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Biomedical subjects

M L Freeman

Publications and source records attributed to M L Freeman.

At least 91 records · Page 5Linked to original sources
PubMed1987

Visualization of metastatic liver disease on technetium-99m bone scintigraphy.

To determine the frequency with which liver metastases are visualized on bone scintigraphy, 425 pairs of liver and bone scans, performed within one month of each other, were reviewed. Sixty-three of the 425 liver scans showed metastases. Of these 63, five cases of carcinoma of the colon and six cases of carcinoma of the lung also visualized by Tc-99m MDP scintigraphy. This represented 46% of colon metastases and 15% of lung metastases detected on liver scan. Liver metastases from other primary tumors were not detected on bone scan, but the numbers for these tumors were small. The liver metastases which were detected on bone scan were significantly larger than those which were not. The literature was reviewed and the primary and secondary tumors of liver with uptake of Tc-99m phosphate compounds listed.

Bone and Bones↗
PubMed1987

Inhibition of heat shock protein synthesis and thermotolerance by cycloheximide.

Chinese hamster ovary (CHO) cells were exposed to a 43 degrees C, 15-min heat shock to study the relationship between protein synthesis and the development of thermotolerance. The 43 degrees C heat shock triggered the synthesis of three protein families having molecular weights of 110,000, 90,000, and 65,000 (HSP). These proteins were synthesized at 37 and 46 degrees C. This heat shock also induced the development of thermotolerance, which was measured by incubating the cells at 46 degrees C 4 h after the 43 degrees C heat treatment. CHO cells were also exposed to 20 micrograms/ml of cycloheximide for 30 min at 37 degrees C, 15 min at 43 degrees C, and 4 h at 37 degrees C. This treatment inhibited the enhanced synthesis of the Mr 110,000, 90,000, and 65,000 proteins. The cycloheximide was then washed out and the cells were incubated at 46 degrees C. HSP synthesis did not recover during the 46 degrees C incubation. This cycloheximide treatment also partially inhibited the development of thermotolerance. These results suggest that for CHO cells to express thermotolerance when exposed to the supralethal temperature of 46 degrees C protein synthesis is necessary.

Adaptation, Physiological↗
PubMed1987

Regional time-based functional imaging of hepatocyte function.

Hepatocyte function was analyzed following the injection of 5 mCi of Tc-99m disofenin by the computer generation of three kinds of functional images designed to portray regional rates of hepatic uptake. Nineteen patients were analyzed, of whom eight had no overt liver disease, five had active hepatitis, five had cirrhosis, and one had acute cholecystitis. Functional images were graded according to lack of regional homogeneity of accumulation. Uptake kinetics were found to be significantly more homogeneous in normal subjects, becoming increasingly heterogeneous in hepatitis and cirrhosis patients, respectively. Thus functional imaging may provide a tool for the quantitative analysis of parenchymal disruption in liver disease.

Adult↗
PubMed1986

Effect of acute postinfusion lipemia and free fatty acids on myocardial contractility: assessment with radionuclide ventriculography.

Equilibrium gated radionuclide ventriculography was used to evaluate the effect of intravenous fat-emulsion overload and excess of free fatty acids (FFA) on left ventricular ejection fraction (LVEF) in 20 patients with and without coronary artery disease (CAD). Fifteen of these patients had normal (greater than 50%) baseline LVEF and 5 had low (less than 50%) baseline LVEF. From 100 to 150 ml of 20% artificial fat emulsion (Liposyn) was infused over 20-25 min. At the end of the infusion, triglyceridemia reached 820 +/- 220 mg% and left ventricular ejection fraction decreased from baseline 62 +/- 19% (mean +/- SD) to 58 +/- 16% (P less than 0.05, paired t-test). After completion of Liposyn infusion, 5,000 U of heparin was administered intravenously and monitoring of LVEF was continued. One and one-half hours following heparin administration, plasma FFA levels reached 3.7 + 2.0 mmol/l and LVEF rose to 69 +/- 19% (P less than 0.001, paired t-test). Our data indicate that acute intravenous fat overload can suppress and high pathophysiologic levels of FFA can increase LVEF. This effect is more uniform and statistically more reliable in patients with normal LVEF. The study failed to demonstrate any significant difference in the effect of this pharmacologic intervention between patients with and without CAD.

Aged↗
PubMed1985

Glutathione pool size affects cell survival after hyperthermic treatment.

Intracellular glutathione (GSH) concentrations were titrated in Chinese hamster ovary cells by exposure to various concentrations of diethylmaleate (DEM). The various steady state levels of GSH obtained were maintained throughout the experimental time course. Cells were incubated at 42 degrees after DEM addition in order to produce thermal dose response curves using colony formation as the end point. The slope of the dose response curve was subsequently determined and compared to the intracellular GSH concentration. This comparison indicated Chinese hamster ovary cells contain multiple reservoirs of GSH which in turn regulate thermal toxicity in a stepwise manner. Removal of 50% or less of the GSH did not affect thermal sensitivity. A small increase in sensitivity occurred when 50 to 80% of the GSH was removed. Removal of greater than 80% of the GSH increased thermal toxicity significantly. The facts that 10 and 20 microM DEM produce extensive GSH depletion and only small changes in survival imply that a threshold concentration of GSH must be removed before thermal toxicity is affected.

Animals↗
PubMed1985

The effects of acute hypertriglyceridemia and high levels of free fatty acids on left ventricular function.

The effects of acute hypertriglyceridemia and of high levels of free fatty acids on the left ventricular ejection fraction were studied by radionuclide ventriculography in 20 subjects with and without coronary artery disease. An infusion of approximately 125 ml of a 20% fat emulsion over 25 minutes resulted in an increase of plasma triglycerides to the mean of 820 mg/dl and a fall of the left ventricular ejection fraction from the baseline mean of 62% to 58% (p less than 0.05). Ninety minutes after the intravenous administration of 5000 units of heparin, plasma free fatty acids rose to the mean of 4.6 mmol/L and the mean left ventricular ejection fraction increased to 69% (p less than 0.001). The observed changes in blood lipids were not associated with clinical or ECG evidence of myocardial ischemia. We conclude that acute hypertriglyceridemia causes slight depression of left ventricular performance, while high levels of free fatty acids augment it. However, neither hypertriglyceridemia per se nor its rapid conversion to free fatty acids are likely to cause angina in stable patients with coronary artery disease.

Aged↗
PubMed1985

Acid modification of thermal damage and its relationship to nutrient availability.

The purpose of this present investigation was to determine if the presence of exogenous nutrients constitutes a prerequisite for acid modification of thermal damage and to determine if thermal cytotoxicity is affected by nutrient availability under acid conditions. To this end, Chinese hamster ovary cells (CHO) were heated (42 degrees or 43 degrees C) and/or irradiated in either McCoy's medium containing 10% fetal bovine serum or glucose free Hanks Balanced Salt Solution (HBSS). Both thermal sensitivity and thermal radiosensitization were increased when CHO cells were treated under acid conditions (e.g., pH 6.8) compared to alkaline conditions (e.g., pH 7.2), independent of the media used. Furthermore, decreasing nutrient availability increased thermal cytotoxicity, but the increase was greatest at pH 7.2 compared to pH 6.8. This study indicates that thermal sensitivity is more dependent upon pH than upon nutrient availability.

Animals↗
PubMed1985

Decreased intracellular glutathione concentration and increased hyperthermic cytotoxicity in an acid environment.

Chinese hamster ovary (CHO) cells were heated at either pH 7.2 to 7.4 or 6.7 to 6.8 in order to determine if conditions which suppress the development of thermotolerance (pH 6.7 to 6.8) reduce intracellular levels of glutathione (GSH). When the pH of the growth medium was reduced from 7.2 to 6.7, a 25 to 30% reduction in GSH was observed in cells maintained at 37 degrees. Cells heated at 42 degrees in medium adjusted to pH 6.7 had lower levels of GSH compared to cells heated at pH 7.2. Cells were also heated for 1 hr at 43 degrees and then incubated at 37 degrees for up to 9.5 hr prior to GSH measurement. The GSH levels of cells treated at pH 7.3 increased approximately 20% above control, whereas treatment at pH 6.7 resulted in a 20% reduction compared to control. Chinese hamster ovary cells were exposed to 5 mM buthionine sulfoximine (BSO) prior to and during 42 degrees heat treatment. BSO exposure at either pH 7.3 or 6.8 reduced the GSH concentration to approximately 65% of control and increased thermal cytotoxicity. The thermal sensitivity of cells incubated at 42 degrees and pH 7.3 was compared to that of cells incubated at pH 6.8. Decreasing the pH from 7.3 to 6.8 increased sensitivity by a factor of 1.87 in the absence of BSO, whereas decreasing the pH in the presence of BSO increased sensitivity by only 1.50. In summary, these results suggest that the increase in thermal sensitivity observed when Chinese hamster ovary cells are heated in acid medium is due partly to the depletion of GSH.

Animals↗
PubMed1985

Hereditary macular dystrophies in relation to radionuclide ocular scintigraphy.

Radionuclide ocular scintigraphy was investigated to determine whether it could detect blood-retinal barrier disruption secondary to retinal disease. Patients were examined who had hereditary macular dystrophies and good correlations were found of the dynamic and equilibrium results obtained on scintigraphy with the clinical disease state. This test may hold promise as another measurement of the disruption of ocular physiology in retinal diseases.

Humans↗
PubMed1985

Role of glutathione in cell survival after hyperthermic treatment of Chinese hamster ovary cells.

Chinese hamster ovary cells cultured in vitro were exposed to hyperthermic treatment at 43 degrees C or 45 degrees C. Depletion of 99.5% of the intracellular glutathione (GSH) by addition of 0.1 mM diethylmaleate (DEM) increased thermal sensitivity. This effect, however, was dependent upon oxygen tension. Decreasing the oxygen tension reduced the effect. Thermal cytotoxicity was further augmented by continued depletion of GSH after hyperthermic treatment. Once cells became thermally tolerant, depletion of GSH did not affect thermal sensitivity. The development of thermotolerance was triggered by exposing Chinese hamster ovary cells to a thermal dose consisting of either 30 min at 43 degrees or 10 min at 45 degrees. After a 4-h incubation at 37 degrees, the cells were reheated at 43 degrees or 45 degrees, respectively. A triggering dose of 30 min at 43 degrees is a nonlethal treatment, while 10 min at 45 degrees kills 50% of the cells. Cells were exposed to 0.1 mM DEM during the triggering and development phases of tolerance. Depletion of GSH by addition of DEM did not inhibit the development of thermal tolerance when triggered by the 30-min-43 degrees thermal dose. However, exposure to DEM did inhibit the development of thermal tolerance if the triggering dose consisted of 10 min at 45 degrees. These results were interpreted to mean that GSH depletion will inhibit the development of thermotolerance only after a sufficiently toxic thermal dose.

Animals↗
PubMed1984

Thallium scintigraphy during dobutamine infusion: nonexercise-dependent screening test for coronary disease.

Exercise thallium scintigraphy has proven to be a sensitive method for detecting coronary artery disease (CAD). However, early redistribution of thallium and inadequate exercise can reduce its sensitivity. In this study, dobutamine was infused in incremental doses (5, 10, 15, and 20 micrograms/kg/min) in 24 patients being evaluated for chest pain. Thallium scintigraphy was completed during the maximum dose of dobutamine tolerated and repeated 4 hours later. Significant CAD was present in 16 patients; the remaining eight had normal coronaries. Exercise ECG was obtained in 23 patients. During dobutamine thallium scintigraphy, reversible perfusion defects occurred in 15 of 16 CAD and in one of eight non-CAD patients, resulting in a sensitivity of 94% and a specificity of 87%. Exercise ECG had a sensitivity of 60% and a specificity of 63%. We conclude that: (1) dobutamine thallium scintigraphy appears to be a sensitive method for detecting significant CAD and provided a more sensitive screening test than exercise ECG; (2) dobutamine thallium scintigraphy is especially useful in patients who cannot exercise; and (3) because imaging occurs during dobutamine infusion, the problem of early redistribution may be mitigated.

Catecholamines↗
PubMed1984

Radionuclide detection of blood-retinal barrier disruption in diabetes mellitus.

Diabetic retinopathy is one of the leading causes of blindness in the United States today. Because early treatment of proliferative retinopathy offers the best chance for visual salvation, there is an essential need for methods of identifying eyes at high risk. Recent research has shown that subclinical leakage from retinal blood vessels is one of the earliest signs of retinopathy. The feasibility of using radionuclide techniques to quantitate blood-retinal barrier disruption is demonstrated by a study in which 23 diabetics and 7 nondiabetics were imaged with an Anger camera in the anterior Waters projection at 2 hours after the administration of Tc-99m DTPA. In the digitized images, regions of interest were placed over each orbit and over one of the cerebral hemispheres. Orbital counts were then compared to cerebral counts on a per pixel basis. Eye to brain ratios were found to be lowest for nondiabetics and highest for patients with proliferative retinopathy. Additionally, the dynamic analysis of the same radiopharmaceutical may allow investigators to further study the pathophysiology of the diabetic eye.

Adult↗
PubMed1984

A comparison of dobutamine infusion and supine bicycle exercise for radionuclide cardiac stress testing.

We have compared the inotropic drug dobutamine to supine bicycle exercise as a means of inducing stress in radionuclide ventriculography studies. Dobutamine has the following properties, making it favorable for widespread usage: 1) ability to be given safely in a peripheral vein, 2) rapid onset, and 3) short duration of action. Each patient underwent supine bicycle progressive resistance testing of 2 minutes per stage followed 30 minutes later by dobutamine administration. Accuracy of diagnosis was 0.93 and sensitivity was 0.89 with dobutamine, while with bicycle the accuracy was 0.93 and sensitivity was 0.94. While not designed to replace supine bicycle testing, incremental infusions of dobutamine appear to be nearly equal in accuracy and sensitivity, providing a satisfactory technique for cardiac evaluation of previously excluded patients.

Catecholamines↗
PubMed1984

Nuclear scintigraphy as a diagnostic tool in venous aneurysms.

Aneurysmal dilatation in the low pressure system of internal jugular vein is rare. A case of an aneurysm of the right internal jugular vein, is presented, which was initially diagnosed by nuclear scintigraphy and confirmed by angiography. Clinical presentation, classification, etiology, pathogenesis, and diagnostic modalities of the disease are also reviewed.

Aneurysm↗