Search PubMed⌕ Search

Biomedical subjects

M D Gross

Publications and source records attributed to M D Gross.

At least 109 records · Page 6Linked to original sources
PubMed1993

Biodistribution, metabolism, and excretion of radioiodinated phospholipid ether analogs in tumor-bearing rats.

The phospholipid ether analog, [125I]-1-O-[12-(m-iodophenyl)dodecyl]propanediol-3-phosphocholine (NM-295) was synthesized and evaluated for its ability to visualize tumors. Preliminary studies were performed in rats bearing the Walker 256 carcinosarcoma. Most of the radioactivity was cleared from the animals during the first 24 hours. However, the tumor showed a decreased rate of clearance of radioactivity when compared with non-target tissue. This difference in the clearance rate allowed for excellent images of the tumor at 24 hours. Scintigraphic images compared favorably with other radioiodinated phospholipid ether analogs such as [125I-rac-1-O-[12-(m-iodophenyl)dodecyl]-2-O-methylglycero-3- phosphocholine (NM-294) and [125I]-12-(m-iodophenyl)dodecyl phosphocholine (NM-324). In contrast with the latter two compounds, however, tissue distribution studies revealed that NM-295 cleared at a much faster rate from all tissues, including tumor. In addition, within 24 hours following administration of NM-295, over 70% of the radioactivity was excreted as compared to 50% and 20% for NM-294 and NM-324, respectively. The majority of excreted radioactivity appeared in the urine for all three compounds. Thin-layer chromatography of urine and fecal extracts showed the presence of metabolites only. In contrast, lipid extracts of either liver or tumor demonstrated only the presence of the parent compound. Therefore, these data suggest that in each case it was the parent phospholipid analog that was taken up and retained by the tissues, while the metabolic product(s) was cleared and excreted from the animal.

Animals↗
PubMed1993

Selective localization of a radioiodinated phospholipid ether analog in human tumor xenografts.

Administration of [125I]-rac-1-O-[12-(m-iodophenyl)dodecyl-2-O-methylglycero-3- phosphocholine (NM-294) to athymic mice implanted with human tumors of several histologies, including adenocarcinoma of the ovary and colon, melanoma and small-cell carcinoma of the lung, resulted in excellent images of the tumors by gamma camera scintigraphy. Images of the tumor were obtained at 5 days or more postinjection, by which time nearly all background activity had cleared from the liver and gastrointestinal tract. Tumor-to-blood ratios at this time were quite high and ranged from approximately 8:1 (melanoma) to 30:1 (ovarian carcinoma), which is consistent with the scintigraphic images obtained in all human tumor models. Lipid extraction of the liver and tumor at 13 days postinjection showed that most of the radioactivity in these tissues remained associated with the parent compound, with only a small amount retained by the liver. Appropriately radioiodinated NM-294 has substantial potential as a tumor-avid radiopharmaceutical.

Adenocarcinoma↗
PubMed1992

Mechanisms for an abnormal radionuclide left ventricular ejection fraction response to exercise in patients with chronic, severe aortic regurgitation.

To clarify the mechanisms for an abnormal radionuclide left ventricular (LV) ejection fraction response to exercise in patients with chronic, severe aortic regurgitation (AR), we studied seven control patients and 21 patients with AR. We used exercise radionuclide angiography and catheterization of the right and left sides of the heart to obtain a calculation of LV chamber elastance. The control and AR groups had similar heart rates, systolic blood pressure responses to exercise, and exercise durations. In both patient groups, LV end-diastolic volume did not change with exercise. In contrast to the decrease in LV end-systolic volume (p less than 0.05) and increase in LV ejection fraction (p less than 0.01) in the control group, LV end-systolic volume in the patients with AR increased, resulting in little change in their LV ejection fraction. By stepwise multiple regression analysis, the radionuclide LV ejection fraction at peak exercise in patients with AR was determined by the LV chamber elastance, LV end-systolic volume, and stroke volume at peak exercise (cumulative r = 0.79, p less than 0.02); the change in radionuclide LV ejection fraction from rest to peak exercise was determined by the corresponding change in systemic vascular resistance, regurgitant index, and LV end-diastolic and end-systolic volumes (cumulative r = 0.88, p less than 0.02). These data demonstrate that in patients with AR, the radionuclide LV ejection fraction at peak exercise is principally determined by the cumulative effects of chronic, severe AR on LV systolic chamber performance, and the change in radionuclide LV ejection fraction from rest to peak exercise is principally established by peripheral vascular responses.

Aortic Valve Insufficiency↗
PubMed1992

Potential organ or tumor imaging agents. 32. A triglyceride ester of p-iodophenyl pentadecanoic acid as a potential hepatic imaging agent.

A triglyceride analog, glycerol-2-palmitoyl-1,3-di-15-(p-iodophenyl)pentadecanoate (DPPG) was synthesized and radiolabeled for evaluation as a potential functional liver scintigraphic agent. Uptake of DPPG was compared in normal, diabetic, tumor-bearing and heparin pretreated rats, revealing differences in uptake and clearance of radioactivity, correlating with hepatic lipase activity of these groups. Similar results were observed by gamma-camera scintigraphy. Comparing the uptake of DPPG with that of its fatty acid component, 15-(p-iodophenyl)pentadecanoic acid (IPPA), revealed that the peak uptake of IPPA in the liver was about half that of DPPG. Based upon these findings, DPPG warrants further study as a hepatic radiodiagnostic agent.

Animals↗
PubMed1992

Selective localization of radioiodinated alkylphosphocholine derivatives in tumors.

We have designed and synthesized two radioiodinated analogs of hexadecylphosphocholine in order to evaluate their tumor imaging potential. 12-(m[125I]iodophenyl)dodecyl phosphocholine (NM-324) and hexadecyl-2-[N,N-dimethyl-N-(m[125I]iodobenzyl)-ammonium] ethyl phosphate (NM-326) demonstrated the ability of such compounds to localize in and thereby visualize the Walker 256 tumor in rats. However, the tumor avidity of NM-324 was far superior to NM-326. In addition, NM-324 showed excellent tumor localization in athymic mice bearing subcutaneous human tumors.

Animals↗
PubMed1992

The identification and partial characterization of acetaldehyde adducts of hemoglobin occurring in vivo: a possible marker of alcohol consumption.

Chromatographic, peptide mapping and mass spectrometric analysis were used to examine hemoglobin (Hb) from heavy drinkers and abstainers for alcohol consumption-related modifications. Heavy drinker and abstainer hemoglobin samples contained similar amounts of glycosylated Hb and significantly different (p < 0.05) amounts of "fast" hemoglobin. The presence of higher amounts of "fast" Hb in heavy drinker relative to abstainer samples suggested the presence of alcohol-consumption related modifications. To further examine Hb for modifications, tryptic peptides of the "fast" hemoglobin HbA1c were isolated and analyzed by plasma desorption mass spectrometry (PDMS). [14C]acetaldehyde (AcH)-Hb was synthesized in vivo for use as a standard. Specific peptides were chosen based on co-migration with radiolabeled peptides from a tryptic digest of the [14C]acetaldehyde-Hb. The masses obtained by PDMS for two heavy drinker peptides were identical to two radiolabeled peptides; the two pairs of peptides co-migrated on HPLC. A comparison of the observed mass for the peptides with the theoretical masses for acetaldehyde-modified Hb peptides suggested that the peptides were AcH-modified alpha and beta chain N-termini of Hb. The modified peptides were found in five of six heavy drinker samples. This is the first description of site-specific AcH-Hb adducts occurring in vivo. The routine detection of such adducts has potential for characterizing usual alcohol intake.

Acetaldehyde↗
PubMed1992

Adrenal scintigraphy of well-differentiated (functioning) adrenocortical carcinomas: potential surgical pitfalls.

Adrenal scintigraphy with 131I-6 beta-iodomethylnorcholesterol (NP-59) has been widely used to evaluate adrenal cortical tumors during the past 20 years. Unilateral visualization on the side of an adrenal tumor has been considered diagnostic of a benign adrenocortical adenoma in the patient with Cushing's syndrome. Bilateral nonvisualization of the adrenal glands in the presence of Cushing's syndrome is considered diagnostic of adrenocortical carcinoma (ACC). ACCs characteristically are unable to incorporate enough NP-59 to be visualized on NP-59 adrenal scintigraphy. Two patients with well-differentiated cortisol-secreting ACCs, in which the primary tumor or subsequent metastases demonstrated intense uptake (visualization) on NP-59 scans are reported here. As a result of these findings on NP-59 adrenal scintigraphy, the lesions were initially misinterpreted to represent benign disease. In each patient the operative approach selected, based on the interpretation of the NP-59 scan, was inappropriate for the management of the respective adrenal neoplasm or its metastasis. A review of the literature reveals 16 other cases of either ACC or their metastases that were visualized with adrenal scintigraphy. Ninety percent of these cases were associated with adrenocortical hormone hypersecretion. It is concluded that in the presence of Cushing's syndrome or another adrenocortical hormone excess state, unilateral visualization of an adrenal tumor on NP-59 scintigraphy cannot be interpreted to represent uniformly benign disease.

Adosterol↗
PubMed1991

Mechanisms for left ventricular systolic dysfunction in aortic regurgitation: importance for predicting the functional response to aortic valve replacement.

To test the hypothesis that the combined use of the time-varying elastance concept and conventional circumferential stress-shortening relations would elucidate differential mechanisms for left ventricular systolic dysfunction in severe, chronic aortic regurgitation and therefore predict the functional responses to aortic valve replacement, 31 control patients and 37 patients with aortic regurgitation were studied. The studies included micromanometer left ventricular pressure determinations, biplane contrast cineangiograms under control conditions and radionuclide angiograms under control conditions and during methoxamine or nitroprusside infusions with right atrial pacing. The patients with aortic regurgitation were classified into three groups: Group I had normal Emax and stress-shortening relations, Group II had abnormal Emax but normal stress-shortening relations and Group III had abnormal Emax and stress-shortening relations. The left ventricular end-diastolic and end-systolic volumes showed a progressive increase and the ejection fraction showed a progressive decrease from Group I to III; these values differed from those in the control patients (p less than 0.001). In Group I, there was a decrease in left ventricular volumes (p less than 0.05) but no significant change in ejection fraction (61 +/- 7% versus 63 +/- 4%) after aortic valve replacement. In contrast, in Group II, reduction in left ventricular volumes (p less than 0.01) was associated with an increase in ejection fraction from 50 +/- 8% to 64 +/- 11% (p less than 0.01). Finally, in Group III, reduction in left ventricular volumes (p less than 0.05) was associated with a further decrement in ejection fraction from 35 +/- 13% to 30 +/- 13%. Group I patients had compensated adequately for chronic volume overload. However, Group II had left ventricular dysfunction that was associated with an increase in the left ventricular volume/mass ratio compared with that in the control patients and Group I (p less than 0.05 for both), suggesting inadequate hypertrophy and assumption of spherical geometry. Finally, irreversible myocardial dysfunction had supervened in Group III. In conclusion, a combined analysis of left ventricular chamber performance using the time-varying elastance concept and myocardial performance using conventional circumferential stress-shortening relations provides complementary information that elucidates differential mechanisms for left ventricular systolic dysfunction and therefore predicts the functional response to aortic valve replacement.

Aortic Valve↗
PubMed1991

Clinical significance of the large adrenal mass.

Current clinical teaching indicates that large (greater than 5 cm in diameter) adrenal masses are often malignant. In a retrospective analysis of patients studied between 1977 and 1988 with computed tomography (CT), adrenal scintigraphy, and when available, magnetic resonance imaging (MRI) 45 were found to have adrenal masses greater than 5 cm (range 5-19 cm) in diameter. Thirty were benign (16 phaeochromocytomas, six adrenocortical adenomas, four adrenal cysts, two myelolipomas, an adrenal hematoma and a ganglioneuroma). Of 15 malignant masses, there were seven adrenocortical carcinomas, five adrenal metastases and three adrenal lymphomas. With the exception of the adrenal myelolipomas, cysts, and the ganglioneuroma neither CT nor MRI demonstrated sufficient diagnostic specificity to distinguish benign from malignant lesions. Functional scintigraphy with 131I-6-beta-iodomethyl-19-norcholesterol for suspected adrenocortical lesions and 131I-metaiodobenzylguanidine for suspected phaeochromocytomas frequently provided useful information.

19-Iodocholesterol↗
PubMed1991

A comparative study of the stereognathic ability between patients with myofascial pain dysfunction syndrome and a control group.

This study compared the stereognathic ability of two groups of subjects. One group comprised 35 myofascial pain dysfunction syndrome (MPDS) subjects and the other, 30 control non-MPDS subjects. Thirteen different acrylic resin shapes were used for oral and manual identification. No statistically significant difference was found between the two groups in the accuracy of identification, time for identification and their ratio. The results indicate no difference in stereognathic ability between the MPDS and the control group.

Adult↗
PubMed1991

Radioiodine uptake following thyroidectomy for thyroid cancer. Recurrence or ectopic tissue?

Post-thyroidectomy I-131 sodium iodide scans revealed foci of uptake outside the thyroid bed in two patients. In each case, these areas corresponded to sites where ectopic or aberrant thyroid tissues could be found. The presence of metastatic disease significantly affects the appropriate therapy, as well as the overall prognosis. An appreciation of the potential locations of ectopic thyroid tissues that may mimic metastatic disease and potentially confound diagnosis are stressed.

Adult↗
PubMed1991

Relation between maximum time-varying elastance pressure-volume areas and myocardial oxygen consumption in dogs.

To establish whether pressure-volume areas (PVAs) calculated using the maximum time-varying elastance (Emax) have a relation with myocardial oxygen consumption (MVO2) that improves on other indexes of myocardial oxygen demand, we studied nine dogs of either sex weighing 19-39 kg, which were instrumented with a micromanometer left ventricular (LV) catheter and a Wilton-Webster coronary sinus flow catheter and had red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamics, coronary sinus flow determinations, and radionuclide angiograms were obtained under control conditions and during three to five steady-state loading conditions (mean +/- SD, 5.6 +/- 0.7). Isochronal pressure-volume data points from each pressure-volume loop were subjected to linear regression analysis to calculate Emax. The Emax relations, diastolic curves, and systolic portions of each pressure-volume loop were used to obtain calibrated PVAs. The Emax PVA (mm Hg.ml.beat-1.100 g-1) and MVO2 (ml O2.beat-1.100 g-1) values correlated in each animal (r = 0.77 to 0.99). Their slopes averaged (3.48 +/- 1.68) x 10(-5) ml O2.mm Hg-1.ml-1, and their y-axis intercepts averaged 0.07 +/- 0.04 ml O2.beat-1.100 g-1. When the MVO2 relations were compared with Emax PVA, LV systolic pressure-rate product, LV stroke work, and a modification of the LV pressure-work index, the Emax PVA, LV systolic pressure-rate product, and LV pressure-work index had similar relations with MVO2, whereas LV stroke work was a weaker index of MVO2 (p less than 0.05 versus Emax PVA). This occurred because the Emax PVA:MVO2 slopes and y-axis intercepts differed in each dog, which was due to differences in basal LV contractility. The Emax PVA:MVO2 slopes correlated with Emax (r = 0.73, p less than 0.05), and the y-axis intercepts were also weakly related to Emax (r = 0.48, p = 0.19). We conclude that the Emax PVAs calculated using data acquisition techniques that are clinically applicable have relations with MVO2 that in general do not improve on other indexes of myocardial oxygen demand in this animal preparation.

Animals↗
PubMed1991

Clinical significance of the solitary functioning adrenal gland.

To assess the compensatory functional and anatomic changes in the remaining adrenal cortex after unilateral adrenalectomy or in the unaffected adrenal in patients with unilateral adrenal destruction by neoplasm, 17 patients with a single, functioning adrenal gland and normal indices of adrenocortical function, nine after adrenalectomy and eight with a unilateral, destructive adrenal lesion were studied with 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy and computed tomography. Adrenal masses with a mean (+/- s.d.) diameter of 2.8 +/- 1.0 cm; (range 1-4 cm; 95% confidence interval (Cl), 2.5-3.1 cm) were identified by computed tomography in seven of nine patients in the remaining adrenal cortex at variable times (6.1 +/- 5.9 y; range 0.5-19 y) after unilateral adrenalectomy. Mean (+/- s.e.m.) NP-59 uptake was elevated (p less than 0.01) in both adrenalectomy and adrenal destruction groups, mean uptake (+/- s.e.m.) was 0.32% +/- 0.04% administered dose (95% Cl, 0.24%-0.4% administered dose) as compared to normal (0.16% +/- 0.05% administered dose, 95% Cl, 0.06%-0.26% administered dose). The remaining adrenal cortex may be anatomically abnormal after unilateral adrenalectomy and demonstrate compensatory, increased NP-59 uptake in the presence of overall, normal adrenocortical function.

Adosterol↗
PubMed1991

Clinical SPRINT imaging. Preliminary results compared to conventional SPECT brain scanning using Tc-99m HMPAO.

We have performed initial clinical studies using the high resolution single photon ring tomograph (SPRINT) and Tc-99m HMPAO. To determine what additional anatomic detail can be depicted using this high resolution, dedicated head, multidetector SPECT device compared to conventional SPECT, six patients with stroke and one normal volunteer were imaged after the injection of 20 mCi Tc-99m HMPAO on a conventional rotating Anger gamma camera (GE-400AC), followed immediately by imaging on SPRINT. Imaging acquisition on the GE-400AC gamma camera was performed using 360 degrees rotation, 64 stops, at 30 sec/stop, yielding an average of 985,714 counts for a 10.0 mm thick slice. GE-400AC images were of good quality, having in-plane full width half maximum (FWHM) resolution of approximately 15 mm. SPRINT acquisition of image data was performed using both the high resolution and high sensitivity apertures, with data collection over 15 or 20 minutes of imaging time accumulating approximately 500,000 counts and 1,000,000 counts, respectively, from patients in a 10.0 mm thick slice, achieving an in-plane FWHM resolution of approximately 8 mm and 10 mm for the two apertures, respectively. Both image resolution and contrast for visualization of gray, white, and cerebral spinal fluid filled brain structures were improved using SPRINT compared with the GE-400AC. We conclude that SPRINT is well suited for brain imaging with Tc-99m HMPAO and is of particular value for applications demanding high resolution.

Adult↗