Pulmonary Hypertension Among End-Stage Renal Failure Patients Following Hemodialysis Access Thrombectomy

Purpose: Percutaneous hemodialysis thrombectomy causes subclinical pulmonary emboli without short-term clinical consequence; the long-term effects on the pulmonary arterial vasculature are unknown. We compared the prevalence of pulmonary hypertension between patients who underwent one or more hemodialysis access thrombectomy procedures with controls without prior thrombectomy.Methods: A retrospective case-control study was performed. Cases (n=88) had undergone one or more hemodialysis graft thrombectomy procedures, with subsequent echocardiography during routine investigation of comorbid cardiovascular disease. Cases were compared with controls without end-stage renal disease (ESRD) (n=100, group 1), and controls with ESRD but no prior thrombectomy procedures (n=117, group 2). The presence and velocity of tricuspid regurgitation on echocardiography was used to determine the prevalence and grade of pulmonary hypertension; these were compared between cases and controls using the chi-square test and logistic regression.Results: The prevalence of pulmonary hypertension among cases was 52% (46/88), consisting of mild, moderate and severe in 26% (n=23), 10% (n=9) and 16% (n=14), respectively. Prevalence of pulmonary hypertension among group 1 controls was 26% (26/100), consisting of mild, moderate and severe pulmonary hypertension in 14%, 5% and 7%, respectively. Cases had 2.7 times greater odds of having pulmonary hypertension than group 1 controls (p=0.002). The prevalence of pulmonary hypertension among group 2 controls was 42% (49/117), consisting of mild, moderate and severe pulmonary arterial hypertension in 25% (n=49), 10% (n=12) and 4% (n=5), respectively. Cases were slightly more likely to have pulmonary hypertension than group 2 controls (OR=1.5), although this failed to reach statistical significance (p=0.14).Conclusion: Prior hemodialysis access thrombectomy does not appear to be a risk factor for pulmonary arterial hypertension. Patients with ESRD are more likely to have pulmonary hypertension.     

The “dural tail” adjacent to meningiomas studied by dynamic contrast-enhanced MRI: a comparison with histopathology

We examined 32 patients with intracranial tumors (17 meningiomas, 8 neuromas, 7 pituitary adenomas) by conventional and dynamic contrast-enhanced MRI. Our aim was to clarify whether the pathological dural contrast enhancement adjacent to meningiomas (the dural tail) is specific to meningiomas and, more important, whether it represents neoplastic dural infiltration or hypervascularization as a tumor accompanying reaction. A dural tail was found in 9 of 17 meningiomas. None of the other extra-axial tumours (neuromas, pituitary adenomas) showed comparable dural enhancement. Dynamic examinations with an ultrafast single slice imaging technique (snapshot-FLASH) after a bolus injection of contrast medium showed a dural tail in seven out of these nine meningiomas, while in two cases the dural tail turned out to be a cortical vein with a characteristic dynamic contrast enhancement pattern. In the dynamic study all seven dural tails were found to have earlier, steeper contrast enhancement than the corresponding tumours. All the tumours and part of the adjacent dura mater in four of the seven meningiomas with dural enhancement were examined histopathologically. In none of these four cases was neoplastic tissue found more than 2 mm away from the main tumour. The results strongly support the suggestion that the dural tail adjacent to meningiomas represents a hypervascular, non-neoplastic dural reaction.     

Usefulness of <Superscript>123</Superscript>I-metaiodobenzylguanidine myocardial scintigraphy for predicting the effectiveness of β-blockers in patients with dilated cardiomyopathy from the standpoint of long-term prognosis

Purpose The usefulness of ¹²³I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in predicting the effectiveness of -blocker therapy in dilated cardiomyopathy (DCM) was investigated from the standpoint of long-term prognosis.Methods The subjects were 53 DCM patients in whom -blockers had been successfully introduced and used for 6 months or longer. When symptoms were stable before the introduction of -blockers and for up to 1 year thereafter, MIBG myocardial single-photon emission computed tomography was performed and the images analysed to obtain the extent score (EXT), severity score (SEV) and washout rate (WR). At the same time, echocardiography was performed to measure left ventricular ejection fraction (LVEF). Thereafter, patients were placed under observation for an average of 1,314±986 days, with the occurrence of cardiac events as the endpoint.Results The degree of improvement in WR after introduction of -blockers was a significant predictor of cardiac events. In fact, none of the patients whose improvement in WR was valued at 10 or higher had cardiac events. Accordingly, using improvement in WR of 10 as the cut-off value, the patients were divided into two groups, improved and unimproved. There were significant differences between the groups in respect of early EXT, early SEV and WR before the introduction of -blockers . As regards predictors of WR improvement, multivariate logistic regression analysis demonstrated that early EXT, WR and LVEF were significant predictors.Conclusion This study shows that, from the standpoint of long-term prognosis, DCM patients who would benefit the most from -blocker therapy are those with low early EXT and early SEV and high WR before -blocker introduction regardless of LVEF values.     

Local Administration of NF-κ B Decoy Oligonucleotides to Prevent Restenosis after Balloon Angioplasty: An Experimental Study in New Zealand White Rabbits

Purpose To evaluate the efficacy of NF- B oligonucleotides (ODN) administered by local administration with the channeled balloon catheter to prevent restenosis after balloon angioplasty in restenotic iliac arteries of New Zealand white rabbits.Materials and Methods In vitro, 8000 rabbit vascular smooth muscle cells (rVSMC) where transfected with a liposomal carrier (TfX50) with 100 ng of decoy and scrambled ODN. Inhibition of proliferation was measured using a MTT assay after 24 hours in comparison to control. In vivo, 22 male New Zealand White rabbits were fed a 1% cholesterol diet and received denudation of both common iliac arteries with a 3 mm balloon catheter to induce an arterial stenosis. Four weeks after stenosis induction, local application of NF- B in two different concentrations (1 g: n=14; 10 g: n=8) was performed randomly on one common iliac artery. Scrambled oligonucleotides without specific binding capacities were injected into the contralateral side. The channeled balloon catheter allows simultaneous balloon dilation (8 atm) of the stenosis and local application of a drug solution (2 atm). Four weeks after local drug delivery the animals were killed and the vessels were excised and computerized morphometric measurements were performed.Results NF- B decoy ODN but not scrambled ODN inhibited proliferation of rVSMC in vitro. Following local ODN application in the animals, no acute vascular complications were seen. NF- B ODN resulted in a statistically non significant reduction of neointimal area compared to the control group. The neointimal area was 0.97 mm² using 1 g NF- B ODN compared to 0.98 mm² in the control group. The higher dose resulted in a neointimal area of 0.97 mm² compared to 1.07mm² at the control side.Conclusions Local drug delivery of NF- B ODN using the channeled balloon catheter could not reduce neointimal hyperplasia in stenostic rabbit iliac arteries. Application modalities have to be improved to enhance the effect of the local application to prevent restenosis after balloon angioplasty.     

A pragmatic approach to metal artifact reduction in CT: merging of metal artifact reduced images

The purpose of this study was to improve metal artifact reduction (MAR) in X-ray computed tomography (CT) by the combination of two artifact reduction methods. The presented method constitutes an image-based weighted superposition of images processed with two known methods for MAR: linear interpolation of reprojected metal traces (LI) and multi-dimensional adaptive filtering of the raw data (MAF). Two weighting concepts were realized that take into account mean distances of image points from metal objects or additional directional components. Artifact reduction on patient data from the jaw and the hip region shows that although the application of only one of the MAR algorithms can already improve image quality, these methods have specific drawbacks. While MAF does not correct corrupted CT values, LI often introduces secondary artifacts. The corrective impact of the merging algorithm is almost always superior to the application of only one of the methods. The results obtained with directional weighting are equal to or in many cases better than those of the distance weighting scheme. Merging combines the advantages of two fundamentally different approaches to artifact reduction and can improve the quality of images that are affected by metal artifacts.Symbols LI linear interpolation algorithm - MAF multi-dimensional adaptive filtering algorithm - MAR metal artifact reduction - f(x, y) object function at (x, y) - F(), F() normalized filter function in the direction of the coordinates and - I primary X-ray intensity - I₀ transmitted X-ray intensity - N_D number of detectors per detector row - p attenuation - p(,), p(,) projection data (fan and parallel geometry) - p_th lower threshold of the attenuation of adaptive filtering - p_max maximum value of the attenuation of adaptive filtering - (x, y) image point - projection angle in fan geometry - angle within the fan relative to the central ray - , , z, , minimum functions for adaptive filtering - projection angle in parallel geometry - orthogonal distance of a ray to the center of rotation in parallel geometry     

Sodium bicarbonate-augmented stress thallium myocardial scintigraphy

It is well known that sodium bicarbonate in pharmacological doses induces transient alkalosis, causing intracellular transport of serum potassium. The aims of this study were (a) to investigate whether, in humans, myocardial thallium-201 uptake can be augmented by pretreatment with a single bolus of sodium bicarbonate at a pharmacological dose, (b) to verify general safety aspects of the intervention and (c) to evaluate the clinical implications of augmentation of ²⁰¹Tl uptake, if any. Routine exercise myocardial scintigraphy was performed twice in eight adult volunteers (five normal and three abnormal), once without intervention and the second time (within a week) following intravenous administration of sodium bicarbonate (88 mEq in 50 ml) as a slow bolus 1 h prior to the injection of ²⁰¹Tl. Conventional myocardial thallium study was compared with sodium bicarbonate interventional myocardial scintigraphy with respect to myocardial uptake (counts per minute per mCi injected dose), washout patterns in normal and abnormal myocardial segments, and overall clinical interpretation based on planar and single-photon emission tomographic (SPET) images. All patients remained asymptomatic after the intervention. A mean increase of 53% in myocardial uptake of thallium was noted in post-exercise acquisitions after the intervention, confirming uptake of the tracer via the potassium-hydrogen pump and its augmentation by transient alkalosis. The washout pattern remained unchanged. The visual quality of planar and SPET images improved significantly after the intervention. Out of the five abnormal myocardial segments identified in three cases, four showed significant filling-in after the intervention, causing the diagnosis to be upgraded from partial scar to ischaemia, or from ischaemia to normal. The overall scan impression changed in two out of three such cases. Sodium bicarbonate augmentation may have significant implications for stress-thallium scintigraphy and may be a new parameter for defining myocardial viability.     

Die besonderen konstruktionsmerkmale des japanischen „Tan-to“-(Messers) als Kriterien für dessen Gefährlichkeit

Zusammenfassung Es wird auf die besondere Klingenform japanischer Blankwaffen und auf die Neuentwicklung eines Verwandlungs-Tan-to verwiesen. Bei letzterem läßt sich die Klinge in der Handgriffmitte um 90° drehen und arretieren, eine ideale Fixierung dieses Messers durch Faustschluß am Quergriff. Durch diese Bedingungen ist eine hohe Verletzungsgefährdung mit tödlichem Ausgang gegeben. Diese seit kurzer Zeit im Handel erhältlichen Messer sollten nach § 37 Waff G umgehend als verbotene Gegenstände definiert werden.     

Das Problem der a-priori-Wahrscheinlichkeit bei Verwendung der Essen-Möller-Formel zur Berechnung der Vaterschaftswahrscheinlichkeit

Zusammenfassung Die Annahme der a-priori-Wahrscheinlichkeit, daß Nichtväter und wahre Väter gleichhäufig zur Begutachtung gelangen, wird an Hand von 408 Aktenfällen bestätigt.Die Berechnung der Vaterschaftswahrscheinlichkeit bietet, insbesondere bei Mehrverkehrsfällen, wertvolle Hinweise für die Vaterschaft oder Nichtvaterschaft eines Probanden, Hinweise, die durch die Angabe der Vaterschaftsausschlußchance aufgrund der Mutter-Kind-Konstellation nicht erbracht werden können. Auf Beziehungen zwischen der Vaterschaftsausschlußchance und der Vaterschaftswahrscheinlichkeit wird hingewiesen.

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The assumption of prior probability computing the plausibility of paternity by the Essen-Möller equation and its problem

Summary Among objectivists the assumption of firsthand probability, that non-fathers and true-fathers are being given an opinion on with equal frequency, yields to a rejection in calculating the probability of fatherhood according to Essen-Möller. By means of 408 cases it is shown, that this assumption does meet the actual situation. Non-fathers and true-fathers are observed equally frequent. Calculation of fatherhood probability renders a valuable reference to paternity or nonpaternity of a subject in cases of multiple intercourses. These references cannot be brought on by the statement of the exclusion chance of fatherhood based on the mother-child-constellation. The relationship between the exclusion chance and the probability of fatherhood is pointed out.

     

Three-dimensional display of myocardial perfusion detection of ischemic lesions using a new image subtraction method

A recent, commercially available computer program for the three-dimensional (3D) display of single-photon emission tomography (SPET) data was used to study myocardial perfusion in patients with coronary artery disease (CAD). To enable the detection of small ischemic lesions, the authors proposed a new distance-subtraction method: after suitable centering of the axial slices, 3D distance-shaded images of the stress study were subtracted from the corresponding views of the rest study. With this technique, small changes in surface-to-observer distance were highlighted, thus enabling us to detect nontransmural ischemic areas of the myocardium. General characteristics and possibilities of the subtraction technique were tested on a simple myocardial phantom. Some clinical results of the application of this method on CAD patients are presented and discussed. In CAD patients in whom only nontransmural ischemic lesions are present, the subtraction of distance-shaded images is decisive for a correct diagnosis.     

Myocardial beta-adrenoceptor downregulation in idiopathic dilated cardiomyopathy measured in vivo with PET using the new radioligand (S)-[11C]CGP12388

Purpose The -adrenoceptor (-AR) plays an important role in heart failure. Recently, the new tracer (S)-[¹¹C]CGP12388 has been developed. It displays excellent properties for investigation of the cardiac -ARs in vivo with positron emission tomography (PET). Furthermore, the simple production method allows its use in a routine clinical setting. The aim of this study was to investigate whether decreased myocardial -AR density in patients with idiopathic dilated cardiomyopathy (IDC) can be estimated using (S)-[¹¹C]CGP12388 PET.Methods Myocardial -AR density was investigated in six patients with IDC and six age-matched healthy controls, using (S)-[¹¹C]CGP12388 PET.Results -AR densities of 5.4±1.3 pmol/g (mean ± SD) were observed in patients; these values were significantly lower than those observed in healthy controls (8.4±1.5 pmol/g, p<0.005).Conclusion This study indicates that PET with (S)-[¹¹C]CGP12388 is applicable for the measurement of myocardial -AR density in patients. A highly significant reduction in -AR density was found in patients with IDC compared with healthy controls.     

New Retrievable Coil Anchors: Preliminary In Vivo Experiences in Swine

Purpose To design and test retrievable coil anchors to improve the safety and efficacy of coil embolization.Methods Fifty-two 0.038-inch homemade retrievable stainless steel coils were equipped with one of four different pre-shaped nitinol anchors and tested in 38 pigs. All coils with the anchor were completely retrieved and redeployed 3–18 times (median 7 times) prior to release. Types 1 and 2 anchored coils were acutely deployed in the external iliac arteries (n=10 each), and chronically tested (1 week) in the common carotid arteries (n=6 each). Larger type 1 (n=4), type 3 (n=6), and type 4 (n=4) anchored coils were acutely deployed in the abdominal aorta. The largest type 1 anchors (n=6) were acutely tested in the inferior vena cava.Results All anchored coils were successfully retrieved and repositioned several times. All but two coils formed a compact plug and there was no coil migration except with two mechanically defective type 3 anchors.Conclusion The use of retrievable anchors allowed the coils to be retrieved and repositioned, prevented coil migration, and enabled compact coil configuration.     

Review of Source Images is Necessary for the Evaluation of Gadolinium-Enhanced MR Angiography for Renal Artery Stenosis

The purpose of this study was to assess interobserver variability and accuracy in the evaluation of renal artery stenosis (RAS) with gadolinium-enhanced MR angiography (MRA) and digital subtraction angiography (DSA) in patients with hypertension. The authors found that source images are more accurate than maximum intensity projection (MIP) for depicting renal artery stenosis. Two independent radiologists reviewed MRA and DSA from 38 patients with hypertension. Studies were postprocessed to display images in MIP and source images. DSA was the standard for comparison in each patient. For each main renal artery, percentage stenosis was estimated for any stenosis detected by the two radiologists. To calculate sensitivity, specificity and accuracy, MRA studies and stenoses were categorized as normal, mild (1–39%), moderate (40–69%) or severe (70%), or occluded. DSA stenosis estimates of 70% or greater were considered hemodynamically significant. Analysis of variance demonstrated that MIP estimates of stenosis were greater than source image estimates for both readers. Differences in estimates for MIP versus DSA reached significance in one reader. The interobserver variance for MIP, source images and DSA was excellent (0.80< 0.90). The specificity of source images was high (97%) but less for MIP (87%); average accuracy was 92% for MIP and 98% for source images. In this study, source images are significantly more accurate than MIP images in one reader with a similar trend was observed in the second reader. The interobserver variability was excellent. When renal artery stenosis is a consideration, high accuracy can only be obtained when source images are examined.     

Usefulness of a latex agglutination assay for FDP D-dimer to demonstrate the presence of postmortem blood

D-dimer, a specific fragment resulting from degradation of cross-linked fibrin, is an essential marker for the diagnosis of disseminated intravascular coagulation (DIC). Rapid assay for D-dimer using monoclonal antibody coated-latex particles might be useful for discriminating between postmortem and antemortem blood in bloodstains. We tried to detect D-dimer in nine postmortem blood samples by the rapid latex agglutination assay and to quantify them automatically using the latex photometric immunoassay system. The results showed that all samples were positive and that their amounts of D-dimer were 335–2,800 g/ml (the normal blood level, <1 g/ml; the pathogenic blood level with DIC, 1–100 g/ml). Next, nine stains made of postmortem blood were examined by the rapid latex agglutination assay. The result showed that only one case (D-dimer 335 g/ml blood) showed weak positive while the others (D-dimer 600–2,800 g/ml blood) were positive. The present study indicates that the latex agglutination assay for D-dimer can be useful to demonstrate the presence of postmortem blood.     

125I-β-iodo-D-alanine-synthesis,biodistribution and antimicrobial activity

Methyl N-carbobenzoxy--iodo-D-alaninate (1) served as an intermediate to synthesize methyl -iodo-D-alaninate (2) and -iodo-D-alanine (3). The ¹²⁵I-labeled compound 1 was synthesized by the melt method and used to synthesize ¹²⁵I-labeled compounds 2 and 3. Compound 3 was shown to be substrate for D-amino acid oxidase. It was also shown that compounds 2 and 3 were rapidly eliminated from normal mammalian tissues and that compound 3 inhibited the Escherichia coli growth in a dose-dependent manner at 100–500 g/ml while compound 2 showed no effect at 500 g/ml level. Therefore, it was suggested that compound 3 may serve as an abscess localizing agent.Research carried out at Brookhaven National Laboratory under contract with the U.S. Department of Energy (No. DE-AC-02-76CH00016) and supported by its Office of Health and Environmental Research     

ROC analysis in radioimmunoassay: An application to the interpretation of thyroglobulin measurement in the follow-up of thyroid carcinoma

This study is an application of the ROC technique to the determination of threshold values (TV) for the interpretation of serum thyroglobulin (Tg) measurements in the follow-up of differentiated thyroid cancer. Serum Tg was assayed using the Henning kit in 1466 samples from 245 individuals. A local or distant recurrence was assessed by clinical examination, radiological and scintigraphic investigations, and was present in 23 patients. The measurements were divided into four groups: 1) measurements performed less than 6 months after thyroidectomy; 2) measurements performed more than 6 months after thyroidectomy; 3) measurements performed during the suppression of pituitary secretion; 4) measurements performed during withdrawal of the substitutive therapy. An ROC curve was calculated for each group and for each curve three TVs were determined: TV1, TV2, and TV3 corresponding to a high sensitivity, a high specificity and a high sum of sensitivity and specificity respectively. TV1 is 3.12 g/l in the four groups. TV2 is 44 g/l, 19 g/l and 30 g/l, in the first, second, third and fourth groups respectively. TV3 is 35 g/l in the first group, 3.12 g/l in both the second and third groups and 30 g/l in the fourth group. When the classical method allows the determination of only one threshold value, the ROC technique allows us to determine threshold values adapted to both the patient clinical status and the chosen sensitivity or specificity.     

Transcatheter Closure of Patent Foramen Ovale in Patients with Platypnea-Orthodeoxia: Results of a Multicentric French Registry

Background Dyspnea and the decrease in arterial saturation in the upright position in elderly subjects is described as platypnea-orthodeoxia syndrome (POS). POS is secondary to the occurrence of an atrial right-to-left shunt through a patent foramen ovale (PFO).Methods This French multicentric study reports on 78 patients (mean age 67±11.3 years) with POS who had transcatheter closure of the PFO; frequently associated diseases were pneumonectomy (n=36) and an ascending aortic aneurysm (n=11). In all patients, the diagnosis was confirmed by transthoracic or/and transesophageal echocardiography. Five different closure devices were used: Amplatz (n=45), Cardioseal (n=13), Sideris (n=11), Das Angel Wings (n=8) and Starflex (n=1). Closure was successful in 76 patients (97%).Results Oxygen saturation increased immediately after occlusion from 84.6±10.7% to 95.1±6.4% (p < 0.001) and dyspnea improved from grade 2.7±0.7 to grade 1±1 (p < 0.001). A small residual shunt was immediately observed in 5 patients (3 with the Cardioseal device, 1 with the Sideris and 1 with the Amplatz) leading to the implantation of a second device in one case (Cardioseal). Two early deaths occurred unrelated to the procedure (one due to sepsis probably related to pneumonectomy, another due to respiratory insufficiency). Other complications were: a small shunt between the aorta and the left atrium, two atrial fibrillations and a left-sided thrombus which disappeared with anticoagulant therapy. At a mean follow-up of 15±12 months, there were 7 late deaths related to the underlying disease.Conclusion Percutaneous occlusion of the foramen ovale is safe and gives excellent results thanks to continuing improvement in available devices. This technique enables some patients in an unstable condition to avoid a surgical closure.     

Zur forensisch-medizinischen Bewertung von Fußspuren

Zusammenfassung Zur Frage der Identifizierung mit Hilfe von Abdruckspuren des unbekleideten menschlichen Fußes wurden Untersuchungen an einem Kollektiv von 100 Personen durchgeführt.Die vergleichende Auswertung von 200 Standspuren und ca. 600 Gangspuren durch Messung und Formbeschreibung diente zunächst der Erkennung der Variabilität innerhalb des Untersuchungskollektives wie zwischen Stand- und Gangspur der gleichen Person. Als typische Gangveränderungen wurden eine Verlängerung des Sohlenabdruckes, insbesondere der Zehen mit spitzer Ausziehung derselben, und eine Verbreiterung der Großzehenbasis beobachtet. Ballen, Brücke und Ferse waren in der Gangspur häufiger verbreitert als verschmälert. Sehr variabel erwies sich die Form des Brückenanteils, relativ konstant hingegen die Anordnung der Zehenbeeren.In den Formmerkmalen völlig übereinstimmende Fußabdrücke zweier Personen wurden nicht gefunden. Die Formunterschiede zwischen Stand- und Gangspur der gleichen Person waren jedoch vereinzelt nicht geringer als die Unterschiede zur Standspur einer anderen Person.Aus diesen Beobachtungen ergaben sich Empfehlungen für die Praxis der Identifizierung von Abdruckspuren des unbekleideten Fußes ohne erkennbare Papillarleistenmuster.

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Summary 100 persons were examined for the footprints using unclad human feet. The comparison of 200 standing footprints and about 600 gait footprints were evaluated w. r. t. the form and served first the purpose of identification of the variability between whole material and between the standing and gait footprints of the same person.The typical changes during the movement were seen to be the elongation of the sole prints, especially of toes and broadening of the proximal part of the first toe. Ball, Bridge and Heel-patterns were in most cases broadened rather than narrowed down. The form of bridge showed the most variation and least variation was found in the position of toes. Completely identical footprints of 2 persons were not found. The variation between the standing and gait-footprints of the same person were sometimes equal to the variation from the standing footprints of another person.According to these observations it would be advisible to identify the prints of unclad human feet without visible dermatoglyphic patterns.

Herrn Prof. Dr. B. Mueller zum 75. Geburtstag.     

In vitro and in vivo characterisation of nor-β-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain

Radiolabelled 2-Cabomethoxy-3-(4-iodophenyl)tropane (-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2-Carbomethoxy-3-(4-iodophenyl)nortropane (nor--CIT) is a des-methyl analogue of -CIT, which in vitro has tenfold higher affinity (IC₅₀=0.36 nM) to the serotonin transporter than -CIT (IC₅₀=4.2 nM). Nor--CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor--CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [¹²⁵I]nor--CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 M) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [¹¹C]nor--CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [¹¹C]nor--CIT were 20%–40% higher than those previously obtained with [¹¹C]-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor--CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain.     

Comparison of iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane for imaging of the dopamine transporter in the living human brain

Several cocaine congeners are of potential for imaging the dopamine transporter (DAT). Previous studies have shown that iodine-123 labelled 2-carbomethoxy-3-(4-iodophenyl)tropane ([¹²³I]-CIT) is a promising radiotracer for imaging the serotonin (5-HT) and dopamine (DA) transporters in the living human brain with single-photon emission tomography (SPET). [¹²³I]-CIT was found to be not very practical for 1-day DAT imaging protocols since peak DAT uptake occurs later than 8 h. Here we report a pilot comparison of [¹²³I]-CIT and 2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ([¹²³I]-CIT FP), using SPET imaging in four healthy male subjects. Peak uptake of [¹²³I]-CIT-FP into the basal ganglia occurred earlier (3–4 h after injection of tracer) than that of [¹²³I]-CIT (>8 h). However, the specific DAT binding of [¹²³I]-CIT-FP in the basal ganglia was somewhat less (0.813±0.047) than that of [¹²³I]-CIT (0.922±0.004). Imaging quality is excellent with both tracers and they are potentially of value for brain imaging in various neuropsychiatric disorders.     

The value of bone imaging in multiple myeloma

In a series of 20 patients with a proven diagnosis of myeloma, both full radiographic skeletal surveys and full ratio-nuclide bone images were performed. When these were compared, they showed that (i) imaging underestimated the number of areas involved by 50%, but there were no false negative whole images when compared with the radiology, (ii) large lytic areas on X-ray show as cold areas on the bone image but small ones show as normal, (iii) images that show areas of increased uptake (hot) are almost always associated with fracture, and (iv) patients with bone pain very commonly had hot images corresponding to the region of pain.4th year medical student