Biomedical subjects
A Arzoumanian
Publications and source records attributed to A Arzoumanian.
Methylenetetrahydrofolate reductase (MR) deficiency: thermolability of residual MR activity, methionine synthase activity, and methylcobalamin levels in cultured fibroblasts.
Methylenetetrahydrofolate reductase (MR) deficiency is the most common inborn error of folate metabolism with more than two dozen patients described. The phenotypic spectrum ranges from severe neurological deterioration and early death to asymptomatic adults. Some patients with a severe deficiency of MR have been shown to have thermolabile reductase at 55 degrees C. Since methyltetrahydrofolate, the product of MR, is a methyl donor for methylcobalamin (MeCbl), the cofactor for methionine synthase (MS), we have looked at MeCbl accumulation and MS activity in fibroblasts from 15 patients with MR deficiency. Thermolabile MR was most often but not always seen in later onset disease. MeCbl levels were often lowest in the patients with early onset disease. All but two patients had levels of methionine synthase within the control range.
Radionuclide esophageal transit studies in progressive systemic sclerosis: an analysis of longitudinal data.
Nineteen patients with progressive systemic sclerosis (PSS) were studied by radionuclide esophageal transit (ET) and followed longitudinally for 3 to 5 years. Results were expressed as percent retention at 20 s and 10 min. There was gradual deterioration of ET at both 20 s and 10 min. When results were grouped into quartiles, deterioration occurred in 58.5% of followup studies in patients who initially had potential to deteriorate regarding 20 s retention and in 48% of similar patients regarding 10 min retention.
Interobserver variability in the interpretation of contrast venography, technetium-99m red blood cell venography and impedance plethysmography for deep vein thrombosis.
Contrast venography (CV) is the standard technique for diagnosing deep vein thrombosis (DVT). Newer noninvasive tests have also proven efficacious. However, there is a lack of data on the level of agreement among observers in their interpretation of the results of the various tests. After agreeing on well-defined criteria, three experienced observers assessed, blindly, the results of tests performed over a 4-month period on 117 patients who were suspected clinically of having had a first episode of DVT. The kappa statistic was used to measure the level of agreement beyond chance for CV (69 patients), red blood cell venography (RBCV) (82 patients) and impedance plethysmography (76 patients). The results of CV were assigned to normal, abnormal or inadequate categories, and those of RBCV and IPG to normal, equivocal or abnormal categories. The kappa values for CV, RBCV and IPG ranged from 0.53 to 0.56, 0.42 to 0.56 and 0.90 to 0.91 respectively. Values greater than 0.75 represented excellent agreement beyond chance and those between 0.40 and 0.75 represented fair to good agreement. Excellent kappa values were obtained for IPG because interpretation of the results of this method is entirely objective. Although the values for CV and RBCV showed good to fair agreement, there was a greater degree of observer variation, despite the well-defined criteria, indicating the subjectivity of interpretation of these test results. It is concluded that the kappa statistic can be used to measure observer variation of the results of tests for diagnosing DVT and may serve as a quality control tool for studies in which more than one person interprets the results.
Nifedipine inhibits cholecystokinin-induced gallbladder contraction.
Nifedipine is a calcium channel blocker which results in relaxation of smooth muscle. Although it has been utilized clinically to treat cardiovascular disease, and more recently spastic disorders of the esophagus and colon, its effects on gallbladder contractility have not been clearly defined. We tested the effects of nifedipine on gallbladder contraction stimulated by cholecystokinin (CCK) in a conscious guinea pig model and in healthy human volunteers. Gallbladder contraction was measured in response to repeated injections of CCK before and after intravenous nifedipine given to groups of five guinea pigs in a dose of 100, 200, or 300 micrograms. Nifedipine virtually abolished spontaneous interdigestive gallbladder contractile activity and decreased resting gallbladder tone. The mean amplitude of gallbladder contraction in response to CCK was decreased by 45, 73, and 67% (P less than 0.01), in response to the nifedipine doses of 100, 200, and 300 micrograms, respectively. The integrated gallbladder contractile response and the rate of rise of gallbladder pressure in response to CCK were also significantly decreased by nifedipine. In nine healthy human volunteers, gallbladder emptying was measured by radionuclide cholescintigraphy in response to CCK infusion; on another day the study was repeated after oral administration of 10 mg nifedipine. Ejection fraction was significantly decreased by nifedipine from 72 +/- 5 to 51 +/- 5% (P less than 0.001). These data demonstrate that nifedipine is a potent inhibitor of gallbladder contractility in guinea pigs and man. This may provide the basis for the use of nifedipine clinically in the treatment of biliary colic and also raises questions about the potential effect of long-term nifedipine use on gallstone formation and cholecystitis.
Technetium-99m red blood cell venography in patients with clinically suspected deep vein thrombosis: a prospective study.
We have compared technetium-99m (99mTc) red blood cell (RBC) venography to serial impedance plethysmography (IPG) in 110 consecutive patients with a first episode of clinically suspected deep vein thrombosis (DVT). IPG was performed at Day 0 and, if abnormal, contrast venography was also performed to rule out a falsely positive result. Patients with an initially normal IPG had the test repeated at Days 1, 3, 5 to 7, and 10 to 14. Contrast venography was not performed and anticoagulant treatment was withheld in all patients who remained normal during repeated IPG testing. Technetium-99m RBC venography was performed at Day 0 in patients with an initially abnormal IPG and during the period of serial IPG testing in those with an initially normal IPG. The sensitivity of [99mTc]RBC venography for proximal DVT was 0.68, with 95% confidence limits (CL) from 0.48 to 0.89. Specificity was 0.88 (95% CL from 0.81 to 0.95). When the findings of [99mTc]RBC venography for the entire lower extremity were compared to the reference method, the sensitivity increased to 0.90 (95% CL from 0.82 to 0.97) but the specificity decreased to 0.56 (95% CL from 0.51 to 0.62). Technetium-99m RBC venography is a sensitive but less specific method for detecting DVT of the entire lower extremity. An abnormal [99mTc]RBC venogram, particularly in the calf region, should always be confirmed by another diagnostic method.
Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology.
Immunization with chondroitinase ABC-digested fetal human cartilage proteoglycan and Freund's complete adjuvant induced polyarthritis and ankylosing spondylitis in female BALB/c mice. The initial external symptoms of the joint inflammation were swelling and redness. This was associated with edema of the synovium and periarticular tissues and gross proliferation of cells, which reached a peak during weeks 7-9 of the experiment. Mononuclear cell infiltration, with perivascular concentration and occlusion of small vessels, was common. Synovitis increased in severity, villous pannus developed, and erosions of bone, articular cartilage, and occasionally, growth plate were observed. The lumbar spine and the proximal intervertebral discs of the tail also exhibited inflammatory and degenerative changes. As the arthritis progressed, sometimes with acute inflammatory exacerbations, more joints became involved and, by the sixteenth to the twentieth weeks of the experiment, a progressive polyarthritis, with gross joint deformities and restricted function, developed in the majority of the limb joints. Clinical and morphologic features of the disease correlated well with radiologic analysis and with an increased deposition of 99mTc-methylene diphosphonate (determined by radionuclide imaging). The development of this arthritis was accompanied by the expression of cell-mediated and humoral immunity to the immunizing antigen. However, this immunity was also observed, although it was generally less well developed, in mice that received the intact or digested proteoglycan without adjuvant. These mice did not usually develop arthritis. Control mice that received only adjuvant did not develop arthritis.
Kupffer cell depletion associated with capillarization of liver sinusoids in carbon tetrachloride-induced rat liver cirrhosis.
Rats were made cirrhotic by carbon tetrachloride inhalation associated with phenobarbital in the drinking water over 10 weeks. After a 1-week recovery period a 99mTc sulphur colloid radioisotope scan of the liver was carried out on each animal following bolus injection into the iliac vein. Kupffer cells were then histologically identified by one of three methods: colloidal carbon uptake, iron staining after ferritin-dextran, or endogenous peroxidase staining. The degree of liver injury was classified into four pathological groups and these were correlated with the phagocytic capacity of each liver as recorded on the isotope scan. All three histological markers demonstrated that in normal liver, Kupffer cells are more plentiful in periportal areas. In cirrhotic liver, there were very few Kupffer cells in nodular regenerative areas, where continuous capillaries are found, but Kupffer cells were present in the remaining more normal trabecular-sinusoidal areas. Morphometric counting of carbon- and ferritin-labelled Kupffer cells demonstrated a significant decrease in cirrhotic livers. A close correlation was also found between increasing degree of liver injury and diminished hepatic phagocytic capacity, as demonstrated by the radioisotope scan. The study demonstrates that where regenerative liver is capillarized, with replacement of fenestrated sinusoids, Kupffer cells are absent.
Observations on the radionuclide assessment of peritoneovenous shunt patency.
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Effect of 99mTc-Sn-colloid incubation time on in vivo distribution.
The in vitro particle size of 99mTc-Sn-colloid preparation increases with the length of incubation time after reconstitution. It was found that the percentage of particles trapped (T) by a 1-micron filter as a function of time (t) could be represented by the logarithmic equation T = 5.3 + 15.7 ln t (r = 0.96). This material was applied to a crossover study involving 25 patients each of whom received preparations of the same reconstituted 99mTc-Sn-colloid that had been incubated for 15 min and (each patient received both) 5 h. It was found that there was a significant shift of radioactivity to the spleen and a significant decrease in background with the material that had been incubated longer. The 99mTc-Sn-colloid is adequate for the disclosure of space-occupying disease in the liver and spleen, but unreliable for drawing conclusions on the status of liver function based on the changes in splenic concentration.
Total body retention measurements of Tc-99m MDP using a simple detector.
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A comparison of Tc-99m colloid labeled leukocytes and Ga-67 citrate for the disclosure of sepsis.
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A crossover study comparing delayed radiohippurate images with furosemide renograms.
109 kidneys in 56 adult patients suspected of having urinary tract obstruction were studied prospectively. All patients underwent a routine 131I-hippurate series for 30 min, and to this was added a delayed image at 2 h. Later in the same day, these patients had a diuretic renogram for the first 30 min in which 40 mg of furosemide were injected simultaneously with a repeat 131I-hippurate dose. In 48 patients (85.7%) the delayed image and diuretic renogram showed mutual agreement as to the presence or absence of urinary tract obstruction, but not necessarily with the final diagnosis. Of the 8 remaining patients with 16 kidneys, there were 6 false positives and 4 false-negatives by diuretic renography, and 1 false positive and no false-negatives by nondiuretic delayed imaging. The only benefit derived from the diuretic renogram was a shortening of the examination from 2 h to 30 min.
Selective right ventricular dysfunction after coronary artery bypass grafting.
Preoperative and postoperative right (RVEF) and left ventricular ejection fractions (LVEF) were studied by means of radionuclide techniques in 15 patients undergoing coronary bypass operations. Three of them, all with right coronary artery lesions, had postoperative depression of RVEF without concomitant decrease in LVEF. In contrast to those with left ventricular dysfunction, the patients with selective RVEF depression did not have significant elevation of myocardial injury index calculated from creatine kinase isoenzyme (CK-MB) curves.
A clinical comparison of MDP and DMAD.
Tc-99m labeled dimethyl-amino-diphosphonate (DMAD) was compared with methylene diphosphonate (MDP) in five healthy volunteers and 28 patients with a variety of bony afflictions. Although the normal bone uptake of DMAD is less than MDP, the lesion-to-normal bone ratio is significantly higher with DMAD. All 71 lesions detected with MDP were also seen with DMAD. However, 10 lesions were disclosed with DMAD that were not seen with MDP. These lesions tended to have low grade concentrations of the radiopharmaceutical and were detected with DMAD by virtue of the lower normal bone uptake rather than higher lesion uptake.
A crossover study comparing Tc-99m-labeled HMDP and MDP in patients.
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Differential diagnosis of jaundice by 99mTc-IDA hepatobiliary imaging.
The utility of 99mTc-IDA imaging in the differential diagnosis of jaundice was assessed. Although overall accuracy was 84%, this method is still inferior to the reported efficiency of ultrasonography and CT in making the correct diagnosis. Radionuclide imaging is a good alternative when these other modalities are not available and it functions well in an adjuvant capacity. The diagnostic limitations of 99mTc-dimethyl IDA imaging in cases of moderate to severe jaundice are largely overcome by the use of 99mTc-p-butyl IDA.
99mTc-IDA imaging in the differential diagnosis of acute cholecystitis and acute pancreatitis.
99mTc-IDA (99mTc-dimethyl-acetanilide-iminodiacetic acid) hepato-biliary imaging was evaluated for its efficacy in distinguishing acute cholecystitis from acute pancreatitis. In a retrospective review, gallbladders were demonstrated by 99mTc-IDA in 13 of 15 patients (87%) with acute pancreatitis. This is significantly higher than reports on the frequency of gallbladder filling with oral and intravenous cholangiography in the presence of acute cholecystitis.