analysis. HAY's diet led to a significantly higher 13C-fat oxidation (15.4 vs. 22.0% P < 0.01), corresponding to a lower respiratory quotient (0.88 vs. 0.81; P < 0.01), whereas the protein turnover remained constant in both diets (3.06 vs. 3.05 g/kg/day). HAY's diet did not reduce total body water, lean body mass, body fat and body weight (72.2 vs. 71.4 kg).