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Purification and properties of sulfoacetaldehyde sulfo-lyase, a thiamine pyrophosphate-dependent enzyme forming sulfite and acetate.

Sulfoacetaldehyde sulfo-lyase, which decomposes sulfoacetaldehyde to sulfite and acetate, was extracted from a bacterium grown on taurine, and purified, and characterized. A method for assay of enzyme activity was devised on formation of a bisulfite adduct with benzaldehyde. The enzyme was purified 14-fold from an extract of cells grown on taurine and appeared homogeneous on disc-electrophoresis. The molecular weight of the enzyme was estimated to be 85,000 by gel filtration. The enzyme required thiamine pyrophosphate (TPP) and Mg2+ for activity and preincubation with TPP and Mg2+ was required for maximum activity. The optimum pH for activity was 7.5. The Km value for TPP was determined to be 2.7 muM and that for sulfoacetaldehyde to be 5.0mM. Sulfite was produced only from sulfoacetaldehyde among a variety of sulfonates tested. rho-Chloromercuribenzoate, EDTA, and sulfite, a reaction product, inhibited the enzyme reaction. The enzyme seemed to be inducible, since activity was found in extracts of cells grown on taurine but not on peptone.

Acetaldehyde↗

Technetium pyrophosphate muscle scans in inflammatory muscle disease.

Technetium-99M pyrophosphate (TcPYP) nuclear scans of extremities were performed on 15 patients at 10 minutes and 2 hours after isotope injection. Scans were carried out both to confirm the diagnosis of myositis and to direct subsequent muscle biopsy. Five of six patients with clinical features strongly suggestive of inflammatory muscle disease had positive scans. All muscle biopsies performed at areas of increased isotope uptake showed inflammatory muscle disease. All nine patients not suspected of active inflammatory muscle disease had negative scans. Two of these underwent muscle biopsy with negative results. Our observations suggest that TcPYP muscle scans may be useful both to confirm the clinical suspicion of inflammatory muscle disease and in directing the choice of site for muscle biopsy.

Biopsy↗

Increase in phosphoribosyl pyrophosphate induced by ATP and Pi depletion in hepatocytes.

A series of compounds that induce depletion of ATP and Pi when added to isolated rat hepatocytes were found to cause a remarkable, although transient, elevation in the concentration of phosphoribosyl pyrophosphate (PRPP) in these cells. After the addition of 5 mM fructose, xylitol, tagatose, or D-xylulose, PRPP increased from a basal value of 6 +/- 1 nmol/g of cells to, respectively, 68 +/- 11, 42 +/- 11, 67 +/- 22, and 530 +/- 50 nmol/g of cells (means +/- SEM of 3-9 experiments). In each case, the increase in PRPP was preceded by a latency period of 5-10 min. PRPP reached maximal levels 15 min after the addition of fructose and 30 min after that of xylitol and D-xylulose, but continued to increase for as long as 60 min after the addition of tagatose. Most striking was that the increase in PRPP closely paralleled the restoration of intracellular Pi. Ribose 5-P increased about two- to fivefold after the addition of fructose, xylitol, and tagatose, and approximately 12-fold after D-xylulose. The mechanism by which ATP- and Pi-depleting compounds stimulate the activity of PRPP synthetase in isolated rat hepatocytes is discussed.

Adenosine Triphosphate↗

Postoperative myocardial infarction documented by technetium pyrophosphate scan using single-photon emission computed tomography: significance of intraoperative myocardial ischemia and hemodynamic control.

The aim of this prospective study was to document postoperative myocardial infarction (PMI) by technetium pyrophosphate scan using single-photon emission computed tomography (TcPPi-SPECT) in 28 patients undergoing elective coronary bypass grafting (CABG). The relationships of intraoperative electrocardiographic myocardial ischemia, hemodynamic responses, and pharmacological requirements to this incidence of PMI were correlated. Radionuclide cardioangiography and TcPPi-SPECT were performed 24 h preoperatively and 48 h postoperatively. A standard high-dose fentanyl anesthetic protocol was used. Twenty-five percent of elective CABG patients were complicated with PMI, as documented by TcPPi-SPECT with an infarcted mass of 38.0 +/- 5.5 g. No significant difference in demographic, preoperative right and left ventricular function, number of coronary vessels grafted, or aortic cross-clamp time was observed between the PMI and non-PMI groups. The distribution of patients using preoperative beta-adrenergic blocking drugs or calcium channel blocking drugs was found to have no correlation with the outcome of PMI. As well, no significant differences in hemodynamic changes or pharmacological requirements were observed in the PMI and non-PMI groups during prebypass or postbypass periods, indicating careful intraoperative control of hemodynamic indices did not prevent the outcome of PMI in these patients. However, the incidence of prebypass ischemia was 39.3% and significantly correlated with the outcome of positive TcPPi-SPECT, denoting a 3.9-fold increased risk of developing PMI. Prebypass ischemic changes in leads II and V5 were shown to correlate with increased CPK-MB release (P less than 0.05) and tends to occur more frequently with lateral myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗

A destructive calcium pyrophosphate dihydrate deposition disease of the temporomandibular joint.

A case of calcium pyrophosphate dihydrate (CPPD) crystal deposition arthropathy of the temporomandibular joint is reported. The patient presented a 10-year history of swelling and pain of the left preauricular region. Magnetic resonance imaging showed a calcified mass filling the joint space and destroying the roof of the joint. Radiographs showed chondrocalcinosis of other joints. The authors discuss the diagnosis of this arthropathy and the reason why the temporomandibular joint is more affected than the other joints in the patient reported.

Calcium Pyrophosphate↗

Calcium pyrophosphate dihydrate crystal deposition and other crystal deposition diseases.

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease continues to be of intense clinical and basic science interest. Follow-up of studies of hereditary CPPD crystal deposition indicate differences from the common sporadic disease. The results of a prospective study of CPPD crystal deposition arthropathy confirm that clinical symptoms appear to be independent of radiologic progression. Novel clinical presentations include association with pregnancy and simulation of meningitis. CPPD crystal deposition pathology in synovium ultrastructurally resembles that in cartilage. Factors such as the presence of ATP can induce experimental calcifications in tissue culture that resemble CPPD crystal deposition. Interleukin-8 and tyrosine phosphorylation of neutrophil protons can mediate CPPD crystal deposition-associated inflammation. The control of crystal function and dissolution recently has been the subject of many general reviews. The theory outlined in these papers is important for understanding CPPD crystal deposition and basic phosphate crystal formation and dissolution.

Arthritis, Gouty↗

Tc-99m-pyrophosphate accumulation on prosthetic valves.

Tc-99m-stannous pyrophosphate myocardial imaging has been one of the most effective and sensitive procedures for detection of acute myocardial infarction since Bonte et al introduced it in 1974. However, many causes of false-positive studies have also been reported since then. Presented here is an abnormal case of a patient with aortic and mitral valve replacement.

Aortic Valve↗

"Doughnut" technetium pyrophosphate myocardial scintigrams. A marker of severe left ventricular dysfunction.

The "doughnut" pattern on Tc-99m pyrophosphate (PPi) myocardial scintigraphy is characterized by a border of tracer uptake surrounding a central zone of relatively decreased activity. This pattern is generally associated with large transmural anterior myocardial infarcts (MI) caused by occlusion or critical stenosis of the left anterior descending coronary artery. Such infarcts typically involve a significant portion of the anterior wall and are associated with a complicated clinical course and poor prognosis. In order to evaluate the relationship between the presence of the doughnut pattern and left ventricular (LV) function, radionuclide ventriculography was performed within 15 days after infarction in 58 patients with transmural anterior MI. In patients without previous MI, 15/38 (39.5%) had doughnut scintigrams. These patients demonstrated significant reductions in LV ejection fraction (EF) (28 +/- 10% versus 45 +/- 12%, P less than 0.001) and normalized LV wall motion scores (29 +/- 11% versus 61 +/- 10%, P less than 0.001) when compared with patients with "nondoughnut" scintigrams. Patients with doughnut scintigrams had a significantly greater incidence of severe septal hypokinesis (P less than 0.001) and apical dyskinesis (P less than 0.03). LV end-systolic volumes were also larger in the patients with doughnut scintigrams (73 +/- 32 ml versus 40 +/- 17 mI/M2, P less than 0.005). In contrast, there was no significant difference in LVEF, normalized LV wall motion score, or LV volumes between doughnut and nondoughnut groups in patients with previous MI.

Diphosphates↗

Comparison of technetium-99m pyrophosphate and technetium-99m methylene diphosphonate with variable amounts of stannous chloride in the detection of acute myocardial infarction.

The authors prospectively compared the ability of Tc-99m pyrophosphate (PYP) and Tc-99m methylene diphosphonate (MDP) to detect acute myocardial infarctions. The agents used were PYP (12 mg) with 3.4 mg of stannous chloride, MDP (10 mg) with 1.0 mg of stannous chloride, and MDP (10 mg) with 3.4 mg of stannous chloride. Imaging was performed on three consecutive days on 34 patients with proven myocardial infarctions, using the same agent on the first and third days of the study and an alternate agent on the second day. Agents were assigned randomly to each of six groups of patients. First images were obtained an average of 3.7 days (range, one to six days) following myocardial infarction. Seventeen of 23 patients (75%) had images positive for acute myocardial infarction with Tc-99m PYP, whereas only two of 21 patients (9.5%) had positive studies with Tc-99m MDP with 3.4 mg of stannous chloride and one of 24 patients (4.2%) had positive studies with Tc-99m MDP and 1.0 mg of stannous chloride. All three myocardial infarctions detected by Tc-99m MDP were extensive and transmural. When MDP and PYP were both positive in the same patient, the apparent size of the myocardial infarction was much smaller with the MDP. It is concluded that MDP can detect only large myocardial infarctions, has poor localization in the infarcted tissue, and varying the stannous chloride content of the preparation does not improve the ability of MDP to detect acute myocardial infarctions.

Adult↗

Technetium-99m pyrophosphate scintigraphy for the detection of acute myocardial infarction. How useful is it?

To evaluate the contribution of Tc-99m pyrophosphate scintigraphy (TPS) on the overall management of patients suspected of having acute myocardial infarction (AMI), hospital records of 58 consecutive patients who underwent TPS, were evaluated in depth. The results indicate that TPS was essential for the diagnosis of AMI in 16% of the patients. TPS was most rewarding in perioperative patients and in patients with borderline or uninterpretable electrocardiographic and enzyme changes. Also, in some cases, TPS was able to confirm or exclude the diagnosis of AMI prior to the confirmation by serial electrocardiograms (ECG) and serial enzyme changes. TPS was less rewarding in patients with clinically low index of suspicion for AMI. It may also be confusing in patients with high clinical likelihood of AMI and a history of prior myocardial infarction because of the possibility of persistently positive TPS in some of these patients. Considering the limitations of ECGs, the cardiac enzymes, and atypical clinical presentations in the patient population we evaluated, TPS appears to be fairly accurate when the scintigraphic findings are compared with the final diagnosis at the time of discharge from the hospital.

Aged↗

Sequential uptake patterns of technetium-99m pyrophosphate in hepatoma.

Sequential liver scintiphotography with Tc-99m pyrophosphate (PYP) was used to prospectively evaluate its uptake patterns in hepatoma. The scintiphotos and time-activity curves of 40 cases were analyzed. Two distinct patterns of tumor activity were noted: gradual but complete extraction and trapping of Tc-99m PYP in hepatoma in 38% of the patients (group 1), and absence of subsequent Tc-99m PYP uptake in hepatoma after initial blood pool activity in 62% of the patients (group 2). Since extraction and trapping of Tc-99m PYP occur approximately in two fifths of the patients with hepatoma, we conclude that Tc-99m PYP liver scintigraphy is not worthwhile supplementing the conventional radionuclide studies for diagnosing hepatoma, even in the selected patients in the countries where the prevalence of hepatoma is high.

Carcinoma, Hepatocellular↗

Myocardial infarct imaging in patients with technetium-99m 2,3-dimercaptosuccinic acid. Superiority of technetium-99m pyrophosphate.

Technetium-99m 2,3-dimercaptosuccinic acid (Tc-99m DMSA) has been used successfully for imaging acute myocardial infarction in a canine model. The application in humans, however, has not been previously reported. In order to determine the feasibility of using this agent in clinical studies and to compare the agent to technetium-99m pyrophosphate (Tc-99m PPi), ten patients with proven myocardial infarction were studied. While imaging of transmural infarctions in humans was achieved using Tc-99m DMSA, scores for the Tc-99m DMSA images (1.8 +/- 0.96) were not as high as for Tc-99m PPi (2.5 +/- 0.45) (P less than 0.05). Discordance among four independent interpreters was greater for images obtained with Tc-99m DMSA. The superiority of Tc-99m PPi was evident whether images were obtained early (within 24 hours) or late (within five days). Although DMSA images were not obscured by rib uptake, they were less sensitive (63%) than Tc-99m PPi (97%). A potential advantage of Tc-99m DMSA in imaging acute myocardial infarction is that radiotracer concentration in the infarct occurs primarily in the early postinfarction period. The longer postinfarction that Tc-99m DMSA imaging was attempted, the lower the concentration of radiotracer. Thus, Tc-99m DMSA would not be expected to have the same persistence pattern as Tc-99m PPi into the remote postinfarction period. The persistent positivity of Tc-99m PPi has made it difficult to diagnose reinfarction.

Aged↗

"Window on the heart" technique for diagnosis of recent myocardial infarction using Tc-99m pyrophosphate SPECT subtraction imaging.

Detection of acute myocardial infarction by SPECT with Tc-99m pyrophosphate is complicated by overlying bony structures, such as the ribs and sternum. The authors report a technique using volume rendered rotating SPECT images with digital subtraction of overlying ribs. The technique is described and illustrated by case reports in which the diagnostic accuracy was improved with its use. This technique has diagnostic use in difficult clinical cases, and where avid radiotracer uptake in the ribs or sternum obscures the underlying myocardium.

Female↗

Usefulness of dual SPECT with Tc-99m pyrophosphate and Tl-201 to predict further events after acute myocardial infarction with single-vessel coronary artery disease.

PURPOSE: This study was undertaken to determine whether the findings of dual SPECT with Tc-99m pyrophosphate (PYP) and Tl-201 were predictive of further cardiac events after acute myocardial infarction. METHODS: The authors evaluated 88 patients with acute myocardial infarction who underwent dual SPECT for single-vessel coronary artery disease. RESULTS: Twenty-nine patients showed overlapping of Tc-99m PYP and Tl-201 in the same location (overlap-positive group), and 59 patients had no overlap (overlap-negative group). In patients in the overlap-positive group, the incidence of subsequent events was significantly higher than in patients in the overlap-negative group (P < 0.001). In the overlap-positive group, the number of overlap segments in patients with further events was significantly greater than that in patients without further events (P < 0.005). CONCLUSIONS: Areas with overlapping of Tc-99m PYP and Tl-201 may contain jeopardized myocardium. These results suggest that patients who have a Tc-99m PYP and Tl-201 overlap-negative scan are a low risk group, whereas patients who have more overlapping segments may require catheterization and revascularization. Thus simultaneous SPECT imaging with Tc-99m PYP and Tl-201 might be useful to identify patients with greater ischemic risk after acute myocardial infarction.

Aged↗

Assessment of tissue viability in complex extremity injuries: utility of the pyrophosphate nuclear scan.

BACKGROUND: Extensive extremity injuries often require difficult decisions regarding the necessity for amputation or radical debridement. During the past decade, we have used technetium-99 pyrophosphate (PyP) scanning as an adjunct in this setting. This study was performed to assess the accuracy of PyP scan in predicting the need for amputation in relation to clinical, operative, and pathologic findings. METHODS: Review of our computerized registry identified 11 patients (10 men, age 36.1 +/- 14.9 years) admitted from 1990 to 1999 who underwent PyP scan. Using operative and pathologic findings, accuracy of the PyP scan was graded as supporting or refuting the clinical assessment of the need for amputation. RESULTS: Eight patients suffered high-voltage electrical injuries, one had severe frostbite, and two suffered soft-tissue infections. In most cases, PyP scan showed clear demarcation of viable and nonviable tissue, verifying the need for amputation (positive); those that demonstrated viable distal tissues confirmed at operation were considered negative. PyP scan had a sensitivity of 94%, a specificity of 100%, and an accuracy of 96% in this setting. CONCLUSION: Technetium-99 PyP scanning is a useful adjunct in predicting the need for amputation in extremities damaged by electrical injury, frostbite, or invasive infection. In addition, by providing an objective "picture" of extremity perfusion, PyP scans can be helpful in convincing patients of the need for amputation.

Adolescent↗