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Biomedical subjects

C Winkler

Publications and source records attributed to C Winkler.

At least 127 records · Page 7Linked to original sources

Captopril mediated decrease of aortic regurgitation.

The effect of captopril mediated afterload reduction on aortic regurgitation was investigated in 10 patients. Regurgitation was quantitated by means of the regurgitation fraction and the relation of regurgitant volume to end diastolic volume. These variables were derived from gated radionuclide ventriculography. After captopril treatment the blood concentration of angiotensin I rose whereas that of angiotensin II fell significantly. The conversion of angiotensin I to II was reduced to about 50% of the control value. Whereas blood pressure and heart rate did not change significantly, the regurgitation fraction and the regurgitant volume, normalised to end diastolic volume, were significantly reduced by captopril treatment. The ejection fraction remained essentially unchanged. These findings suggest that captopril reduces aortic regurgitation by reducing afterload.

Angiotensin I↗

[Localization of pre-excitation in the WPW syndrome by analysis of the ventricular contraction course].

Fourier phase analysis of gated radionuclide ventriculography (RNV) was applied in 23 patient for the identification of cardiac contraction patterns in WPW syndrome (controls with normal ventricular function and sinus rhythm, n = 30). The sequence and velocity of regional ventricular wall motion was determined and correlated to the results of electrophysiological studies. In 3/23 patients the contraction pattern was not different from controls. Indicating the preexcitation in 20/23 patients the earliest ventricular contraction was localized as follows: right atrial n = 5, paraseptal right n = 2, paraseptal left n = 6 and atrial left n = 7. In 15/16 patients nuclear data corresponded with electrophysiological endocardial mapping. Phase analysis of RNV provides a reliable non-invasive method for localization of preexcitation in WPW syndrome.

Electrocardiography↗

[Cerebral emission computer tomography (SPECT) with 123I-labeled amphetamines].

Amphetamine is stored by brain tissue and permits its scintigraphic imaging, particularly with the single-photon emission computed tomography (SPECT). A total of 60 scintigraphic investigations in 54 patients were done. Investigations were done using an emission computed tomograph (rotating gamma-camera) after application of 123I-N-isopropyl-amphetamine. In 6 out of 24 patients with epilepsy a focus in agreement with EEG findings could be established despite negative cranial computed tomography (CT). In 4 out of 25 patients with cerebrovascular disease diminished perfusion was demonstrated although cranial CT was normal. In 10 out of 20 cases the extent of functional lesions demonstrated by SPECT was larger than could be assumed by cranial CT findings. Three patients with migraine and negative CT findings showed disorders of perfusion in the amphetamine-SPECT which were in agreement with the EEG. Brain SPECT using 123I-labelled amphetamines thus offers the possibility to demonstrate functional perfusion and metabolic disorders which show no morphologic correlate in the cranial CT. In addition, foci demonstrated in cranial CT can be more precisely defined in their functional extent using the SPECT.

Amphetamines↗

Unpaired bases in phage DNA after gamma-irradiation in-situ and in-vitro.

Phage Lambda DNA, gamma-irradiated in-situ and in-vitro, has been analyzed for unpaired bases by melting, reannealing, and cleavage with Sl nuclease which is specific for single-stranded DNA. DNA, irradiated in-situ, i.e., in the phage particle, contained sites being sensitive to Sl nuclease. These single-stranded lesions were passed over and conserved during reannealing, whereas adjacent DNA regions reannealed specifically. Complementary base-pairing was restored after Sl nuclease treatment. Comparison of the Tm-data before and after Sl nuclease treatment indicated that the single-stranded regions were removed by the enzyme. In contrast, DNA irradiated in-vitro, i.e., gamma-irradiated in aqueous solution, failed to match complementarily and was not sensitive to Sl nuclease. Thus it appears that lesions leading to unpaired bases were randomly distributed in DNA irradiated in-vitro, but occurred in clusters after irradiation in-situ. Most probably these clusters contain damaged bases which in turn caused localized disruption of the hydrogen bonds between complementary base pairs.

Bacteriophage lambda↗

Elimination of porcine heptadecapeptide gastrin (G17) and human leu big gastrin (G34) by the perfused pig liver.

In order to study some of the molecular events during the hepatic passage of gastrin, we perfused sulfated natural porcine gastrin (G17 II) through isolated pig livers. The disappearance half time of G17 II was about 20-30 min when the starting gastrin concentrations were greater than 100 pM; lower concentrations were reduced with half times of 40-100 min. Synthetic human leu-32 (G34) was not eliminated. The use of region-specific antibodies to gastrin indicated that degradation was more effective at the N-terminus of gastrin. Whereas Sephadex chromatography revealed no change of the molecular size, SDS-polyacrylamide gel electrophoresis showed the presence of smaller immunoreactive fragments of gastrin in addition to immunoreactive fragments of gastrin of the heptadecapeptide size. These findings indicate that the isolated porcine liver degrades porcine G17 to smaller fragments.

Animals↗

15(p-[123I]Iodophenyl)pentadecanoic acid as tracer of lipid metabolism: comparison with [1-14C]palmitic acid in murine tissues.

Uptake and turnover of 15-(p-[123I]iodophenyl)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in heart, lung, liver, kidneys, and spleen and compared with that of [1-14C]palmitic acid (PA). High cardiac uptake of both I-PPA (4.4% dose/g) and PA (2.8% dose/g) was followed by a two-component tracer clearance. Kinetics of I-PPA were linked to those of PA in tissues with primary oxidation of free fatty acids or their preferential storage. Tissue lipids of all organs investigated were labeled concordantly by both tracers. Fractional distributions of PA and I-PPA incorporation in tissue lipids were significantly correlated. Thus general pathways of FFA tissue metabolism are traced by this radioiodinated free-fatty-acid analog. High-quality metabolic imaging of the heart is possible by means of I-PPA with conventional scintigraphic equipment or cross-sectional imaging with single photon emission computerized tomography facilities.

Animals↗

Splenectomy in hematologic malignancy.

Fifty patients undergoing splenectomy for complications of hematologic malignancy were reviewed to define indications and results. Primary diseases included lymphoma (n = 14), chronic lymphatic leukemia (n = 13), hairy-cell leukemia (n = 12), myeloid metaplasia (n = 6), and other similar disorders (n = 5). Indications for splenectomy in these patients included cytopenia (n = 37), diagnostic laparotomy (n = 8), "small stomach" syndrome (n = 3), and abdominal pain (n = 2). Splenectomy was performed by the midline approach in 32 patients. In 40 patients, the splenic artery was ligated prior to mobilization of the spleen. The spleens averaged 1650 g; in eight patients accessory spleens were removed. Additional surgical procedures included liver biopsy (n = 30), lymph node biopsy (n = 15), and cholecystectomy (n = 3). Intraoperative blood loss averaged 750 ml. In 14 patients, drainage of the left subphrenic space was used. Splenectomy was effective in 36 of 50 patients. In seven patients, splenectomy was ineffective in correction of cytopenia. Seven mortalities were from bleeding (n = 2), pulmonary embolus (n = 2), postoperative sepsis (n = 2), and progression of primary disease (n = 1). Additional complications included reoperation for bleeding (n = 3), septic complications including pneumonia (n = 14), wound infection (n = 4), and intra-abdominal abscess (n = 2). Splenectomy for the patients with hematologic malignancy is generally effective. Meticulous hemostasis, timely administration of intraoperative platelets, surgical asepsis, and aggressive pulmonary care are essential to reduce morbidity and mortality.

Adult↗

Relation of myocardial blood flow and initial cardiac uptake of 15-(p-123I-phenyl)-pentadecanoic acid in the canine heart.

In 8 pentobarbital-anesthetized mongrel dogs the correlation between regional myocardial blood flow (RMBF) and regional cardiac uptake of 15-(p-123I-phenyl)-pentadecanoic acid (IPPA) was determined. Three animals were studied under control conditions, in three dogs an acute ischemia was produced by LAD ligation, and two dogs were paced at 195 beats/min. RMBF values were 20-50 ml/min X 100 g in acutely ischemic myocardium. 90-120 ml/min X 100 g under normal conditions and 200-250 ml/min X 100 g during pacing-induced stimulation. Total cardiac uptake of IPPA was 4.5-6% of the injected dose. In normal and acutely ischemic myocardium a good correlation between RMBF and IPPA uptake was obtained. Under stimulated conditions only a moderate increase of IPPA accumulation was found. At RMBF values above 150-170 ml/min X 100 g an upper limit of IPPA uptake was observed and can be explained by limited diffusion or an increased utilization of alternative substrates.

Animals↗

Cardiac metabolism of omega-(p-iodo-phenyl)-pentadecanoic acid: a gas-liquid chromatographic-mass spectrometric analysis.

The omega-(p-iodo-phenyl)-pentadecanoic acid (I-PPA) has been used successfully for the investigation of the cardiac metabolic activity and for the imaging of the myocardium (Machulla, H. J., M. Marsmann, and K. Dutschka. 1980. Eur. J. Nucl. Med. 5: 171-173). In the present study, the metabolic fate of I-PPA in the perfused rat heart was investigated. After application of I-PPA to the perfused rat heart, lipids were extracted, separated by thin-layer chromatography, and transesterified. The gas-liquid chromatographic-mass spectrometric (GLC-MS) analysis yielded the following results. Heart triglycerides contained 73% of the recovered I-PPA; only small amounts of unesterified I-PPA were found in the heart. This finding is in good agreement with the radioactivity distribution determined simultaneously. Three metabolites could be detected and characterized by GLC-MS: omega-(p-iodo-phenyl)-propionic acid, omega-(p-iodo-phenyl)-propenoic acid, and p-iodo-benzoic acid. These short chain metabolites were found only in the perfusion medium demonstrating that they are not enriched but rapidly eliminated from the perfused rat heart.

Animals↗

Cardiac metabolism of 15 (p-I-123 phenyl-) pentadecanoic acid after intracoronary tracer application.

Myocardial turnover of omega-(p123I-Phenyl-) pentadecanoic acid and release of its metabolites into the coronary sinus and peripheral blood has been studied in patients with coronary artery and valvular heart disease. After intracoronary tracer injection myocardial extraction fractions of 45-53% in control subjects were observed. In patients with coronary artery disease (CAD) normal to reduced values (34-61%) were established. Hydrophilic catabolites of I-PPA, probably p123I-benzoic and -hippuric acid as well as small amounts of the non-metabolized tracer were found in coronary sinus and peripheral blood. Myocardial tracer uptake and clearance patterns were clearly different in normal myocardium when compared to that obtained in patients with CAD. Thus, evaluation of myocardial I-PPA metabolism might provide a new diagnostic tool for assessment of integrity of the heart's muscular metabolic function.

Coronary Disease↗

[Determination of the optimal L-thyroxine dosage for treating nontoxic goiter].

303 patients with non-toxic goitre (aged 14-85 years) were studied to determine the extent to which the level of thyroid-hormone dosage until a negative TRH test is reached can be defined in terms of age, body surface area and goitre size. In all instances detailed examination had determined regular hormone intake. The required L-thyroxine dose (until negative TRH test) was 100 micrograms/d in 75.6% of cases, 125 micrograms/d in 9.2% and 150 micrograms/d in 8.6% of cases. In 2.6% of cases was a satisfactory suppression reached at 50 microgram/d and in 4% at 75 micrograms/d. There was no correlation of the level of L-thyroxine dose to body surface area, age, T3 level, delta-TSH or goitre size. There was a slight correlation between T4 level and optimal L-thyroxine dose, but not significant because of the wide range of normal. The results indicate that the only way to obtain optimal L-thyroxine dosage in the treatment of goitre is by doing a TRH test in the given patient.

Adolescent↗

Radiolabeled DNase, a potential indicator for noninvasive detection of tissue damage.

Pancreatic DNase I was labeled with 131I or fluorescamine and injected IV into NMRI mice bearing a sarcoma 180. Of the injected tracer, 1.5%-2% was found to accumulate per g tumor. In sections of tumor tissue DNase was localized in damaged cells in solid and necrotic tumor regions. This binding is most probably due to specific interaction of DNase with actin, an ubiquitous cytoskeletal protein. Two-component blood clearance with a rapid first component (two-thirds of applied radioactivity) was observed. The labeled tumor could easily be visualized by gamma camera imaging. The findings suggest DNase to be a potent radiopharmaceutical for imaging damaged tissue, occurring in malignant tumors as well as in infarcts, and inflammatory lesions.

Animals↗

Should treatment of highly differentiated thyroid carcinoma be conservative?

On the basis of three selected cases (one with clinically occult follicular and two with metastatic papillary carcinoma) the necessity of a comprehensive therapeutic concept even in highly differentiated thyroid cancer is stressed. Thyroid tissue and regional metastases should be eliminated by surgery, followed by radioiodine therapy in any event. Radiation teletherapy should be reserved to patients with invasive tumor growth exceeding the organ capsule, with lymph node metastases, and with massive angioinvasive growth.

Adenocarcinoma↗

Single photon emission computed tomography of the lung: preliminary results.

Single photon emission computed tomography (SPECT) of the lung was performed, in addition to conventional camera scintigraphy, in 41 patients with pulmonary disorders as well as with regular pulmonary perfusion. For SPECT investigation a rotating gamma camera (Gammatome) was used consisting of a system with a high-resolution parallel-hole collimator interfaced with a digital computer. In 6 of 41 patients the diagnostic accuracy of pulmonary scintigraphy was improved by SPECT. Topographic identification of segmental perfusion defects in pulmonary embolism seems to be particularly promising. Special abnormalities that cannot be assessed by conventional lung imaging are mediastinal hernia and recessus retrotrachealis as a normal variant. For a detailed evaluation of this method a large number of patients must be investigated.

Humans↗

Assessment of regional myocardial uptake and metabolism of omega-(p-123I-phenyl) pentadecanoic acid with serial single-photon emission tomography.

The utility of myocardial imaging and assessment of regional myocardial metabolism of omega-(123I-paraphenyl-)pentadecanoic acid (I-PPA) by means of serial single-photon tomography is demonstrated in animal experiments. High quality cross sectional images of dog hearts with clear delineation of left ventricular walls are obtained. Myocardial infarcts are visualized as areas of deficient radioactivity uptake. I-PPA elimination from non-infarcted myocardial regions is significantly (p less than 0.001) prolonged when compared with unaffected controls. Hence, not only localized absence of uptake of free fatty acid by infarcted myocardium can be demonstrated with serial single-photon tomography but also general impairment of cardiac FFA-metabolism.

Animals↗