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Biomedical subjects

M M Graham

Publications and source records attributed to M M Graham.

At least 73 records · Page 4Linked to original sources

Localization of inflammation with 111In IgG and 99Tcm albumin colloid labelled leukocytes in a rabbit model.

Localization of inflammation with two recently described radiotracers, 111In-labelled polyclonal IgG and 99Tcm albumin colloid labelled leukocytes (Tc-WBC), was studied. Accumulation of activity was compared with 111In-labelled leukocytes (In-WBC) using 131I human serum albumin as a control. Ratios of activity in a chemically induced abscess in the thigh of rabbits compared with normal muscle tissue were measured. The results showed that all agents localize in inflammation but Tc-WBC consistently localizes to a greater degree than the other agents. At 2 h the inflammed-to-normal ratios for Tc-WBC were 4, IgG 2.1, albumin 1.9 and In-WBC 1.7. The pattern of the ratios remained similar over the 18 h period of the study. The short time in which leukocytes can be labelled and the quality of the images obtained suggest that Tc-WBC imaging is the method of choice for this model.

Animals↗

A multi-center study: clinical practices of HIV infected patients on CAPD/CCPD.

Our statistics reveal the average patient in our study to be a young black male with a history of IVDA with CAPD as the initial dialysis modality. He was most often trained on a mechanical assist device, but he still developed frequent peritonitis episodes, predominantly gram positive. His survival rate was less than 2 years, but he was able to remain independent until he died. Our fears about caring for the HIV infected individual cannot be denied. Even though we may never be truly comfortable when caring for someone with this disease, it is possible to train them to perform home peritoneal dialysis safely and effectively. By doing this, we can preserve the patients' independence and maintain their dignity while they cope with this overwhelming illness.

Acquired Immunodeficiency Syndrome↗

Measurement of left ventricular ejection fraction and volumes with three-dimensional reconstructed transesophageal ultrasound scans: comparison to radionuclide and thermal dilution measurements.

A transesophageal, ultrasonic cardiac imaging probe was built that incorporated a mechanism for changing the angle of the imaging plane of a conventional phased array in a precise and known manner. This probe was used to acquire an angular spatial sequence of two-dimensional images of the left ventricular cavity over a series of cardiac cycles by sweeping the imaging plane through it stepwise. The endocardial borders of these images were manually outlined off-line and the application of a three-dimensional reconstruction algorithm was then used to compute the left ventricular end-diastolic and end-systolic volumes and ejection fraction. A study was conducted with seven anesthesized dogs to compare ultrasonic determinations by this method with determinations and measurements made using radionuclide and thermal dilution methods. Comparison of 33 ejection fractions, measured by the ultrasonic volume method and by the gated blood pool radionuclide approach, yielded a correlation coefficient of 0.87 and a standard error of the estimate of 5.7% measured over a range of 10% to 58% (average, 40%). Comparison of the ultrasonically measured volumes with those calculated from stroke volume (derived from thermal dilution cardiac output measurement) and ejection fraction (measured by radionuclide technique) produced a correlation coefficient of 0.92 and a standard error of the estimate of 10.3 mL over a range of 18 to 130 mL (average, 56 mL). The accuracy of volume and ejection fraction measurements with this new ultrasonic method seems comparable to that of other currently used clinical approaches such as radionuclide and angiography.

Animals↗

Deoxyglucose kinetics in a rat brain tumor.

Accurate quantitation of local glucose metabolic rates (LMRglc) of abnormal tissues such as brain tumors with the 2-deoxyglucose (DG) method requires knowledge of the tissue rate constants and lumped constant. The deoxyglucose rate constants were measured in an experimental intracerebral glioma in 24 awake rats with a dual tracer [(3H)-DG and (14C)-DG] method. Tissue time points were obtained at 2, 5, 10, 18, 30, 60, 90, and 180 min after injection by decapitation and liquid scintillation counting. Blood samples were obtained at 1 min intervals initially and at longer intervals later. The rate constants were estimated with parameter estimation. LMRglc was calculated from the rate constants, assuming a lumped constant of 0.5. K1 for normal cerebrum was found to be 0.258 ml/g/min, and k2-k4 were 0.406, 0.075, and 0.0103 min-1; LMRglc = 65.1 mumol/100 g/min. The corresponding values for the glioma were 0.108, 0.126, 0.040, and 0.0019 with LMRglc = 41.7. The considerably lower k4 in the glioma was reflected in persistent higher activity in the glioma at longer times. Thus, tissue activity alone cannot be used to assess relative glucose metabolic rates in abnormal tissues such as gliomas, particularly at late times after injection.

Animals↗

Determination of the deoxyglucose and glucose phosphorylation ratio and the lumped constant in rat brain and a transplantable rat glioma.

Mitochondrially bound hexokinase (ATP-D-hexose-6-phosphotransferase; EC 2.7.1.1) was dissociatively extracted from normal rat brains and intracerebral and subcutaneous implants of the 36B-10 glioma. At least 70% of the total hexokinase enzyme activity in normal and glioma tissue was associated with the mitochondrial fraction. Purification of the crude tissue extracts by ion-exchange and affinity chromatography followed by analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a successive purification of the enzyme to homogeneity with a molecular size of 98 kilodaltons. Enzyme kinetics with glucose or 2-deoxyglucose (2-DG) as the substrate were measured spectrophotometrically by coupling the appropriate reactions to either NADPH or NAD+ formation. The Km of hexokinase with glucose as the substrate in the intracerebral glioma (0.138 mM) and subcutaneous glioma (0.183 mM) tissues was 2.1-2.7-fold higher than that observed in normal brain tissue (0.067 mM) (p less than 0.001). No significant differences were observed in the Km for hexokinase with 2-DG as the substrate in the glioma and normal brain tissue. The phosphorylation ratio for normal brain was 0.320 and was increased in the intracerebral glioma to 0.694 and in the subcutaneous glioma to 0.519. The ratios of deoxyglucose and glucose volumes of distribution in normal brain and intracerebral glioma tissues were 1.70 and 1.85, respectively. The lumped constants calculated directly from the phosphorylation ratios and the volumes of distribution of deoxyglucose and glucose were 0.517 in normal brain and 1.168 in intracerebral glioma. Our results indicate the lumped constant is increased 2.26-fold in intracerebral glioma compared with normal brain.

Animals↗

Radioisotope penile plethysmography: a technique for evaluating corpora cavernosal blood flow during early tumescence.

Radioisotope penile plethysmography is a nuclear medicine technique which assists in the evaluation of patients with erectile dysfunction. This technique attempts to noninvasively quantitate penile corpora cavernosal blood flow during early penile tumescence using technetium-99m-labeled red blood cells. Penile images and counts were acquired in a steady-state blood-pool phase prior to and after the administration of intracorporal papaverine. Penile counts, images, and time-activity curves were computer analyzed in order to determine peak corporal flow and volume changes. Peak corporal flow rates were compared to arterial integrity (determined by angiography) and venosinusoidal corporal leak (determined by cavernosometry). Peak corporal flow correlated well with arterial integrity (r = 0.91) but did not correlate with venosinusoidal leak parameters (r = 0.01). This report focuses on the methodology and the assumptions which form the foundation of this technique. The strong correlation of peak corporal flow and angiography suggests that radioisotope penile plethysmography could prove useful in the evaluation of arterial inflow disorders in patients with erectile dysfunction.

Adult↗

Blood flow changes following 137Cs irradiation in a rat glioma model.

Blood flow changes in response to 20 Gy 137Cs whole brain irradiation were measured with quantitative autoradiography of [14C]iodoantipyrine (IAP) in intracerebral grafts of the 36B-10 rat glioma, the brain around tumor (BAT), the contralateral corpus callosum, and the contralateral cerebral cortex. Irradiations were delivered on Day 14 post-transplantation, and measurements of flow (F) were performed with IAP on Day 15 or Day 16. Mean values of F were determined in individual tumors and in treatment groups. In 15- and 16-day-old unirradiated control tumors, the group mean F was 0.31 ml.g-1.min-1. In both 15- and 16-day-old tumor groups irradiated on Day 14 (Day 1 and 2 postirradiation tumors) the mean F for each day's group was 0.52 ml.g-1.min-1, 68% higher than the control (P less than 0.01). Flow in the BAT and the contralateral corpus callosum similarly was increased at these times (P less than 0.01). Flow in the contralateral cerebral cortex was 1.1, 1.5, and 1.3 ml.g-1.min-1 in the control, 1 day postirradiated, and 2 day postirradiated groups, respectively, but these increases were not significantly different from the control. These data indicate that flow increases in the intracerebral gliomas as well as in normal brain regions during the 2 days following 20 Gy irradiation. Changes such as these following radiotherapy may have important effects on the bioavailability of chemotherapeutic drugs.

Animals↗

Considerations in the purchase of a nuclear medicine computer system.

Selection of a nuclear medicine computer system is a process that should be approached with care and forethought. The general scheme should be to define your needs and constraints, determine what is available, investigate the leading candidates, make a site visit, and, finally, submit an order. Through a series of discussions between members of the Computer Council of the Society of Nuclear Medicine and representatives from the manufacturers of computer systems, a set of important considerations emerged, which are reported in this paper. This paper is not intended to be a step-by-step guideline to the purchase of a computer system. Rather, it is a set of concepts and considerations with which the prospective purchaser should be familiar before undertaking such a purchase.

Computer Systems↗

Blood flow in an experimental rat brain tumor by tissue equilibration and indicator fractionation.

The tissue equilibration technique (Kety) was compared with the indicator fractionation technique for the measurement of blood flow to normal brain and an experimental brain tumor in the rat. The tumor was a cloned astrocytic glioma implanted in the cerebral hemisphere of F-344 rats. I-125 Iodoantipyrine, using a rising infusion for one minute, was used for the tissue equilibration technique. C-14 butanol, injected as a bolus 8 seconds before sacrifice, was used for the indicator fractionation technique. Samples were assayed using liquid scintillation counting and the iodoantipyrine results were regressed against the butanol results. For normal tissue R = 0.832, SEE = 0.115 ml/g/min, and Slope = 0.626. For tumor R = 0.796, SEE = 0.070 ml/g/min, and Slope = 0.441. The iodoantipyrine tissue/blood partition coefficient for normal hemisphere (gray and white matter) was 0.861 +/-0.037 (SD) and for tumor was 0.876 +/-0.042. The indicator fractionation technique with C-14 butanol underestimated blood flow in a consistent manner, probably because of incomplete extraction, early washout of activity from tissue and from evaporation of butanol during processing. Our experiments revealed no differences between tumor and normal brain tissue that might invalidate the comparison of iodoantipyrine blood flow results in brain tumors and surrounding normal brain.

1-Butanol↗

Use of steroids to suppress vascular response to radiation.

A quantitative measure of the vascular permeability surface area product (PS) for albumin has been made using a double isotope technique. PS was significantly elevated in irradiated rat lung, heart, skin, and muscle, between 19 and 26 days following 18 or 25 Gray thorax irradiation. Administration of dexamethasone from 2 days before irradiation through the day of measurement suppressed the expected increase in PS in lung, heart, and muscle, but not in skin. Shorter periods of steroid administration were not as effective in suppressing this response to radiation exposure. Increased vascular permeability following radiation may be an essential element in the development of radiation fibrosis. We hypothesize that the ability to suppress this response could result in a long term reduction in the incidence of fibrosis.

Animals↗

Regional blood-to-tissue transport in an irradiated rat glioma model.

To assess vascular permeability in intracerebral grafts of the 36B-10, F-344 rat glioma following 20 Gy 137Cs whole brain irradiation, the blood-to-tissue transport constant, K, of [14C]-alpha-aminoisobutyric acid (AIB) was measured with quantitative autoradiography. Mean, 90th percentile, and 95th percentile values of K were determined in individual tumors and in treatment groups. In 15-day-old unirradiated control tumors, mean, 90th percentile, and 95th percentile values of K were, respectively, 11.3, 18.4, and 20.8 ml kg-1 min-1. In 15-day-old tumors irradiated on Day 14 (Day 1 postirradiation tumors) the K values were 5.9, 9.4, and 10.4, all of which were significantly less than the respective control values (P less than 0.01). In 16-day-old tumors irradiated on Day 14 (Day 2 postirradiation tumors), the K values were 10.8, 15.0, and 16.0, respectively, none of which was significantly different from control tumors. Mean K values for Day 2 vs Day 1 postirradiation tumors (10.8 vs 5.9) yielded P less than 0.05, but the 90th percentile and 95th percentile values for Day 2 vs Day 1 yielded 0.05 less than P less than 0.10. Separate experiments measured AIB and 86RbCl uptake in 36B-10 cells in vitro 1 and 2 days following 20 Gy irradiation to assess whether this radiation dose reduced the capacity of tumor cells to trap AIB or Rb+. Irradiation did not reduce the accumulation of either tracer, but rather was associated with an increased accumulation of AIB. Therefore, the AIB transport data suggest that vascular permeability and/or surface area decreases significantly in the day following 20 Gy irradiation and that this decrease reverses by the second day following irradiation.

Aminoisobutyric Acids↗

Quantitative autoradiography using a personal computer.

A video digitizing system based on an Apple II personal computer has been developed for use in quantitative autoradiography. The selection process of an acceptable video camera, an illumination system, and the functions provided in the software are discussed. This system is in routine use and has been duplicated by several other laboratories.

Autoradiography↗

Changes in vascular permeability following thorax irradiation in the rat.

A double isotope technique was used to measure changes in the vascular permeability surface area product (PS) for albumin after irradiation. PS was measured in several tissues of the rat during the first 38 days following 11, 13.5, 18, or 25 Gy whole thorax irradiation. After 18 and 25 Gy most irradiated and nonirradiated (shielded) tissues showed elevated permeability at 1 day after radiation, which declined to control levels by Day 4. All irradiated tissues showed a second wave of increased permeability between 14 and 38 days after radiation that varied in onset and extent depending upon tissue and dose. Lung and heart showed a direct response to dose between 11 and 18 Gy during this period. Peak lung values averaged three times control values at 19 days after 18 Gy. Peak heart values averaged twice control values at the same time and dose. The double isotope technique has proven to be a reliable means of quantitatively determining vascular permeability response to radiation over time.

Animals↗

Measurement of left ventricular volume using single-photon emission computed tomography.

A count-based method for measuring left ventricular (LV) volume using technetium-99m-labeled red cells and ungated single-photon emission computed tomography is described. The tomographic slices were used to determine the counts per milliliter in the center of the left ventricle and total LV counts, which were used to derive mean LV volume. End-diastolic and end-systolic volumes were calculated from the mean volume using the LV time-activity curve from planar gated blood pool images. Phantom evaluation with simulated LV volumes (50 to 400 ml) in air, in a phantom filled with water, with 10% background, and with a simulated right ventricle, showed excellent accuracy. For clinical validation, 30 patients underwent electrocardiographically gated planar and nongated tomographic acquisition of the cardiac blood pool followed by single-plane cineangiography. For end-diastolic and end-systolic volumes combined, the correlation with cineangiography showed a standard error of the estimate (SEE) of 24 ml and 14 ml, respectively. Mean intra- and interobserver deviation was 12 ml and 14 ml (SEE 13 ml and 16 ml), respectively. It is concluded that this noninvasive count-based technique, requiring no assumptions regarding LV geometry, is an accurate and reproducible way to measure LV volume.

Adult↗

Salmonellae in sewage sludge and abattoir effluent in south-east Scotland.

A survey into the prevalence of salmonella organisms in sewage in the Borders Region of South-east Scotland is described. A total of 317 isolates representing 34 different serotypes were made, of which only 5 serotypes appeared in animals, supporting the view that the spreading of sewage sludge on to pastureland presents little risk to livestock provided the recommended guidelines are followed. Nevertheless, Salmonella typhimurium phage type 12, identified in sewage, was also recovered from animals in incidents on 11 farms, including 4 which had received sludge from this source. A further 48 isolates (13 serotypes) were obtained from the parallel monitoring of abattoir effluents, indicating that the background level of salmonella infection in the animal population appears to be low in comparison to that in humans.

Abattoirs↗