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[Bayesian analysis of myocardial scintigraphy using 99mTc-Sn(II)-methylenediphosphonate and using 99mTc-Sn(II)-pyrophosphate].

Myocardial scintigraphy with 99mTc-Sn (II)-Methylenediphosphonate (MDP) and with 99mTc-Sn (II) pyrophosphate (PPi) was performed in 185 patients with proven acute myocardial infarction (90 with MDP; 95 with PPi), and in 65 subjects with acute chest pain of a different etiology (37 with MDP; 28 with PPi), during the first five days after the onset of illness. Sensitivity, specificity and accuracy of the procedure were higher with PPi (0.895, 0.893, 0.894) than with MDP (0.822, 0.865, 0.835) in the diagnosis of AMI. Based on the usual clinical electrocardiographic and biochemical criteria, the likelihood of AMI on the population studied with MDP was of 70.9% and with PPi of 77.2%. Application of Bayes' theorem showed an increase in the likelihood of AMI, when myocardial scintigraphy was positive, from 70.9% to 93.7% when MDP was used, and from 77.2% to 96.6 when PPi was the tracer, with incremental ruling in gaings of 22.8% and 19.4%) respectively. A normal scintigraphy, on the other hand, reduced the likelihood of AMI from 70.9% to 33.4% when MDP was used, and from 77.2% to 29.2% when PPi was the tracer, with respective incremental ruling-out gains of 37.5% and 48.0%. Although homogeinity between the populations studied with each tracer was not proven, existing practical, clinical and biochemical evidence allows the conclusion that PPi is a better agent than MDP in the study of patients with acute chest pain.

Adolescent↗

[Mechanism of action of vitamin B1, thiamine pyrophosphate, and FAD on smooth muscle cells].

The contractile activity of the guinea pig taenia coli longitudinal muscle was studied as affected by exogenic thiamine, thiamine pyrophosphate and FAD. The mentioned substances in a concentration of 1 . 10(-3) M relax the smooth-muscular cells. Against a background of apamine FAD causes a contraction of taenia coli, which is not observed with application of thiaminepyrophosphate. Evidently, there are two, types of receptors sensitive to FAD and one sensitive to vitamin B1 on the membrane of the smooth-muscular cell.

Animals↗

Simultaneous display of gated technetium-99m stannous pyrophosphate and gated blood-pool scintigrams.

We have developed a method by which any two sets of R-wave-synchronized radionuclide images may be registered, color-coded, and displayed in cinematic fashion so that the image sets are superimposed and shown simultaneously in contrasting colors. The technique has been applied to technetium-99m stannous pyrophosphate (Tc-99m PPi) and equilibrium blood-pool images. Gated Tc-99m PPi and gated blood-pool image sets (16 frames per cardiac cycle) were acquired in identical projections. Image sets were then registered, if necessary, and color-coded by a computer algorithm. Our initial experience suggests that this overlay technique may be of value to: (a) detect right ventricular infarction with greater precision; (b) provide a better estimate of anatomic location and circumferential extent of Tc-99m PPi myocardial uptake relative to the ventricular blood pool; and (c) distinguish between segmental contraction abnormalities caused by recent infarction (identified by abnormal Tc-99m PPi uptake) and segmental contraction abnormalities caused by ischemia or previous myocardial infarction.

Adult↗

[Free and bound thiamine pyrophosphate level in rat liver mitochondria in various saturation of the body with thiamine].

Content of tree and bound thiamine pyrophosphate (TPP) was measured by means of gel filtration and equilibrium dialysis procedures in mitochondria of normal rats, the rats under conditions of alimentary B1 avitaminosis and loading with thiamine. The content of protein-bound TPP was stable and equal to 20% of its total level in the mitochondria of control rats and in the rats loaded with thiamine. The content of free form of TPP was decreased in B1 avitaminosis; a severe form of the avitaminosis was accompanied by a decrease in content of the bound form. Concentration of the free form of TPP did not increase if the organism of the rats was loaded with thiamine. These data suggest existence of specific systems controlling the vitamin uptake in mitochondria. The active transport of thiamine across the mitochondrial membranes is considered as the most important process. Administration of the high doses of the vitamin led only to an increase in the non-coenzymatic form of the vitamin, indicating the absence of thiamine pyrophosphokinase in rat liver mitochondria. A possible mechanism of TPP transport in mitochondria is discussed.

Animals↗

99Tcm-pyrophosphate myocardial scintigraphy: the role of volume-rendered three-dimensional imaging in the diagnosis of acute myocardial infarction.

The aim of this study was to evaluate the role of volume-rendered three-dimensional imaging in the diagnosis of acute myocardial infarction (AMI) using 99Tcm-pyrophosphate (99Tcm-PYP) scintigraphy in a diagnostically difficult group of patients. In total, 117 patients were studied using planar, single photon emission tomography (SPET) and 3-D volume-rendered imaging performed 3 h after receiving 555 MBq (15 mCi) of 99Tcm-PYP intravenously. 555MBq (15 mCi) of 99Tcm-PYP intravenously. Two teams of physicians reported in a blinded and random fashion on each planar, SPET and 3-D rotating image study. Individual reports were compared with reports that used all three imaging modalities in combination. Observer reproducibility was between 85 and 90% and inter-observer team agreement was between 87 and 91%. A score based on clinical history, electrocardiography, serum cardiac enzyme levels and cardiac risk factors was validated and used as a de facto 'gold standard' for AMI for 75 of the subjects for whom all these details were available. The sensitivity, specificity and overall accuracy of combined planar, SPET and 3-D rotating image modalities were all 84%. Analysis of each modality in isolation showed SPET imaging to have the highest sensitivity (74%) and specificity (89%). In combination with SPET and planar imaging, 3-D rotation image presentation increases diagnostic sensitivity without appreciably altering overall diagnostic accuracy. 99Tcm-PYP myocardial SPET imaging shows good utility in the diagnosis of AMI in diagnostically difficult patients.

Adult↗

Effect of oestradiol on the carbohydrate metabolism of immature rat uterus: the role of fructose-2, 6-bis-phosphate and of phosphoribosyl pyrophosphate.

Enzymes and metabolic intermediates of glycolysis, pentose phosphate pathway and the tricarboxylic acid cycle were measured in immature rat uterus after treatment with oestradiol. The flux of glucose through alternative pathways was examined. Fructose-2,6-bis-phosphate, the well known regulator of glycolytic pathway, increased after the injection of oestradiol and remained elevated. This increase was accompanied by raised levels of most of glycolytic intermediates and by increase in glycolytic flux. The key enzymes of glycolysis and all the enzymes of pentose phosphate pathway showed a gradual increase in the activity with administration of oestradiol up to 48 hours. Phosphoribosyl pyrophosphate, the metabolite required in nucleotide synthesis, was also elevated. Marked changes in the levels of key metabolic intermediates and the enzyme activities are correlated with the increased nucleic acid, protein and lipid synthesis occurring following oestradiol treatment.

Animals↗

[The solubility of calcium pyrophosphate dihydrate crystals].

The solubility of calcium pyrophosphate dihydrate crystals (CPPD crystals), which cause pseudogout, was studied in vitro and vivo. The in vitro experiment using 0.1 M tris buffer and 0.2 M glycine buffer indicated that changes in pH and pyrophosphatase activity played a major role in the solubility of CPPD crystals. An experiment using the synovial fluid from patients with pseudogout, rheumatoid arthritis, and from those with osteoarthritis suggested that changes in the synovial fluid pH due to inflammation affected the solubility of these crystals. In addition, an experiment using the air pouch in rat showed that inflammation due to the CPPD crystals was maximum at about 9 hours after CPPD injection, and that inflammatory cells appearing at this time then had a major influence on the crystals' solubility. From these results, it appeared that CPPD crystals released into the joint cavity were mostly dissolved by inflammatory cells, but that crystal dissolution was also affected by changes in the synovial fluid itself, particularly by a change in pH.

Animals↗

Technetium-99m-pyrophosphate scintigraphic findings of intestinal perforation in dermatomyositis.

Gastrointestinal complications are more common in children than in adults and present a serious problem with dermatomyositis. We report on a 66-yr-old man with dermatomyositis who suffered from intestinal perforation. The abdominal plain radiograph revealed only dilatation of the intestinal loops; increased radioactivity, however, was clearly demonstrated in the early 5-min and delayed 3-hr 99mTc-pyrophosphate images.

Aged↗

Inhibition of 5-phosphoribosyl-1-pyrophosphate synthetase by the monophosphate metabolite of 4-amino-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine: a novel mechanism for antitumor activity.

The aminopyrimidopyrimidine nucleoside 4-amino-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (APP), which was previously shown to possess experimental antitumor and antiviral activity, was metabolized within WI-L2 human lymphoblastoid cells to a derivative identified as the beta-D-ribonucleotide (APP-MP). In a subline of WI-L2 cells deficient in adenosine kinase, this metabolite was not formed and APP was not cytotoxic, suggesting that APP is converted by adenosine kinase to its 5'-monophosphate. Because no evidence of di- or triphosphates was seen, the monophosphate appeared to be the active species. Treatment of WI-L2 or L1210 cells with APP (10 microM) for 30 min caused extensive depletion of both purine and pyrimidine ribonucleotides. Purine and pyrimidine deoxyribonucleotides were also depleted. Cells were not protected from the cytotoxicity of APP by hypoxanthine plus uridine, but uridine plus adenosine plus 2-deoxycoformycin gave considerable protection. This result was consistent with APP-MP acting as an inhibitor of 5-phosphoribosyl-1-pyrophosphate (PRPP) synthetase, a hypothesis that was confirmed by preparing PRPP synthetase from Novikoff hepatoma cells; APP-MP was a noncompetitive inhibitor, with a Ki of 0.43 mM. APP-MP was found to accumulate in APP-treated cells to a concentration of almost 3 mM. The relevance of PRPP synthetase inhibition to the cytotoxic mechanism of APP is indicated by the fact that depletion of the PRPP pool was seen as early as 15 min after treatment, before any change was apparent in cellular levels of ATP or UTP. DNA synthesis was markedly suppressed within 30 min of APP treatment of WI-L2 cells, and a lesser degree of inhibition of RNA synthesis was apparent after 45 min.

Animals↗

[Clinical evaluation of patients with right ventricular infarction detected by dual SPECT imaging of thallium-201 and technetium-99m pyrophosphate].

We evaluated clinical significance of dual-nuclide SPECT imaging (D-SPECT) of thallium-201 and technetium-99m pyrophosphate (PYP) in patients of acute inferior left ventricular infarction with PYP uptake in the right ventricle (PYP (+) group) in comparison with those without PYP uptake (PYP (-) group). There was no difference in coronary risk factors, history of angina, blood pressure, heart rate, and hemodynamics on admission between PYP (+) group and PYP (-) group. The duration from onset to admission was longer in PYP (+) group and coronary reperfusion therapies were carried out in few cases. In 7 of 8 PYP-positive patients, the diagnosis of right ventricular infarction was made only by D-SPECT. Four of 8 were complicated with shock within three days, and the duration of hospitalization was longer. Coronary angiography demonstrated many proximal lesions (50%) in PYP (+) group but few ones (18%) in PYP (-) group. D-SPECT was very useful for diagnosing acute right ventricular infarction, and it might contribute to the prevention of shock if performed within a few days.

Aged↗

The use of Technetium-99 pyrophosphate scanning in management of high voltage electrical injuries.

The surface thermal burn associated with high voltage (HV) electrical injuries represents only the tip of the iceberg. Occult muscle damage may not become apparent for 5 to 10 days. In this study, the efficacy of Technetium-99m (Tc) pyrophosphate scanning was investigated. Early scanning (within 3 days of injury) of 19 limbs in 15 patients demonstrated a sensitivity of 75 per cent, with a specificity of 100 per cent. The predictive value of a positive test, however, was 100 per cent. Compared to a control group of 17 patients treated without Tc scan, the scan was not associated with reduced hospital length of stay or with decrease in the number of surgical procedures.

Arm Injuries↗

Pelvic pseudotumoral calcium pyrophosphate dihydrate deposition: an ultrastructural study.

We analyzed large periarticular calcifications of the hips and pubis in a woman with diffuse primary chondrocalcinosis, symptomatic in the knees. Serial articular and periarticular biopsies were obtained during surgery for osteoporotic hip fracture. Histologic examination showed diffuse nonbirefringent clumps in red alizarin stained cartilage, capsula and tendon. Scanning electron microscopy with microanalysis indicated a calcium/phosphorus atomic ratio of about 1. Transmission electron microscopy, electron diffraction and Raman spectroscopy assessed calcium pyrophosphate dihydrate (CPPD) in cartilage, synovia, capsula, tendon and muscle. The cause of these hard to observe, bulky CPPD periarticular deposits, which resembled basic calcium phosphate on radiography, is still unclear.

Aged↗

Calcium pyrophosphate dihydrate crystal deposition disease and pseudogout of the acromioclavicular joint: radiographic and pathologic features.

OBJECTIVE: To correlate the radiographic and pathologic findings in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease and the pseudogout syndrome in the acromioclavicular (AC) joint, a relatively infrequent, but clinically important site. METHODS: We describe a case with a definite diagnosis of CPPD crystal deposition leading to pseudogout of the AC joint. We also identified 17 other patients with CPPD crystal deposition disease who showed intraarticular or periarticular calcification in this joint and investigated the radiographic findings in 26 AC joints in these 17 patients. We then correlated the results with the pathologic findings in 2 cadavers with AC joint manifestations of the disease. RESULTS: Intradiscal calcification, mainly linear or punctate in configuration, was found between adjacent bony margins in 9 of 26 AC joints (35%) or between the bony margins and extending above the upper articular bony margin in 14 AC joints (54%). Two joints (8%) showed diffuse calcification within the discs between, above, and below the articular bony margins. The remaining joint (3%) had intradiscal calcification only above the upper bony margins of the AC joint. All the joints with calcifications above the articular margins had associated globular or tumor-like soft tissue masses. A pseudogout attack at the AC joint may have nonspecific shoulder pain as its presenting symptom. CONCLUSION: CPPD crystal deposition disease leading to pseudogout syndrome of the AC joint is a clinically significant condition. We emphasize that careful assessment of the AC joint and adjacent soft tissue using intensive bright light on routine shoulder radiographs may increase the sensitivity of detecting discal and capsular calcifications in patients with pseudogout of the shoulder.

Acromioclavicular Joint↗

Technetium-99m-pyrophosphate uptake as an indicator of myocardial injury without infarct.

UNLABELLED: Technetium-99m-pyrophosphate (PYP) is bound to calcium in necrotic myocardium and has been used clinically to evaluate myocardial infarction. Technetium-99m-PYP is also reported to accumulate in myocardium with unstable angina pectoris and it is speculated that severe ischemia with noninfarcted tissue may also increase uptake of 99mTc-PYP. In this paper, 99mTc-PYP uptake was determined in various models of myocardial ischemia of short duration to examine its applicability to the assessment of myocardial viability. METHODS: In 23 open-chest dogs under anesthesia, models of ischemia-reperfusion of the left anterior descending artery (LAD) subjected to ischemia for 10, 30 or 60 min were produced. Wall motion was examined by echocardiography and myocardial blood flow was calculated using colored microspheres. Technetium-99m-PYP was injected after each ischemic intervention and reperfusion. RESULTS: Technetium-99m-PYP showed 1.18 +/- 0.009 in the uptake ratio (ischemic area/normal area) following 10-min ischemia (11 dogs). The uptake ratio following 30-min ischemia (8 dogs) showed a significantly higher increase than that following 10-min ischemia (4.09 +/- 1.75; p < 0.05), permitting in vivo and ex vivo imaging. After 60-min ischemia resulting in infarction (4 dogs), 99mTc-PYP uptake of the ischemic area showed an uptake ten times that of the normal area (transmural: 12.2 +/- 2.9, epicardium: 7.5 +/- 1.9, endocardium: 16.8 +/- 4.1). CONCLUSIONS: These findings indicate that since 99mTc-PYP accumulates in injured myocardium, its concurrent use with blood flow imaging is useful for the assessment of severity of ischemia, injured area and myocardial viability.

Animals↗

Cytosolic Ca2+ concentration determinations in neutrophils stimulated by monosodium urate and calcium pyrophosphate crystals: effect of protein adsorption.

OBJECTIVE: To develop methods to correct for light scattering artifacts produced by monosodium urate monohydrate (MSUM) and calcium pyrophosphate dihydrate (CPPD) crystals in the measurement of the levels of cytosolic free calcium, [Ca2+]i, in neutrophils and to quantitate the extent of association of neutrophils with crystals. METHODS: The association of neutrophils with crystals through binding of crystals onto the neutrophil plasma membrane and/or internalization was quantitated by mixing crystals with diphenyl hexatriene (DPH) loaded neutrophils and monitoring the fluorescence intensity of supernatants ("free" neutrophils) following gravity sedimentation of "free" crystals and neutrophils with bound/internalized crystals. The effects of precoating CPPD and MSUM crystals with IgG, plasma, serum and BSA on crystal-neutrophil association and [Ca2+]i were determined. RESULTS: MSUM produced a large increase in [Ca2+]i that reached maximal values in less than 1 min, whereas CPPD produced a smaller and slower increase in [Ca2+]i. IgG adsorbed onto CPPD increased the rate and extent of increase in [Ca2+]i. Heparinized plasma and serum adsorbed onto CPPD increased the extent but not the rate of increase in [Ca2+]i. CONCLUSION: [Ca2+]i increases induced by MSUM were not affected by IgG, serum or heparinized plasma precoating. IgG, serum, or heparinized plasma adsorbed into CPPD amplified neutrophil activation increasing the extent of the increase in [Ca2+]. Neither MSUM nor CPPD induced increases in [Ca2+]i were sensitive to precoating crystals with bovine serum albumin.

Adsorption↗

[Significance of Tc-99m pyrophosphate accumulation in unstable angina: clinical characteristics and evidence for myocardial stunning].

Tc-99m pyrophosphate (PYP) and Tl-201 simultaneous dual energy single photon emission computed tomography (SPECT) were performed for 33 patients with clinically diagnosed unstable angina. Twenty-two patients (76%) showed PYP accumulation in the myocardium (PYP+group). Clinical features, types of unstable angina, electrocardiographic changes during and after the anginal attack, and serial creatine kinase (CK) sampling data were reviewed and compared in the 2 groups. Selective coronary angiography was performed in all patients, and contrast left ventriculography was carried out in 29 patients both in unstable and stable states. In the study of left ventriculograms, the ejection fraction (EF) was calculated by the area-length method and the wall motion abnormality index was calculated by the centerline method. The PYP(+)group differed significantly from the PYP(-)group in several features as follows: 1) the "new angina at rest" type of unstable angina was more frequent in the PYP(+)group than in the PYP(-)group. The ratios of new angina at rest/effort angina (including new angina of effort and angina of effort with changing pattern) were 16/6; 2/9 for the PYP(+) and (-)groups, respectively (p < 0.05). 2) ST elevation during the heart attack was seen more in the PYP(+)group. The ratios of ST elevation/ST depression were 13/22 (59%); 5/22 (23%) for the PYP(+)group, and 2/11 (18%); 7/11 (64%) for the PYP(-)group, respectively (p < 0.05). 3) EF was improved in the PYP(+) group to the normal range. EF in the PYP(+)group changed from 57 +/- 12 in the unstable state to 62 +/- 11% in the stable state (p < 0.02), while that of the PYP(-)group showed no significant difference between the unstable state (59 +/- 9%) and the stable state (59 +/- 11%). 4) Wall motion abnormality index (WMI) in the PYP(+)group was poorer than in the PYP(-)group, but it improved markedly in one month to the same level as that of the PYP(-)group. WMI in the PYP(+)group in the unstable state (21.7 +/- 26.2) was worse than that in the PYP(-)group in unstable state (5.7 +/- 8.2) (p < 0.001). WMI in the PYP(+)group in the unstable state markedly improved in the stable state (from 21.7 +/- 26.2 to 8.4 +/- 19.8) (p < 0.025); whereas, WMI of the PYP(-)group showed no significant improvement (from 5.7 +/- 8.2 to 15.5 +/- 19.6). These data suggest that the area showing PYP(+) may represent stunned myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina, Unstable↗

Geographic distribution of calcium pyrophosphate (CPPD) deposition disease in pre-Columbian North America: independent validation of CPPD criteria.

Calcium pyrophosphate deposition disease (CPPD), a form of crystalline arthritis, has a unique distribution in the Early to Middle Archaic Periods (3000 to 8000 years before the present) of North America, contrasting with the generalized geographic distribution of osteoarthritis. Incursion of CPPD into specific regions suggests possible migration patterns. The disparate geographic distribution of CPPD and osteoarthritis provide independent verification of the validity of diagnostic criteria utilized for the identification of CPPD.

Arthritis↗

Thiamine pyrophosphate as an effector of 2-oxoglutarate dehydrogenase complex from European bison heart.

The purified 2-oxoglutarate dehydrogenase complex (OGDC) from the European bison heart was near saturated with endogenous bound thiamine pyrophosphate (TPP). Exogenous TPP added to the full OGDC reaction medium decreased S0.5 for 2-oxoglutarate approximately 2.6-fold without any notable change in the maximum reaction rate. The TPP effect was observed in the presence of 1 mM ADP which alone is a strong positive allosteric effector of OGDC. At an unsaturating 2-oxoglutarate concentration the A50 value for TPP was approximately 0.05 mM. The ADP-like action of exogenous TPP was also found in the 2-oxoglutarate dehydrogenase (E1) reaction, determined in the presence of 2,6-dichlorophenoloindophenol as an electron acceptor.

Adenosine Diphosphate↗