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Jan Müller-Brand

Publications and source records attributed to Jan Müller-Brand.

8 recordsLinked to original sources

Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison.

PURPOSE: Carbimazole ameliorates hyperthyroidism but reduces radioiodine uptake and adversely affects the outcome of simultaneous radioiodine therapy. We explored whether withdrawal of carbimazole for 3 days can restore the outcome of radioiodine treatment without concurrent exacerbation of hyperthyroidism. By generating three groups with comparable radioiodine uptake, we also investigated whether the effect of carbimazole depends on the radioiodine uptake. METHODS: Stratified by a radioiodine uptake >30%, 227 consecutive adult patients were prospectively assigned to radioiodine therapy (target dose 200 Gy) without, on or 3 days off carbimazole. Patients were clinically (Crooks-Wayne score) and biochemically (T(3), fT(4), TSH) followed up after 3, 6 and 12 months. Primary endpoint was outcome 12 months after radioiodine therapy. RESULTS: A total of 207 patients completed follow-up (toxic nodular goitre, n=117; Graves' disease, n=90). The overall success rate was 71.5%. Patients without and 3 days off carbimazole had similar biochemical (81.4% and 83.3%, respectively; p=0.82) and clinical outcomes [median (range) Crooks-Wayne score 0 (0-16) and 1 (0-10), respectively; p=0.73], which were both higher than in patients on carbimazole [42.6%, p<0.001; Crooks-Wayne score 3 (0-30), p<0.03]. Time to achieve cure was delayed on carbimazole. No changes in thyroid hormone levels occurred after 3 days' discontinuation of carbimazole. Logistic regression revealed that all observed cure rates were independent of entity, sex, age, thyroid volume, radioiodine uptake, radioiodine half-life, fT(4), T(3) and TSH. CONCLUSION: Patients under carbimazole treatment can be referred for radioiodine therapy after withdrawal of carbimazole for only 3 days. Three days of carbimazole withdrawal is long enough to restore the success of radioiodine therapy and short enough to avoid the risk of exacerbation of hyperthyroidism.

Adult↗

Extraction of high-integrity RNA suitable for microarray gene expression analysis from long-term stored human thyroid tissues.

INTRODUCTION: Isolation of high-quality RNA from fresh-frozen thyroid tissues stored for more than a decade would open novel options for gene expression profiling. Herein, we describe successful extraction of high-integrity RNA from human thyroid tissues that were stored for more than a decade. METHODS: Seventy-nine samples (15 goitres, 20 follicular adenomas, 30 papillary carcinomas, 14 follicular carcinomas) that were shock-frozen in isopentane and stored for a median of 11 years (range 1-16 years) were processed using standard precipitation and column filtration techniques. RNA integrity was assessed by electrophoresis using the RNA integrity number (RIN) algorithm and by gene expression profiling determining the 3'/5' ratio of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene and the percentage of transcripts detected on the Affymetrix U133 2.0 human genome GeneChip. RESULTS: The median RNA yield was 1.9 microg/mg tissue (papillary carcinoma 2.1 microg/mg, range 0.2-7.2 microg/mg; follicular carcinoma 2.4 microg/mg, range 0.2-3.2 microg/mg; goitre 1.4 microg/mg, range 0.1-5.4 microg/mg; follicular adenoma 1.6 microg/mg, range 0.1-6.2 microg/mg; p = 0.46) with an 8.6 (7.3-9.8) median RIN. The median GAPDH gene 3'/5' ratio was 1.43 (1.34-1.52) and the median percentage of present calls was 48.1% (42.7-52.0%). CONCLUSIONS: Age and entity independent RNA suitable for expression profiling can be extracted from long-term stored fresh-frozen human thyroid tissues.

Adenocarcinoma, Follicular↗

The value of [18F]FDG-PET in the diagnosis of large-vessel vasculitis and the assessment of activity and extent of disease.

PURPOSE: This study was performed to investigate the value of( 18)F-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) in the diagnosis of large-vessel vasculitis and the assessment of activity and extent of disease. METHODS: Twenty-six consecutive patients (21 females, 5 males; median age - years, range 17-86 years) with giant cell arteritis or Takayasu's arteritis were examined with [(18)F]FDG-PET. Follow-up scans were performed in four patients. Twenty-six age- and gender-matched controls (21 females, 5 males; median age 71 years, range 17-86 years) were included. The severity of large-vessel [(18)F]FDG uptake was visually graded using a four-point scale. C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured and correlated with [(18)F]FDG-PET results by logistic regression. RESULTS: [(18)F]FDG-PET revealed pathological findings in 18 of 26 patients. Three scans were categorised as grade I, 12 as grade II and 3 as grade III arteritis. Visual grade was significantly correlated with both CRP and ESR levels (p=0.002 and 0.007 respectively; grade I: CRP 4.0 mg/l, ESR 6 mm/h; grade II: CRP 37 mg/l, ESR 46 mm/h; grade III: CRP 172 mg/l, ESR 90 mm/h). Overall sensitivity was 60% (95% CI 40.6-77.3%), specificity 99.8% (95% CI 89.1-100%), positive predictive value 99.7% (95% CI 77-100%), negative predictive value 67.9% (95% CI 49.8-80.9%) and accuracy 78.6% (95% CI 65.6-88.4%). In patients presenting with a CRP <12 mg/l or an ESR <12 mm/h, logistic regression revealed a sensitivity of less than 50%. In patients with high CRP/ESR levels, sensitivity was 95.5%/80.7%. CONCLUSION: [(18)F]FDG-PET is highly effective in assessing the activity and the extent of large-vessel vasculitis. Visual grading was validated as representing the severity of inflammation. Its use is simple and provides high specificity, while high sensitivity is achieved by scanning in the state of active inflammation.

Adolescent↗

Three-year recurrence-free survival in a patient with recurrent medulloblastoma after resection, high-dose chemotherapy, and intrathecal Yttrium-90-labeled DOTA0-D-Phe1-Tyr3-octreotide radiopeptide brachytherapy.

BACKGROUND: Most medulloblastomas express high levels of somatostatin type 2 receptors (sst2). DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) specifically binds sst2 in the low nanomolar range. The cytotoxic effect is mediated by the chelated, beta-emitting, metallic radionuclide Yttrium 90 (90Y). The authors applied this innovative treatment option in a boy age 8 years who presented with a recurrent medulloblastoma of the cauda equina: a prognostically poor condition. Targeted radiotherapy was administered to treat minimal sst2-expressing tumor remnants, which persisted despite conventional and high-dose chemotherapy and intercurrent resection of the lesion. METHODS: A medulloblastoma arising from the floor of the fourth ventricle had been removed surgically; then, the patient was treated with standard adjuvant chemotherapy and craniospinal irradiation according to the prospective HIT '91 protocol. Complete remission was achieved for 20 months, when a drop metastasis of the cauda equina manifested with sensorimotor lumbosacral deficits and urinary incontinence. After four cycles of neoadjuvant chemotherapy (which consisted of combined ifosfamide, carboplatinum and etoposide), two cycles of high-dose chemotherapy and autologous stem cell transplantation were performed; in between, the responding residual tumor within the lumbosacral nerve fibers was microscopically removed. Thereafter, an Indium-111-DOTATOC test injection indicated sst2-expressing tumor remnants within the cauda equina. Consequently, 4 cycles of [90Y]-DOTATOC (4x562.5 megabecquerels) were injected directly into the cerebrospinal fluid in monthly intervals. RESULTS: The consolidating intrathecal brachytherapy using [90Y]-DOTATOC was tolerated well. A complete remission was achieved for a 3-year period. The only remaining deficit was urinary incontinence. CONCLUSIONS: Intrathecal administration of targeted radiopeptide brachytherapy in combination with conventional and high-dose chemotherapy and surgical removal represents a promising new option to treat recurrent medulloblastoma and should be explored further.

Antineoplastic Agents↗

Evidence for left ventricular remodeling after percutaneous coronary intervention: effect of percutaneous coronary intervention on left ventricular ejection fraction and volumes.

BACKGROUND: Post-stress ejection fraction (EF), end-diastolic (EDV) and end-systolic (ESV) volumes by gated myocardial perfusion SPECT (MPS) are well validated, reproducible and of prognostic significance. However, little is known about the impact of percutaneous coronary intervention (PCI) on left ventricular volumes and remodeling. METHODS: Thirty-eight patients who underwent MPS before and 6 months after PCI were evaluated. MPS were interpreted deriving summed stress (SSS), rest (SRS) and difference (SDS = SSS-SRS; extent of ischemia) scores. EF, EDV and ESV were generated by QGS trade mark. Pre-PCI MPS were compared to post-PCI MPS. RESULTS: Single vessel disease was present in 63% of patients. PCI of one vessel was performed in 82% of patients. After 6 months, SSS (10.6 +/- 6.3 vs. 2.8 +/- 4.3, p < 0.001) and SDS (8.2 +/- 5.6 vs. 1.4 +/- 2.3, p < 0.001) had improved; however, EF did not change significantly (55 +/- 10 vs. 57 +/- 13, p = ns). Still, EDV (105 +/- 25 ml vs. 96 +/- 25 ml, p = 0.006) and ESV (49 +/- 19 ml vs. 41 +/- 18 ml, p = 0.001) were significantly reduced. CONCLUSION: Results of MPS documented the beneficial effect of PCI on symptoms and extent of ischemia. In addition, the findings showed a significant decrease in ESV and EDV after PCI as compared to pre-PCI findings which points to a positive effect on left ventricular remodeling even in the absence of significant changes in EF.

Aged↗