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Biomedical subjects

M M Graham

Publications and source records attributed to M M Graham.

At least 91 records · Page 5Linked to original sources

Absorption of starch by healthy ileostomates: effect of transit time and of carbohydrate load.

Recently, breath hydrogen studies and intubation techniques have indicated that in excess of 10% of starch in normal foods may be malabsorbed in the small intestine and enter the colon. We evaluated starch absorption in healthy subjects with ileostomy. First, unabsorbed starch was quantified in ileostomy effluent from six ileostomates who ingested constant diets of wheat and potato starch for four days. Daily unabsorbed starch ranged from 1.3% to 5.0% of total ingested starch. Second, starch from a radiolabeled solid meal containing 50 g potato starch was measured under control conditions and after altering transit time with either loperamide, or magnesium citrate. Loperamide significantly decreased the amount of unabsorbed starch in all six ileostomates (p less than 0.05), while magnesium citrate significantly increased starch malabsorption in all six subjects (p less than 0.05). Third, starch absorption was measured after single solid meals containing 25, 50, 75, and 100 g potato starch. There was a linear relationship between starch input and output. Mean output expressed as a percent of input remained constant. We conclude that the degree of starch malabsorption by the small intestine of ileostomates may be less than that estimated by indirect methods in intact humans. The amount of unabsorbed starch is directly related to the quantity ingested and to the small intestinal transit time.

Adult↗

High-speed bubble-segmented blood sampler for the rat.

An arterial blood sampler for use in the conscious rat is described. With this apparatus it is possible to obtain small (10 microliter) whole-blood or plasma samples as frequently as 1/s and to derive accurate arterial time-concentration curves in the first 60-120 s after compounds are injected for regional blood flow or pharmacokinetic measurements. The blood is withdrawn from an implanted arterial catheter into polyethylene tubing at a constant rate while bubbles are introduced at regular intervals via a side channel into the column of blood. Although some dispersion of blood samples occurs as the tubing is traversed, this can be mathematically corrected. However, correction is unnecessary if the information of interest is the area under the time-concentration curve.

Animals↗

Short-term thymidine uptake in normal and neoplastic tissues: studies for PET.

Uptake of H-3 thymidine was studied in mice, both normal and with spontaneous lymphoma, and in the organs and tumors of dogs with spontaneous tumors. Uptake was compared with relative blood flow as measured by the distribution of C-14 iodoantipyrine. Initial distribution of thymidine in normal mice measured 20 sec after injection, correlated with the relative perfusion measurements; however, all measurements of thymidine uptake made between 1 and 60 min after injection showed no correlation with perfusion. This indicates that the distribution more than 1 min after injection is primarily dependent on subsequent redistribution and/or metabolism of thymidine. A time-course study demonstrated that normal mouse organs with high rates of proliferation retained all the labeled thymidine initially taken up. Organs with low rates of proliferation lost their label in a nearly exponential washout. These studies provide further evidence of the feasibility of using C-11 thymidine for positron emission tomography (PET).

Animals↗

Localization of 131I-labeled p97-specific Fab fragments in human melanoma as a basis for radiotherapy.

33 patients with advanced malignant melanoma were studied after intravenous administration of 131I-labeled Fab fragments specific for p97, an oncofetal glycoprotein of human melanoma. In all, 47 gamma camera imaging studies were performed for the purpose of localization of metastatic deposits. In addition to tumor, 131I-Fab uptake was also seen in liver and kidney. 20 of these studies included simultaneous administration of both an 131I-labeled Fab specific for p97, and an 125I-labeled Fab not specific for p97. Blood clearance of p97-specific Fab was significantly more rapid than for nonspecific Fab. Eight of these patients had biopsies of subcutaneous nodules at 48 and 72 h postinjection in order to assess whether localization of radioactivity was antigen specific. Antigen-specific localization was observed with average ratios of specific/nonspecific uptake of 3.7 (48 h) and 3.4 (72 h); uptake was strongly correlated with tumor p97 concentration (r = 0.81, P less than 0.01). Also, imaging studies of the bio-distribution of 131I-labeled anti-p97 Fab in patients selected for high p97 tumor concentration showed avid tumor uptake and more prolonged retention of labeled Fab in tumor than in normal tissues. Based on these studies, we estimated that total 131I doses of 500 mCi could be safely given to patients before dose-limiting toxicity would be observed. Accordingly, in seven selected patients, phase I radiotherapeutic trials were begun. For improved radiation safety, we developed automated methods to label Fab fragments with up to 200 mCi of 131I. So far, a total of 12 individual therapeutic doses, ranging from 34 to 197 mCi of 131I-labeled to 5 to 10 mg of Fab, have been administered with excellent tumor localization and without major target organ toxicity. Cumulative doses ranged from 132 to 529 mCi 131I. Side effects attributable to the radiation were mild, with a transient drop slightly greater than 50% in platelet and absolute neutrophil counts being observed in the two patients who received cumulative doses greater than 500 mCi. In the combined series of 47 diagnostic and 12 therapeutic studies, four acute reactions were observed: one episode each of transient chills and fever; flushing and hypotension; and two skin rashes. All of these reactions responded promptly to symptomatic therapy. After multiple administrations of 131I-(anti-p97) Fab (IgG1), isotype-specific immunity was observed in three patients. In two of these patients it was possible to successfully reinfuse after immunity had developed with 131I-(anti-p97) Fab of a different isotype (IgG2a). Dosimetry estimates were performed based on the biodistribution of (131)I-Fab in these patients,and for every 100 mCi of (131)I-Fab given, tumor receives 1,040 rads; liver. 325 rads; and bone marrow, 30 rads. Marrow would be expected to be the critical organ, if doses >500 mCi (131)I-Fab are given. These studies demonstrated that, with proper precautions, large doses (of an (131)I-labeled murine Fab fragments immunologically specific for a human melanoma-associated antigen) could be safely given to humans by using repetitive intravenous injections.

Animals↗

Imaging of an adrenal cortical carcinoma and its skeletal metastasis.

Though the typical scintigraphic appearance in adrenal cortical carcinoma is bilateral nonvisualization of the adrenal glands, we report a case with simultaneous visualization of both an adrenal cortical carcinoma and its skeletal metastasis using 6-beta-[131I]iodomethyl-19-norcholesterol.

Adenoma↗

A study of occlusal relationships and the incidence of myofacial pain.

A survey of 123 subjects (dental students) was performed to evaluate quantitative data that may be of value in the incidence and treatment of myofacial pain. Social statistics, subjective and objective symptoms, and the influence of occlusal interferences on these symptoms were quantitated and recorded. The data indicated that, 123 subjects, 26% had maximum intercuspation of the teeth at terminal hinge closure, 42% had maximum intercuspation of the teeth with the condyles located symmetrically anterior to terminal hinge, and 32.5% had maximum intercuspation of the teeth with assymmetric variations of the condyles anterior to terminal hinge. Averages were obtained for the maximum intercuspal open, the condylar inclination, and the distance anterior from the terminal hinge of both condyles in symmetrical and asymmetrical variations. The location of the transverse (terminal hinge) axis from the external auditory meatus was measured on the ala-tragus line. These latter averages indicate that a significant occlusal discrepancy can result from prevailing techniques of locating an arbitrary hinge axis 10 to 13 mm anterior from the external auditory meatus. The results showed that most subjects demonstrated, both subjectively and clinically, symptoms of neuromuscular dysfunction without occlusal interferences. Therefore, it may be concluded that treatment modalities considered within the first 6 weeks should be conservative and reversible to eliminate or decrease myofascial trigger zones and their areas of referred pain. Alteration of the existing occlusion and maxillomandibular relations may be adjusted with caution, if necessary.

Adult↗

Comparison of methods of recording and analysis of Doppler blood velocity signals in normal subjects.

Doppler blood velocity signals were recorded from the aorta and pulmonary artery in normal adults, children and premature infants, using three different pulsed, range-gated instruments. The tracings analyzed by three independent methods of spectral analysis with axially aimed transducers showed velocity patterns with a narrow range of frequencies (blunt velocity profile) with a constant acceleration of blood flow in early systole. A similar velocity pattern was seen in the premature infant's aorta in which the transducer beam was larger than the vessel insonated. We conclude that the normal velocity pattern in the central circulation is close to blunt, and that tracings obtained with transducers that insonate varying proportions of the vessel give similar signals.

Adult↗

Limitations of Kr-81m for quantitation of ventilation scans.

Predictions of Kr-81m behavior in the lungs have been based on a single-compartment model of well-mixed gas. To determine the validity of this model, anesthetized, paralyzed dogs were ventilated mechanically over a wide range of ventilations with Kr-81m in the inspirate. Averaged data obtained from 1.5- to 2-min images were compared with the model's predictions. Krypton-81m concentration appeared more linearly related to ventilation than the model predicts. This suggests that the Kr-81m may not be distributed to the entire resident gas volume or that its distribution changes with lung volume. Estimation of end-expiratory volume (FRC)--based on the tidal volume and the maximum-to-minimum count ratio over the lung during gated acquisitions--underestimated the true FRC by about 40%. The magnitude of error depended upon the combination of tidal volume and frequency and the inspiratory time. Thus, Kr-81m does not mix well with resident lung gas, and the well-mixed, single-compartment model is not a good predictor of Kr-81m behavior in the lung.

Animals↗

Positron imaging feasibility studies. I: Characteristics of [3H]thymidine uptake in rodent and canine neoplasms: concise communication.

Uptake [3H] thymidine was studied in BALB/c mice with EMT-6 sarcoma, in Buffalo rats with Morris 7777 hepatoma, and in nine dogs with spontaneous neoplasms: four lymphomas, two osteosarcomas, two soft-tissue sarcomas, and a thyroid carcinoma. High tumor-to-tissue ratios were observed for all tumor types assayed, and absolute uptakes, when computed as percent dose per gram tumor normalized for body weight, were similar for transplanted and spontaneous tumors. In the rodent tumors, radiothymidine was retained for at least 3 hr in the tumor without appreciable loss. In canine neoplasms, although the highest uptakes were observed in cellular tumors with many mitotic figures, tumor uptake showed significant variability that did not correlate with any obvious histologic change, and thus may reflect true biologic differences in metabolism among tumors at different sites in the same animal. These studies provide additional experimental evidence that the ratios of neoplastic to normal tissue and the kinetics of thymidine uptake by tumors are suitable for positron emission tomography of neoplasms in small and large animals, including both transplanted and spontaneous tumors.

Animals↗

Positron imaging feasibility studies. II: Characteristics of 2-deoxyglucose uptake in rodent and canine neoplasms: concise communication.

Uptake of [3H]2-deoxyglucose was studied in BALB/c mice with EMT-6 sarcoma, in Buffalo rats with Morris 7777 hepatoma, and in eight dogs with spontaneous neoplasms: five osteosarcomas and three diffuse lymphomas. High tumor-to-tissue ratios were observed for all tumor types studied. In rodents, peak levels of uptake occurred between 30 min and 1 hr, with a slow loss from the tumor of about 10% per hour thereafter. In dogs there was considerable variability in uptake, both between individuals and at different tumor sites within an individual. Necrotic tumor did not take up the radiotracer. Absolute uptakes, when normalized for body weight, were similar for spontaneous and transplanted neoplasms. These studies provide additional support for the concept that positron emission tomography can be used to obtain functional images of important metabolic processes of tumors, including glycolysis.

Animals↗

A low-contrast phantom for daily quality control.

A simple phantom is proposed to provide a low-contrast test object for daily quality assurance. The phantom consists of four quarters and five dimes taped to a Plexiglas plate. For daily quality control, the phantom is used with 5 cm of Plexiglas as scattering material and a flood source. Examples of images are presented for several gamma cameras, illustrating some of the information that can be obtained. In particular, we present examples of cameras providing improper imaging performance with the coin phantom but with "normal" floods and bar-phantom images. The major conclusion is that daily quality-control images should include significant of scattering material and low-contrast objects.

Models, Structural↗

A prescreening device for cancer of the uterus.

A prescreening device for cancer of the uterus was based on the slower sedimentation rate of cells from a vaginal aspirate in the presence of cancer than in its absence. The apparatus recorded the increase in light transmission through the test tube as the cells fell. This mechanical examination of the rate of fall of vaginal and cervical cells did not diagnose cancer, but it identified the normal specimens free of cancer or infections. The negative specimens comprised the bulk of diagnostic material. There was a small increase in false-negative rate compared with the false-negative rate in standard cytologic tests, but this was counterbalanced by the increase in the number of specimens examined.

Adult↗