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Biomedical subjects

M Mix

Publications and source records attributed to M Mix.

At least 19 recordsLinked to original sources
PubMed2004

Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer.

PURPOSE: The purpose of this study was to evaluate the impact of [18F]fluorodeoxy-D-glucose positron emission tomography (FDG-PET) on the primary staging of patients with small-cell lung cancer (SCLC). METHODS: FDG-PET was performed in 120 consecutive patients with SCLC during primary staging. In addition, brain examinations with both FDG-PET and cranial magnetic resonance imaging (MRI) or computed tomography (CT) were performed in 91 patients. Results of FDG-PET were compared with those of conventional staging procedures. FDG-PET detected markedly increased FDG uptake in the primary tumours of all 120 patients (sensitivity 100%). RESULTS: Complete agreement between FDG-PET results and other staging procedures was observed in 75 patients. Differences occurred in 45 patients at 65 sites. In 47 sites the FDG-PET results were proven to be correct, and in ten, incorrect. In the remaining eight sites, the discrepancies could not be clarified. In 14/120 patients, FDG-PET caused a stage migration, correctly upstaging ten patients to extensive disease and downstaging three patients by not confirming metastases of the adrenal glands suspected on the basis of CT. Only 1/120 patients was incorrectly staged by FDG-PET, owing to failure to detect brain metastases. In all cases the stage migration led to a significant change in the treatment protocol. Sensitivity of FDG-PET was significantly superior to that of CT in the detection of extrathoracic lymph node involvement (100% vs 70%, specificity 98% vs 94%) and distant metastases except to the brain (98% vs 83%, specificity 92% vs 79%). However, FDG-PET was significantly less sensitive than cranial MRI/CT in the detection of brain metastases (46% vs 100%, specificity 97% vs 100%). CONCLUSION: The introduction of FDG-PET in the diagnostic evaluation of SCLC will improve the staging results and affect patient management, and may reduce the number of tests and invasive procedures.

Brain Neoplasms↗
PubMed2004

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.

Adenocarcinoma↗
PubMed2003

Regional myocardial perfusion defects during exercise, as assessed by three dimensional integration of morphology and function, in relation to abnormal endothelium dependent vasoreactivity of the coronary microcirculation.

OBJECTIVE: To test the hypothesis that scintigraphic regional myocardial perfusion defects during exercise in patients with normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory in response to cold pressor testing. METHODS: 38 patients were classified into two groups according to the presence or absence of exercise induced scintigraphic myocardial perfusion defects. A cold pressor test was done in all patients during routine coronary angiography, followed by dynamic positron emission tomography to establish coronary blood flow mediated vasoreactivity of the epicardial coronary artery and the myocardial territories supplied by the left anterior descending, left circumflex, and right coronary arteries. RESULTS: 28 patients had regional myocardial perfusion defects while 10 had normal scintigraphic imaging. The three dimensional scintigraphic fusion image revealed 49 regional myocardial perfusion defects with a mean (SD) reversibility of the original stress defect of 20 (3)%. In patients with exercise induced regional myocardial perfusion defects, the responses of epicardial luminal area and regional myocardial blood flow (RMBF) to cold pressor testing were reduced compared with patients with normal perfusion imaging (epicardial luminal area: 5.2 (1.2) to 4.2 (0.86) mm2 v 4.7 (0.5) to 5.8 (0.5) mm2; RMBF: 0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.15) to 1.38 (0.26) ml/g/min; p < or = 0.03, respectively). In patients with regional abnormal scintigraphic perfusion, the corresponding RMBF response to cold pressor testing was more severely impaired than the mean myocardial blood flow in the remaining two vascular territories, but the difference was not significant (0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.10) to 0.87 (0.12) ml/g/min; NS). The endothelium independent increase in RMBF induced by glyceryl trinitrate did not differ between patients with exercise induced myocardial perfusion defects and those with normal perfusion images (0.75 (0.16) to 0.94 (0.09) ml/g/min v 0.75 (0.15) to 0.94 (0.09) ml/g/min; NS). There was a highly significant correlation between the endothelium dependent responses of RMBF to cold pressor testing and the severity of exercise induced scintigraphic regional myocardial perfusion defects (r = 0.95, p = 0.001). CONCLUSIONS: Exercise induced scintigraphic regional myocardial perfusion defects in patients with angina but normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory.

Cold Temperature↗
PubMed2003

[Appropriate uptake period for myocardial PET imaging with 18F-FDG after oral glucose loading].

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.

Aged↗
PubMed2002

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.

Adult↗
PubMed2001

FDG-PET imaging for the staging and follow-up of small cell lung cancer.

The staging procedures for small cell lung cancer do not differ appreciably from those for other forms of lung cancer. For practical purposes, the TNM stages are usually collapsed into a simple binary classification: limited disease and extensive disease. This study was performed to answer the question of whether fluorine-18 labelled 2-deoxy-2-D-glucose positron emission tomography (FDG-PET) imaging permits appropriate work-up (including both primary and follow-up staging) of patients presenting with small cell lung cancer, as compared with currently recommended staging procedures. Thirty-six FDG-PET examinations were performed in 30 patients with histologically proven small cell lung cancer. Twenty-four patients were examined for primary staging while four were imaged for therapy follow-up only. Two patients underwent both primary staging and up to four examinations for therapy follow-up. Static PET imaging was performed according to a standard protocol. Image reconstruction was based on an ordered subset expectation maximization algorithm including post-injection segmented attenuation correction. Results of FDG-PET were compared with those of the sum of other staging procedures. Identical results from FDG-PET and the sum of the other staging procedures were obtained in 23 of 36 examinations (6x limited disease, 12x extensive disease, 5x no evidence of disease). In contrast to the results of conventional staging, FDG-PET indicated extensive disease resulting in an up-staging in seven patients. In one patient in whom there was no evidence for tumour on conventional investigations following treatment, FDG-PET was suggestive of residual viability of the primary tumour. Furthermore, discordant results were observed in five patients with respect to lung, bone, liver and adrenal gland findings, although in these cases the results did not affect staging as limited or extensive disease. Moreover, FDG-PET appeared to be more sensitive for the detection of metastatic mediastinal and hilar lymph nodes and bone metastases. Finally, all findings considered suspicious for tumour involvement on the other staging procedures were also detected by FDG-PET. It is concluded that FDG-PET has potential for use as a simplified staging tool for small cell lung cancer.

Adult↗
PubMed2001

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).

Adult↗
PubMed2001

Metastatic lymph nodes in patients with cervical cancer: detection with MR imaging and FDG PET.

PURPOSE: To compare the diagnostic accuracy of magnetic resonance (MR) imaging with that of positron emission tomography (PET) with 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) for detecting metastatic lymph nodes in patients with cervical cancer. MATERIALS AND METHODS: Before radical hysterectomy and pelvic lymphadenectomy in 35 patients with International Federation of Gynecology and Obstetrics stage IB or II cervical cancer, abdominal FDG-PET and MR imaging were performed. Malignancy criteria were a lymph node diameter of 1 cm or more at MR imaging and a focally increased FDG uptake at PET. The findings of FDG-PET and MR imaging were compared with histologic findings. RESULTS: Histologic examination revealed pN0-stage cancer in 24 patients and pN1-stage cancer in 11 patients. On a patient basis, node staging resulted in sensitivities of 0.91 with FDG-PET and 0.73 with MR imaging and specificities of 1.00 with FDG-PET and 0.83 with MR imaging. The positive predictive value (PPV) of FDG-PET was 1.00 and that of MR imaging, 0.67 (not significant). The metastatic involvement of lymph node sites was identified at FDG-PET with a PPV of 0.90; at MR imaging, 0.64 (P <.05, Fisher exact test). CONCLUSION: Metabolic imaging with FDG-PET is an alternative to morphologic MR imaging for detecting metastatic lymph nodes in patients with cervical cancer.

Adult↗
PubMed2001

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.

Age Determination by Skeleton↗
PubMed2000

Impact of 18F-FDG-positron emission tomography for decision making in colorectal cancer recurrences.

Diagnostic imaging for suspected tumour recurrence of primary colorectal cancer frequently lacks specificity and sensitivity. The impact of whole body 18F-FDG-positron-emission tomography (PET) on detection of local recurrences and hepatic or pulmonary metastases was evaluated in a prospective study. Results were compared with computed tomography (CT), ultrasonography, magnetic resonance imaging and conventional chest X-ray. The study included 71 patients (77 investigations) with suspected local recurrence, hepatic metastases or unexplained raised level of the tumour marker carcinoembryonic antigen (CEA). The results demonstrate that 18F-FDG-PET was clearly superior to CT with regard to detection of hepatic metastases. Sensitivity was 1.0 and specificity 0.98 compared with 0.87 and 0.91 for CT. In four cases, 18F-FDG-PET clarified otherwise unclear local recurrences. In five patients, 18F-FDG-PET showed pulmonary metastases that had previously been unknown. In a total of 16 patients (20.8%), 18F-FDG-PET provided additional information leading to a change of the treatment strategy. 18F-FDG-PET clearly has the ability to detect colorectal tumour recurrence and its metastases in a whole body format. Therefore, it may be applied in the follow-up of patients with primary colorectal cancer. Despite the costs, it is certainly recommended for patients with an otherwise unclear increase of CEA level or with unproven local recurrence.

Adult↗
PubMed1999

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.

Child↗
PubMed1998

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.

Adult↗
PubMed1992

Stimulation of nitrogen and whole-body protein metabolism in growth hormone-deficient children by recombinant human growth hormone: relationship to growth.

The effect of a mammalian-cell-derived recombinant human growth hormone (rhGH) on nitrogen and whole-body protein metabolism was assessed in 12 children with complete growth hormone (GH) deficiency. All the patients received single oral doses of 15N-glycine (95 atom % 15N), 20 mg/kg body weight, prior to and following 7 days of treatment with rhGH, 1.7 IU/m2 body surface area (BSA) per day, administered subcutaneously. Prior to rhGH, mean urinary 15N-nitrogen excretion was 42.8 +/- 8% of the administered dose, which fell significantly to 22.8 +/- 7% during rhGH administration (p < 0.0001). Stimulation of protein metabolism by rhGH resulted in a protein net gain rate of 1.1 +/- 0.4 g/kg/day, which was significantly higher than the 0.6 +/- 0.5 g/kg/day rate seen prior to rhGH (p < 0.001). In patients subsequently placed on daily subcutaneous injections of rhGH 1.7 IU/m2 BSA, mean height velocity standard deviation score (HV SDS) for chronological age significantly increased from -3.8 +/- 2.6 to +8.5 +/- 3.1 and +3.3 +/- 2.2, during the 1st and 2nd years of treatment, respectively. However, there was no correlation between the long-term response to rhGH treatment and the short-term changes in nitrogen or protein metabolism in GH-deficient children.

Adolescent↗
PubMed1989

[15N tracer kinetics of the utilization of yeast nitrogen].

The utilization of nitrogen from 15N-labeled Saccharomyces cerevisiae cells was studied in 6 infants by means of oral pulse labeling, comparing native and heat-treated yeast cells. The 15N dose used was 3 mg/kg. The body weight of the subjects varied between 5500 and 9400 g. The yeast cells were harvested from a culture medium which contained 15N ammonium chloride as the only source of nitrogen. The 15N-enrichment of the cells amounted to 95 atom-%. In the course of 48 h following the administration of the native yeast cells, 11% of the tracer dose were renally excreted. The corresponding value after labeling with heat-treated yeast cells was 17.9%. The cumulative renal excretion of the tracer tended to be faster as compared with pulse labeling of the native yeast cells. A paired comparison with labeled native and heated yeast cells in 3 subjects did not reveal any differences in the retention rate of 15N. When untreated 15N yeast cells were administered, 13.2% of the tracer dose were excreted in the urine and 10% respectively in the faeces. The retention was 76.8%. After single pulse labeling with 3 mg 15N/kg from heat-treated yeast cells the corresponding values were 19.4%, 4.4% and 76.2%, respectively. The kinetic of the renal 15N excretion points at the partial absorption of the yeast nitrogen from the colon.

Feces↗