Real-time visualization of PH domain-dependent translocation of phospholipase C-delta1 in renal epithelial cells (MDCK): response to hypo-osmotic stress

BACKGROUND: The aim of this study was to compare the prognostic efficacy of cardiac troponin T (cTnT) and I (cTnI) in patients with clinical unstable angina. METHODS: We studied 74 patients with chest pain at rest, electrocardiographic evidence of myocardial ischemia, and normal (<6.7 ng/mL) values of creatine kinase-MB. cTnT was measured with a commercial assay (cutoff level 0.1 ng/mL) and cTnI with a preliminary research application (cutoff level 3.1 ng/mL). All patients had blood drawn at baseline and 8 hours thereafter. The prospectively defined end point was the proportion of patients identified by each assay as having myocardial damage. RESULTS: cTnT and cTnI were elevated in the same percentage of patients (18 of 74; 24%). Overall, 23 patients had elevations of 1 or both markers. In 13 there were elevations of both. Ten patients had elevations of only one (5 for each marker). In 51 patients, no elevations were present. Death or nonfatal myocardial infarction was more frequent in patients with elevated cTnI (27.7% vs 5.3%; P =.02) than those with normal values. The prognostic influence of cTnT was less (17% vs 8.5%; P =.2). However, the difference between the 2 markers when compared directly was not statistically significant (27.7% vs 17%; P = NS). CONCLUSIONS: These data indicate that both markers identify myocardial damage in equal numbers of patients with clinical unstable angina. Patients with elevations had a worse short-term outcome. The significance of the minor differences in prognostic value will require additional studies.     

Thoracic trauma

Blunt chest trauma is the leading cause of thoracic injuries in Germany, penetrating chest injuries are rare. Hereby, single or multiple rib fractures, hemato-pneumothorax and pulmonary contusion represent the most common injuries. The early management of thoracic injuries consists of detection and sufficient therapy of acute life threatening situations like tension pneumothorax, acute respiratory insufficiency or severe intrathoracic bleeding. Most of the isolated thoracic injuries are adequately treated by conservative means, sufficient analgesia, drainage of intrapleural air or blood, physiotherapy and clearance of bronchial secretions provided; operative intervention is rarely indicated. In multiple injured patients however, severe blunt chest trauma and especially pulmonary contusion negatively affects outcome with a significant increase of morbidity and mortality. Hence, patients with this combination of pulmonary injuries, such as lung contusion and associated severe injuries, carry a particular high risk of respiratory failure, ARDS and MOF with a considerable mortality. Therefore, early exact diagnosis of all thoracic injuries is essential and can be achieved by thoracic computed tomography, which becomes more and more popular in this setting. Early intubation and PEEP-ventilation, alternate prone and supine positioning of multiple injured patients with lung contusion and differentiated concepts of volume- and catecholamine therapy represent the basic therapeutic principles. Additionally, the entire early trauma management of multiple injured patients must focus on the presence of pulmonary contusion. Every additional burden on their pulmonary microvascular system like microembolisation during femoral nailing, the trauma burden of extended surgery or mediator release in septic states may cause rapid decompensation and organ failure and therefore, has to be avoided.     

Concentration time courses of troponin and myosin subunits after acute myocardial infarction

BACKGROUND: As a result of the limited sensitivity and specificity of creatine kinase and lactate dehydrogenase (LDH) as well as their isoenzymes, there is increasing interest in the use of cardiac contractile proteins for the diagnosis of acute myocardial infarction (AMI) and myocardial damage. METHODS: This study compared the release of creatine kinase, creatine kinase MB, myoglobin, cardiac troponin I (cTnI), cardiac troponin T (cTnT), cardiac myosin light chain-1 (cMLC-1), and beta-type myosin heavy chains (bMHC) in serial blood samples from 13 patients (10 men, three women; median age 54 years, range 40-74 years) with first-time AMI (11 Q-wave, two non-Q-wave AMI; three anterior and 10 inferior wall AMI). All but one patient received intravenous thrombolytic treatment. RESULTS: Myoglobin was the first marker to increase in blood after AMI and showed the earliest peak levels, whereas bMHC increased latest, showing the latest peak levels. cTnI and cTnT increased significantly earlier than cMLC-1 and bMHC. cTnI and cTnT increased and reached peak levels parallel to each other, but the latter tended to stay increased longer. cTnT time courses were biphasic in the majority of AMI patients, unlike cTnI time courses. cMLC-1 release was mostly biphasic. cMLC-1 allows diagnosis during the acute phase as well as several days after the onset of AMI. The time courses of bMHC were usually monophasic. Its delayed appearance makes it useful for the diagnosis of remote infarction. In contrast to cTnI and cTnT, cMLC-1 and bMHC time courses were not significantly influenced by early reperfusion. CONCLUSION: Our results demonstrate the impact of the intracellular compartmentation of an intramyocardial protein (cytosolic, structurally bound, or structurally bound with soluble pool) on its concentration time course after AMI, particularly on the rapidity of its release.     

Different intracellular compartmentations of cardiac troponins and myosin heavy chains: a causal connection to their different early release after myocardial damage

We investigated the net myocardial release of creatine kinase isoenzyme MB (CKMB), myoglobin, cardiac troponin T (cTnT), cardiac troponin I (cTnI), and cardiac beta-type myosin heavy chain (beta-MHC) into the coronary circulation after cardioplegic cardiac arrest in humans. Cardiac markers were measured in paired arterial, central venous, and coronary sinus blood in 19 patients undergoing elective coronary artery bypass grafting (CABG) before aortic cross-clamping and 1, 5, 10, and 20 min after aortic declamping. cTnT and cTnI were released into the coronary sinus in parallel to each other and almost simultaneously to myoglobin and CKMB within 20 min of reperfusion. In contrast, no beta-MHC was released in the same patients during the study period. The average soluble cTnT and cTnI pools in right atrial appendages of 11 patients with right atrial and right ventricular pressures within reference values were comparable and were approximately 8% of total myocardial troponin content. The soluble beta-MHC pool was <0.1% in all patients. Our results demonstrate the impact of the different intracellular compartmention of regulatory and contractile proteins on their early release from damaged myocardium.     

An evaluation of serum troponin T and signal-averaged electrocardiography in predicting electrocardiographic abnormalities after blunt chest trauma

OBJECTIVE: Despite multiple inquiries, there are no available tests to definitively detect blunt myocardial injury. The evaluation of patients with chest wall injuries without other indications for intensive care unit (ICU) admission has ranged from a single emergency department electrocardiogram (ECG) to 72 hours of continuous electrocardiographic monitoring. Recently, signal-averaged ECG and serum cardiac troponin T have demonstrated clinical utility in the evaluation of ischemic heart disease. The purpose of this study is to determine the ability of these diagnostic tests to predict the occurrence of significant electrocardiographic rhythm disturbances for patients with chest wall injuries and no other indication for ICU admission. METHODS: We prospectively evaluated 71 consecutive adult patients admitted to a regional Level I trauma center with chest wall injuries not requiring ICU admission. We obtained admission signal-averaged ECG, serum troponin T level, standard ECG, and creatine phosphokinase (CPK-MB) level. Patients received continuous electrocardiographic monitoring, follow-up 12-lead electrocardiography, and serial monitoring of troponin and CPK-MB. Echocardiography was performed for patients with abnormal CPK-MB levels. Electrocardiographic events were graded as normal, abnormal but clinically insignificant, or clinically significant. Multiple stepwise logistic regression analysis was used to evaluate predictors for the development of clinically significant electrocardiographic events. RESULTS: On admission, 17 of 71 patients (23.9%) had normal sinus rhythm; 13 (18.3%) had a clinically significant finding. For 50 patients, follow-up ECG was abnormal; for 26, the findings were clinically significant. Of 17 patients with normal initial ECGs, 7 (41%) developed a clinically significant abnormality. Six patients received intervention for ECG findings. Eleven of 71 patients (16%) had positive troponin T; 5 of 71 (7%) had positive CPK-MB; 15 of 71 (21%) had positive signal-averaged ECG; and 4 of 13 had positive echocardiograms. Initial electrocardiographic abnormalities and a troponin T level > 0.20 microg/L were the only variables found to predict clinically significant electrocardiographic events. Sensitivity and specificity of troponin T in predicting clinically significant abnormalities were 27 and 91%, respectively. CONCLUSIONS: 1. The best predictors for the development of significant electrocardiographic changes are an admission ECG abnormality and an elevated serum troponin T level. 2. Both tests have high specificity with low to moderate sensitivity. 3. Patients with normal ECGs may develop clinically significant events. 4. CPK-MB and echocardiograms continue to be poor predictors of significant electrocardiographic events.     

Determination of cardiac troponin I forms in the blood of patients with acute myocardial infarction and patients receiving crystalloid or cold blood cardioplegia

To determine the forms of cardiac troponin I (cTnI) circulating in the bloodstream of patients with acute myocardial infarction (AMI) and patients receiving a cardioplegia during heart surgery, we developed three immunoenzymatic sandwich assays. The first assay involves the combination of two monoclonal antibodies (mAbs) specific for human cTnI. The second assay involves the combination of a mAb specific for troponin C (TnC) and an anti-cTnI mAb. The third assay was a combination of a mAb specific for human cardiac troponin T (cTnT) and an anti-cTnI mAb. Fifteen serum samples from patients with AMI, 10 serum samples from patients receiving crystalloid cardioplegia during heart surgery, and 10 serum samples from patients receiving cold blood cardioplegia during heart surgery were assayed by the three two-site immunoassays. We confirmed that cTnI circulates not only in free form but also complexed with the other troponin components (TnC and cTnT). We showed that the predominant form in blood is the cTnI-TnC binary complex (IC). Free cTnI, the cTnI-cTnT binary complex, and the cTnT-cTnI-TnC ternary complex were seldom present, and when present, were in small quantities compared with the binary complex IC. Similar results were obtained in both patient populations studied. These observations are essential for the development of new immunoassays with improved clinical sensitivity and for the selection of an appropriate cTnI primary calibrator.     

Value of thoracic computed tomography in the first assessment of severely injured patients with blunt chest trauma: results of a prospective study

OBJECTIVE: The aim of this prospective study was to evaluate whether early thoracic computed tomography (TCT) is superior to routine chest x-ray (CXR) in the diagnostic work-up of blunt thoracic trauma and whether the additional information influences subsequent therapeutic decisions on the early management of severely injured patients. PATIENTS AND METHODS: In a prospective study of 103 consecutive patients with clinical or radiologic signs of chest trauma (94 multiple injured patients with chest trauma, nine patients with isolated chest trauma), an average Injury Severity Score of 30 and an average Abbreviated Injury Scale thorax score of 3, initial CXR and TCT were compared after initial assessment in our emergency department of a Level I trauma center. RESULTS: In 67 patients (65%) TCT detected major chest trauma complications that have been missed on CXR (lung contusion (n = 33), pneumothorax (n = 27), residual pneumothorax after chest tube placement (n = 7), hemothorax (n = 21), displaced chest tube (n = 5), diaphragmatic rupture (n = 2), myocardial rupture (n = 1)). In 11 patients only minor additional pathologic findings (dystelectasis, small pleural effusion) were visualized on TCT, and in 14 patients CXR and TCT showed the same pathologic results. Eleven patients underwent both CXR and TCT without pathologic fundings. The TCT scan was significantly more effective than routine CXR in detecting lung contusions (p < 0.001), pneumothorax (p < 0.005), and hemothorax (p < 0.05). In 42 patients (41%) the additional TCT findings resulted in a change of therapy: chest tube placement, chest tube correction of pneumothoraces or large hemothoraces (n = 31), change in mode of ventilation and respiratory care (n = 14), influence on the management of fracture stabilization (n = 12), laparotomy in cases of diaphragmatic lacerations (n = 2), bronchoscopy for atelectasis (n = 2), exclusion of aortic rupture (n = 2), endotracheal intubation (n = 1), and pericardiocentesis (n = 1). To evaluate the efficacy of all those therapeutic changes after TCT the rates of respiratory failure, adult respiratory distress syndrome, and mortality in the subgroup of patients with Abbreviated Injury Scale thorax score of > 2 were compared with a historical control group, consisting of 84 patients with multiple trauma and with blunt chest trauma Abbreviated Injury Scale thorax score of > 2, prospectively studied between 1986 and 1992. Age (38 vs. 39 years), average Injury Severity Score (33 vs. 38), and the rate of respiratory failure (36 vs. 56%) were not statistically different between the two groups, but the rates of adult respiratory distress syndrome (8 vs. 20%; p < 0.05) and mortality (10 vs. 21%; p < 0.05) were significantly reduced in the TCT group. CONCLUSIONS: TCT is highly sensitive in detecting thoracic injuries after blunt chest trauma and is superior to routine CXR in visualzing lung contusions, pneumothorax, and hemothorax. Early TCT influences therapeutic management in a significant number of patients. We therefore recommend TCT in the initial diagnostic work-up of patients with multiple injuries and with suspected chest trauma because early and exact diagnosis of all thoracic injuries along with sufficient therapeutic consequences may reduce complications and improve outcome of severely injured patients with blunt chest trauma.     

Comparison of myoglobin, creatine kinase-MB, and cardiac troponin I for diagnosis of acute myocardial infarction

Serial plasma concentrations of myoglobin, creatine kinase MB (CK-MB) isoenzyme, and cardiac troponin I (cTnI) were measured in 25 patients with a confirmed diagnosis of acute myocardial infarction (AMI), and 74 patients who were suspected of AMI but were subsequently ruled out for this diagnosis. The cutoff concentration for the cTnI assay was optimally determined to be 2.5 ng/mL. Of the three markers, myoglobin had the highest clinical sensitivity (50 percent) when blood was collected between 0 to 6 h after the onset of chest pain. Assays for all serum markers used had high clinical sensitivity (> 93 percent) 6 to 24 h after onset. The CK-MB remained highly sensitive for 48 h, while cTnI was sensitive for up to 72 h. Between 72 and 150 h, cTnI had a clinical sensitivity of 70 percent as compared to 21 percent and 18 percent for myoglobin and CK-MB, respectively. The clinical specificity of cTnI for non-AMI patients was equivalent to CK-MB and significantly higher than for myoglobin. The clinical efficiency of cTnI for all samples was better than either CK-MB or myoglobin, owing mainly to the wider diagnostic window. The specificity of cTnI for 59 patients with chronic renal failure, skeletal muscle trauma and disease was better than all of these markers including cardiac troponin T (cTnT). Results of this study show that cTnI is an effective marker for the retrospective diagnosis of AMI, and consideration should be given to its use in place of CK-MB.     

Posttraumatic empyema thoracis: a 24-year experience at a major trauma center

The purpose of this paper is to review the outcome of patients with posttraumatic empyema thoracis. Between April 1972 and March 1996, the Division of Cardiothoracic Surgery at the King-Drew Medical Center managed or was consulted on 5,474 trauma patients (4,584 patients with penetrating injuries and 890 with blunt injuries) who were admitted emergently for thoracic and thoracoabdominal injuries and who underwent tube thoracostomy. Patients were not given routine prophylactic antibiotics merely because they had a chest tube placed. Based on our previous reports on thoracic trauma, our criteria for empiric antibiotic administration included (1) emergent or urgent thoracotomy, (2) soft-tissue destruction of the chest wall by shotgun injuries, (3) lung contusion with hemoptysis, (4) associated abdominal trauma requiring exploratory laparotomy, or (5) associated open long-bone fractures. Eighty-seven of these 5,474 patients developed posttraumatic empyema thoracis, for an incidence of 1.6%. These 87 patients were treated with tube thoracostomy, image-guided catheter drainage, or open thoracotomy with decortication. Seventy-nine of 87 patients (91%) were cured without conversion to open thoracostomy. Four patients required conversion to open thoracostomy, and there were three deaths. Even though a majority of our patients required decortication, successful management of posttraumatic empyema thoracis also was achieved with closed-tube thoracostomy or image-guided catheter drainage based on clinical and radiographic findings with appropriate patient selection. When thoracic empyema did occur in our group, Staphylococcus aureus was the most common microbe isolated, followed by anaerobic bacteria. In correlating microbiologic data with outcomes, S. aureus, especially methicillin-resistant S. aureus, was the most frequent cause of antibiotic failure. Because of the low incidence of posttraumatic empyema thoracis, we do not recommend routine antibiotic prophylaxis for all trauma patients who undergo closed-tube thoracostomy. A review of the role of tube thoracostomy, intrapleural fibrinolytic therapy, image-guided catheter drainage, video-assisted thoracoscopy, and open thoracotomy for the management of thoracic empyema is provided.     

Noniatrogenic esophageal trauma

Few guidelines are available with which to facilitate treatment in patients with noniatrogenic injuries of the esophagus. Early diagnosis and proper management are essential if a good outcome is to be expected. In an effort to define better the treatment of patients with penetrating and blunt injuries of the esophagus, we report our recent 5-year experience at an urban trauma center. From July 1988 to June 1993, nineteen patients with esophageal perforations from penetrating (18) and blunt (1) trauma were identified by our trauma registry. There was no mortality in this group of patients and morbidity was mostly due to associated injuries. Eleven cervical esophageal injuries were repaired. One cervical injury was treated by stopping oral intake and giving intravenous antibiotics. The neck was not drained in 10 of the surgical cases. In 1 patient a tracheoesophageal fistula developed, which later was repaired with a pectoralis muscle flap. Seven perforations were identified in the thoracic (2) and abdominal (5) portions of the esophagus. All were due to gunshot wounds. In 4 cases, a fundal wrap was used to reinforce the repairs. Postoperative contrast studies confirmed that all repairs were intact. We conclude that penetrating and blunt tears of the esophagus can be repaired safely with minimal mortality. Morbidity is usually from associated injuries such as to the spinal cord and trachea. When identified early, cervical esophageal injuries do not need to be drained routinely.     

Development of approaches to improve the healing following muscle contusion

Muscle injuries are a challenging problem in traumatology, and the most frequent occurrence in sports medicine. Muscle contusions are among the most common muscle injuries. Although this injury is capable of healing, an incomplete functional recovery often occurs, depending on the severity of the blunt trauma. We have developed an animal model of muscle contusion in mice (high energy blunt trauma) and characterized the muscle's ability to heal following this injury using histology and immunohistochemistry to determine the level of muscle regeneration and the development of scar tissue. We have observed a massive muscle regeneration occurring in the first 2 wk postinjury that is subsequently followed by the development of muscle fibrosis. Based on these observations, we propose that the enhancement of muscle growth and regeneration, as well as the prevention of fibrotic development, could be used as approach(es) to improve the healing of muscle injuries. In fact, we have identified three growth factors (bFGF, IGF-1, and NGF) capable of enhancing myoblast proliferation and differentiation in vitro and improving the healing of the injured muscle in vivo. Furthermore, the ability of adenovirus to mediate direct and ex vivo gene transfer of beta-galactosidase into the injured site opens possibilities of delivering an efficient and persistent expression of these growth factors in the injured muscle. These studies should help in the development of strategies to promote efficient muscle healing with complete functional recovery following muscle contusion.     

Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.     

Inducing effect of dimethy-4, 4''-dimethoxy-5, 6,5'',6-dimethylenedioxybipheny-2, 2''-dicarboxylate (DDB) on differentiation of leukemia HL-60 cells

OBJECTIVE: Myocardial injury is an important cause of mortality and morbidity after paediatric cardiac surgery. Data obtained from studies in animals imply that juvenile myocardium is more resistant to the effects of ischaemia and reperfusion than adult myocardium but there is little confirmatory evidence in the clinical setting. DESIGN: Prospective observational study of biochemical markers of myocardial injury in a paediatric population undergoing cardiac surgery. SETTING: Tertiary referral centre for paediatric cardiac surgery. PATIENTS: Forty patients undergoing paediatric cardiac surgery of varying complexity including closure of atrial and ventricular septal defects and arterial switch for simple transposition. A control group included patients undergoing thoracotomy for closure of a patent ductus arteriosus or repair of a coarctation. INTERVENTIONS: Serial measurements of myoglobin, the MB isoenzyme of creatine kinase (CK-MB), and the highly specific markers of myocardial damage cardiac troponin T (cTnT) and I (cTnI) were made before and 1, 6, 24, and 48 to 72 hours after operation. RESULTS: There were significant increases in myoglobin and CK-MB, but not cTnT or cTnI, in the control group. There were significant increases in the four biochemical markers in all the cardiac operations but especially in the ventricular septal defect and transposition group. Increases in CK-MB and cTnT were about five times greater than those previously reported in adult patients. CONCLUSIONS: (i) Cardiac troponins are more specific markers of myocardial injury in paediatric cardiac surgery than myoglobin and CK-MB. (ii) Paediatric myocardium seems to be more vulnerable to injury during cardiac surgery than adult myocardium.     

Expression of inducible nitric oxide synthase in the brains of scrapie-infected mice

Thoracic trauma in the elderly population constitutes a major challenge for both thoracic and trauma surgeons as their presentation and outcomes differ from the adult population in addition to their high morbidity and mortality. One hundred and one patients, 60 years of age or older, with thoracic trauma were treated at Dicle University School of Medicine during a 6-year period. Eighty-five per cent were male and 15% were female with a mean age of 64.5 years. The cause of thoracic injury was blunt in 77.2% and penetrating in 22.8% of the patients. Sixty-two patients (61.4%) had isolated thoracic injuries. The median Injury Severity Score (ISS) was 23. The morbidity rate was 23.8%. The mortality rate was 16.8%. Seven of 10 patients (70%) who had an ISS greater than 25 died, whereas six of 24 (25%) patients with an ISS between 17 and 25, and four of 67 (5.9%) patients with an ISS less than 16 died. In the elderly the morbidity and mortality rates were higher for blunt trauma compared with penetrating trauma. For ISS greater than 25 the mortality rate was 71.4% for blunt and 66.6% for penetrating trauma. As the morbidity and mortality rate are significantly higher in the elderly patients the approach to these patients should include recognition of their high risk for morbidity and mortality, especially for those who had an ISS greater than 25.     

Prognostic role of troponin T versus troponin I in unstable angina pectoris for cardiac events with meta-analysis comparing published studies

Controversy exists as to the clinical roles and relative specificities of cardiac troponin T or I in patients with unstable angina pectoris (UAP). We measured troponin T and I levels on admission in 123 patients with UAP. Of the 107 patients with normal creatine kinase during the first 24 hours, troponin T and I were elevated in 14 and 13 patients, respectively. At 30 days, 5 of 14 patients (36%) with elevated troponin T and 3 of 93 patients (3.2%) with normal troponin T had acute myocardial infarction (odds ratio [OR], 16.7; 95% confidence interval [CI] 3.4 to 81.5; p <0.001). Of 13 patients with elevated troponin I, 5 patients (39%) and 3 of 94 patients (3.2%) with normal troponin I had acute myocardial infarction (odds ratio, 21.7; 95% CI 4.3 to 110; p <0.001). No deaths occurred within 30 days. Both markers demonstrated equivalent sensitivity (63%) and specificities (troponin T: 91%; troponin I: 92%) for myocardial infarction. Meta-analysis of 12 published troponin T and 9 troponin I studies in patients with UAP produced risk ratios of 4.2 (95% CI 2.7 to 6.4, p <0.001) for troponin I compared with 2.7 (95% CI 2.1 to 3.4, p <0.001) for troponin T. Comparison of the sensitivities and specificities of both markers using summary receiver operating characteristic curves showed no significant difference in their abilities to predict acute myocardial infarction and cardiac death. Troponin T and I show similar prognostic significance for acute myocardial infarction or death in the same patients with UAP. The 2 markers are equally sensitive and specific, as confirmed by meta-analysis, and this supports a role in risk stratification.     

Epitope mapping of anti-troponin I monoclonal antibodies

Two groups of monoclonal antibodies (MAbs) specific to human cardiac troponin I (cTnI) were generated by immunization of mice by isolated cTnI (group I, 16 MAbs) or by the whole troponin complex (group II, 15 MAbs). Two sets of overlapping decapeptides covering the complete sequence of cTnI were prepared and used for epitope mapping by SPOT technique. Majority of MAbs (28 out of 31) interacts with synthetic peptides thus indicating that they recognize liner epitopes. MAbs raised against isolated cTnI preferentially recognize epitopes located at the N- or C-terminal ends of cTnI. Nine out of fifteen MAbs raised against whole troponin complex interact with epitopes located in the N-terminal part of cTnI. Generation of MAbs recognizing both isolated cTnI and cTnI inside of troponin complex and mapping their epitopes provides reliable detection of TnI in serum of patients with acute myocardial infarction.     

Malformations of neocortical development: magnetic resonance imaging correlates

BACKGROUND: The objective of this study was to assess the diagnostic and therapeutic effectiveness of videothoracoscopy in thoracic trauma patients. METHODS: The design was a retrospective review. The setting was a major trauma center at an urban county hospital. Forty-one hemodynamically stable patients sustaining thoracic trauma were reviewed (34 penetrating and 7 blunt injuries). In the acute setting (< 24 h), videothoracoscopy was used for continued bleeding(6) and suspected diaphragmatic injury(17). Thoracoscopy was used in delayed settings (> 24 h) for treatment of thoracic trauma complications(18) including clotted hemothorax(14), persistent air leak(1), widened mediastinum(1), and suspected diaphragmatic injury(2). RESULTS: The average Injury Severity Score (ISS) of these patients was 18.9 +/- 10.0. Three of 6 patients (50%) with continued bleeding were successfully treated thoracoscopically. Nine of 10 (90%) diaphragmatic injuries were confirmed by thoracoscopy, and 7 of these 9 patients (77%) were repaired thoracoscopically. Thirteen of 14 patients (93%) with clotted hemothoraces and one with a persistent air leak were treated successfully using thoracoscopy. An aortic injury was ruled out in one patient. CONCLUSIONS: Videothoracoscopy is a safe, accurate, minimally invasive, and potentially cost-effective method for the diagnosis and therapeutic management of thoracic trauma patients.     

Stepwise subunit interaction changes by mono- and bisphosphorylation of cardiac troponin I

Four phosphorylation degrees of cardiac troponin I (cTnI) have been characterized, namely, a dephospho, a bisphospho, and two monophospho states. Here we describe for the first time a role of the monophosphorylated forms. We have investigated the interaction between the cardiac troponin subunits dependent on the phosphorylation state of cTnI by surface plasmon resonance (SPR) spectroscopy. The monophosphorylated forms were generated by mutating each of the two serine residues, located in human cTnI at positions 22 and 23, to alanine. Association and dissociation rate constants of binary (cTnI-cTnT and cTnI-cTnC) and ternary (cTnI/cTnC complex-cTnT) complexes were determined. Mono- and consecutive bisphosphorylation of cTnI gradually reduces the affinity to cTnC and cTnT by lowering the association rate constants; the dissociation rate constants remain unchanged. Phosphorylation also affects formation of the ternary complexes; however, in this instance, association rate constants are constant, and dissociation rate constants are enhanced. A model of cardiac troponin is presented describing an induction of distinct conformational changes by mono- and bisphosphorylation of cTnI.     

Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I

This study compared the diagnostic accuracy of the measurement of serum cardiac troponin I (cTnI) with creatine kinase (CK) MB mass in patients with minor myocardial injury whose measured total CK activity did not exceed twice the upper reference limit (300 U/L for men; 200 U/L for women). Forty-eight consecutive patients presenting with chest pain and with in-hospital documentation of myocardial injury were enrolled. Electrocardiogram, echocardiogram, and serial serum CK-MB mass, cTnI, and total CK were measured over 36 h after admission. Peak total CK activity was within normal limits in 28 patients (58%). The mean (+/- SD) peak CK-MB mass and cTnI concentrations were: 16.4 (11.8) micrograms/L and 132 (13.0) micrograms/L; respectively. The peak biochemical marker index (defined as CK-MB or cTnI divided by its respective upper reference limit) was significantly (P < 0.05) higher for cTnI than for CK-MB from 7 to 36 h. The clinical sensitivity for detection of myocardial injury for cTnI was 100% [95% confidence interval (CI): 87.2% to 100%], compared with 81.8% (CI: 67.3% to 91.8%) for CK-MB. Thus, cTnI was more sensitive than CK-MB mass for detection of myocardial injury in patients with small increases of total CK.     

Cardiac troponin T and cardiac troponin I: relative values in short-term risk stratification of patients with acute coronary syndromes. GUSTO-IIa Investigators

We compared cardiac troponins T (cTnT) and I (cTnI) collected within 3.5 h of ischemic symptoms for predicting clinical outcomes in 770 patients. cTnT (cutoff > 0.1 microgram/L) and cTnI (cutoff > 1.5 micrograms/L) were concordant (both positive or negative) in 90.4% of patients. Among discordant results, 66 were cTnT positive and cTnI negative vs 8 who showed the reverse (P < 0.001). Five cTnT-positive and cTnI-negative patients died within 30 days; none who were cTnT negative and cTnI positive died. cTnT showed a slightly greater association (chi 2 = 18.0, P < 0.001) with 30-day mortality than cTnI (chi 2 = 12.5, P = 0.002). The area of the ROC curve for predicting 30-day mortality was significantly larger (Z = 2.08; P = 0.0375) for cTnT, at 0.68 [95% confidence interval (CI) 0.60-0.75], compared with cTnI, at 0.64 (95% CI 0.56-0.72). When cTnI and the electrocardiogram (ECG) were put in a logistic multiple regression model, cTnT added significant information (chi 2 = 8.03, P = 0.045); however, cTnI did not add to a model containing cTnT and the ECG (chi 2 = 0.84, P = 0.657). cTnT provided more information than cTnI for predicting 30-day mortality early after presentation with acute coronary syndromes.