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Biomedical subjects

W H Knapp

Publications and source records attributed to W H Knapp.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Striatal uptake of I-123-beta-CIT and I-123-IBZM in patients with extrapyramidal symptoms].

AIM: This pilot study deals with the question whether characteristic changes in local cerebral dopamine transporter function and D2-receptor binding capacity can be shown with SPET in idiopathic Parkinson syndrome (IPS) and secondary Parkinson syndrome (SPS). METHODS: In 16 patients (6 with IPS, 6 with SPS except Wilson's disease, and 4 with Wilson's disease) SPET studies were performed using I-123-beta-CIT and I-123-IBZM and a dual-head gamma camera. Images were obtained 20-24 h and 2 h post injection, respectively. For semiquantitative analysis count density ratios of basal ganglia (BG) and cerebellum (CER) were determined for I-123-beta-CIT and ratios between BG and medial frontal cortex (MFC) for I-123-IBZM. RESULTS: The BG/CER ratio in the I-123-beta-CIT studies averaged 3.04 +/- 0.83 in IPS and 7.73 +/- 3.28 in SPS (p < 0.01) (except Wilson's disease). In patients with IPS, the BG/MFC I-123-IBZM ratios of basal ganglia contralateral to the symptomatic side exceeded that of the individual ipsilateral BGs (1.75 +/- 0.12 vs. 1.61 +/- 0.16); these ratios were significantly reduced when compared with those of SPS patients, although the differences were less pronounced than those of I-123-beta-CIT uptake values. In some of the patients with Wilson's disease the BG/MFC ratio for I-123-IBZM was dramatically reduced (as low as 1.29), whereas I-123-beta-CIT uptake was only slightly reduced when compared with that of SPS patients (8.00 +/- 2.90, p < 0.01). CONCLUSION: It is concluded that the neurochemical changes that can be anticipated in the above diseases can be monitored with SPET. I-123-beta-CIT, however, appears to be more adequate to differentiate IPS from SPS than I-123-IBZM.

Adult↗
PubMed1996

Changes in local cerebral blood flow by neuroactivation and vasoactivation in patients with impaired cognitive function.

Imaging of local cerebral blood flow (lCBF) may serve as an important supplementary tool in the aetiological assessment of dementias. In early or preclinical disease, however, there are less characteristic changes in lCBF. In the present study it was investigated whether vasoactivation or neuroactivation may produce more pronounced local lCBF deficits. Local CBF was investigated by using technetium-99m hexamethylpropylene amine oxime and single-photon emission tomography (SPET) in 80 patients (50 with mild cognitive impairment and 30 with dementia of Alzheimer type (DAT), all without evidence of cerebrovascular disease) at rest (baseline) and during activation. In 31 studies patients underwent vasomotor activation with acetazolamide, while 62 studies were performed under cognitive challenge (neuroactivation by labyrinth task). Cortical activity relative to that of cerebellum increased significantly in a right temporal region and tended to increase in other cortical regions upon vasoactivation. In contrast, neuroactivation reduced cortical activity relative to that of cerebellum in several left and right temporal and in left parietal regions. Visual classification of SPET images of patients with probable DAT by three observers resulted in a reduction of the number of definitely abnormal patterns from 9/12 to 4/12 by vasoactivation and an increase from 10/18 to 15/18 by neuroactivation. Correspondingly, abnormal ratings in patients with mild cognitive dysfunction were reduced from 7/19 to 5/19 by vasoactivation and were increased from 12/21 to 18/21 by neuroactivation. In conclusion, vasoactivation does not enhance local relative perfusion deficits in patients with cognitive impairment of non-vascular aetiology, whereas neuroactivation by labyrinth task produces more pronounced local flow differences and enhances abnormal patterns in lCBF imaging.

Acetazolamide↗
PubMed1996

Radioiodination of nicotine with specific activity high enough for mapping nicotinic acetylcholine receptors.

A novel radiochemical method is presented to synthesize 5-[123I/125I/131I]-dL-nicotine by radioiodination of 5-bromonicotine. Radioiodination of the precursor 5-dL-bromonicotine was achieved using a copper (I)-assisted nucleophilic exchange reaction in the presence of reducing agent. The reaction conditions were optimized by varying pH, concentration of Sn(II) salt, ascorbic acid, Cu(I)chloride and reaction temperature. After purification by high-performance liquid chromatography the radiochemical purity of the product exceeded 98%, with a radiochemical yield of 55% and a specific activity > or =5 GBq/micromol. Specific binding of the iodinated nicotine was demonstrated in rat brain by autoradiography. The radioactivity from the specific structures was displaced by an excess of non-radioactive nicotine (10(-3)M) with KD and Bmax of 13.1+/-7.8 nM and 22+/-2.7 fmol/mg protein and unspecific binding of about 40%. The in vivo distribution of 5-[131I]iodonicotine was determined in 20 female Wistar rats at various time intervals of 15s to 90 min post injection (p.i.) by well counting and autoradiography. Brain activity peaked within 0.5 min p.i., and then showed a biexponential washout. Initially, activity within the cerebral cortex exceeded that of the cerebellum by a factor of 1.5-2.0. It was also increased in the striatum and thalamus. However, as soon as 15 min p.i. activity was almost homogeneously distributed. In conclusion, synthesis of 5-iodo-dL-nicotine (labelled with 131I, 125I or 123I, respectively) with appropriately high specific activity for receptor studies was achieved and specific binding to nicotine receptors in rat brain was demonstrated; following intravenous injection, however, there is considerable unspecific binding, obviously due to highly flow-dependent tissue retention.

Animals↗
PubMed1996

Non-uniform attenuation correction for myocardial SPET using two Gd-153 line sources.

AIM: This study deals with the effect of the non-uniform attenuation correction method on myocardial tomograms of normal subjects. METHOD: A total of 35 patients (20 female, 15 male) without evidence of cardiac disease underwent SPET with and without attenuation correction using a dual head camera and transmission data obtained by two scanning Gd-153 line sources after administration of 400 MBq Tc-99m-tetrofosmin RESULTS: In non-corrected (NC) stress studies the lowest count rates were found in the inferior segments with mean differences in count rates between maxima and minima of 35.8 +/- 10.8%. In attenuation corrected (AC) images the respective segmental differences averaged only 20.9 +/- 3.3% and the images did not show significant count deficiency in the inferior segments. The effects of correction revealed to be sex dependent, but independent of body mass on average. CONCLUSION: AC using the above technique significantly reduces the variability of count rate distribution in normal subjects and improves the preconditions for accurate diagnostic evaluation of coronary artery disease using SPET.

Adult↗
PubMed1995

[Potential and limitation of myocardial perfusion scintigraphy for detection of viability].

Scintigraphic detection of myocardial viability is required for treatment planning and prognostication in patients with contractile dysfunction. There are four pathophysiological entities of dysfunction in coronary artery disease; one of them, "hibernating" myocardium, cannot be differentiated from scar or necrosis by mere perfusion imaging. Due to the determinants of delayed activity distribution after 201Tl injection, optimized imaging protocols using this tracer allow for adequate differentiation in many instants. Differentiation between "stunned" and "hibernating" myocardium or scar is achieved with all perfusion indicators actually available. Though 201Tl imaging with optimized protocols is almost as efficacious in viability detection as 18F-FDG positron emission tomography, the latter actually remains the reference method particularly in patients with severe left ventricular dysfunction at coronary occlusions.

Coronary Disease↗
PubMed1993

Myocardial scintigraphy with thallium-201 and technetium-99m-hexakis-methoxyisobutylisonitrile in left bundle branch block: a study in patients with and without coronary artery disease.

In left bundle branch block (LBBB) thallium-201 myocardial scintigraphy frequently reveals septal abnormalities in the absence of coronary artery disease (CAD) and gives rise to "false-positive" results in patients with suspected CAD. It has not yet been clarified which pathophysiological mechanism is responsible for these perfusion abnormalities. A total of 66 patients with constant LBBB were investigated with 201Tl or technetium-99m-hexakis-methoxyisobutylisonitrile (MIBI), 62 underwent coronary angiography. Of 12 patients without left anterior descending artery (LAD) or right coronary artery (RCA) stenoses, 11 had a reversible septal activity deficit after 201Tl stress injection, whereas 20 of 22 patients without relevant CAD showed a constant stress/rest septal deficit using MIBI. Regarding patients with significant LAD and/or RCA stenoses, both radio-pharmaceuticals almost always showed a "reversible" septal deficit: with 201Tl in 15 of 16 individuals and with MIBI in 14 of 15. In 12 patients 201Tl was reinjected at rest. In those who had LAD or RCA stenoses (n = 5), early septal activity uptake after stress injection was poorer than that after rest injection; in the absence of CAD (n = 7), septal stress uptake corresponded with that of rest injection. It is concluded that septal perfusion abnormalities in LBBB and the absence of CAD are characterized by an exercise-independent reduction of septal blood flow per mass of viable myocardium and that stress/rest injection protocols of myocardial perfusion tracers are able to differentiate between LBBB with and without CAD.

Aged↗
PubMed1993

Indium-111-labelled antimyosin antibody imaging in a patient with cardiac sarcoidosis.

The aetiology of cardiac dysfunction caused by sarcoid granulomatous inflammation may be difficult to clarify, and the potential of imaging methods is limited. We report on a patient who presented with acute biventricular decompensation. Pulmonary sarcoidosis was confirmed after hospitalization. Four weeks after the initiation of corticosteroid treatment, scintigraphy with indium-111-labelled antimyosin antibody Fab fragments (AMAB) revealed distinct activity accumulation in major parts of the left ventricular wall (heart-lung ratio: 1.6) 72 h following injection. There may be a role for AMAB scintigraphy in the early detection of cardiac sarcoidosis.

Adult↗
PubMed1991

[Results of myocardial scintigraphy in patients with left bundle-branch block using Tl-201 and Tc-99m-MIBI].

Tl-201 myocardial scintigrams in patients with left bundle-branch block (LBBB) are frequently non-diagnostic with respect to presence or absence of coronary artery disease (CAD). The new myocardial perfusion tracer Tc-99m-MIBI requires a different protocol due to its insignificant redistribution. Therefore, scintigraphic patterns in LBBB cannot be deduced from experiences with Tl-201. In a total of 132 patients with LBBB, 81 studies were carried out with Tl-201, another 81 studies with Tc-99m-MIBI. In 30 patients both radiopharmaceuticals were employed. 72% of the Tl-201 scintigraphies in constant LBBB resulted in a reversible septal deficit and 9% in a constant septal deficit. In contrast, 70% of the Tc-99m-MIBI scintigraphies resulted in a constant septal deficit and only 19% in a reversible septal deficit. Similar "discrepancies" were found in LBBB patients in whom CAD has been angiographically excluded (N = 17). All patients, however, with LAD or RCA stenoses and constant LBBB showed reversible septal deficits with either tracer, Tl-201 (N = 12) or Tc-99m-MIBI (N = 10). It is concluded: 1) that the majority of patients with LBBB has reduced septal perfusion, 2) that this reduction is typically stress-independent in absence of CAD, and 3) that this stress-independent perfusion deficit is, in general, only differentiated from stress-induced ischemia (in case of CAD) with using the Tc-99m-MIBI protocol.

Adult↗
PubMed1989

Increased thermal response to ultrasound in the Walker carcinosarcoma treated with vasoactive drugs.

In order to evaluate the potential of a highly selective Ca2+ entry blocker (nisoldipine) and of 5-hydroxytryptamine (5-HT) as adjuvant in hyperthermia treatment, we studied the differential flow response and time-course of tumor and normal tissue temperature following the administration of the two substances and during ultrasound heating. In 12 rats bearing Walker 256 carcinomas i.p. injection of 0.2-0.4 mg/kg nisoldipine caused a reduction in the tumor-to-muscle flow relationship of 4.4 +/- 1.9 (SD) to 1.74 +/- 0.86 as determined by intraarterial 133Xe injection; i.p. injection of 2-8 mg/kg 5-HT (N = 13) caused a respective reduction from 3.9 +/- 2.67 to 1.3 +/- 1.59. During a 20-min period of 41 degrees C normal tissue temperature-controlled ultrasound heating without drugs, tumor temperature attained 40.8 +/- 0.9 degrees C (N = 16). Nisoldipine or 5-HT injection at continuing 41 degrees C normal tissue temperature controlled energy delivery produced an instantaneous further increment of tumor temperature, eventually to 44.0 +/- 1.14 degrees C or 44.2 +/- 1.26 degrees C, respectively, after a period of 20 min. Injection of 0.9% NaCl (N = 4) solution caused only insignificant changes. Blood pressure and muscle perfusion were distinctly influenced by nisoldipine, but not by 5-HT. Since both drugs instantaneously increased the temperature differential between tumor and normal tissue, though by different vasoaction, they should be considered as adjuvants in hyperthermia.

Animals↗
PubMed1988

Regional myocardial nitrogen-13 glutamate uptake in patients with coronary artery disease: inverse post-stress relation to thallium-201 uptake in ischemia.

The purpose of the present study was to evaluate the clinical significance of myocardial scintigraphy with nitrogen-13 (N-13) glutamate as a marker of myocardial metabolism. Within 2 weeks after cardiac catheterization, 25 patients with single vessel left anterior descending coronary artery disease underwent thallium-201 imaging (5 min and 3 h after injection) and N-13 glutamate scintigraphy (10 min after injection). Radionuclide studies were performed in the 30 degrees left anterior oblique projection after symptom-limited bicycle exercise, and regional tracer uptake was quantified by computer-assisted placement of regions of interest within the regions of myocardial activity. Poststenotic tracer uptake in the perfusion bed of the left anterior descending coronary artery (septum) was then normalized to the tracer uptake in the nondiseased left circumflex territory (posterolateral segments = 100%). In 14 patients with a history of previous myocardial infarction (Subgroup A), deficient poststenotic N-13 uptake correlated closely with thallium-201 uptake in both initial (r = 0.82, p less than 0.001) and redistribution (r = 0.74, p less than 0.01) scintigrams. By contrast, in 11 patients with no previous myocardial infarction and normal left ventricular function at rest (Subgroup B), initial uptake of both tracers was inverse: poststenotic N-13 glutamate uptake increased with decreasing thallium-201 uptake during exercise-induced ischemia (r = -0.64, p less than 0.05) and was closely correlated with the percent thallium-201 redistribution (r = 0.74, p less than 0.01). Thus, augmented accumulation of N-13 glutamate in reversibly ischemic (that is, viable) myocardium, and decreased uptake in myocardial scar tissue suggest the clinical usefulness of this metabolic tracer in the differentiation between viable (metabolically active) and irreversibly damaged myocardium.

Coronary Disease↗
PubMed1988

Noninvasive assessment of coronary artery bypass patency: determination of myocardial thallium-201 washout rates.

This prospective study was undertaken to investigate the response of thallium-201 washout rates to coronary artery bypass surgery. Thirty-four patients with coronary heart disease were studied before and after coronary artery bypass grafting, 27 patients with normal coronary arteries serving as controls. All patients underwent cardiac catheterization and thallium-201 serial imaging, including assessment of myocardial washout rates. Pre-operatively, thallium-201 washout rates yielded a considerably higher sensitivity in detection of coronary artery disease, without significant loss of specificity compared to qualitative evaluation of serial static thallium-201 scintigrams. Post-operatively, 50 of 57 segments supplied by a patent graft showed normal washout rates, while in 9 out of 11 segments an occlusion of the graft was indicated by decreased washout rates. Compared to pre- and post-operative qualitative interpretation of static thallium-201 images, the post-operative assessment of washout rates increased both sensitivity (82% vs. 64%) and specificity (88% vs. 77%) for the evaluation of bypass graft patency. Thus, quantitative assessment of thallium-201 washout rates improves the diagnostic reliability of noninvasive detection of myocardial ischaemia with regard to the evaluation of coronary artery bypass graft patency.

Coronary Artery Bypass↗
PubMed1988

Regional myocardial free fatty acid extraction in normal and ischemic myocardium.

The rate constant for free fatty acid influx (k1) was studied in normal and ischemic myocardium. In 15 normal subjects and 30 patients with coronary artery disease, 201Tl and 15-(p-123I-iodophenyl)-pentadecanoic acid (IPPA) were administered during exercise under fasting conditions and at rest. In 10 patients, the study was repeated after percutaneous transluminal coronary angioplasty; in three patients, the study was repeated after infarction. The initial accumulation of IPPA, related to that of 201Tl (both background and crossover corrected), was used for determinations of the regional rate constant of IPPA influx into myocardial tissue (k1*). In normal subjects, no significant differences in k1* between major myocardial segments were found; the average value of k1* was 0.57 +/- 0.13/min (mean +/- SD) at rest and 0.42 +/- 0.06/min at exercise (average workload, 123 +/- 47 W). With increasing free fatty acid plasma concentration and perfusion, free fatty acid influx increased in a saturable fashion. The Michaelis-Menten constant (KM*) and the maximal velocity (Vmax*) for IPPA influx into myocardial tissue were estimated to be 470 nmol/g and 430 nmol/g.min, respectively. In ischemic areas, k1* was reduced to 57 +/- 18% of k1* value in nonaffected segments. The areas were larger than those showing reduced 201Tl uptake. Preinfarction and postinfarction studies showed that the size of 201Tl defects in postinfarction images corresponded with the size of the area with reduced k1* observed in preinfarction scintigrams. Revascularization led to an increase of 201Tl uptake and to normalization of k1*.

Coronary Disease↗
PubMed1988

Effect of methotrexate on perfusion and nitrogen-13 glutamate uptake in the Walker-256 carcinosarcoma.

The tissue uptake of [13N]glutamate (glu) was related to that of [11C]butanol (but), a highly diffusible perfusion tracer. In 25 rats bearing Walker-256 carcinomas tumor-to-muscle glu uptake averaged 6.34 +/- 2.84 (s.d.) prior to interventions and the respective uptake of but was 6.79 +/- 3.08 (y = 0.03 + 0.94x). One hour after selective intraarterial administration of methotrexate (mtx), glu uptake fell by 47%, whereas blood flow remained within the pretreatment range (N = 9). Four hours after mtx, perfusion was reduced by approximately 40%, and 2 days later both perfusion and glu uptake reached extremely low levels. No significant difference in the effect of 10 and 50 mg/kg mtx was observed. Regional tissue mtx uptake estimations using 77Br-labeled bromomethotrexate did not reveal any significant uptake in muscle. The relationship between tumor-to-muscle uptake of glu and but (13N/11C-index) was 0.94 +/- 0.015 (s.e.m., N = 25) before intervention. After methotrexate (1 hr, 4 hr, and 2 days) this index was 0.58 +/- 0.06 (N = 9), and 0.85 +/- 0.04 (N = 11) and 1.03 +/- 0.05 (N = 5), respectively. These values demonstrate an early mtx-induced uncoupling of glu uptake with respect to perfusion.

Animals↗