Robert J. Boudreau

Suppression of plasma renin activity by cyclosporine

Cyclosporine treatment is associated with hypertension and suppression of plasma renin activity, the causes of which are unclear. To determine whether suppressed plasma renin activity is due to extracellular fluid volume expansion, 10 cyclosporine-treated renal transplant recipients were compared with 10 azathioprine-treated renal transplant recipients and seven patients with renal insufficiency. Glomerular filtration rate and effective renal plasma flow were significantly lower in cyclosporine-treated patients than in azathioprine-treated patients. Upright plasma renin activity was suppressed in cyclosporine-treated patients (cyclosporine 2.9 +/- 0.9, azathioprine 4.7 +/- 0.9, renal insufficiency 5.2 +/- 1.9 ng/ml/hour) but could be stimulated by a four-day period of dietary sodium restriction and diuretic administration (cyclosporine 15.8 +/- 4.4 ng/ml/hour). Extracellular fluid volume tended to be higher in cyclosporine-treated patients (cyclosporine 30.7 +/- 2.3, azathioprine 26.7 +/- 2.5, renal insufficiency 25.5 +/- 1.4 percent lean body mass), although the difference between cyclosporine-treated and azathioprine-treated patients did not attain statistical significance. There were no differences in the urinary excretion of prostaglandin E2 or 6-keto prostaglandin F1 alpha between the two groups of renal transplant recipients. It is concluded that suppression of plasma renin activity by cyclosporine is physiologic and may reflect expansion of extracellular fluid volume, which can be reversed by sodium depletion.

Strontium-89 chloride (Metastron) for palliative treatment of bony metastases : The University of Minnesota experience

Strontium-89 chloride (Metastron) is an FDA-approved treatment for palliation of cancer pain. We evaluated blood count changes and pain relief in 28 patients with widespread painful bony metastasis treated with strontium-89 at the University of Minnesota Hospital and Clinics. Eighteen patients had prostate cancer (all hormone-refractory cancer), seven patients had breast cancer, and three patients had lung cancer, all previously treated with either radiation, chemotherapy, or a combination of the two. Serial blood counts were performed weekly up to 8 weeks and at 12 weeks after administering Metastron. Pain scale and blood values were monitored simultaneously. The mean baselines of hemoglobin (Hgb), white blood count (WBC), and platelets (Plts) were 11.4, 5900, and 258,000, respectively. The mean dose of Metastron was 3 mCi (range 2.2-4.4). The median time (range) to nadir was about 6 weeks. The percentage reductions relative to baseline were 32% (range 0-72%) for WBC; 14% (range 0-50%) for Hgb; 15% (range 0-47%) for the red blood cell (RBC) count; and 40% (range 0-85%)for Plts. We did not find a close relationship among the baseline blood count, reduction of subsequent blood counts, or previously irradiated active bone marrow volume. The median time of survival was 23 weeks (range 2-66 weeks). At 12 weeks, 29% of patients had moderate to dramatic improvement of pain, 32% had some relief of pain, and 50% had no improvement in pain. Thirty-two percent of the treated patients required additional palliative external beam radiation to their bony lesions within the study period. Our results show that Metastron for palliation for bony metastases should be used with caution because of moderate to severe bone marrow toxicity, especially in platelets, associated with its use. Careful evaluation of patients given Metastron is needed to assess accurately its full benefit.

Postoperative diuresis renography and ultrasound in patients undergoing pyeloplasty: Predictors of surgical outcome

The authors reviewed 50 pediatric patients (56 renal units) who underwent pyeloplasty and had serial preoperative and postoperative diuresis renogram and ultrasound studies. Of those patients that clinically improved with surgery, 73% and 91% showed improved renographic patterns in postoperative studies at 3 and 12 months, respectively. Ultrasound demonstrated more gradual improvement in grade and pelvic diameters over longer study intervals. Diuresis renography is an excellent predictor of surgical outcome within 3 months of pyeloplasty and showed change well in advance of that seen on ultrasound. Sonography is better suited to longer term evaluation of grade, pelvic diameter, and renal size.

Liver transplant rejection and cholestasis : comparison of technetium 99m-diisopropyl iminodiacetic acid hepatobiliary imaging with liver biopsy

To determine whether the scintigraphic evaluation of technetium-99m diisopropyl iminodiacetic acid (DISIDA) uptake and excretion can distinguish among liver transplant patients with biopsy evidence for rejection, cholestasis or neither condition, we reviewed scintigrams and biopsies in 36 patients. There were 76 scintigrams with corresponding biopsies. Uptake and excretion were graded from image data on scales reflecting normal through severely abnormal values. Biopsies were evaluated for findings of cholestasis and rejection. The majority of scintigrams demonstrated normal uptake (60/75, 80%) and delayed excretion (65/76, 85%), which was most marked immediately after transplantation. One-way analysis of variance showed that the mean excretion values significantly differed between patients with normal biopsies and those with cholestasis and/or rejection (P =0.0003). However, mean uptake scores demonstrated no statistically significant difference between these two groups of patients (P =0.1). These findings suggest that 99mTc-DISIDA scintigraphy can differentiate between transplants with and without rejection/cholestasis but not between rejection and cholestasis. If 99mTc-DISIDA excretion is normal, rejection and cholestasis are unlikely.

Clinical use of indium-111 labeled blood products.

Following the introduction of In-111 oxine as a label for blood cells by McAffee and Thakur in 1976, these procedures have become increasingly important in the practice of nuclear medicine. Of particular interest are studies involving the use of labeled leukocytes for the detection of focal infection. The clinical utility of labeled platelets is less well developed, although the use of platelets to detect the formation of thrombi in blood vessels and on vascular grafts and prostheses is gaining prominence. This report summarizes the techniques presently employed at the University of Minnesota for the labeling of blood products, and their clinical use. Consideration also is given to the desired expertise and cost factors involved in the labeling of leukocytes and platelets.

Resting Tl-201 scintigraphy in the evaluation of coronary artery disease in children with Hurler syndrome.

Severe coronary artery disease may occur early in the course of mucopolysaccharidosis. The authors present radiologic, scintigraphic, and pathologic findings in five patients with Hurler syndrome. Thallium-201 myocardial scintigraphy and selective coronary angiography obtained within 2 days to 6 months were correlated in five patients. Postmortem examination of the coronary arterles was obtained in one patient within hours of angiography. Interobserver agreement on grading of scintigraphic abnormalities was poor. Nonspecific findings on TI-201 studies included septal abnormalities in all five patients. Scintigraphic findings were corroborated by angiography and postmortem results in only 3 of 5 patients. Our findings suggest that resting TI-201 scintigraphy has limited value in the detection of coronary artery disease in patients with Hurler syndrome.

Aerosol scintigraphy in the assessment of therapy for cystic fibrosis.

Thirteen patients with cystic fibrosis (aged 11 to 32 years) who were hospitalized for exacerbation and who had sputum cultures positive for Pseudomonas organisms were treated initially for 4 days with bronchodilators and physiotherapy followed by the addition of antibiotic (14 days, n = 8) or placebo (14 days, n = 4; 7 days, n = 1). Tc-99m DTPA aerosol scintigraphy was performed on the day before bronchodilators and physiotherapy, on the day before antibiotic or placebo, and on the day after completion of antibiotic or placebo therapy. Scintigrams were evaluated for change in the number of nonventilated segments and change in the number of bronchial deposits of aerosol. Sixty-nine percent of patients showed improvement after bronchodilators and physiotherapy alone. Sixty-two percent showed further improvement after antibiotic or placebo was added; this improvement was independent of whether antibiotic or placebo was administered (P > 0.1). These aerosol scintigraphy results failed to demonstrate that the effectiveness of bronchodilators and physiotherapy is enhanced by antibiotics in the treatment of cystic fibrosis exacerbations.

Reverse mismatch between perfusion and aerosol ventilation in transplanted lungs

Thirty ventilation-perfusion pulmonary scintigraphic studies were performed in 13 patients who had undergone unilateral lung transplantation. Ventilation–perfusion mismatch (ventilation better than perfusion) was judged absent, mild, moderate, or severe in the transplanted and native lungs. Ventilation-perfusion mismatch was significantly worse in the transplanted lungs (p<.0001). Findings of lung biopsies and chest roentgenograms failed to correlate with the severity of ventilation-perfusion mismatch. Hypoxic pulmonary vasoconstriction appears to be significantly impaired in most unilateral lung transplants; the mechanism for this impairment is unclear.

Exercise-induced muscle uptake of technetium-99m MDP

Intense muscle localization of Tc-99m MDP to upper extremity musculature was noted three days following weight lifting exercises. This phenomenon is due to an unknown mechanism although several causative factors have been suggested.

The prediction of the structure of technetium (V) complexes using density-functional techniques

Electronic structure calculations using the local-density functional method were shown to accurately reproduce the geometry of five oxo-Tc (V)-based radiopharmaceuticals containing a variety of donor ligands. Calculations were performed using the DGauss program on a Cray C90 supercomputer, requiring approximately 40 CPU h for each molecule. The predicted bond lengths were within +/- 0.04 A of the crystallographic coordinates, and bond angles within +/- 4 degrees. Root mean square (RMS) deviations between the predicted and crystallographic coordinates were less than 0.06, and visual inspection demonstrated nearly perfectly superimpossible structures.