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Biomedical subjects

W H Knapp

Publications and source records attributed to W H Knapp.

At least 91 records · Page 5Linked to original sources
PubMed1988

Double-nuclide study of the myocardium using 201Tl and 123I-labeled fatty acids in non-ischemic myocardial diseases.

Metabolic impairment and perfusion abnormalities are known to occur in hypertensive heart disease (HHD) and in cardiomyopathies. Free fatty acid (FFA) extraction is severely inhibited in a number of pathobiochemical reactions. This parameter was assessed using the radiolabeled FFA analogue 123I-(p-iodo-phenyl-)-pentadecanoic acid (IPPA) and 201Tl as perfusion marker, both of them injected at maximal physical workload. The regional extraction fraction of IPPA (IPPA-EF) was estimated by relating the regional IPPA and 201Tl uptake to each other. In HHD (normal coronary arteries) with posterior wall thickness less than or equal to 12 mm IPPA-EF was 77 +/- 18% (SD) in septum and 92 +/- 17% in the posterolateral wall (N = 13), with thickness of greater than 12 mm 60 +/- 23% in septum and 61 +/- 20% in the posterolateral wall (N = 8) when compared with IPPA-EF in normal subjects (= 100%, N = 9). In hypertrophic cardiomyopathy (HCM) IPPA-EF averaged 51 +/- 20% in septum and 87 +/- 10% in the posterolateral wall (N = 11). In these patient groups no systematic regional changes in 201TI uptake were observed. In dilated cardiomyopathy (DCM) both IPPA-EF and 201Tl uptake showed distinct regional variations and a great interindividual variability with a mean IPPA-EF reduction of 12% (N = 9). Thus, IPPA uptake in primarily non-ischemic myocardial disease may already be compromised when 201Tl uptake is unchanged. The double-nuclide method for IPPA-EF determination allows to eliminate the influence of flow in FFA imaging and enhances the potential of scintigraphy in the differential diagnosis of HHD versus coronary artery disease.

Cardiomyopathies↗
PubMed1986

Automated determination of the right ventricular ejection fraction by digital processing of 81mKr scintigrams.

A method is presented for the automated determination of the right ventricular ejection fraction (RVEF) by digital image processing of scintigrams obtained by intravenous infusion of Krypton 81m (81mKr) dissolved in a glucose solution. End-diastolic and end-systolic sum pictures were computed by the addition of approximately 30-40 frames selected from the time-activity curve of a preliminary, manually drawn, right ventricular region of interest. After processing these two images with an adaptive Wiener filter, the right ventricular contour was determined by a recently developed algorithm using morphological and functional criteria. The RVEF was calculated for a series of 51 patients from the counts in the detected right ventricular regions in the end-diastolic and end-systolic sum images. In 16 patients without evidence of cardiopulmonary disease, the mean RVEF was 50 +/- 6.1%. RVEF was significantly reduced in 18 patients with obstructive pulmonary disease (42 +/- 6.5%) and in 17 patients with congestive cardiomyopathy (36 +/- 7.1%). The correlation coefficient between two determinations of the RVEF was r = 0.94. Through digital image processing, the determination of the RVEF by radioventriculography with 81m Kr showed high reliability and reproducibility.

Algorithms↗
PubMed1986

Imaging of cerebral blood flow-to-volume distribution using SPECT.

The ratio between cerebral blood flow (CBF) and cerebral blood volume (CBV) has been proposed as an adequate parameter for the evaluation of cerebrovascular disease (CVD), but to date it has not been assessed with SPECT. We have chosen [123I]IMP for CBF and [99mTc] erythrocytes for CBV imaging. The distribution of both nuclides was investigated in succession using corrections for the contamination of the 99mTc tomograms by 123I. The ratio between 123I and 99mTc tomograms yielded the CBF/CBV distribution. Quantitation was obtained by side-to-side comparison of both hemispheres and of segments containing the territories affected by CVD. In 16 patients with CVD, CBF of the affected territories was 85 +/- 19% (s.d.) when related to the nonsymptomatic contralateral side (100%). When the regions of interest defined within one slice encompassed the entire affected hemisphere, the average CBF was 95 +/- 9%, again related to the nonsymptomatic side. The corresponding CBF/CBV data in 15 of these 16 patients were 60 +/- 32% and 81 +/- 16%. In unilateral internal carotid artery stenoses greater than 50% (N = 10), segmental CBF averaged 81.1 +/- 10.1% and CBF/CBV 49.6 +/- 15.5% relative to the contralateral side. The figures for the hemispheres were 92.8 +/- 5.8 and 75.8 +/- 12.6, respectively. These clinical findings mirror the characteristics of CBF autoregulation, namely the vasodilation of small vessels in decreased arterial perfusion pressure. They, therefore, substantiate SPECT imaging of CBF/CBV for the assessment of cerebral perfusion reserve in CVD.

Adult↗
PubMed1986

Nitrogen-13 glutamate uptake and perfusion in Walker 256 carcinosarcoma before and after single-dose irradiation.

Nitrogen-13 (13N) glutamate uptake was recorded in 18 anesthetized rats, both before and at least once after intervention. Each investigation was immediately followed by imaging of blood flow distribution using [11C]butanol. All animals had Walker 256 carcinosarcoma implants in one hind leg. Tumors were locally irradiated with a dose of 800 rad in 14 rats; in four rats, the vasoactive substance 5-hydroxytryptamine (5-HT) was administered. Prior to interventions, the [13N]glutamate tumor-to-muscle uptake showed a linear correlation with blood flow close to identity (y = 0.117 + 0.915x, r = 0.97). After irradiation, a discordant pattern was observed: blood flow tended to increase, while [13N]glutamate tumor-to-muscle uptake dropped from 4.30 +/- 0.66 (s.e.m.) to 3.06 +/- 0.36 (p less than 0.005) during 30 min and attained 4.04 +/- 0.67 2 days later. If [13N]glutamate tumor-to-muscle uptake was related to that of [11C] butanol in each individual animal, this index dropped from 0.93 +/- 0.03 (s.e.m.) to 0.62 +/- 0.04 (p less than 0.001) 30 min after irradiation and attained 0.90 +/- 0.09 after 2 days. In animals treated with 5-HT, [13N]glutamate and [11C]butanol showed a parallel drop from 6.60 +/- 0.84 to 2.10 +/- 0.60 (p less than 0.05) and from 6.8 +/- 0.78 to 2.08 +/- 0.74 (p less than 0.05), respectively. Thus, single-dose irradiation causes [13N]glutamate uptake to be uncoupled with respect to flow, while [13N]glutamate uptake in untreated tumors is flow-limited and responds together with flow on vasomotion.

Animals↗
PubMed1985

11C-butanol for imaging of the blood-flow distribution in tumor-bearing animals.

1-11C-n-Butanol produced semiautomatically using a cyclotron was employed to investigate the whole-body distribution and kinetics of the label of this compound. Following the administration of 11C-butanol into the aorta of two dogs, more than 80% of the activity was cleared from the blood within 1 min. The activity distribution mirrored the cardiac output distribution as determined using 121I microspheres. Within 25 min p.i., a significant release of decay-corrected activity was only observed for the liver, spleen, and kidneys. Muscle and whole-body activity showed constant levels during this period. In 45 tumor transplants from rats, the dynamic behavior of the label was studied. The tissue retention of activity following injection into the a. femoralis was approximately 100% during the 1st 15 s for both tumor and muscle (n = 6). The activity release by tumors during the 1st 10 min after intra-aortic injection was 18% +/- 4.5% (n = 39; decay corrected). In five different tumor lines (n = 10), the initial 11C-butanol uptake was related to that of muscle, and the results were correlated with the tumor-to-muscle retention of 121I-microspheres (r = 0.89). In 17 tumors, the correlation between 11C-butanol uptake and the washout rate of 133Xe resulted in a correlation coefficient of 0.96. Tumor-to-muscle uptake ratios could be equally determined using intra-aortic and intravenous injection, as evaluated by intraindividual comparison in 12 rats (y = 0.01 + 0.98x; r = 0.98). 11C-Butanol appears to be an appropriate radiotracer for the assessment of blood supply to malignant tumors relative to muscle.

1-Butanol↗
PubMed1985

Selective drug-induced reduction of blood flow in tumor transplants.

The effect of a calcium antagonist and a physiologic amine on tumor and muscle perfusion was investigated with the aim of improving the preconditions for external hyperthermia treatment of cancer. Nisoldipine (0.04-4.0 mg/kg) and 5-hydroxy tryptamine (5-HT) (0.2-8.0 mg/kg) were administered i.p. in Sprague-Dawley rats bearing Walker 256 carcinoma, Yoshida sarcoma, or a homologous tumor transplant derived from a spontaneous leiomyosarcoma of the uterus. At the maximum dosage used, nisoldipine injection caused a decrease of the regional washout rate of Xenon-133 of 63 +/- 8% (SEM) in the Walker carcinoma and an increase of 80 +/- 41% in the muscle of the hind leg. 5-HT (8 mg/kg) caused a drop of 79 +/- 29% in the Walker carcinoma and only a slight fall of the washout rate in muscle of 14 +/- 4.8%. Tumor-to-muscle uptake ratios of 11C-butanol fell from 5.63 +/- 1.98 to 3.32 +/- 1.21, and from 5.3 +/- 0.56 to 2.98 +/- 0.30, after injection of 0.2 mg/kg nisoldipine and 4 mg/kg 5-HT, respectively. Similar reaction patterns and percentage changes were observed in different tumor lines at constant doses of 0.2 mg/kg nisoldipine and 4 mg/kg 5-HT. Both drugs representing two different rationales of vasomotor action were able to reduce blood flow specifically in transplanted tumors; nisoldipine increased muscle blood flow and decreased arterial blood pressure, whereas 5-HT acted without substantial systemic effects.

Animals↗
PubMed1984

N-13 L-glutamate uptake in malignancy: its relationship to blood flow.

Studies on glutamate uptake, with special reference to perfusion, were carried out in 35 rats, each bearing one of five different tumor transplants; also in 15 rats after bone fracture, and in three rabbits. Single-pass extraction of N-13 glutamate was 85-93% in the VX2 tumor of the rabbit and in muscle. Bone fracture in rats caused a threefold increase of tracer uptake 2 days after the event. In tumor transplants, the tumor-to-muscle uptake ratio reached a maximum immediately following injection of the tracer. Comparing N-13 glutamate uptake with the retention of 1-121 microspheres, identical tumor-to-muscle ratios were found for three out of five tumor lines. Comparing the uptake with that of C-11 butanol (ten rats), a close correlation was observed throughout the range of tumor lines. The results suggested that glutamate uptake by malignant tumors is related to blood flow. In nine patients with malignant or benign lesions tumor-to-muscle uptake of N-13 glutamate and TI-201 showed a linear correlation close to identity.

Adolescent↗
PubMed1984

[Improvement of the non-invasive diagnosis of coronary heart disease using a new double-isotope method for the noninvasive determination of coronary transit times].

In conventional myocardial Thallium-201 scintigraphy, regional myocardial Thallium-201 activity is compared to the area of normal, i.e., maximal activity. In the presence of multivessel coronary artery disease, this mode of evaluation may yield false negative results. -In 87 patients suffering from coronary artery disease and in 26 controls, after simultaneous i.v. injection of Thallium-201 and Technetium-99m coronary transit times of Thallium-201 were determined as the interval between arrival of the tracer in the aortic root and the onset of its extraction in different myocardial areas. - Patients with hemodynamically significant coronary artery stenoses (greater than or equal to 75%) revealed a significant increase in coronary transit times over septum, apex, or posterolateral wall of the left ventricle. Using maximal coronary transit times, i.e., the largest of the regional values, an excellent discrimination between patients with severe coronary artery stenoses and controls was achieved. Following coronary vasodilatation with dipyridamole, even subcritical (50-75%) coronary artery stenoses could be detected with high sensitivity, since the shortening of coronary transit times in patients with subcritical stenoses was less pronounced as compared to controls. - Especially in the presence of diffuse three-vessel coronary artery disease, the quantitative assessment of regional coronary transit times yields important parametric data in addition to those obtained by conventional Thallium-201 scintigraphy combining static imaging with rapid sequence analysis of time-activity curves.

Coronary Disease↗
PubMed1982

Processing of 201T1 serial images for the assessment of myocardial clearance and redistribution.

Regional activity changes over the myocardium after IV injection of 201T1 were assessed in 90 patients by applying a superposition algorithm for paired images. The kinetics were expressed as quotients C1/C2 of the initial divided by the delayed count rate within any myocardial segment. Regarding the total left ventricular myocardium, normal subjects showed count rate ratios (C30 min/C4 h) of 1.75 +/- 0.075 (SD, n = 19) when the nuclide was injected under submaximal (80% of maximum) exercise. In patients with triple-vessel disease (n=21) the corresponding values were 1.46 +/- 0.05, in single-vessel (n=14) disease the quotients averaged 1.62 +/- 0.12. Average quotients in poststenotic myocardial segments increased from 1.46 before to 1.73 following bypass surgery in cases of graft patency (n=8), while a decrease was observed in a patient with occlusion of the bypass graft. In small-vessel disease and in congestive cardiomyopathy, global values of 1.50 +/- 0.07 (n=7) and 1.53 +/- 0.12 (n=19) were obtained. The display of C1/C2 matrices provided typical patterns in uptake defects caused by ischemic heart disease and by congestive cardiomyopathy. The procedure described may provide diagnostic information in addition to conventional myocardial scintigraphy in triple-vessel disease, in patients with angina who fail to demonstrate hemodynamically significant coronary artery stenoses, and in patients with inhomogeneous T1-scintigrams.

Coronary Disease↗
PubMed1982

Uptake and turnover of L-(13N)-glutamate in the normal human heart and in patients with coronary artery disease.

L-(13N)-glutamate (4-8 mCi) was administered IV to 27 patients with coronary artery disease and to 12 control subjects. Quantitative whole body imaging of the 13N label was performed in 31 individuals at different time intervals following the injection. Initial uptake of the total myocardium was estimated to be 5.0 +/- 0.88% of the dose. Standardized areas of reduced size on the projection plane contained 2.38 +2- 0.41% of the total dose in control subjects and 2.67 +/- 0.49% in coronary patients. Subsequent imaging exhibited significant differences in the dynamic behavior of both groups: 13N activity loss within 10 min was 3.2 +/- 4.2% of the initial value in control subjects and 16.0 +/- 9.8% in coronary patients. In individual cases a high myocardial accumulation of the 13N label was observed in regions of reduced 201Tl uptake. The findings are explained by an augmented extraction efficiency in cases of flow reduction. Glutamate utilization may be involved in metabolic adaptations of the myocardium to chronic or repetitive ischemia and may be worthy of further investigation by positron emission tomography.

Adolescent↗
PubMed1981

Efficacy of two dosage schedules of cephalexin in dermatologic infections.

Is the administration of oral antibiotics four times a day as necessary as some pharmacokinetic studies indicate? The efficacy of cephalexin administered twice a day was compared to the same drug administered four times a day for the treatment of skin and skin structure infections due to staphylococcus and/or streptococcus. The 154 outpatients in this four-clinic study ranged in age from 1 month to more than 70 years. A random number table was used to assign patients to either the twice a day or the four times a day regimen. The total daily dosage was the same in each regimen. Administration twice a day proved equally effective to the four times a day regimen. Both regimens were more than 97 percent effective and side effects were minimal.

Adolescent↗
PubMed1980

Kr-81m for determination of right ventricular ejection fraction (RVEF).

A 10--12 mCi 81Rb leads to 81mKr generator was connected to a specially designed short-period infusion set, to produce an equilibrium activity distribution in the right heart. This procedure was tested in 25 individuals to calculate the right ventricular ejection fraction (RVEF). On average 30 heart cycles were analyzed per study. No background activity from the left heart was visualized because of the radionuclide exhalation. The background from the lungs could be neglected, which is partially due to the ultra-short half-life of the nuclide (t 1/2 = 13 S). Thus, an easy automatic procedure can be applied to delineate the ventricle and to calculate the RVEF. The data showed excellent reproducibility, when investigations were repeated. The method would benefit from use of higher activity generators.

Adult↗
PubMed1980

Short-lived radionuclides for the assessment of rapid cardiovascular drug effects.

Continuous monitoring of cardiac output and sequential studies of right ventricular ejection fraction and of fractional myocardial uptake of substances with high cell affinity can be realized using 13N (t 1/2 = 9.6 min) and 81mKr (t 1/2 = 13 sec). Thus, it is possible to measure rapid changes of absolute myocardial blood flow and of the inotropic state of the right heart myocardium. This is shown in patients who underwent interventions with Dipyridamole and with Dobutamine which produce a marked increase in myocardial blood flow or cardiac dynamics, respectively.

Cardiac Output↗
PubMed1979

Calculation of residence time distributions of intravascular radioactive tracers in fields of external registration.

Because of the physiological significance of the mean velocity of blood flow, indicator dispersion models are of special interest and possess practical relevance, if biological and extraneous variables can be altered. The variables being considered are flow characteristics of the streaming blood, tracer distribution at the entrance into the flow system, and the area in which impulses are collected to form the time-activity curve. Using a simplified version of the general convective diffusion equation (diffusion model) in which the diffusion constant D includes all propagation and mixing of the tracer, a simple numerical method can be applied. The method is used to determine influences of injection and changed regions of interest on the time-activity curve and the following parameters: appearance times, peak times, mean circulation times, and the times of the first inflection points. For this purpose, the range of D was determined in 14 patients by applying experimental data to the model. The calculations on the variables show, that the advantage of this method is its applicability to any experimental case by simply adapting the input data to the recordings.

Blood Circulation↗
PubMed1978

Relationships between mean velocity of circumferential fiber shortening (VCF) and heart rate - the diagnostic value of a normalization of VCF to heart rate.

Previous studies relating mean velocity of circumferential fiber shortening (VCF) to heart rate suggested a linear correlation. Since there is considerable variability in the heart rate of normal subjects and in patients with myocardial disease, a normalization of VCF to heart rate could possibly increase the reliability of this echocardiographic parameter of myocardial function. In 106 normal subjects, a linear correlation between VCF and heart rate was confirmed (r=0.87). Values normalized to an arbitrary heart rate of 60/min by the calculated regression were called "relative velocity of contraction" (RVC). Because of the independence of RVC from heart rate, the RVC shows an obviously smaller physiological variation than VCF. Two hundred seventy-six patients were grouped and classified according to hemodynamic and angiographic parameters. These parameters correlated closer to RVC than to VCF. In addition, RVC gave definitely superior diagnostic information in separating patients with cardiac abnormality from normal individuals than did VCF.

Echocardiography↗
PubMed1978

[Radiocardiographic procedures during the first passage of an intravascular tracer in diagnostic context with echo- and angiocardiography (author's transl)].

In 107 patients having coronary artery disease in their majority, left ventricular ejection fraction and minimal cardiac transit times (MTT) were determined by precordial registration during the first passage of the radioactive tracer. 87 patients underwent echocardiographic examination. Data were compared with ventriculography and coronarography: left ventricular ejection fraction, if radiographically evaluated, shows a low sensitivity in indicating myocardial disorder. MTTs are reduced in more than 80% of patients with CAD at rest. With a few exceptions, all patients with disorders in the ventriculogram show reduced MTT values. MTTs, however, do not react specifically for myocardial performance. They also indicate disorders of central hemodynamics caused by vitia cordis. In these cases myocardial function can not be evaluated. Echocardiography can only be applied in about 85% of patients. It possesses a high sensitivity in discrimination of lower degree failures. Results are misleading in old infarctions with dyskinesia. It is concluded that best diagnostic information concerning global myocardial function results if direct hemodynamic parameters as MTT are combined with echocardiography.

Angiocardiography↗