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Biomedical subjects

C Winkler

Publications and source records attributed to C Winkler.

At least 109 records · Page 6Linked to original sources

[Nuclear medicine in Germany: a look back at the beginning].

The development of nuclear medicine in Germany from early approaches with 32P and 131I to the first radioiodine therapy of thyroid cancer up to the clarification of basic principles for current thyroid diagnostics and for functional scintigraphic imaging are presented. Selected references are used in portraying scientific stepping stones of our speciality as well as its establishment in clinical practice during the first two decades. Researchers, places, and facts are specified and interpreted in their relation to the state-of-the-art of nuclear medicine.

Germany↗

Magnetic resonance (MR) imaging of prostatic tumours, a comparison with X-ray CT and transrectal sonography (TRS).

A total of 7 healthy volunteers and 31 patients have been examined clinically, by MRI, TRS, and biopsy. In those patients with established carcinoma, a CT examination was also performed. For the MRI study, a superconducting MR 2000 imager (Picker International) operated at 0.15 T was used with multiplanar SE and IR sequences. SE sequences with long echo times detected prostatitis, adenoma and carcinoma of the prostate with a high degree of sensitivity. However, at present, differentiation between adenoma, prostatitis and carcinoma is not possible with sufficient accuracy. In these studies we were unable to establish a correlation between the signal pattern and staging and/or grading of the carcinoma. Reliable diagnosis of a prostate carcinoma still requires a biopsy. Because of the high soft tissue contrast and the possibility of selecting any orientation for the plane under investigation, however, MRI represents an improvement in the preoperative diagnosis of local spread.

Aged↗

Neurenteric cyst diagnosed by technetium-99m pertechnetate sequential scintigraphy.

Neurenteric cysts are rare congenital anomalies which present as mediastinal tumors associated with vertebra anomalies. Two-thirds of them are lined with gastric mucosa and are potentially life threatening. An exact differential diagnosis is difficult preoperatively but is absolutely necessary because of the grave prognosis if left untreated. We present a case in which [99mTc]pertechnetate sequential scintigraphy demonstrated gastric mucosa in the cyst and helped to confirm the diagnosis. The scintigraphic findings are correlated with radiologic, sonographic, and pathologic features.

Female↗

Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123.

The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid 14C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides.

Animals↗

Experimental basis of metabolic imaging of the myocardium with radioiodinated aromatic free fatty acids.

For the investigation of myocardial perfusion and left ventricular pump function, advanced radioisotopic techniques have been established. New developments in radiopharmacology and single-photon emission computed tomography have recently enabled the investigation of parameters of regional energy metabolism in well defined areas of the heart muscle. For this purpose, various iodine (123I)-labeled free fatty acids (FFA) have been synthesized. The diagnostic application of labeled FFA in heart disease may be important, since FFA are the preferred substrates for cardiac energy production at rest in the fasting state. In addition, regional myocardial FFA uptake and regional myocardial blood flow are tightly coupled in normal myocardium with beta-oxidation which is extremely sensitive to oxygen deprivation. This article outlines the basic physiologic pathways of FFA in normal and ischemic myocardium and reviews the results of animal experiments validating the application of these principles for metabolic imaging of the heart by means of the aromatic radioiodinated FFA, 15-(p-iodophenyl)pentadecanoic acid. In addition, the development, physiologic properties, and potential applications of a new generation of 3-methyl-substituted radioiodinated fatty acids that show high myocardial uptake but prolonged retention are discussed.

Animals↗

[Results of fatty acid SPECT of the myocardium in coronary disease].

New developments in radiopharmacology of 123I-labeled metabolic tracers and single-photon emission computerized tomography (SPECT) allow now-a-days the assessment of parameters of cardiac energy metabolism in well-defined areas of the heart muscle. This article will present a brief outline of the basic pathophysiological principles used in the application of 123I-labeled phenyl fatty acids for the evaluation of CAD. First clinical results suggest an important application of cardiac fatty acid metabolic imaging to the detection, localisation and conceivable quantitation of myocardial ischemia, myocardial infarction and assessment of tissue viability. In addition to the diagnostic applications in CAD, cardiac fatty acid metabolic imaging may provide new perspectives to pathophysiological investigations of the coupling of local flow and substrate utilisation in vivo and the effect of therapeutic interventions.

Coronary Disease↗

A comparative study of the brain uptake and early kinetics of 99mTc-dl HM-PAO and other PnAO derivatives in baboons.

Derivatives of propylene-amine-oxime (PnAO) have been synthesized which form a neutral lipid-soluble complex with 96mTc and can be supplied as freeze-dried kits. The complexes cross the intact blood-brain barrier. This report shows the brain uptake, early kinetics and biodistribution in normal adult baboons of 5 99mTc-PnAO derivatives and 2 isomers of one of the tested derivatives (HM-PAO). The brain uptake of the favoured dl-isomer of HM-PAO reaches its maximum of 4.3% (whole brain/whole body) 1 min p.i. and a clearance of less than 8% was observed 23 min p.i.

Animals↗

Selective loss of a family of gene transcripts in a hereditary murine cataract.

The eye lens of the Fraser mouse contains a dominantly inherited cataract with reduced amounts of seven distinct but homologous gamma crystallins encoded by a family of gamma-crystallin genes. The results of experiments with cultured lenses, cell-free RNA translation, and Northern blot hybridization indicated a specific loss of the family of gamma-crystallin messenger RNA's in the Fraser mouse lens. Southern blot hybridization of genomic DNA's from normal and Fraser mice showed no differences in gamma-crystallin coding sequences.

Animals↗

Metabolism of 15 (p 123I iodophenyl-)pentadecanoic acid in heart muscle and noncardiac tissues.

The uptake and turnover of omega(p 123I iodophenyl-)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in the heart, lung, liver, kidneys, spleen, and skeletal muscle of rats. At 2 min post injection, a high cardiac uptake of 4.4% dose per gram had already been achieved; this was followed by a rapid, two-component, tracer clearance. The kinetics of tissue concentrations of labeled hydrophilic catabolites indicated a rapid oxidation of I-PPA and the subsequent washout of I-PPA catabolites from heart-muscle tissue. The fractional distribution of the labeled cardiac lipids compared favorably with previously reported values for 3H-oleic- or 14C-palmitic-acid-labeled myocardial lipids. Typical patterns of I-PPA metabolism were observed in tissues depending on primary fatty-acid oxidation, lipid metabolism regulation, or I-PPA-catabolite excretion. The tissue concentrations and kinetics of I-PPA and its metabolites in the heart muscle indicated that general pathways of cardiac-lipid metabolism are traced by this new gamma-emitting isotope-labeled radiopharmaceutical.

Animals↗

Differential metabolism of deoxyribonucleosides by leukaemic T cells of immature and mature phenotype.

Experimental evidence has indicated that T lymphoblasts are more sensitive to deoxynucleoside toxicity than are B lymphoblasts. These data have led to the use of purine enzyme inhibitors as selective chemotherapeutic drugs in the treatment of T cell malignancies ranging from T cell acute lymphoblastic leukaemia to cutaneous T cell lymphomas. We have compared the toxicities of 2'-deoxyadenosine, 2'-deoxyguanosine, and thymidine for T cell lines derived from patients with T cell acute lymphoblastic leukaemia with those for mature T cell lines derived from patients with cutaneous T cell leukaemia/lymphoma. We have found that both deoxynucleosides are far less toxic to the mature T cell lies than to T lymphoblasts and that the mature cells accumulate much lower amounts of dATP and dGTP when exposed to deoxyadenosine and deoxyguanosine, respectively. Similar studies performed on peripheral blood cells from patients with T cell leukaemias of mature phenotype and on peripheral blood T cells demonstrate similar low amounts of deoxynucleotide accumulation. Measurements of the activities of several purine metabolizing enzymes that participate in deoxynucleoside phosphorylation or degradation do not reveal differences which would explain the toxicity of deoxynucleosides for immature, as compared to mature, T cells. We conclude that deoxynucleoside metabolism in leukaemic T cells varies with their degree of differentiation. These observations may be relevant to the design of chemotherapeutic regimes for T cell malignancies.

Adult↗