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Biomedical subjects

K Hahn

Publications and source records attributed to K Hahn.

At least 19 recordsLinked to original sources
PubMed1992

Patterns of elevated free calcium and calmodulin activation in living cells.

The temporal and spatial dynamics of intracellular signals and protein effectors are being defined as a result of imaging using fluorescent reagents within living cells. We have described a new class of fluorescent analogues termed optical biosensors, which sense chemical or molecular events through their effects on protein transducers. One example of this new class of indicators is MeroCaM, an environmentally sensitive fluorophore which when it is attached to calmodulin reflects the activation of calmodulin by calcium in vitro. We report here that the rise in free calcium and MeroCaM activation occur in the same period during serum stimulation of quiescent fibroblasts. MeroCaM activation also correlates with the spatial pattern of increased free calcium and the contraction of transverse fibres during wound healing. Finally, migrating fibroblasts in the later stages of wound-healing exhibit an increasing gradient of free calcium and MeroCaM activation from the front to the rear.

3T3 Cells↗
PubMed1992

Proton NMR studies of Cucurbita maxima trypsin inhibitors: evidence for pH-dependent conformational change and His25-Tyr27 interaction.

A pH-dependent His25-Tyr27 interaction was demonstrated in the case of Cucurbita maxima trypsin inhibitors (CMTI-I and CMTI-III) by means of nuclear magnetic resonance (NMR) spectroscopy. pH titration, line widths, peak shapes, deuterium exchange kinetics, and two-dimensional nuclear Overhauser effect spectroscopy (NOESY) were employed to characterize a conformational change involving Tyr27, which was shown to be triggered by deprotonation of His25 around pH 6. A hydrogen bond is proposed to be formed between N epsilon of His25 and OH of Tyr27, as a distance between the atoms, His25 N epsilon and Tyr27 OH, of 3.02 A is consistent with a model built with NOE-derived distance constraints. Both the X-ray [Bode, W., Greyling, J.H., Huber, R., Otlewski, J., & Wilusz, T. (1989) FEBS Lett. 242, 282-292] and NMR [Holak, T.A., Gondol, D., Otlewski, J., & Wilusz, T. (1989) J. Mol. Biol. 210, 635-648] structures of CMTI-I at low pH (4.7-5.3) rule out such an interaction between the two aromatic rings, as the ring planes are oriented about 10 A away from each other. The presently characterized relative orientations of His25 and Tyr27 are of functional significance, as these residues make contact with the enzyme in the enzyme-inhibitor complex. Furthermore, trypsin assay and inhibitor-binding studies showed that conformations of trypsin and the squash inhibitor were functionally relevant only in the pH range 6-8. The pKa of His25 was determined and found to be influenced by Glu9/Lys substitution and by the hydrolysis of the reactive-site peptide bond between Arg5 and Ile6.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

A new principle to normalize plasma concentrations allowing single-sample clearance determinations in both children and adults.

A sufficiently accurate quantification of renal function requiring only one plasma sample without an additional gamma-camera study has, until now, only been possible in adults. A new principle will be presented here allowing the universal application of known algorithms, regardless of the clearance substance used, by normalizing the plasma concentrations with respect to the individual body dimensions of the patients--for infants as well as for adults. In this respect, algorithms are developed for clearance determinations using technetium-99m mercaptoacetyltriglycine (99mTc-MAG3), which are based on steady-state studies as the reference. They allow the calculation of quantitative clearance values in infants, requiring only one blood sampling at any time between the 25th and the 40th min postinjection. The comparison with a combined camera/two-plasma-sample technique performed in 46 children aged between 9 days and 14 years (mean 6.05 years) resulted in a standard error of 8.5% from the line of identity (r = 0.94). Moreover, this procedure also increases the accuracy of results in adults.

Adolescent↗
PubMed1992

Prevention of deep vein thrombosis in neurosurgical patients: a prospective double-blind comparison of two prophylactic regimen.

In a prospective, randomized, double-blind investigation of anticoagulant agents for prevention of deep vein thrombosis in patients undergoing operations at the lumbar-vertebral disc, 179 patients were randomly allocated to two groups. 87 patients received a fixed combination of low-molecular weight heparin 1,500 U-aPTT plus dihydroergotamine 0.5 mg (LMWH/DHE) once a day and additionally one injection of placebo per day, 92 patients received a fixed combination of sodium heparin 5,000 U plus dihydroergotamine 0.5 mg (HDHE) twice a day. Treatment was initiated two hours preoperatively in both groups and continued for at least seven days. Deep vein thrombosis (DVT), detected by the 125Iodine-labelled fibrinogen uptake-test, occurred in four patients treated with LMWH/DHE and in three patients with HDHE. In all seven patients phlebography was performed, confirming the diagnosis of DVT in one patient of the LMWH/DHE group and in two patients of the HDHE group, only. No increased bleeding was found in either group. Especially no neurological complications caused by epidural bleeding were observed. We therefore recommended to treat routineously all patients undergoing operations at the vertebral disc with antithrombotic agents. The advantages of the once daily regimen with low-molecular weight heparin include better patients' acceptance and less nursing time.

Adult↗
PubMed1992

[Importance of whole body skeletal scintigraphy within the scope of staging of neoplasms in the ENT area].

Concerning malignant tumours of the oral cavity, pharynx and larynx, bone metastases are in general rarely seen. For the specification to which patients the whole body bone scintigraphy as detection method should be applied, the findings of 370 patients were analysed retrospectively. In respect of primary staging, bone metastases could be found by scintigraphy in only 1.4% of the patients. On the other hand, there was a detection rate of 12% during the further course of the disease, especially in case of clinical symptoms pointing at spreading metastases or in tumour recurrences. Nevertheless, positive scan findings which were not due to metastases could be found in both groups with equal frequency (12 and 13%, respectively). Therefore the routine performance of whole body bone scintigraphy as a screening method does not seem to be useful in the primary staging of cancer of the mouth, pharynx and larynx. Contrary to this, in the follow-up of these tumours bone scanning proves to be a valuable and sensitive method for detecting skeletal metastases.

Bone Neoplasms↗
PubMed1992

[The clinical relevance of anti-CEA immunoscintigraphy with the 99mTc-labelled monoclonal antibody BW 431/26. A critical assessment after 119 studies].

The results of 119 radioimmunoscintigraphies (RIS) in 113 patients with the 99mTc-labeled monoclonal anti-CEA-antibody BW 431/26 (Behring) have been analysed. The aim of our study was the estimation of the method's sensitivity and specificity under different aspects to find out for which indications and questions the 99mTc-RIS is useful. Colorectal primary tumours in 19 patients were scintigraphically detected with a sensitivity of 83% and a specificity of 100%; 3 out of 7 other tumour sites were localised correctly. 55 patients were examined during the follow-up of colorectal cancer. There were 17 out of 22 true positive findings of local recurrences (sensitivity 77%, specificity 88%). Liver metastases were imaged as hot lesions with only 41% sensitivity and 86% specificity. The detection of extrahepatic tumour sites is difficult because of the persistently high blood-pool activity of the monoclonal antibody and, in the pelvic area, the unspecific bowel activity. Skeletal metastases were recognised in 7 out of 9 cases. In 14 patients with other non-colorectal carcinomas, RIS was successful in single cases. It is not helpful, however, when searching for tumours of unknown origin or for the screening of patients with elevated CEA levels without tumour history. The high technical, methodological and time effort required by RIS is justified in the follow-up of cancer patients when conventional diagnostic procedures are inconclusive or the status of morphological findings remains unclear. The use of RIS as an unspecific screening tool in tumour diagnosis must be rejected because of the not completely explored risks of the examination. Repeated applications of monoclonal antibodies require controls of the patients' HAMA titers before performing RIS.

Adult↗
PubMed1992

[99m-Technetium-mercaptoacetyltriglycine (MAG3) for the demonstration of the kidney changes following extracorporeal shockwave lithotripsy. A prospective study of 117 patients].

Extracorporeal shock wave lithotripsy (ESWL) has become the treatment of choice for urinary calculi. 117 patients were studied prospectively with 99mTc mercaptoacetyltriglycine (MAG3) before and after ESWL. 79 (66%) of the 119 kidneys treated had abnormal findings. Of these 63/119 (53%) had abnormal scans. 41 (65%) had focal lesions with a delayed intrarenal transport. The remaining 22 had a diffuse delay of intrarenal transport. A loss of relative renal function of 3% and more compared to the pretreatment values was observed in 50/119 (42%) patients. 99mTc MAG3 should be done routinely together with radiologic tests (CT or MRI) before and after ESWL to select the patients at risk for post ESWL hypertension.

Female↗
PubMed1992

[Combined bilateral idiopathic necrosis of the humerus and femur heads: bone scintigraphy, x-ray, CT and MRT findings].

Aseptic bone necrosis in adults is usually caused by circulation defects or metabolic diseases but may also occur without any obvious reason. In these "idiopathic" cases, alcoholism seems to play a prominent role. In addition to the frequently affected femoral heads other bones may be involved. Here a remarkable pattern of localizations is reported: the bilateral idiopathic necroses of the heads of both humerus and femur. Untreated aseptic bone necroses close to a joint commonly leads to severe secondary arthrosis and destruction of the joint within a short time. Therefore, only a diagnosis in an early stage of the disease offers the chance of a successful joint-preserving therapy. In cases of clinically suspected aseptic bone necrosis but still negative or doubtful X-ray findings, bone scans or MRI are reliable methods of verifying the diagnosis.

Adult↗
PubMed1992

Intermediate dosimetric quantities.

The transfer of energy from ionizing radiation to matter involves a series of steps. In wide ranges of their energy spectra photons and neutrons transfer energy to an irradiated medium almost exclusively by the production of charged particles which ionize and thereby produce electrons that can ionize in turn. The examination of these processes leads to a series of intermediate quantities. One of these is kerma, which has long been employed as a measure of the energy imparted in the first of the interactions. It depends only on the fluence of uncharged particles and is therefore--unlike absorbed dose and electron fluence--insensitive to local differences of receptor geometry and composition. An analogous quantity for charged-particle fields, cema (converted energy per unit mass), is defined, which quantifies the energy imparted in terms of the interactions of charged particles, disregarding energy dissipation by secondary electrons. Cema can be expressed as an integral over the fluence of ions times their stopping power. However, complications arise when the charged particles are electrons, and when their fluence cannot be separated from that of the secondaries. The resulting difficulty can be circumvented by the definition of reduced cema. This quantity corresponds largely to the concept employed in the cavity theory of Spencer and Attix. In reduced cema not all secondary electrons but all electrons below a chosen cutoff energy, delta, are considered to be absorbed locally. When the cutoff energy is reduced, cema approaches absorbed dose and thereby becomes sensitive to highly local differences in geometry or composition. With larger values of delta, reduced cema is a useful parameter to specify the dose-generating potential of a charged-particle field 'free in air' or in vacuo. It is nearly equal to the mean absorbed dose in a sphere with radius equal to the range of electrons of energy delta. Reduced cema is a function of the fluence at the specified location at and above the chosen cutoff energy. Its definition requires a modification of restricted linear collision stopping power, L delta, and it is recommended that the definition of L delta be so changed.

Models, Theoretical↗
PubMed1992

[Scintigraphic use of 87Y during 90Y therapy of bone metastases].

Carrier-free 87Y is produced by cyclotron irradiation of Rb. It decays with a half-life of 80.3 h, transforming via 87mSr to stable 87Sr with the emission of gamma lines of 0.48 and 0.39 MeV. Experience in 6 patients shows good scan quality and correspondence between 99mTc-DPD and 87Y images useful in 90Y-citrate therapy for bone metastases. 87Y offers new possibilities of studying biological kinetics in 90Y therapy. To avoid contamination this should only be used in departments with possibilities of radioactive waste storage and controlled disposal.

Aged↗
PubMed1991

Paediatric nuclear medicine.

Until the 1980s no serious attempts were made to develop paediatric nuclear medicine, as for various reasons many centres were reluctant to perform radionuclide examinations on children. Then two books were published on paediatric nuclear medicine in 1984 and 1985, respectively. In 1987, a group of physicians formed an informal club of paediatricians and nuclear medicine specialists in an effort to improve the relationship and cooperation between these specialties. Carrying out nuclear medicine examinations on children requires a completely different approach than on adults. Suggestions are made and tips given, and the specific problems involved are discussed in detail.

Child↗
PubMed1991

[Stomach emptying after stomach resection with and without retention of duodenal passage].

On domestic pigs 2/3 gastrectomies with retention and elimination of the duodenal passage were carried out. Postprandial gastric emptying was measured scintigraphically for 4 h and compared with a control group (laparotomy only). For the semi-solid, 99mTc-labeled test meal delayed gastric emptying after elimination of the duodenal passage by Roux reconstruction could not be shown. There was no difference in gastric emptying between B-I and Roux-en-Y partial gastrectomy. Also alteration of the length of the jejunum loop from 40 to 20 cm after Roux-en-Y reconstruction had no influence on gastric emptying. Roux reconstruction (40 cm loop) in combination with truncal vagotomy led to a non-uniform gastric emptying, but there was a statistically proven acceleration compared with B-I resection. After 240 min the mean residual intragastric activity of the control group (n = 5) was 47.8%, 78.9% after B-I resection (n = 5), 59% after Roux reconstruction with 40 cm jejunal loop (n = 5), 38.1% after Roux reconstruction with 20 cm jejunal loop (n = 5) and 20.9% after Roux-en-Y (40 cm loop) with truncal vagotomy (n = 4).

Anastomosis, Roux-en-Y↗
PubMed1991

Assessment of ventricular function with first-pass radionuclide angiography using technetium 99m hexakis-2-methoxyisobutylisonitrile: a European multicentre study.

In the context of a multicentre study on the use of technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi), we evaluated the accuracy of the ventricular function assessed at rest by means of first-pass radionuclide angiocardiography acquired during the injection of the tracer for myocardial perfusion scintigraphy. The results were compared with first-pass studies performed using reference tracers sodium pertechnetate Tc 99m or technetium 99m diethylene triamine penta-acetic acid or with gated radionuclide angiocardiography. A total of 66 patients of the 105 enrolled in the study could be evaluated. The comparison of the first-pass studies was possible in 33 subjects with regard to the left ventricular ejection fraction, yielding r = 0.909 (P less than 10(-6)), and in 22 cases with regard to the right ventricular ejection fraction, yielding r = 0.712 (P less than 0.001). The comparison between the first-pass study using 99mTc-Sestamibi and the equilibrium gated radionuclide angiocardiography was possible for the left ventricular ejection fraction in 26 cases, with r = 0.937 (P less than 10(-6)), and for the right ventricular ejection fraction in 15 subjects, with r = 0.783 (P less than 0.001). In conclusion, the assessment of ventricular function performed by acquiring a first-pass radionuclide angiocardiograph during the injection of 99mTc-Sestamibi for perfusion myocardial scintigraphy can be considered reliable and accurate, when compared with the usually employed techniques. This result confirms the feasibility of a combined evaluation of perfusion and function at rest and during stress testing, which represents one of the most interesting advantages offered by the use of 99mTc-Sestamibi.

Coronary Disease↗
PubMed1990

Nuclear medicine studies in the differential diagnosis of diseases with spinal involvement.

Plain X-rays computed tomographic and magnetic resonance images all yield information on the pathophysiology of diseases with spinal involvement. Descriptions of the following nuclear medicine methods are presented: Bone scanning with 99 m-technetium labeled phosphonate complexes used for the evaluation of skeletal metastases, primary bone tumors, traumatic, degenerative, and postoperative changes as well as in inflammatory conditions. Specific radionuclides used for the localization of inflammatory conditions are radioactive labeled leucocytes. Iodine total body scans used to detect spinal metastases of follicular and papillary thyroid carcinoma. 201-thalliumchloride is used as a tumor-marker with high affinity and sensitivity in malignant thyroid tumors. 131- or 123-iodine-meta-iodobenzylguanidine scans used in the detection of metastases of pheochromocytoma and neuroblastoma. Immunoscintigraphy with radioactive labeled anti-CEA antibodies used for the specific labelling of metastases of gastrointestinal tract tumors, melanoma, breast, and ovarian carcinoma. The value of the various nuclear medicine methods in the diagnostic schedule is illustrated in case reports.

Humans↗
PubMed1990

A radiopharmaceuticals schedule for imaging in paediatrics. Paediatric Task Group European Association Nuclear Medicine.

There is no standard schedule for the amounts of radiopharmaceutical administered to children at present. Various alternative methods are currently in practice, all with some support from the literature. Optimization of the amount of radiopharmaceutical to be administered is discussed in relation to the radiation burden of such an examination. The Paediatric Task Group of the European Association of Nuclear Medicine has investigated the current situation and now suggests a method for standardization of administered amounts of radiopharmaceutical in paediatrics. The fraction of the adult amount of radiopharmaceutical to be administered should be calculated from the child's body weight according to the accompanying table. In small infants, the minimum amount of a radiopharmaceutical is discussed and suggested amounts to be administered are presented.

Body Weight↗
PubMed1990

[Immunoscintigraphy in colorectal cancers from the viewpoint of the gastroenterologist].

In the last decade radioimmunoscintigraphy developed from an experimental approach to a clinically useful method. First promising results were obtained with Technetium-99m labelled murine monoclonal antibodies against carcinoembryonic antigen (CEA). Routine clinical application is restricted to colorectal carcinoma at the moment. Radioimmunoscintigraphy is recommended in case of recurring disease when conventional methods are ineffective or doubtful, especially in the pelvic region. The availability of monoclonal antibodies to new tumor-associated antigens will extend the spectrum to other gastrointestinal tumors. The possibility to generate recombinant humanized monoclonal antibodies and antibody fragments are encouraging new perspectives. These developments and the use of biological immune response modifiers to increase antigen expression could provide means to consider radioimmunotherapy of gastrointestinal cancers.

Antibodies, Monoclonal↗