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Biomedical subjects

M C Graham

Publications and source records attributed to M C Graham.

At least 55 records · Page 3Linked to original sources

Xenon-127m: a new radionuclide for applications in nuclear medicine.

Xenon-127m (127mXe) emits two gamma rays in cascade, with half-life of 69.2 +/- 0.9 sec. The first has the energy of 172.5 keV, and is emitted from the nucleus in 38% of the decays. The second gamma ray has the energy of 124.8 keV and is emitted from the nucleus in 69% of the disintegrations. Together they furnish 107 easily collimated gamma rays per 100 decays. Xenon-127m is generated readily by bombarding nearly saturated aqueous solutions of sodium or potassium iodide with 14-MeV protons. The 127mXe is swept out continuously, as it is produced, by bubbling helium upward through the solutions. Up to approximately 100 mci/l are obtained from the resulting mixture of gases. The 127mXe + helium is admixed with about five volumes of air (or oxygen) and then driven continuously to a scintillation camera located approximately 200 yd distant. When the mixture of gases is inhaled, high quality images of the lungs are obtained by means of an Anger scintillation camera.

Half-Life↗

Parthenogenesis of human oocytes as a function of vacuum pressure.

The effect of different vacuum pressures on the rate of parthenogenesis was studied in 109 cycles of laparoscopic follicle aspiration. A total of 388 follicles was aspirated at settings of vacuum pressure of 100, 75, and 50 mm Hg. Parthenogenesis occurred at the rates of 5.9, 7, and 1%, respectively. The difference between 100 and 50 mm Hg was statistically significant (P less than 0.025). We conclude that the rate of parthenogenesis is influenced by the magnitude of vacuum pressure.

Female↗

Effect of the antiviral compound MDL 20,610 on some aspects of murine immune function.

At physiologically relevant concentrations an antiviral compound should not perturb the host's ability to mount an immune response against the infecting virus or some other opportunistic pathogen. The purpose of this study was to evaluate the immunomodulatory activity of the antiviral compound MDL 20,610 using murine models. When tested in vitro at the limit of aqueous solubility (6 microM), MDL 20,610 has no significant effect on neutrophil function as assessed by cell migration against FMLP and LTB4 gradients, myeloperoxidase secretion or 0.-2 production. In addition, 6 microM MDL 20,610 has no significant effect on macrophage function as determined by 0.-2 production, Ia and Mac-1 antigen expression and expression of Fc gamma receptors. Finally, MDL 20,610 does not significantly affect in vivo (1-100 mg/kg/day) NK cell activity or DTH to oxazolone; but treatment of mice with 50 or 100 mg MDL 20,610/kg/day significantly (P less than 0.01) enhances SRBC IgM antibody synthesis. These data indicate that MDL 20,610 is relatively devoid of immunomodulatory activity.

Adjuvants, Immunologic↗

Cortical somatosensory-evoked potentials in the horse.

Cortical somatosensory-evoked potentials (SEP) were recorded from thoracic and pelvic limbs in 15 horses (13 Thoroughbreds and 2 Quarter Horses). Ulnar nerve SEP were evoked by electrical stimulation of the lateral palmar branch of the ulnar nerve at the level of the metacarpophalangeal joint. Recordings were taken between electrodes at 2 cm lateral to the vertex (contralateral to the stimulated limb) and the midpoint of the interorbital line. Four peaks were found in all recordings: N1, P1, N2, and P2. Latencies to the peaks were 39.0 +/- 2.7, 45.5 +/- 5.3, 50.4 +/- 5.2, and 62.3 +/- 3.7 ms (mean +/- SD), respectively. Tibial nerve SEP were evoked by stimulation of the lateral plantar nerve branch of the tibial nerve at the level of the metatarsophalangeal joint. Recordings were taken between electrodes at the vertex (contralateral to the stimulated limb) and the midpoint of the interorbital line. Four peaks were also found in all tibial nerve SEP recordings: N1, P1, N2, and P2. Latencies to the peaks were 64.6 +/- 11.8, 84.5 +/- 9.7, 121.2 +/- 11.6, and 134.0 +/- 11.1 ms, respectively. Amplitude variability was high for the ulnar nerve and the tibial nerve SEP. There was no effect of sex seen on peak latency or amplitude, and peak latencies were not affected by body length.

Animals↗

Brain-stem auditory evoked potentials in the alligator. Effects of temperature and hypoxia.

Brain-stem auditory evoked potentials (BAEPs) were recorded from young alligators (Alligator mississippiensis), and the effects of hypothermia, hyperthermia and hypoxia on the wave forms were determined. The wave form shape was similar to the human BAEP, although extra waves were routinely seen. The responses were highly repeatable and varied in a predictable manner as a function of stimulus frequency, polarity, intensity, and body temperature. Rarefaction clicks produced longer wave form latencies than condensation clicks. BAEPs were present over the entire temperature range studied (0-36 degrees C). In contrast, mammalian BAEPs disappear over the temperature range of 20-27 degrees C, and seizures occur at 20-21 degrees C. At temperatures below 20 degrees C, the alligator BAEP peak amplitudes decreased with decreased temperature, but latencies only decreased slightly. At temperatures above 20 degrees C the peak amplitudes increased, and the latencies decreased with temperature. Peak I was largely unaffected by temperature change, while peaks IIIa and V increased 0.015 and 0.018 msec/degree C, respectively, at temperatures above 24 degrees C. Transient brain hypoxia, achieved by inverting the alligator, produced a progressive decrease in BAEP waves to an isoelectric amplitude without greatly altered latencies. The reverse sequence of changes was seen during recovery. Postural effects on blood flow were documented in two alligators with implanted flow probes. Carotid artery blood flow decreased 43% with body inversion, in both anesthetized and unanesthetized alligators, but no sequelae from the hypoxia could be detected. Metabolic differences between mammals and the alligator may account for the alligator's resistance to hypothermia, hyperthermia and hypoxia.

Alligators and Crocodiles↗

The outcome of continued treatment of luteinizing hormone-surged cycles in in vitro fertilization with the use of human menopausal gonadotropin.

Over a 2-year period 75 patients were treated for 109 cycles with human menopausal gonadotropin for in vitro fertilization. The occurrence of endogenous luteinizing hormone (LH) surges was monitored by daily blood sampling. Forty-six cycles (42%) showed an endogenous LH surge. Instead of canceling the treatment cycle as other programs do, we proceeded to oocyte collection when the surge was detected. Human chorionic gonadotropin was administered routinely to the "surge" patients as soon as the LH surge was determined. The oocyte collection was carried out around 24 hours after the "surge" blood had been drawn, although the beginning of the endogenous LH surge was unable to be pinpointed. Significantly more immature oocytes, lower fertilization rate, and lower cleavage rate were seen in the "surge" patients than in the "nonsurge" patients. In five "surge" cycles laparoscopy for oocyte collection was canceled, but none was canceled because of premature ovulation detected by the immediately preoperative ultrasonography. In four "surge" cycles no potentially fertilizable egg was recovered. This was not significantly different from that of the "nonsurge" group. The pregnancy rate of the "surge" group (4/41 or 9.8% per laparoscopy and 4/34 of 11.8% per embryo transfer) was not statistically different from that of the "nonsurge" group (7/61 or 11.5% per laparoscopy and 7/56 or 12.5% per embryo transfer). This study presents the possibility of proceeding to oocyte collection, fertilization, embryo transfer, and pregnancy in patients with endogenous LH surge in in vitro fertilization procedures with the use of human menopausal gonadotropin treatment.

Chorionic Gonadotropin↗

Serum progesterone levels in women treated with human menopausal gonadotropin and human chorionic gonadotropin for in vitro fertilization.

For evaluation of the adequacy of luteal function after in vitro fertilization-embryo transfer (IVF-ET), serum progesterone (P) levels were measured on days 3, 7, and 10 after laparoscopic follicle aspiration. Fifty-six infertile patients were treated during 86 cycles with human menopausal gonadotropin-human chorionic gonadotropin (hMG-hCG) for stimulation of follicular development. Serum estradiol (E2) levels were measured daily during hMG-hCG treatment. P levels were determined in 67 cycles. The mean (+/- standard deviation [SD]) of the sums of 3 P levels was 55.63 +/- 24.13 ng/ml. There were 11 pregnancies. The mean of the sums of 3 P levels of pregnant patients was 64.45 +/- 26.23 ng/ml and of 56 nonpregnant cycles was 53.90 +/- 23.35 ng/ml. The duration of luteal phase varied from 9 days to 15 days. The mean of the sums of 3 P values of patients with different luteal phase lengths ranged from 28.8 ng/ml to 60.51 +/- 25.68 ng/ml. The mean of the sums of 3 P levels of women with normal luteal phase and that of women with luteal phase defect by endometrial biopsy study were used as controls for comparison. There was poor correlation (r = 0.3441) between E2 peak levels and P levels; the sum of 3 P levels did not indicate luteal phase inadequacy in IVF-ET patients; and the majority of the nonpregnant cycles (32/56) showed a luteal phase of 11 days or less, in spite of adequate P levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

In vitro antiviral activity of the 6-substituted 2-(3',4'-dichlorophenoxy)-2H-pyrano[2,3-b]pyridines MDL 20,610, MDL 20,646, and MDL 20,957.

The 6-substituted 2-(3',4'-dichlorophenoxy)-2H-pyrano[2,3-b]pyridines MDL 20,610 (6-SO2CH3), MDL 20,646 (6-Br), and MDL 20,957 (6-Cl) are potent antirhinovirus compounds with median plaque 50% inhibitory concentrations (IC1/2s) of 0.03, 0.006, and 0.006 micrograms/ml, respectively, against the 32 serotypes evaluated. The 6-halogenated analogs produced 99% reductions in progeny virion yields at concentrations as low as 0.004 micrograms/ml. However, these analogs perturbated HeLa cell metabolism at lower concentrations (at or above 5 micrograms/ml) than did the 6-methylsulfonyl analog (at or above 20 micrograms/ml). Compound MDL 20,610 was also active against human, simian, and bovine rotaviruses (cytopathic effect IC1/2s of 0.8 to 1.5 micrograms/ml) and possessed variable enterovirus and paramyxovirus activity.

Antiviral Agents↗

Krypton-79m: a new radionuclide for applications in nuclear medicine.

Krypton-79m emits 130-keV gamma rays in 27 +/- 1% of its disintegrations and decays with a half-life of 50 +/- 3 sec. It is generated readily by bombarding nearly saturated aqueous solutions of bromide salts, or bromoform, with 14-MeV protons. The 79mKr is swept out continuously as it is produced by bubbling helium upward through the liquids. Up to 200 mCi per I are obtained of the resulting mixture of gases. The 79mKr + helium is mixed with about five volumes of air and then driven continuously through a small-bore tube to an Anger scintillation camera located approximately 200 yards away. The rate of flow is adjusted so that the amounts of 13-sec 81mKr and of 35-hr 79Kr are inconsequential at the time and point of use. When the gases are inhaled, good images of the lungs are obtained with an Anger scintillation camera. The trachea and bronchi commonly are revealed also.

Humans↗

Early detection of anthracycline-induced cardiotoxicity by stress radionuclide cineangiography in conjunction with Fourier amplitude and phase analysis.

Thirty-three cases of anthracycline related cardiotoxicity occurred in our institution in patients with a previously negative cardiovascular history, physical examination, and normal ECG. A total of 95 RNCA studies were performed in this group (73 studies included both rest and exercise RNCA). Twenty-one patients had two or more serial studies. Seventeen had a normal, baseline prechemotherapy study and 16 had studies done following the initiation of therapy. Fourier analysis, consisting of amplitude and phase images, were created for each study. In the subset with a baseline study, the rest LVEF became abnormal first in two of 17 patients (12%), the rest or stress LVEF in ten of 17 (59%), the rest Fourier image analysis in ten of 17 (59%), and the rest or stress Fourier image analysis in 16 of 17 (94%). In the subset without a baseline study, the rest LVEF was abnormal in ten of 16 (63%), the rest or stress LVEF in 15 of 16, (94%), the rest Fourier image analysis in 16 of 16 (100%), and the rest or stress Fourier image analysis in 16 of 16 (100%). The authors conclude that: 1) the exercise RNCA is superior to the rest RNCA alone in the early detection of anthracycline related cardiotoxicity, 2) the single most sensitive indicator of cardiotoxicity is Fourier image analysis; and 3) sequential rest and stress RNCA studies with Fourier amplitude and phase analysis is the most sensitive, noninvasive method of evaluating patients who receive potentially cardiotoxic agents.

Adolescent↗

PET tomography in studies of distributions of 7.6-min potassium 38 in the dog heart.

Potassium 38 emits a 2.68-MeV (max) positron, followed promptly by a 2.17-MeV gamma-ray in 99.8% of its disintegrations. A positron is emitted also, followed by a 3.94-MeV gamma-ray, in 0.2% of the decays. The pairs of 511-keV PET +/- gamma-quanta, which are emitted at 180 +/- 0.3 degrees to each other, are in true coincidence with the prompt gamma-rays emitted by the daughter nucleus, within the resolving time of PET instrumentation. Studies made with phantoms by means of a commercial version of the MGH PET camera demonstrated that quantitatively satisfactory images are derived, despite the presence of the prompt gamma-rays. Two-dimensional (2-D) focal-plane images reveal high uptake of 38K promptly in the myocardium of dogs, under barbiturate sedation. Third-dimensional (3-D) transverse section PET tomographic images, through four 1.0-cm-thick heart "slices" orthogonal to the plane of the 2-D images and with 1.4-cm sequential spacing, show 38K uptake to be concentrated especially highly in the left ventricle, as expected. Peak levels of activity were observed over the myocardium at 12 s after intravenous bolus injection of ionic 38K. Dynamic mode 2-D images were taken at intervals as short as 0.5 s and extending to 1 h.

Animals↗

Fourier amplitude and phase analysis in the clinical evaluation of patients with cardiomyopathy.

Fifty-four patients with a cardiomyopathy were studied by RNCA and Fourier amplitude and phase image analysis. The study group included patients with ischemic cardiomyopathy (27) and an equal number of patients with a primary cardiomyopathy: drug-induced (22), idiopathic (three), radiation-induced (one), and amyloidosis (one). Twenty-eight patients had rest studies alone and 26 had both rest and stress studies (80 total). The mean rest LVEF in the ischemic group was 27.9%, in the drug-induced group 36.5%, and in the idiopathic group 30%. The stress LVEF decreased in 92% of patients with ischemic cardiomyopathy and 45% of patients with primary (drug-induced) cardiomyopathy. Fourier amplitude and phase images were generated for each study. Amplitude and phase images were abnormal in all patients with an ischemic cardiomyopathy. LV amplitude abnormalities were regional and phase was directional. A zone of dysynergy on phase analysis was present in 44% of patients with ischemic cardiomyopathy. In the drug-induced primary cardiomyopathy group, all patients had abnormal amplitude and 86% had abnormal phase. Amplitude abnormalities were global rather than regional and phase patterns were nondirectional. Only one patient had a zone of dysynergy on the phase image. We conclude that the stress LVEF alone cannot consistently differentiate between ischemic and primary cardiomyopathies and that Fourier amplitude and phase analysis may be useful in determining the etiology of a cardiomyopathy (ischemic vs primary).

Adolescent↗

A clinical evaluation of the RNCA study using Fourier filtering as a preprocessing method.

Forty-one patients (25 male, 16 female) were studied by RNCA in our institution. There were 42 rest studies and 24 stress studies (66 studies total). Sixteen patients were normal, 15 had ASHD, seven had a cardiomyopathy, and three had left-sided valvular regurgitation. Each study was preprocessed using both the standard nine-point smoothing method and Fourier filtering. Amplitude and phase images were also generated. Both preprocessing methods were compared with respect to image quality, border definition, reliability and reproducibility of the LVEF, and cine wall motion interpretation. Image quality and border definition were judged superior by the consensus of two independent observers in 65 of 66 studies (98%) using Fourier filtered data. The LVEF differed between the two processes by greater than .05 in 17 of 66 studies (26%) including five studies in which the LVEF could not be determined using nine-point smoothed data. LV wall motion was normal by both techniques in all control patients by cine analysis. However, cine wall motion analysis using Fourier filtered data demonstrated additional abnormalities in 17 of 25 studies (68%) in the ASHD group, including three uninterpretable studies using nine-point smoothed data. In the cardiomyopathy/valvular heart disease group, ten of 18 studies (56%) had additional wall motion abnormalities using Fourier filtered data (including four uninterpretable studies using nine-point smoothed data). We conclude that Fourier filtering is superior to the nine-point smooth preprocessing method now in general use in terms of image quality, border definition, generation of an LVEF, and cine wall motion analysis. The advent of the array processor makes routine preprocessing by Fourier filtering a feasible technologic advance in the development of the RNCA study.

Adult↗

Combined Fourier amplitude and phase imaging in patients with coronary artery disease.

Fourier amplitude and phase image analysis were evaluated in 66 patients. Thirty patients served as a control group and 36 had coronary artery disease (CAD). Each patient in our control group had a rest and exercise radionuclide cineangiogram (RNCA) study (60 total). The amplitude and phase images for controls were uniform. No statistically significant difference in the histogram distribution of amplitude or phase occurred between rest and exercise. Twenty-five patients with CAD had a prior myocardial infarction (MI). Fourier analysis, when compared to the left ventricular ejection fraction (LVEF) and visual cine wall motion analysis, improved the sensitivity of the rest RNCA study to detect CAD from 68% to 92%. Regional Fourier amplitude and phase image analysis demonstrated an 85% sensitivity in localizing regions of previous infarction. Thirteen of 25 patients with prior MI and an additional 11 patients with recent onset of angina but no previous infarction, had exercise RNCA studies. When compared to cardiac catheterization data, regional Fourier amplitude and phase image analysis demonstrated sensitivities of 87% and 80%, respectively, in correctly identifying clinically significant major coronary artery involvement in these two subsets of patients. Fourier amplitude and phase image analysis were also able to distinguish normals from patients with previous MI, and patients with CAD but no prior infarction. All comparisons were statistically significant. We conclude that the semiquantitative image analysis of Fourier amplitude and phase data increases the clinical utility of the RNCA study in patients with CAD.

Adult↗

PET tomographic imaging of the human heart, pancreas, and liver with nitrogen-13 derived from [13N]-L-glutamate.

The first commercial version of the Massachusetts General Hospital (MGH) positron camera was used to image the relative distributions of 13N (T1/2 = 9.96 min) in the human heart, pancreas, and liver after intravenous administration of [13N]-L-glutamate. The instrument was operated in two imaging modes. Conventional 2-dimensional (2-D) focal-plane images showed high concentrations of 13N in the heart and pancreas, and lower levels in the liver. Five PET tomographic transverse section (3-D) images were made through the heart and three through the pancreas. Our results suggest that further studies designed to gain an improved understanding of the biochemistry of [13N]-L-glutamate aided by PET imaging, especially with newer instrumentation, are worthy of further investigation.

Aged↗

Thallium-201 myocardial scintigraphy: improved sensitivity, specificity and predictive accuracy by application of a statistical image analysis algorithm.

Exercise and 3 hour delayed redistribution thallium-201 myocardial perfusion imaging was performed in 107 patients including 87 patients with documented coronary artery disease and 20 patients with normal coronary arteriograms. A computer algorithm for statistical analysis and redisplay of the analog scintillation data was developed to augment the visual analysis of the standard analog image. The basic algorithm identified the myocardial area (pixel) with the most absolute counts and developed an appropriate standard deviation range from a table. All pixels in the area of the myocardium containing absolute counts below three standard deviation ranges (or approximately 6 standard deviations) were deleted from the final image. The remaining pixels were redisplayed in a digitized bimodal format and the image photographed. Two experienced observers compared visual analysis of the analog image alone and the analog image in conjunction with the computer-analyzed image for sensitivity, specificity and predictive accuracy in the detection of perfusion defects in patients with coronary artery disease and in normal subjects. Sensitivity in patients with coronary artery disease and in normal subjects. Sensitivity in patients with coronary artery disease for the analog scintillation image alone was 79 percent (69 of 87) and with computer analysis 95 percent (83 of 87). Specificity in the patients with no coronary disease was 100 percent (20 of 20) for both techniques. The predictive accuracy of the test was 83 percent (89 of 107) for the analog image alone and 96 percent (103 of 107) for the two images combined. It is concluded that use of a computer statistical analysis algorithm of thallium-201 analog myocardial perfusion images improves the accuracy of detection of perfusion defects in patients with coronary artery disease.

Computers↗