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Biomedical subjects

A A Driedger

Publications and source records attributed to A A Driedger.

At least 19 recordsLinked to original sources
PubMed1996

Early detection of cancer cachexia in the rat using 31P magnetic resonance spectroscopy of the liver and a fructose stress test.

The dynamic metabolic effects of a fructose infusion challenge on hepatic intracellular levels of adenosine 5'-triphosphate (ATP), inorganic phosphate (Pi) and phosphomonoesters (PME) were monitored noninvasively by 31P MRS in a remote tumour-bearing rat model. Fisher male rats were inoculated with a methylcholanthrene-induced sarcoma. Seventeen rats were randomized into three groups: control (n = 6), low tumour burden (LTB, n = 6), or moderate tumour burden (MTB, n = 5). The LTB group had tumour burdens of 0.2-2.0% while the MTB group had tumour burdens of 2.6-5.7%. All rats were in the pre-clinical phase of cancer cachexia as determined by food intake and body weight. Rats were infused with 1.2 g/kg of fructose i.v. and the metabolic response of the liver was monitored with time over 1 h via 31P MRS. In all groups an immediate increase in hepatic levels of PME was noted, which returned to baseline values over the course of the experiment, reflecting the phosphorylation of fructose to fructose 1-phosphate. For the MTB rats, the return to baseline levels was more rapid than in the control or LTB group. All groups experienced a 20% decrease in hepatic ATP levels which did not return to baseline over the 1 h observation period. As well, all groups experienced an initial fall in Pi, which recovered to prefructose levels or greater. MTB rats demonstrated a 30-40% increase in Pi concentration and a 60-70% increase in Pi/ATP ratio after infusion with fructose as compared to LTB and control rats (ANOVA;p<0.05). This is consistent with cachexia-induced enhancement of hepatic gluconeogenic activity, and hence more rapid release of Pi from the phosphorylated metabolites in the MTB rats. Thus fructose infusion and hepatic 31P MRS permit pre-clinical detection of cancer cachexia as reflected by increased Pi generation and more rapid removal of PME.

Analysis of Variance↗
PubMed1996

Effect of anaemia correction on skeletal muscle metabolism in patients with end-stage renal disease: 31P magnetic resonance spectroscopy assessment.

Skeletal muscle metabolism during exercise was compared in 5 patients with end-stage renal disease (ESRD) and 8 healthy controls, using a noninvasive technique, 31P magnetic resonance spectroscopy (MRS). After 3 months of anaemia correction with recombinant human erythropoietin (rHuEPO) these patients were re-evaluated. Maximal power achieved by the ESRD patients during a dynamic wrist flexion exercise test was 33% lower (p < 0.05) than the controls. Similarly in the ESRD group, the power at the onset of metabolic acidosis (the intracellular threshold) was 29% less than controls. The metabolic differences observed in the patients indicated a lower aerobic capacity. Three months of rHuEPO treatment resulted in a 55% increase in mean haematocrit but conferred no significant improvement in metabolic parameters at rest or during exercise. The lack of any significant changes in muscle metabolism following the correction of anaemia suggests that oxygen availability is not the exclusive limiting factor for aerobic metabolism in ESRD patients.

Adult↗
PubMed1994

Insulin protects against hepatic bioenergetic deterioration induced by cancer cachexia: an in vivo 31P magnetic resonance spectroscopy study.

The bioenergetic effects of cancer cachexia on the livers of male Fischer rats inoculated with a methylcholanthrene-induced sarcoma were assessed using serial in vivo 31P magnetic resonance spectroscopy. Rats were randomized into three groups: tumor-bearing controls (n = 7); an insulin-treated group receiving 2 units/100 g body weight/day starting 21 days after implantation (n = 8); and a chronic insulin-treated group receiving insulin every day after implantation (n = 3). During the 32-day study, serial measurements of food intake, body weight, and tumor volume were taken, and 31P magnetic resonance spectroscopy analyses of the livers were conducted every 7 days after tumor implantation. Neither the short-term nor the chronic insulin treatment regimens stimulated the progress of tumor growth. However, both treatments prevented body weight loss, and the short-term insulin treatment prevented tumor-induced decrease in food intake relative to the control group. Liver bioenergetic deterioration was evaluated from the increase in the ratio of Pi to ATP obtained from the hepatic 31P magnetic resonance spectra. At day 28 postimplantation, control rats exhibited appreciable hepatic bioenergetic deterioration, i.e., a Pi/ATP ratio of 1.41 +/- 0.35 (SE), significantly higher (P < 0.05) than the Pi/ATP ratio for short-term or chronic insulin treatment groups (Pi/ATP 0.92 +/- 0.22 and 0.84 +/- 0.22, respectively) or rats before tumor implantation (Pi/ATP 0.76 +/- 0.14). This insulin-induced bioenergetic protection occurred at any given tumor burden up to at least 10%. Thus, both short-term insulin given just prior to the frank manifestations of cancer cachexia and chronic insulin treatment given throughout tumor growth ameliorated host hepatic bioenergetic deterioration without significantly stimulating tumor growth. Insulin may act by altering the host metabolism (stimulation of liver glucose uptake and utilization, decreased energy-requiring gluconeogenesis, and general protein-sparing action) at the expense of the tumor.

Adenosine Triphosphate↗
PubMed1993

Pulmonary uptake of sestamibi on early post-stress images: angiographic relationships, incidence and kinetics.

Early post-stress imaging with 99Tcm-sestamibi has the potential to reveal ancillary markers of severe coronary artery disease. Lung/myocardial ratios of sestamibi were assessed after pharmacologic, exercise or combined stress, and these were compared with historical controls who were stressed similarly, but imaged with 201Tl. Forty initial patients had planar imaging and correlating angiograms; pulmonary uptake for sestamibi related to severe coronary artery stenoses when measured on immediate images, started at 4 min post-stress (P = 0.04), but had a poor relationship to angiographic findings when measured on delayed clinical images. Of 180 subsequent studies, increased pulmonary uptake of sestamibi was seen more frequently (incidence = 34%) in those with abnormal tomograms compared to those with normal tomograms (incidence = 13%, P < 0.01), but appeared less frequently than on abnormal 201Tl studies (incidence = 60%). With sequential imaging for 5 min after injection, pulmonary uptake showed a greater fall with time on sestamibi studies than on matched 201Tl studies. No consistent differences were seen among the stress modalities. As an ancillary sign of haemodynamically severe disease, increased pulmonary uptake can be seen after various stress modalities, but may be more difficult to apply with sestamibi than with thallium imaging.

Coronary Angiography↗
PubMed1992

Forearm P-31 nuclear magnetic resonance spectroscopy studies in oculopharyngeal muscular dystrophy.

Five siblings with autosomal dominant oculopharyngeal muscular dystrophy (OPMD) underwent P-31 Nuclear Magnetic Resonance Spectroscopy studies of forearm flexor muscles. Mean values of PCr/(PCr+Pi) in the patients were reduced (p = 0.01) and pH elevated (p = 0.02) in resting muscle when compared to controls. During exercise PCr/PCr+Pi) fell quickly to values less than controls (p less than 0.0001) despite submaximal exercise output and developed exercise-induced acidosis which exceeded that of controls (p = 0.05). Acidosis recovered slowly despite relatively normal recovery of PCr/(PCr+Pi) following exercise. Within the patient group, however, one member had normal resting, exercise and recovery values. The studies suggest that OPMD is a more widespread disorder of striated muscle than clinically appreciated. The pattern of findings observed in OPMD differs from those identified in denervation, disuse and mitochondrial myopathy.

Acidosis, Lactic↗
PubMed1991

A preliminary study of magnetic resonance relaxation times (T1 and T2) in inflammatory and degenerative synovial fluids.

Multiple synovial fluid samples from 21 patients were analysed using standard synovial analysis techniques and by nuclear magnetic resonance spectroscopy. Significant negative correlations were noted between both T1 (P less than 0.01) and T2 (P less than 0.0006) relaxation times and synovial fluid total protein. No differences in T1 or T2 relaxation times were noted in synovial fluid between 16 patients with inflammatory forms of arthritis and five patients with degenerative arthritis. In a single rheumatoid arthritis patient with concurrent staphylococcal arthritis, T1 and T2 relaxation times did not vary between the active phase and the recovery phase. The lack of any significant differences in the measured relaxation times as a function of joint condition suggest that in vivo magnetic resonance measurements of T1 or T2 for joint analysis may not reveal information of either a diagnostic or pathophysiological nature.

Analysis of Variance↗
PubMed1991

Coincident thresholds in intracellular phosphorylation potential and pH during progressive exercise.

Dynamic changes in intracellular phosphocreatine (PCr), inorganic phosphate (Pi), and pH in human forearm muscle were studied from rest through heavy exercise by means of a ramp exercise protocol and 31P nuclear magnetic resonance spectroscopy. Eighteen healthy volunteers performed an isotonic wrist flexion exercise of repeated contractions at a frequency of 0.5 Hz. Work rate was increased continuously (ramped) at approximately 0.13 W each minute from 0.34 to 1.5 W or until fatigue. Pi/PCr was used as an estimate of the cellular phosphorylation potential of the muscle. Exercise caused a progressive increase in Pi/PCr with an initial slow and later fast component. The transition between these components was distinct and corresponded to the onset of pH decline in all subjects. These changes in Pi/PCr and pH were best fit (P less than 0.05) by a piecewise linear regression model with a break point or threshold. Repeated ramp testing of six subjects showed that the threshold was reproducible (r = 0.98). The results of this study demonstrate the existence of an intracellular metabolic threshold and suggest that indirect threshold measures (lactate and ventilatory thresholds) may reflect events at the cellular level.

Adult↗
PubMed1991

Post-polio fatigue: a 31P magnetic resonance spectroscopy investigation.

Changes in high energy phosphates (HEP) and intramuscular pH during exercise were measured in 17 patients with post-polio fatigue and in 28 healthy controls using 31P magnetic resonance spectroscopy (MRS). Subjects performed a dynamic hand grip exercise at low and high intensity. Mean changes in the HEP and pH showed no significant differences between the groups, although the post-polio group's response was highly variable. Six patients showed evidence of a lower lactate accumulation during the high intensity exercise when compared with controls. These data suggest that the whole body fatigue experienced by polio survivors is not related to any systemic metabolic abnormality.

Adult↗
PubMed1991

Differential renal uptake of 201Tl: requirements for acquisition, display and quantification.

Renal uptake of 201Tl may have a role in screening for renal asymmetry in hypertensive patients (HP) who are referred for myocardial scintigraphy. The qualitative aspects of digitized planar images, and quantified differential renal uptake (DRU) of 201Tl were rated by comparing a simple technique (S) for outlining each kidney with an interpolative background subtracted technique (IB). These parameters were assessed in an initial series of patients by varying the length of acquisition (from 1 to 5 min), delay in acquisition (from 10 to 210 min after injection), and image preparation (nine-point smoothing). Six blinded observers rated the quality of coded images. Image quality was improved (P less than 0.01) by increasing the length of acquisition to at least 2 min, by smoothing of the images and by imaging within 2 h of 201Tl injection. Variability in quantification of DRU was suboptimal with acquisition for only 1 min and was more adversely affected with S than with IB. Clinical application of the quantitative technique was assessed in 180 HP and 32 normotensive controls. With IB, the normal range for DRU was slightly greater than for S. The two techniques were comparable in identifying abnormal cases and found 21 +/- 3% (S) and 19 +/- 3% (IB) of HP as lying outside the normal 99% confidence interval. Both quantitative techniques showed excellent agreement with renal angiography (n = 24). Furthermore, preliminary experience with surface markers and with 180 degrees tomography suggests the potential for simultaneous correction for renal depth. These data justify the use of adjunctive renal imaging during myocardial scintigraphy with 201Tl.

Heart↗
PubMed1991

Spectroscopy of the isolated rabbit heart: effects of perfusion with oxygenated crystalloid cardioplegia at 4 degrees C and 20 degrees C.

Factors that limit survival of explanted cardiac allografts include intracellular acidosis and loss of high energy phosphates. This study was undertaken to determine if these processes could be retarded by specific interventions during organ storage and to determine the capabilities of phosphorus-31 (31P) nuclear magnetic resonance spectroscopy to monitor these intracellular changes noninvasively. Thirty-six excised rabbit hearts were studied in six groups according to the storage temperature and conditions of their perfusion: nonperfused, aerated perfusate or oxygenated perfusate, each at 4 degrees C and 20 degrees C. 31P spectra were continuously obtained starting 20 mins post explanation and continuing for at least 5 h. The resulting data were analyzed to determine metabolite concentration and intracellular pH. The phosphodiesters, inorganic phosphates and phosphomonoesters, as well as the phosphocreatine and adenosine triphosphate peaks, could be reproducibly resolved. Comparisons at 0.5, 1, 2, 3, 4, and 5 h indicated that high energy phosphates were the most quickly degraded, and intracellular acidosis progressed most rapidly in nonperfused hearts at 20 degrees C. Hearts perfused with oxygenated cardioplegic solution at 4 degrees C showed significantly prolonged preservation of high energy phosphates and delayed development of intracellular acidosis. It was concluded that continuous infusion of oxygenated cardioplegic solution improves preservation of high energy phosphates at low temperatures, and that 31P magnetic resonance spectroscopy can be used to monitor these important intracellular changes rapidly and nonivasively, permitting serial studies on the same heart. This technique substantially reduced the number of animals needed for the study (36 were used in this study rather than the 216 required by traditional techniques).

Adenosine Triphosphate↗
PubMed1990

Metabolic response to exercise in malignant hyperthermia-sensitive patients measured by 31P magnetic resonance spectroscopy.

The currently favored theory of pathogenesis of malignant hyperthermia (MH) implicates an abnormality in skeletal muscle calcium ion transport. During a MH crisis a profound lactic acidosis occurs and in MH-sensitive individuals a delayed recovery of venous lactate has been previously noted postexercise. We have used 31P magnetic resonance spectroscopy to follow noninvasively in vivo changes in muscle of intracellular pH and high-energy phosphate metabolites during rest, exercise, and recovery of MH-sensitive subjects. Eleven biopsy-positive MH-sensitive patients have been studied and compared to 26 normal subjects. The MH-sensitive subjects as a group prematurely dropped their intracellular pH during mild aerobic exercise and they demonstrated a marked delay before the recovery of pH after maximal exercise. PCr/(PCr + Pi) ratios also dropped early during exercise but recovered normally. The observed changes in pH and PCr/(PCr + Pi) are consistent with a myopathy in MH-susceptible individuals.

Adenosine Triphosphate↗
PubMed1990

Quantitative analysis of myocardial ischaemia on end-diastolic thallium 201 perfusion images.

ECG gating of images with thallium 201 (201Tl) may improve the representation of myocardial perfusion by allowing isolation of the end-diastolic (ED) portion of the cardiac cycle. To characterize this phenomenon, circumferential distribution profiles for ED and conventional total-cycle images (TC) with 201Tl were analysed after summing ECG gated acquisitions; redistribution was defined as net washing of 201Tl for specific myocardial segments visualized on the left anterior oblique images. Scintigraphic data were compared with the presence of coronary stenoses in 150 patients. ED images had relatively less activity in the inferoseptal and inferoapical region than TC profiles. The ED mode of washout analysis provided more frequent confirmation of visually suggested redistribution than did the TC mode (84% incidence of net wash in for ED, 69% for TC). ED analysis showed a higher incidence of net 201Tl wash in in relation to critical circumflex and left anterior descending artery lesions, but yielded a similar overall performance to TC analysis in distinguishing patients with diseased coronary arteries from normal subjects. Thus, in selected cases, analysis of ED images could assist in confirming 201Tl redistribution.

Coronary Disease↗
PubMed1990

Dipyridamole combined with symptom-limited exercise for myocardial perfusion scintigraphy: image characteristics and clinical role.

Although dipyridamole can be used with myocardial scintigraphy to demonstrate reversible perfusion defects, combining exercise with the pharmacologic tool could improve image quality and information yield. The incidence of perfusion defects and the quality of thallium 201 images were reviewed in a series of 820 patients who had been assigned to a specific stress-test mode. Supine bicycle exercise alone was used (group I) where no pharmacologic or physical factors (e.g., beta-blockers, arthritis) limited performance; otherwise, intravenous dipyridamole was followed by symptom-limited exercise (group II). Angiographic correlation was available in 57 patients in group I, and in 158 in group II; of these, 109 performed significant exercise (greater than or equal to 3 min at increasing workloads) following dipyridamole (group IIA), whereas in 49 (group IIB) the exercise phase following dipyridamole was truncated. All test-mode groups were similar with respect to the incidence of ST segment depression during testing, patient throughput, and the sensitivity of perfusion defects. Chest pain and reversible defects were induced more frequently in group II than in group I. In group IIA, splanchnic background activity was lower (P less than 0.001) than in group IIB, and the false-positive rate tended to be lower. Thus, combining exercise with dipyridamole in patients with non-cardiac limitations to exercise enabled the achievement of optimal results for perfusion scintigraphy.

Cardiac Catheterization↗
PubMed1990

Renal uptake of Tl-201 in hypertensive patients undergoing myocardial perfusion imaging.

The detection of renovascular disease (RVD) has particular relevance in hypertensive patients (HP) who have symptoms of target organ damage. To evaluate the possibility of RVD in HP undergoing myocardial perfusion scintigraphy for chest pain symptoms, posterior renal images were obtained at 1-3 hours after Tl-201 injection. Analog and computer images were obtained for 5 minutes in 45 HP; 12 patients with no history of hypertension or renal disease served as normal controls. For qualitative analysis, images were coded and read by three observers as to symmetry of renal uptake. Differential renal uptake of Tl-201 (DRU) was quantitated on computer images. In normal controls, uptake was agreed on as symmetric. In HP, 6 patients had marked asymmetry of DRU and 4 had possibly significant asymmetry; 2 had decreased uptake in both kidneys suggesting bilateral RVD or nephrosclerosis. Objective correlation with DRU was obtained in 10 HP who had contrast angiography, confirming 4 cases of unilateral RVD and 2 of bilateral RVD. Thirteen patients also had renography with Tc-99m DTPA; differential renal function by this modality correlated well with DRU of Tl-201 (r = 0.98). Thus, DRU of Tl-201 can be used as a supplement to myocardial scintigraphy to identify HP who require further evaluation and treatment of RVD.

Adult↗
PubMed1990

Amino and iodotamoxifens: synthesis, estrogen receptor affinity and biodistribution.

Both geometrical isomers (E and Z) of an aminotamoxifen (2) have been prepared as precursors of the corresponding E and Z iodotamoxifens (1). The ability of E and Z-1 and 2 to compete with [3H]estradiol for estrogen receptors in rat uterine cytosol was measured relative to Z-tamoxifen and estradiol. The four tamoxifen derivatives showed affinities ranging from 50% to 1600% of that of tamoxifen. Under the same conditions, tamoxifen's relative binding affinity was 0.2% of that of estradiol. Preparative routes to the radioiodo-tamoxifens, [131I]-E and Z-1, were also developed and provided approximately 100 MBq of 'no carrier added' material in 40-60% radiochemical yield. Study of the biodistribution of these radioligands in tumor-bearing mice demonstrated significant radioactivity in the tumors and in the uterus. For [131I]-E-1, target to background ratios reached 28 for uterus/blood and 10 for tumor/blood; corresponding optimum ratios for [131I]-Z-1 were 10 and 5. A washout study using estradiol indicated selective uptake in the uterus of Swiss white mice. However, tumor uptake and image contrast in humans following intravenous administration of either [131I]-E or Z-1 were insufficient to allow diagnostic use of the radioiodotamoxifens.

Aged↗