Search PubMed⌕ Search

Biomedical subjects

H Spies

Publications and source records attributed to H Spies.

At least 37 records · Page 2Linked to original sources
PubMed1999

Synthesis and autoradiographic evaluation of a novel high-affinity Tc-99m ligand for the 5-HT2A receptor.

The synthesis and in vitro autoradiography of a novel Tc-99m ligand with subnanomolar affinity to the 5-HT2A receptor is reported. The complex combines the 4-(4-fluoro)-benzoyl piperidine portion derived from the 5-HT2A receptor antagonist ketanserin with a neutral oxotechnetium(V) chelate in form of a mixed ligand "3 + 1" unit containing the SNS/S donor set. The analogous rhenium compound has been synthesized as a surrogate for the Tc-99m complex for use in receptor binding assays and for complete structural characterization. In competition experiments the Tc-99 complex as well as its Re analogue display subnanomolar affinity toward the 5-HT2A receptor (Ki 0.44 nM for Tc, 0.25 nM for Re). The subnanomolar 5-HT2A receptor binding of the Re complex was confirmed by functional in vitro antagonism of contractile effects evoked by 5-HT in rat arterial tissue. Re 1 inhibited 5-HT-induced, 5-HT2A receptor-mediated contractions of isolated rat tail artery in a competitive fashion and possessed nanomolar affinity (pA2 = 9.08, pA2 representing the negative decadic logarithm of the Re 1/5-HT2A-receptor dissociation constant [mol/L]). Like ketanserin, Re 1 displayed moderate affinity for adrenergic alpha1D (pA2 = 8.23) and histamine H1 receptors (pA2 = 8.00), and was >600-fold up to 10,700-fold less active at several neurotransmitter receptor subtypes. In vitro autoradiographic studies clearly indicate the accumulation of the Tc-99m compound in 5-HT2A-receptor-rich areas of the brain. This enrichment can be blocked by 5-HT2A receptor antagonists such as mianserin and ketanserin and is therefore specific.

Animals↗
PubMed1998

Initial clinical experience with the new EBI (BARD-XT) flexible coronary stent: acute results and follow-up.

The EBI (BARD-XT, C.R. Bard, Murray Hill, NJ) stent is a new radiopaque balloon expandable coronary stent with high resistance to external radial forces. It does not shorten significantly with expansion and allows stent implantation in bifurcation lesions. A total of 28 EBI stents were implanted in 23 lesions in 21 patients. Indications for stent implantation were acute closure in 1, threatened closure in 15, and electively in 7 lesions. In 2 cases, the lesion involved a bifurcation where a stent was implanted in both vessels. All patients received aspirin and ticlopidine. No anticoagulant therapy was given. The stenting procedure was successful in 22 of 23 lesions. No complications occurred with the exception of 1 patient with a thrombotic reocclusion within 1 hr after stent implantation and 1 patient with a temporary occlusion of a side branch. The mean minimal luminal diameter (MLD) increased from 0.74+/-0.46 mm before balloon dilatation to 1.27+/-0.62 mm before stent implantation and 2.32+/-0.57 mm after stent implantation. Percent stenosis decreased from 71+/-19% before angioplasty to 46+/-25% after angioplasty to 5+/-8% after stent implantation. MLD at the time of follow-up angiography after 4 months was 1.98+/-0.77 mm and percent stenosis was 26+/-21%. Restenosis of more than 50% occurred in 2 lesions. In these lesions, a second percutaneous transluminal coronary angioplasty was performed. Advantages of this stent are its flexibility together with an acceptable radial strength as well as enabling radiopacity without obscuring the arterial lumen. Stenting of bifurcation lesions is possible.

Angioplasty, Balloon, Coronary↗
PubMed1998

Stability versus reactivity of "3+1" mixed-ligand technetium-99m complexes in vitro and in vivo.

"3+1" technetium-99m mixed-ligand complexes as relevant to the development of a third generation of 99mTc radiopharmaceuticals were investigated in vivo and in vitro in the blood of rats. Surprisingly, in whole blood the complexes, which proved to be stable in saline, PBS of pH 7.4 and in plasma, were converted into two radioactive, more hydrophilic metabolites. Small structural differences in the complex molecule have a profound influence on the rate of metabolism of the complexes. To obtain an understanding of this unexpected reactivity, transchelation reactions with glutathione (GSH) were hypothesized and this hypothesis substantiated by challenge experiments carried out with a series of 99mTc and analogous rhenium complexes and GSH. In vitro studies in human plasma, whole blood and erythrocytes also revealed conversion of the complexes, though, at a much slower rate. Structural parameters influencing the stability of the complexes and consequences for the radiopharmaceutical design are discussed.

Animals↗
PubMed1998

Synthesis and binding affinities of new 17 alpha-substituted estradiol-rhenium "n + 1" mixed-ligand and thioether-carbonyl complexes.

The development of technetium and rhenium-based radiotracers for the steroid receptor system requires the use of suitable donor groups on the steroid to provide stable binding sites for the metal. Previous approaches have mainly exploited methods involving various N- and S-coordinating chelate systems or organometallic complexes. In this work, we have prepared several novel chelate systems attached to a series of 17 alpha-substituted estradiol derivatives and examined their binding to the estrogen receptor (ER). The neutral "n + 1" mixed-ligand and dithioether-carbonyl complexes that we prepared contain the metal in three oxidation states, +5, +3 or +1, attached to a 17 alpha-substituted estradiol derivative through a thiol group, an isocyanide group, or a dithioether unit, respectively. In our preliminary investigations, we used rhenium as a nonradioactive analog of the radionuclide technetium. All complexes synthesized were evaluated in a competitive radiometric receptor binding assay at 0 degree C and 25 degrees C to determine their relative binding affinities (RBA) to the ER (relative to 3,17 beta-estradiol, RBA = 100%). The complexes show binding affinities up to 23.4% at 0 degree C and 14.1% at 25 degrees C.

Animals↗
PubMed1998

Novel rhenium complexes derived from alpha-tropanol as potential ligands for the dopamine transporter.

A series of rhenium complexes was synthesized as model compounds for the corresponding radioactive technetium-99m complexes for preliminary biological investigations. In a '3 + 1' mixed-ligand approach the tropanol molecule was linked with the metal core through a omega-mercaptoester group as monodentate ligand. Bis(thioethyl)sulphide was used as the tridentate dithiol ligand to block the remaining free coordination sites. The omega-mercaptoesters were synthesized via the trityl-protected precursors. Binding tests on the cloned human dopamine transporter revealed moderate binding affinities for some of the prepared compounds. The complexes were characterised by X-ray and the lipophilicity as well as pKa values were determined.

Carrier Proteins↗
PubMed1997

Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake.

Low brain uptake is a generally accepted problem in developing technetium-99m brain receptor imaging agents. For a class of potential 5-HT2A receptor-binding agents we tried to improve the original low brain uptake of 0.4% injected dose (ID) in rats 5 min p.i. by modifying the lipophilic properties of the molecules. Because of the presence of a protonable nitrogen, which according to the pKa value leads to ionization of the molecule at blood pH, the pKa value was considered to be the parameter most suitable for adjustment of lipophilicity. Insertion of ether-oxygen in the molecule of five candidates lowers the apparent pKa value from 10.0 to 8.3 and dramatically increases the brain uptake to 1.3% ID at 5 min. The direct relationship between brain uptake and apparent pKa cannot be simply explained by the increase in the pKa-governed proportion of the neutral species.

Animals↗
PubMed1997

Transcatheter closure of patent ductus arteriosus with the Rashkind occluder. Acute results and angiographic follow-up in adults.

We performed catheter closure of a patent ductus arteriosus with a Rashkind occluder in 51 adult patients (aged 14 to 76 years). The diameter of the ductus ranged from 2 to 13 mm (mean 4.5 +/- 2.0 mm), QP:QS from 1.0 to 2.6 (mean 1.6 +/- 0.3). The procedure was successful in 50/51 patients, in one of them at a second attempt. In one patient, the ductus could not be closed even with additional occluders. This patient was sent for surgery. In two patients with a large ductus, two Rashkind umbrellas were implanted simultaneously. Immediately after ductus closure, there was a residual shunt in 40/50 patients decreasing to 26/50 after 20 min. Two of the patients with a residual shunt suffered from haemolysis. In 16 patients, the residual shunt disappeared spontaneously within some months. In 15 patients, additional occluders (a second occluder in 12, a third occluder in one, and a fourth and fifth occluder in another) were implanted during the initial procedure or during follow-up. All patients were followed until angiography proved complete closure of the ductus. At the time of the last follow-up angiogram, the ductus was occluded in 49/50 patients; one patient refused a follow-up angiogram. Ductus occlusion with the Rashkind umbrella can be considered a technique with a high success rate and low rate of complications in adults. However, a residual shunt is not uncommon. Additional occluders have to be implanted in many patients.

Adolescent↗
PubMed1996

Recanalization of chronic coronary occlusions using a laser wire.

Between August, 1993-December, 1994, recanalization of a chronically occluded coronary artery was attempted in 412 patients, with an overall success rate of 77%. The main reason for failure was subintimal tracking of the guide wire. However, in 13 patients, advancing the guide wire was not possible either subintimally or in the former true lumen. In 8 of these 13 patients with failed conventional recanalization, a second attempt was made using a 0.018" laser wire. The suspected occlusion duration was 6 wk-6 yr, and the occlusion length 6-21 mm. Successful crossing of the occlusion was achieved in 7 of 8 patients. One patient experienced pericardial hematoma without severe clinical consequences. Adjunctive conventional laser angioplasty and/or balloon dilatation led to a residual stenosis of < 50% in 7 patients. The laser wire technique may become an important new method for recanalizing chronic total coronary occlusions in selected patients.

Angioplasty, Balloon, Coronary↗
PubMed1996

Brachial artery approach for transluminal angioplasty of the internal carotid artery.

One possible problem in internal carotid angioplasty is inaccessibility of the lesion due to elongation of the aortic arch, the brachiocephalic trunk, or the carotid artery itself. A new approach to performing angioplasty of the right or left internal carotid artery utilizing the brachial artery was used after failure of the transfemoral approach in 5 lesions (4 patients). The common carotid artery was cannulated with performed 5F catheters. Angioplasty was performed with a conventional balloon dilatation catheter. If required, a Wall stent was implanted to optimize the angiographic result. After failure of the conventional transfemoral technique, the brachial technique permitted successful angioplasty of the ipsilateral internal carotid artery in 4 lesions and the contralateral internal carotid artery in 1 lesion. In 1 patient, a stent was implanted. No complications occurred. The mean stenosis diameter decreased from 77.8 +/- 6.3% to 17.8 +/- 9.1%. Doppler sonography performed 4-6 months later showed no restenosis. The brachial artery approach seems to be a suitable alternative to the femoral technique.

Aged↗
PubMed1996

Technetium(V) and rhenium(V) complexes for 5-HT2A serotonin receptor binding: structure-affinity considerations.

Starting from the lead structure of ketanserin, a prototypic serotonin (5-HT) antagonist, new oxotechnetium(V) and oxorhenium(V) complexes were synthesized that are able to compete with [3H]ketan-serin in receptor-binding assays. To imitate organic 5-HT2 receptor ligands, fragments of ketanserin were combined with chelate moieties. Neutral compounds of the general formula [MOL1L2] (M = Tc, Re; L1 = HS-CH2CH2-S-CH2CH2-SH, N-(2-mercaptophenyl)salicylideneimine, N-(2-mercaptoethyl)-salicylideneimine, 3-(2-([N,N-bis(2-mercapto-S-ethyl)]-amino)ethyl)-2,4-(1H, 3H)-quinazolinedione and L2 = HS-R with R = subst. alkyl) were prepared by common action of a Tc(V) or Re(V) precursor with a mixture of equimolar amounts of a tridentate ligand L1 and a monodentate thiolate L2 bearing fragments of the lead structure. Lipophilic complexes consisting of a small S4 thiolate/thioether chelate unit, protonable nitrogen-containing spacer, and simple benzyl moiety significantly inhibited the specific binding of [3H]ketan-serin with IC50 values between 10 and 50 nM.

Animals↗
PubMed1996

-Occlusion of atrial septal defect with a new occlusive device-.

An atrial septum defect was closed with an ASDOS (Babic) occluder in 13 patients aged from 22 to 67 years. The diameters of the ASD ranged from 12 to 36 mm, the left to right shunt from 35% to 70%. With one exception, the occluder could be implanted in all patients. Two patients with an oversized ASD (diameter 31 and 36 mm respectively) had to be operated after 8 h and 2 weeks, respectively. In one patient, a small asymptomatic hemopericardium was detected after 24 h by routine echocardiogram and in another patient a single umbrella arm fracture was noticed by routine x-ray 4 months after the implantation. No further complications occurred. Follow-up is now 3 months to 1 year. With one exception, there was no residual shunt as measured by oximetry.

Adult↗
PubMed1995

Transcatheter closure of large atrial septal defects with the Babic system.

An improved 10 Fr version of the atrial septal defect (ASD) occlusion system consisting of two umbrellas for transvenous introduction over the long veno-arterial guide-wire was used to attempt closure in five adult patients with large defects (26-35 mm). The umbrellas are made of nitinol wire frame and a thin membrane of microporous polyurethane. Supported by the metal cannula and guided by selective left atriography, the umbrellas of 45-60 mm were placed individually into the atria and screwed together at the septum level by means of a torquer catheter. Positioning and screwing on, unscrewing, separating, and repositioning the umbrellas up to 17 times were needed to anchor the prosthesis correctly in a patient. The prosthesis could be implanted primarily in all patients (in one at second session). Dislodgement of a 60 mm prosthesis and left atrial perforation with a 55 mm prosthesis required surgery in two patients 8 hours and 2 weeks post procedure, respectively. A single umbrella-arm fracture was noticed in one patient 4 months after the implantation. All five patients were free of symptoms at follow-up after 7-10 months. Transcatheter closure of large ASDs is technically feasible with this system. The morbidity is mainly associated with the implantation of very large umbrellas.

Adult↗
PubMed1995

Transcatheter closure of oversized persistent ductus arteriosus by simultaneous delivery of two Rashkind umbrella devices.

Transcatheter closure of persistent ductus arteriosus (PDA) with a diameter of > 9 mm is considered to be impossible or at least difficult with the occlusion systems that are currently available. We report a simple technique for occluding oversized PDAs with two diameter of 13 mm was successfully occluded in a 40-year-old man. Complete closure without residual shunt was documented by echocardiogram and angiogram.

Adult↗
PubMed1995

Sources of radiochemical impurities in the 99mTc/S-unprotected MAG3 system.

With the aim of obtaining a general insight into the technetium/S-unprotected MAG3 system, the reactions of technetium with the unprotected MAG3 ligand, both at c.a.- and n.c.a.-level, were investigated. Based on a profound knowledge of the reaction route and the TcMAG3 complexes, sources of by-products were identified and eliminated as far as possible. Only a small percentage (< 5%) of intermediate Tc-MAG3 complexes occurs, but this may increase by improper handling of the kit, such as insufficient reaction time. In conclusion, two kinds of impurity may occur in the Tc/MAG3 kit: One is derived from impurities in the ligand (MAG3 disulphide), which can be excluded by careful preparation and storage. The other is caused by insufficient reaction time according to the scheme (Fig. 3) during the labelling procedure. Its content can be minimized by optimization of the reaction time. A reaction time of at least 10 minutes gives about 98% of the renal agent.

Drug Contamination↗
PubMed1994

[Long term dilatation after unsuccessful percutaneous transluminal coronary angioplasty].

Between August 1991 and December 1993, a total of 7011 percutaneous transluminal coronary angioplasties (PTCA) were performed. In 24 of them, the acute results were unsatisfactory, an autoperfusion balloon catheter was tolerated without complications and prolonged inflation (30 min to one hour) brought no improvement. In these 24 patients (22 men, two women; mean age 60 [33-81] years) the duration of inflation was, if possible, increased to at least 6 hours. In three patients the inflation had to be terminated after 2 or 4 hours, respectively, because of angina or for technical reasons. In 18 of the 24 patients subsequent angiography demonstrated residual restenosis of less than 50%, with a mean degree of stenosis of 18 +/- 14%. But lasting dilatation was not achieved in 6 patients: occlusion persisted in one and marked residual stenosis in two patients, while stent implantation was required in three. These results indicate that, in case of dissection or acute occlusion with failure after prolonged balloon inflation of 30 to 60 min, extending the duration of inflation to many hours can often produce good results so that stent implantation can be avoided.

Adult↗
PubMed1994

[Non-surgical closure of atrial septal defect in adults. Experiences with the Rashkind and the Sideris occluder].

The possibility of closing an atrial septal defect in adults by means of a percutaneously introduced catheter with an umbrella-type occluder was tested in seven consecutive patients with this defect (two men and five women, aged 35 to 69 years). The diameter of the defect (echocardiographic measurement) ranged from 7 to 25 mm, the left to right shunt from 11% to 54% of pulmonary flow and the pulmonary artery pressure from 24/8 to 110/25 mmHg. In one patient no attempt was made to close the defect because of its size (invasively measured: 40 mm). In another patient the method failed. Closure was successful in four of the patients (left to right shunt < 5%), while in a fifth patient a haemodynamically significant residual shunt (38%) remained, but was closed 2 months later with a second occluder. In one of the patients a portion of the device embolized to the pulmonary artery from which it was removed by catheter.--Thus the intervention was successful in five of six patients. This experience suggests that this type of occluder can also be used successfully in adults.

Adult↗