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We measured concentrations of guanosine 3',5'-monophosphate (cGMP) in plasma and urine of healthy subjects and patients with congestive heart failure, renal impairment, neoplastic disease, and hepatic cirrhosis. There was no correlation between cGMP concentrations in urine and in plasma. In all patients except those with renal impairment, urinary cGMP concentrations were significantly higher than in healthy persons. Only patients with heart failure or renal impairment showed significantly increased plasma cGMP concentrations. In contrast, cGMP in urine does not relate to the clinically assessed severity of heart failure (New York Heart Association functional classes). Determination of cGMP in plasma results in higher sensitivity and specificity for diagnosing heart failure than measurement of cGMP in urine.

The purpose of this study was to evaluate cardiac troponin T (TnT) in the diagnosis of minor perioperative myocardial tissue damage and small myocardial infarctions during aortocoronary bypass surgery. In 15 patients without enzymatic or electrocardiographic signs of perioperative myocardial ischemia (group 1, uncomplicated bypass surgery), TnT did not exceed 3.55 micrograms/L. In 3 patients with perioperative non-Q-wave infarctions (group 2), TnT was significantly higher than in group 1 patients. In all 3 patients, TnT peak concentrations exceeded 3.5 micrograms/L. Thirteen patients (group 3, borderline cases) showed either signs of perioperative myocardial ischemia by creatine kinase isoenzyme MB (CKMB) activity levels (CKMB > 20 U/L on the first postoperative day, 3 patients) or by electrocardiography (new ST-T segment alterations, 10 patients). TnT concentrations were comparable to group 1 patients and indicated uncomplicated bypass surgery in all 3 patients with solely elevated CKMB activities. On the other hand, TnT concentrations in 3 patients with electrocardiographic signs of perioperative myocardial ischemia were significantly higher than in uncomplicated patients (group 1) with peak values exceeding 3.5 micrograms/L. Thus, TnT indicated perioperative non-Q-wave infarctions not detected by CKMB activity in these 3 patients. These results are in accordance with findings in nonsurgical patients. They suggest a higher sensitivity and specificity of cardiac TnT compared to CKMB activity in the diagnosis of small perioperative myocardial infarctions after bypass surgery.

Plasma concentrations of polymorphonuclear granulocytes elastase (PMN elastase) in complex with alpha-1 proteinase inhibitor are a marker of neutrophil activation. The latter complex, creatine kinase and cardiac troponin T, were measured in peripheral venous blood samples serially drawn in 39 patients with acute myocardial infarction. Of the total, 29 received intravenous thrombolytic therapy either with streptokinase (n = 15), urokinase (n = 7) or recombinant tissue type plasminogen activator (n = 7). Creatine kinase activities and cardiac troponin T concentrations were used as markers of myocardial tissue injury. In all patients with acute myocardial infarction, PMN elastase was elevated (median 80 micrograms/l, interquartile range 71 to 100 micrograms/l). Peak and cumulative (area under curve) concentrations of PMN elastase did not correlate closely with determinants of myocardial injury (r < 0.2, n.s.). PMN elastase increased during the first 6 h after starting thrombolytic therapy, whereas it decreased in conventionally treated patients and 12 h later increased. Maximum concentrations of PMN elastase, however, were not significantly higher in patients with thrombolytic therapy than in those without. In acute myocardial infarction patients with complications such as cardiac arrest with subsequent resuscitation (n = 5), cardiac rupture (n = 1) or cardiogenic shock (n = 2), PMN elastase plasma concentrations were significantly higher (p = 0.04) than in uncomplicated infarctions. In the complicated patients, changes in elastase concentrations paralleled or even preceded changes in the clinical presentation. Therefore, thrombolytic treatment seems not to significantly influence the amount of systemic neutrophil activation, but plasma PMN elastase could be a useful marker to monitor and identify complications in acute myocardial infarction.

Endothelin is a potent vasoconstrictor of coronary arteries. We measured plasma concentrations of immunoreactive endothelin (irET) in 46 patients with confirmed acute myocardial infarction (AMI). When compared with irET concentrations in healthy individuals who served as controls, irET concentrations in patients were already significantly elevated at the time of admission (P = 0.002) and remained significantly elevated for at least 2 days after AMI (P < 0.01). IrET concentrations peaked 1 h (mean) after admission (8.5 +/- 3.9 ng/L, P = 0.02 compared with values at time of admission). Reperfusion of the infarct-related artery markedly influenced irET release. Before the start of thrombolytic therapy, irET concentration in patients with early reperfusion did not differ significantly from that of those without early reperfusion. However, irET time courses were significantly (P = 0.03 by analysis of variance) different in patients who did and did not have early reperfusion. In the latter, peak irET concentrations correlated closely with the angiographic left ventricular ejection fraction (r = -0.71, P = 0.03), maximum creatine kinase MB mass concentrations (r = 0.69, P = 0.01), and creatine kinase activities (r = 0.59, P = 0.03). Reflow and reversion of myocardial ischemia are associated with a reduced irET release in patients with AMI.

Background: This study compared clinical-chemical estimates of infarct size with scintigraphic estimates of myocardial scar in patients with first-time acute myocardial infarction (AMI)., Methods: Levels of the cardiac isoform of the contractile protein troponin T (TnT), of creatine kinase (CK), and of the isoenzyme MB of CK (CK MB) were tested in serially drawn blood samples from 21 patients (two females and 19 males; median age, 55 years). Of these 21 patients, five had anterior- and 16 had inferior-wall AMI; all patients received intravenous thrombolytic therapy. Single-photon emission computed tomography (SPECT) with technetium-99m-isonitrile (Tc-sestamibi) was performed at rest after the onset of AMI (median time, 5 weeks). Scintigraphic defects were calculated using "bull's-eye" polar coordinate maps. All patients had an uncomplicated course between discharge and myocardial scintigraphy., Results: Scintigraphic defect sizes ranged from 3.2% to 47.8% of the left ventricle (median, 27.3%). Cardiac TnT and CK MB release correlated closely with each other and with scintigraphic estimates of myocardial scar. Significant correlates were found between cardiac TnT and CK MB peak values (r = 0.87, P = 0.0001), CK MB peaks and Tc-sestamibi defect sizes (r = 0.73, P = 0.0014), and TnT peaks and scintigraphic defect sizes (r = 0.73, P = 0.0011)., Conclusions: Because animal studies have already shown a very close correlation between histologic infarct size and SPECT Tc-sestamibi defect size, our results indicate that cardiac TnT is a useful marker to assess infarct size noninvasively in man.

Study Objectives: To evaluate measurements of myoglobin in the diagnosis of perioperative myocardial tissue damage in aortocoronary bypass surgery. A new immunoturbidimetric myoglobin assay, which yields quantitative concentrations of myoglobin within approximately 1 min, was used., Design: Prospective clinical study., Patients: Thirty-two patients scheduled for elective aortocoronary bypass surgery., Measurements and Results: Myoglobin concentrations in patients without perioperative myocardial infarction (n = 27) increased with aortic unclamping, peaked after 1 h, and decreased to almost baseline values within 4 h. By contrast, myoglobin concentrations in patients with perioperative myocardial infarction (n = 5) further increased after 1 h of aortic unclamping and were significantly higher (p < 0.05) than in patients without myocardial infarction as soon as 3 h after aortic unclamping. In all patients with myocardial infarction, myoglobin concentrations exceeded 400 micrograms/L over a minimum period of 4 h. Ten of 27 patients without perioperative myocardial infarction had episodes of minor perioperative myocardial ischemia (defined as ST-T segment changes in the ECG without a concomitant increase in the activity of creatine kinase isoenzyme MB). Myoglobin concentrations (but not creatine kinase isoenzyme MB activity) were significantly higher in these 10 patients when compared to the 17 completely uneventful cases., Conclusions: Plasma concentrations of myoglobin are a sensitive marker of perioperative myocardial tissue damage in aortocoronary bypass surgery. Myoglobin measurements with the immunoturbidimetric assay have an important contribution to make to the early and rapid diagnosis of perioperative myocardial infarction.

Endothelin-1 concentrations were measured in peripheral venous blood samples from 42 patients with acute myocardial infarction. In patients with ischemic or hemodynamic complications (n = 11), endothelin-1 concentrations were significantly higher already on admission (P = 0.008) and remained significantly higher until day 6 after admission compared to patients with uncomplicated infarctions (n = 31; P = 0.035). There were no close correlations between peak concentrations of endothelin-1 and creatine kinase or creatine kinase isoenzyme MB mass in either group. Only in complicated patients did left ventricular ejection fraction correlate closely and inversely with peak endothelin-1 concentrations (r = -0.71; P = 0.03). Therefore, plasma endothelin-1 concentrations in patients with acute myocardial infarction patients may reflect states of markedly depressed cardiac performance and recurrent myocardial ischemia.

Plasma concentrations of calcitonin gene-related peptide (CGRP), a potent regulator of vascular tone, creatine kinase, myoglobin, and cardiac troponin T were assessed in 31 patients with acute myocardial infarction. In patients who had sustained acute myocardial infarctions, maximum CGRP concentrations (median, 3.2 pmol/L; interquartile range, 1.5 to 4.8 pmol/L) were markedly elevated as compared with healthy control subjects (n = 23; median, 1.02 pmol/L; p = 0.02). However, no marked differences in CGRP levels were observed between patients with early reperfusion (n = 19; median, 3.5 pmol/L) and patients without early reperfusion (n = 12; median, 2.6 pmol/L; p = 0.96), as well as between those with congestive heart failure (n = 8; median, 3.9 pmol/L) and those without congestive heart failure (n = 23; median, 3.2 pmol/L; p = 0.62). CGRP did not correlate closely with myocardial protein release or hemodynamic parameters (heart rate and blood pressure) or the occurrence of arrhythmias. Therefore we conclude that elevated peripheral venous CGRP concentrations in patients who have sustained an acute myocardial infarction are independent of successful reperfusion and hemodynamic state. Although the cause of CGRP increase is not yet identified, CGRP may play a role in the regulation of coronary vascular tone in patients after acute myocardial infarction.

Objective: To evaluate a rapid immunoturbidimetric assay for myoglobin and to investigate its clinical usefulness in the early detection of acute myocardial infarction., Design: Prospective study. Immunoturbidimetrically determined myoglobin concentrations were compared with radioimmunoassay results obtained with the same blood samples. The diagnostic performance of myoglobin determination was compared with creatine kinase and creatine kinase MB activity (current standard of routine diagnosis)., Settings: Part 1: coronary care unit. Part 2: emergency room in a university hospital., Patients: Part 1:30 patients with acute myocardial infarction admitted not later than four hours (median two hours) after the onset of symptoms. Part 2: 126 patients admitted to the emergency room with chest pain not caused by trauma (51 cases of acute myocardial infarction, 51 cases of angina pectoris, and 24 cases of chest pain not related to coronary artery disease)., Interventions: Part 1: routine treatment including intravenous thrombolytic treatment (28 patients). Part 2: routine emergency treatment without thrombolytic treatment., Main Outcome Measures: The analytical quality of the immunoturbidimetric myoglobin assay and a comparison between the myoglobin assay and creatine kinase and creatine kinase MB for diagnostic sensitivity and performance., Results: The immunoturbidimetric myoglobin assay was fast and convenient and gave myoglobin determinations of high analytical quality. The concentration of myoglobin increased, peaked, and returned to the reference range significantly earlier than creatine kinase (p < or = 0.0001) and creatine kinase MB (p < or = 0.0002). Before thrombolytic therapy was started the diagnostic sensitivity of myoglobin was significantly higher than that of creatine kinase MB activity 0-6 h after the onset of chest pain and significantly higher (0.82 v 0.29) than creatine kinase 2-4 h after the onset of chest pain. In almost all patients (92%) plasma myoglobin concentrations were increased 4-6 h after the onset of chest pain., Conclusion: Myoglobin was more sensitive in detecting early myocardial infarction than creatine kinase and creatine kinase MB activity. Immunoturbidimetric myoglobin measurements could be useful in the early evaluation of patients with suspected myocardial infarction because this assay takes less than two minutes.

In a prospective, randomized, assessor-blind multicentre study two antithrombotic subcutaneous regimens were compared in patients undergoing total hip replacement. Group 1 (154 patients) received 750 anti-Xa units of a new low molecular weight heparinoid (Lomoparan) subcutaneously twice a day and group 2 (155 patients) received 5000 units heparin and 0.5 mg dihydroergotamine (heparin-DHE 5000) twice a day. The incidence of deep vein thrombosis, assessed by routine bilateral venography on day 10 (+/- 1), was 17 and 32 per cent in groups 1 and 2 respectively (risk reduction 47 per cent; P = 0.007). One patient in each group developed a symptomatic pulmonary embolism confirmed by lung scanning. Major bleeding complications occurred in one patient in each group and no significant difference was observed between the two groups with respect to minor bleeding complications. Subcutaneous Lomoparan appears to be as safe as heparin-DHE 5000 at the above doses with regard to bleeding complications, and is more efficacious with respect to venous thrombosis.

Concentrations of creatine kinase (CK) MB mass and cardiac troponin T were measured in serial peripheral venous blood samples from 21 patients who underwent percutaneous transluminal coronary angioplasty (PTCA). Angiography showed side-branch occlusion during PTCA without clinical signs of myocardial injury in 5 patients. After PTCA, CKMB mass concentrations were substantially higher than normal in all 5 patients with side-branch occlusion, and troponin T concentrations were high in 3. By contrast, only 2 patients and 1 patient, respectively, without side-branch occlusion had slight rises in CKMB and troponin T. Release of the contractile protein troponin T reflects more severe damage to myocytes than simple leakage of CKMB. Therefore, myocardial damage induced by side-branch occlusion can be graded by measurement of troponin T in plasma.

The right of a child born disabled as a result of a negligent act committed by another whilst the child was in utero is a recognized principle of law in the major common law countries. It is also recognized that a child who suffers injuries caused to it due to a negligent act committed prior to conception may also have a right to seek compensation. The right to bring such an action is contingent upon the child being born alive and being able to prove a causal connection between the alleged negligent act and the injuries complained of. However, with few exceptions, such legal actions have to date been taken against third parties whose negligence allegedly caused the injuries complained of. It was only a matter of time before courts would be called upon to consider an action taken against the mother of the child for the mother's alleged negligence causing harm to the child during pregnancy.

The effects of a single series of high-force eccentric contractions involving the quadriceps muscle group (single leg) on plasma concentrations of muscle proteins were examined as a function of time, in the context of measurements of torque production and magnetic resonance imaging (MRI) of the involved muscle groups. Plasma concentrations of slow-twitch skeletal (cardiac beta-type) myosin heavy chain (MHC) fragments, myoglobin, creatine kinase (CK), and cardiac troponin T were measured in blood samples of six healthy male volunteers before and 2 h after 70 eccentric contractions of the quadriceps femoris muscle. Screenings were conducted 1, 2, 3, 6, 9, and 13 days later. To visualize muscle injury, MRI of the loaded and unloaded thighs was performed 3, 6, and 9 days after the eccentric exercise bout. Force generation of the knee extensors was monitored on a dynamometer (Cybex II+) parallel to blood sampling. Exercise resulted in a biphasic myoglobin release profile, delayed CK and MHC peaks. Increased MHC fragment concentrations of slow skeletal muscle myosin occurred in late samples of all participants, which indicated a degradation of slow skeletal muscle myosin. Because cardiac troponin T was within the normal range in all samples, which excluded a protein release from the heart (cardiac beta-type MHC), this finding provides evidence for an injury of slow-twitch skeletal muscle fibers in response to eccentric contractions. Muscle action revealed delayed reversible increases in MRI signal intensities on T2-weighted images of the loaded vastus intermedius and deep parts of the vastus lateralis. We attributed MRI signal changes due to edema in part to slow skeletal muscle fiber injury.(ABSTRACT TRUNCATED AT 250 WORDS)

In the last several decades serum levels of cardiac enzymes and isoenzymes have become the final arbiters by which myocardial damage is diagnosed or excluded. Because conventionally used enzymes are neither perfectly sensitive nor specific, there is need for a new sensitive and cardiospecific marker of myocardial damage. Cardiac troponin T (TnT) is a contractile protein unique to cardiac muscle and can be differentiated by immunologic methods from its skeletal-muscle isoform. An enzyme immunoassay specific for cardiac TnT is now available in a commercial kit for routine use. The biggest advantage of this assay is its cardiospecificity. TnT measurements, however, are also highly sensitive in diagnosis of myocardial injury and accurately discern even small amounts of myocardial necrosis. TnT measurements are, therefore, particularly useful in patients with borderline CK-MB and in clinical settings in which traditional enzymes fail to diagnose myocardial damage efficiently because of lack of specificity--for example, perioperative myocardial infarction or blunt heart trauma. TnT release kinetics reveal characteristics of both soluble, cytoplasmic, and structurally bound molecules. It starts to increase a few hours after the onset of myocardial damage and remains increased for several days. TnT allows late diagnosis of myocardial infarction. The diagnostic efficiency remains at 98% until 6 d after the onset of infarct-related symptoms. TnT is also useful in monitoring the effectiveness of thrombolytic therapy in myocardial infarction patients. The ratio of peak TnT concentration on day 1 to TnT concentration at day 4 discriminates between patients with successful (greater than 1) and failed (less than or equal to 1) reperfusion. TnT measurements are very sensitive and specific for the early and late diagnosis of myocardial damage and could, therefore, provide a new criterion in laboratory diagnosis of the occurrence of myocardial damage.

The diagnostic sensitivity and performance of immunoenzymometric measurements of creatine kinase (CK)-MB mass concentrations in the early diagnosis of acute myocardial infarction (AMI) were examined and compared with the sensitivities and performances of CK and CK-MB activity, in the context of simultaneous measurements of CK, CK-MB activity, and CK-MB mass concentrations in serially drawn blood samples obtained immediately from 36 patients with AMI and 126 patients with chest pain on admission to the emergency room of the department of internal medicine. In the 36 patients with AMI, who were all admitted no later than 4 hours after the onset of chest pain, pathologic increase occurred significantly earlier in CK-MB mass than in both CK and CK-MB activity, with a median difference of 1 hour each. In patients coming to the emergency room (51 with AMI, 51 with angina pectoris and 24 with chest pain not related to coronary artery disease), CK-MB mass was the best diagnostic measurement for AMI of all markers tested (significantly higher efficiency, Youden index and likelihood ratio than both CK and CK-MB activity). Before initiating thrombolytic therapy, the sensitivity of CK-MB mass is significantly higher than CK-MB activity during the 0- to 6-hour period and significantly higher than CK activity during the 2- to 4-hour period after the onset of chest pain. Consequently, it is often possible to diagnose an AMI on the basis of increased CK-MB mass concentrations even at a time when CK and CK-MB activities are still within the reference interval.

Until 1932 in England the right to sue for injuries caused by the fault of another was not recognised in the absence of contract. The law of negligence has expanded and developed as new facts are presented to the courts of their decision. One of the basic elements of the tort of negligence is proof that the defendant owed a duty of care to the plaintiff. The law with respect to those who suffer injury who are in being has been clearly defined. However, the law has now developed to hold that a child is born with injuries caused by the negligence of another whilst the child was in utero has a right to bring an action for compensation for those injuries provided the child is born alive. A further development in this area of law has been the legal recognition of a claim by a child who suffers injuries in utero caused by a negligent act committed against the mother at a time when the child was not even conceived provided the child can prove a duty of care was owed and that the injuries complained of were caused by the alleged negligent act. Thus midwives and other health professional who care for and advise pregnant women need to keep in mind that a duty of care may be owed to an unborn child or a future unborn child as well as to the pregnant women.

Troponin T is a structurally bound protein found in striated muscle cells. We tested concentrations of its cardiac-specific isotype in peripheral venous blood samples serially drawn from 72 patients with confirmed myocardial infarction. Fifty-nine patients received thrombolytic treatment with intravenous streptokinase, urokinase, or recombinant tissue-type plasminogen activator; because of contraindications, the remaining 13 patients did not. Concentrations of troponin T in plasma, measured by an enzyme-linked immunosorbent assay, started increasing within a few hours after the onset of symptoms (median, 4 h; range, 1-10 h). The sensitivity of troponin T for detecting myocardial infarction was 100% from 10 to 120 h after the onset of symptoms; sensitivity on the seventh day after admission was 84%. Concentrations were increased for up to three weeks in some patients with late or high peak values. Successful reperfusion in Q-wave infarction obviously influences the release of troponin T into plasma, with all such cases showing peak values less than or equal to 26 h (median, 14 h) after the onset of symptoms. Troponin T concentrations in these patients returned to within the reference interval more rapidly than in nonreperfused subjects. In the 13 patients without fibrinolytic therapy, troponin T tended to peak approximately 48 h (median) after the onset of chest pain. Troponin T concentrations in patients for whom thrombolysis was unsuccessful resembled those in patients without fibrinolytic therapy. The specificity of the assay was 96% as tested in samples of 96 emergency-room patients. The reference interval (less than 0.5 micrograms/L) was established from samples of 100 healthy blood donors. Troponin T measurements are a specific and sensitive method for the early and late diagnosis of acute myocardial infarction and could, therefore, provide a new criterion in laboratory diagnosis of its occurrence.

Concentrations of atrial natriuretic peptide (ANP) are increased in plasma of patients with impaired cardiac and renal function. The second messenger of ANP, cyclic guanosine monophosphate (cGMP), is released into the plasma specifically upon stimulation of cells with ANP. Although nitrates can also activate intracellular cGMP synthesis, we detected no increase in plasma cGMP concentrations after infusions of glycerol trinitrate. Because immunoreactive ANP is highly susceptible to degradation and nonspecific influences in blood samples, determinations of ANP require immediate centrifugation and storage of plasma at -20 degrees C. In contrast, we found that cGMP is stable for five days in vitro in blood samples containing EDTA. In 147 healthy blood donors, the upper cutoff value for plasma cGMP was 6.60 nmol/L, not significantly different (P greater than 0.05) from that for 222 patients with disorders other than cardiovascular and renal. In 69 patients with manifest congestive heart failure (NYHA stages II-IV), 65 had increased cGMP values. Using the above cutoff value for cGMP gave diagnostic sensitivity of 94.2% and specificity of 93.7%. Plasma cGMP may thus provide an alternative for routine clinical measurements of ANP in cardiac diseases in the absence of renal disorders.

1. Pharmacological effects of delta-aminolaevulinic acid (ALA), protoporphyrin IX and haemin were examined in isolated preparations of rabbit jejunum and gastric fundus suspended in oxygenated Ringer-Locke solution at pH 7.0. 2. In jejunal preparations, delta-aminolaevulinic acid (3.0-4.5 mM), protoporphyrin IX (1.1-2.2 mM) and haemin (3.0-4.5 mM) dose-dependently reduced the amplitude of contractions and increased resting length. Pretreatment with prazosin (10(-7) M) inhibited effects produced by delta-aminolaevulinic acid (3 mM) and protoporphyrin IX (1.1 mM) but not those of haemin (3 mM). 3. In fundic preparations, dose-dependent contracture occurred in response to delta-aminolaevulinic acid (0.1-3.0 mM) protoporphyrin IX (0.1-2.2 mM) and haemin (0.6-6.3 mM). Effects qualitatively resembled those of noradrenaline (0.1-0.4 microM). Prazosin (10(-7) M) attenuated these effects, depressing the maximum response and causing a rightward shift of the concentration-response curves. 4. It is concluded that actions of delta-aminolaevulinic acid at alpha 1-adrenoceptor sites are unlikely to be related to the autonomic neuropathy of acute porphyria. Its in vitro effects occurred only at comparatively high concentrations and were mimicked by protoporphyrin IX and haemin. It is suggested that ALA is more likely to modify autonomic functions by an indirect action, since it is known at low dose levels to influence GABA-ergic functioning.