Biomedical subjects
Publications and source records attributed to M A Patel.
Aortoesophageal fistula due to an aortic arch aneurysm is a rare entity with an extremely high mortality. There are few reports of successfully managed cases and even fewer of long term survival. We report a case of an aortoesophageal fistula resulting from a mycotic pseudoaneurysm of the distal aortic arch in a patient with melioidosis, its surgical management, and outcome.
Inadequate myocardial protection continues to be encountered despite improved methods of cardioplegia delivery. Although myocardial temperature is commonly monitored to assess the adequacy of cardioplegia delivery, its relationship to the metabolic status of the myocardium has not been investigated. We prospectively reviewed patients who underwent valvular heart surgery with blood (n = 47) or crystalloid (n = 48) cardioplegia and continuous measurement of intraoperative myocardial tissue pH and temperature. We previously demonstrated a high correlation (r = 0.99) between extracellular myocardial pH, levels of intracellular hydrogen ion concentration, and a lowering of tissue ATP during coronary occlusion. Clinically, optimal metabolic protection was defined as the absence of myocardial tissue acidosis during the period of aortic occlusion as quantified by a temperature-corrected integrated mean pH of 6.8 or greater, which has been shown to be predictive of a favorable postoperative outcome. Age, bypass time, myocardial temperature, myocardial tissue pH at the onset of aortic occlusion, cross-clamp time, and volume of cardioplegia were not significantly different between blood and crystalloid groups. Linear regression analysis demonstrated no significant correlation between mean myocardial tissue pH and the corresponding mean myocardial temperature in either group during aortic occlusion. There was also no correlation between the mean myocardial tissue pH and volume of cardioplegia delivered in both groups. These data demonstrate wide intercardiac and intracardiac variability in the degree of regional tissue acidosis encountered during of hypothermic cardioplegia. Cardioplegia delivery guided by measurement of myocardial temperature or by standardized protocol did not prevent the occurrence of tissue acidosis and thus, did not ensure optimal metabolic protection of the heart. In 95 patients undergoing valvular heart surgery with cold blood or crystalloid cardioplegia, there was no correlation between myocardial tissue pH and mycardial temperature or between myocardial tissue pH and volume of cardioplegia administered. Temperature is a poor indicator of the metabolic state of the myocardium.
OBJECTIVE: To compare a second-generation thoracic electrical bioimpedance (TEB) hemodynamic monitoring system with the clinically used pulmonary artery catheter thermodilution (TD-PAC) system. DESIGN: Blinded, simultaneous measurements at specified key time points during surgery. SETTING: University teaching hospital cardiac surgical operating rooms. PARTICIPANTS: Forty-seven patients undergoing primary elective coronary artery bypass surgery. INTERVENTIONS: Timed cardiac output measurements by thermodilution and continuous monitoring of bioimpedance were performed. MEASUREMENTS AND MAIN RESULTS: Cardiac index (TEB and TD-PAC) and other hemodynamic parameters were measured at 4 time points: (1) after anesthesia induction, (2) with the mediastinum open, (3) immediately after cardiopulmonary bypass, and (4) at the end of the case. Pearson's correlation and Bland-Altman analysis were carried out. Cardiac index by TEB and TD-PAC had an overall correlation of r = 0.71 (p < 0.0001). The Bland-Altman statistics showed a mean difference of -0.28 L/min/m2 and precision of 0.67 L/min/m2. The best correlation was at time 1, and the lowest correlation was at time 4. Mediastinal opening and cardiopulmonary bypass had little or no effect on the correlation between technologies. CONCLUSION: TEB reporting of cardiac index during coronary artery surgery generally agreed with TD-PAC cardiac index except at the end of the case (time 4).
Reduced factor XIIIA levels and decreased clot strength have been associated with increased bleeding after cardiopulmonary bypass (CPB). The purpose of this study was to evaluate the relationship between hemostatic factors, including factor XIIIA, and clot strength before, during and after CPB. Factor XIIIA antigen, platelet counts, fibrinogen, factor V activity, tissue plasminogen activator and clot strength (by thromboelastograph) were measured at baseline, after 45 min of CPB, at the end of CPB and 4 h post-operatively in 34 patients. Baseline factor XIIIA antigen was 5.2 +/- 1.4 mg/l. On average, factor XIIIA levels dropped to 64% and clot strength to 77% of baseline values after 45 min on CPB and remained below baseline during the immediate post-operative period. Clot strength was significantly correlated (r = 0.81) with platelet count and fibrinogen but not plasma factor XIIIA levels. Addition of 10 mg/l recombinant factor XIII[a2] significantly increased clot strength. Postoperative bleeding at 2 h was inversely correlated with platelet count, factor XIIIA antigen and clot strength measured at the end of CPB. Maintenance of adequate platelet counts and factor XIIIA levels at the end of CPB may play a role in maintaining clot strength and reducing blood loss.
OBJECTIVE: To determine the effects of hemofiltration on serum aprotinin levels during cardiopulmonary bypass (CPB) surgery. DESIGN: Prospective, randomized study. SETTING: University of Washington Medical Center, single institution. PARTICIPANTS: Patients undergoing cardiac surgery without contraindications to aprotinin administration. INTERVENTIONS: Patients were randomized to full-Hammersmith and half-Hammersmith dosing regimens of aprotinin and were further randomized to hemofiltration or no hemofiltration. MEASUREMENTS AND MAIN RESULTS: Serum aprotinin levels were studied before CPB, 60 and 120 minutes into CPB, and at the end of CPB before protamine administration. Each group experienced a decrease in serum aprotinin levels with the institution of CPB, attributable to hemodilution and redistribution of aprotinin outside of the vascular compartment. During CPB, aprotinin levels declined further, but no significant difference was observed between patients who received hemofiltration and those who did not. Hematocrit values were significantly higher at the end of CPB in the hemofiltration groups. Patients receiving half-Hammersmith dosing regimens maintained aprotinin levels throughout CPB, which have been shown to inhibit plasmin but were lower than levels previously shown to inhibit kallikrein. CONCLUSIONS: Hemofiltration during CPB did not significantly alter serum aprotinin levels in patients receiving half-Hammersmith and full-Hammersmith dosing regimens of aprotinin.
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The enzyme 3-deoxy-D-manno-octulosonic acid 8-phosphate synthase (EC 4.1. 2.16) (KDO 8-P synthase) that catalyzes the condensation of D-arabinose 5-phosphate (A 5-P) with phosphoenolpyruvate (PEP) to give 3-deoxy-D-manno-octulosonic acid 8-phosphate (KDO 8-P) and inorganic phosphate (Pi) was inactivated by the thiol-modifying reagents 5,5-dithiobis (2-nitrobenzoate) (DTNB) and methyl methanethiosulfonate (MMTS). Reaction of cloned native KDO 8-P synthase with DTNB correlated with modification of two of the four cysteine sulfhydryls per monomer of enzyme and total loss of enzymatic activity which could be partially restored by treatment with dithiothreitol (DTT). Cyanolysis of the DTNB-inactivated enzyme with KCN led to the elimination of 2 equiv of 5-thio-2-nitrobenzoate and partial recovery of activity. The presence of either substrate(s) or product(s) provided no protection against inactivation nor affected the number of cysteines modified, indicating that the cysteines modified are most likely not at the active site of KDO 8-P synthase. Titration of denatured enzyme with DTNB resulted in the modification of all four cysteines. After treatment of native enzyme with MMTS, no cysteines could be titrated with DTNB and no enzymatic activity could be detected. Treatment of the MMTS-inactivated KDO 8-P synthase with DTT resulted in restoration of enzymatic activity and the presence of two DTNB-titratable cysteine residues. Based on these observations and a report that KDO 8-P synthase is inactivated in a time-dependent manner with 3-bromopyruvate and that the substrate PEP protects against this inactivation, all four cysteines (38, 166, 206, and 249) were individually mutated to alanines via a modified PCR methodology. The C206A and C249A mutants were both enzymatically active with K(m) and Vmax values approximately identical to those of wild-type KDO 8-P synthase, and both native mutants reacted with DTNB to modify only one of the three remaining cysteine sulfhydryls per monomer of enzyme. Titration of denatured C206A and C249A mutants resulted in the modification of three cysteines. The C38A and C166A mutants were both for the most part enzymatically inactive. Titration of native C38A and C166A with DTNB resulted in modification of two cysteines while titration of the denatured mutant protein resulted in modification of the three remaining cysteines. Circular dichroism measurements of wild-type KDO 8-P synthase and the four C --> A mutants indicate modest but significant changes in the structure of the mutants. These results indicate that C206 and C249 in native KDO 8-P synthase are readily accessible to the modification reagent DTNB and therefore inactivation may result from structural changes in the DTNB-modified KDO 8-P synthase or blockage of access of substrates to the active site. The C38 and C166 in native KDO 8-P synthase are inaccessible to the modification reagent DTNB, indicating that they are located in the interior of KDO 8-P synthase, and loss of activity in the C38A and C166A mutants suggests their essentiality in the KDO 8-P synthase reaction.
BACKGROUND: To reevaluate the sensitivity of impedance plethysmography (IPG) for proximal deep vein thrombosis (DVT) and to establish a relationship between the location and size of thrombi and the results of IPG. DESIGN: Prospective cohort study. METHODS: One hundred thirty-two consecutive patients with clinically suspected DVT underwent IPG testing and most (n = 118) underwent contrast-enhanced venography; in 14 patients, venous ultrasonography was performed and demonstrated definitive proximal DVT in which the size and extent of the thrombus could be delineated. All patients with dubious or normal ultrasound results underwent contrast-enhanced venography. All tests were performed and test results were interpreted without knowledge of the results of the other tests. Patients were considered to have proximal DVT if this was demonstrated on venography or ultrasound, calf DVT if this was demonstrated on venography, or no DVT if venography yielded normal findings. The sensitivity and specificity of IPG for DVT were calculated. RESULTS: Of the 132 patients, 40 (30%) had proximal DVT, seven (5%) had calf DVT, and 85 (64%) had no DVT. The sensitivity of IPG for proximal DVT was 65% and the specificity was 93%. Of the proximal vein thrombi, IPG detected three (23%) of 13 that involved the popliteal vein but not the superficial femoral vein and 23 (85%) of 27 proximal vein thrombi that involved the superficial femoral vein. CONCLUSIONS: Our study demonstrated that the sensitivity of IPG for proximal DVT at our center is only 65%, a figure that is much lower than those reported in earlier studies from our institution. We hypothesize that because of a change in referral practice, an increased proportion of patients with less severe symptoms are now referred to our center than in the past. These patients have thrombi that are smaller, less likely to be occlusive, and therefore less likely to yield abnormal IPG findings.
This prospective study was designed to determine whether use of nonwashed shed mediastinal blood exacerbated platelet and related hematologic dysfunctions after cardiopulmonary bypass, compared with the alternative use of autologous and homologous standard liquid preserved blood for volume support. Thirty-two patients undergoing cardiopulmonary bypass for open heart operations were randomized to receive either nonwashed shed mediastinal blood (group 1; n = 16) or liquid preserved packed red blood cells (group 2; n = 16) for transfusion therapy in the management of postoperative bleeding. Patient blood samples and bleeding times were obtained preoperatively, after cardiopulmonary bypass but before transfusions, 2 and 24 hours after transfusion, and on postoperative days 2, 3, and 7. Group 1 patients received an average of 710 +/- 90 mL (range, 300 to 1,700 mL) of nonwashed shed mediastinal blood containing significantly greater (p < 0.0001) amounts of fibrin degradation products and D-dimer protein. Of the hematologic, microaggregate, and plasma protein measurements performed, only the protein C level was significantly greater in group 1 (p < 0.05) after transfusion. Patient bleeding times were not significantly different between the groups at any of the time points, and the total postoperative blood loss was not different between the groups. There was a trend toward less need for homologous transfusion in group 1 (p < 0.1). This study documents the safety and ease of using nonwashed shed mediastinal blood as a primary blood volume support after an open heart operation.
To determine the ability of extracellular myocardial tissue pH measured with an intramural electrode to reflect myocardial intracellular metabolic status during normothermic ischemia, we studied 14 open-chest dogs with in vivo phosphorus 31-nuclear magnetic resonance spectroscopy during left anterior descending coronary artery occlusion (experimental group, group I, n = 7) or after a sham operation (control group, nonischemic, group II, n = 7). Phosphorus nuclear magnetic resonance spectra were acquired every 5 minutes at 4.7 tesla (256 averages, TR = 1000 msec, pulse width = 30 microseconds) with a 2 cm two-turn radiofrequency surface coil. Intracellular myocardial adenosine triphosphate peak area was normalized to an external phosphate standard. The change in adenosine triphosphate peak area was expressed as percent of baseline value. During 3 hours of normothermic ischemia the observed extracellular myocardial pH correlated with nuclear magnetic resonance-calculated myocardial pH in the ischemic dogs with an average r value of 0.94 (p less than 0.0001). During this same interval, the fall in extracellular myocardial pH correlated with the loss of adenosine triphosphate peak in each ischemic dog, with an average r value of 0.91 (p less than 0.0001). Thus extracellular myocardial pH, measured with an intramural electrode, correlated with nuclear magnetic resonance-derived myocardial pH and loss of myocyte adenosine triphosphate peak content and reflected the metabolic status of the myocyte during ischemia. These data validate the use of extracellular myocardial pH to assess the adequacy of myocardial preservation during aortic crossclamping for cardiac operations.
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A spectrophotometric determination of isoniazid in the presence of its hydrazones was developed. The method involves the reaction between isoniazid and 2,3-dichloro-1,4-naphthoquinone in the presence of ammonia in an ethanolic medium. The colored product has an absorbance maxium at 640 nm. The Lambert-Beer law is obeyed in the 1--14-microgram/ml range. The proposed method was applied to the analysis of isoniazid tablets. In commercial tablets, hydrazone formation due to the reaction between isoniazid and lactose was detected by TLC. The analysis of lactose-containing isoniazid tablets showed 10--22% lower recovery than that obtained by the official method. Hydrazone formation in tablets probably interferes with isoniazid bioavailability.
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