Gallbladder volume and contractility in term and preterm neonates: normal values and clinical applications in ultrasonography

BACKGROUND: Normovolemic hemodilution is a well-accepted method for intraoperative blood salvage. However, some controversy exists concerning the possible risk of myocardial fiber injury as consequence of the reduced oxygen content. Laboratory diagnosis of perioperative myocardial fiber injury is difficult, since biochemical markers are elevated postoperatively due to the surgical trauma. Cardiac troponin I (cTnI) is a new, highly sensitive and specific marker for the detection of myocardial injury. The aim of our study was to investigate whether normovolemic hemodilution in patients with major orthopedic surgery (13 hemodiluted patients, 15 control) induces a release of cTnI. METHODS: cTnI as a highly specific and sensitive cardiac parameter, as well as total creatine kinase (CK), creatine kinase isoenzyme MB mass (CKMB mass) and myoglobin were measured after induction of anesthesia, after normovolemic hemodilution, prior to retransfusion of blood components, 3 h after surgery, and on the first and third postoperative days. RESULTS: Prior to retransfusion of blood components the hematocrit was decreased to 25.4 +/- 1.2% (mean +/- SEM; range: 18%-34%) in the control group and to 20.2 +/- 0.8% (mean +/- SEM; range: 17%-24%) in the hemodilution group. Total CK, CKMB mass as well as myoglobin concentration increased significantly in both groups, reaching their maxima within the first day of surgery. In contrast, cTnI was below the detection limit of assay (< 0.5 micrograms/L) at any time. CONCLUSIONS: We suggest that pre- and intraoperative hemodilution to a hematocrit of approximately 20% by maintaining normovolemia does not induce myocardial fiber injury in patients without preexisting cardiac diseases.     

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.     

Absorptive function following small intestinal transplantation

Detection of cardiac troponin I (cTnI) in patients suspected of having an acute coronary syndrome is highly predictive for an adverse outcome. We evaluated a bedside test for cTnI that uses a polyclonal capture antibody and two monoclonal indicator antibodies. Clinical studies were performed in patients with acute coronary syndrome and patients with chest pain but no evidence of acute myocardial injury. The whole-blood, 15-minute assay had a concordance of 98.9% with an ELISA for cTnI and a detection limit of 0.14 microg/L, and the device tolerated temperatures between 4 degrees C and 37 degrees C. Diagnostic sensitivity for myocardial infarction at arrival (3.5 +/- 2.7 h after onset of symptoms) was 60% [creatine kinase isoenzyme MB (CK-MB) mass, 48%; CK activity, 36%; P < 0.01], and 4 h later, diagnostic sensitivity was 98% (CK-MB mass, 91%; CK activity, 61%; P < 0.01). In 38% of the patients with unstable angina, at least one positive cTnI test was found (CK-MB mass, 4%; CK activity, 2%). No false-positive test results were found in renal failure or injury of skeletal muscle. We conclude that the diagnostic efficacy of the cTnI rapid test was comparable with the cTnI ELISA and superior to CK-MB determination. Therefore, this device could facilitate decision-making in patients with chest pain at the point of care.     

Effects of benzodiazepine agonists on punished responding in pigeons and their relationship with clinical doses in humans

We evaluated the AxSYM troponin I (cTnI) immunoassay for assisting in the detection of acute myocardial infarction (AMI). At four sites, the total imprecision (CV) over 20 days was 6.3-10.2%. The minimum detectable concentration was 0.14 +/- 0.05 microgram/L. Comparison of cTnI measurements between the AxSYM and Stratus (n = 406) over the dynamic range of the AxSYM assay demonstrated good correlation, r = 0.881, with a proportional bias: AxSYM cTnI = 3.50(Stratus cTnI) - 1. 10. The confidence intervals (95%) for the slope and intercept were 3.39-3.64 and -1.32 to -0.95, respectively. The expected cTnI concentration in healthy individuals was /=96%, in skeletal muscle injury, chronic renal disease, and same-day noncardiac surgery patients.     

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.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.     

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.     

Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography

Transfusion-dependent (TD) patients develop cardiac iron overload that will eventually lead to cardiac pump failure. Low-dose dobutamine stress echocardiography may complement resting echocardiography and identify preclinical myocardial dysfunction caused by early cardiac hemosiderosis. Twenty-six iron-overloaded TD patients had stress echocardiography with 5 microg/kg per minute of dobutamine. Indexed left ventricular (LV) mass, LV dimensions, meridional wall stress, and cardiac index were significantly increased. TD patients had similar LV shortening fraction by M-mode (40.5% +/- 5.6% vs 39.4% +/- 4.5%) but had a lower mean LV ejection fraction (53.3% +/- 3.9% vs 46.8% +/- 6.9%, P < .002) and a subnormal increase in cardiac index during dobutamine stress (35% +/- 20% vs 11% +/- 16%, P < .0001). Impairment in LV relaxation was demonstrated by a prolonged isovolumetric relaxation time (0.060 +/- 0.005 vs 0.088 +/- 0.019 seconds, P < .0001), increased peak mitral E wave, and abnormal E/A ratio. Asymptomatic TD patients demonstrate decreased systolic functional reserve and abnormal left ventricular relaxation that may be caused by cardiac hemosiderosis. Low-dose dobutamine stress echocardiography may be useful for detecting and following cardiac dysfunction in patients at risk for cardiac hemosiderosis.     

Poor long-term survival after acute myocardial infarction among patients on long-term dialysis

BACKGROUND: Cardiovascular disease is common in patients on long-term dialysis, and it accounts for 44 percent of overall mortality in this group. We undertook a study to assess long-term survival after acute myocardial infarction among patients in the United States who were receiving long-term dialysis. METHODS: Patients on dialysis who were hospitalized during the period from 1977 to 1995 for a first myocardial infarction after the initiation of renal-replacement therapy were retrospectively identified from the U.S. Renal Data System data base. Overall mortality and mortality from cardiac causes (including all in-hospital deaths) were estimated by the life-table method. The effect of independent predictors on survival was examined in a Cox regression model with adjustment for existing illnesses. RESULTS: The overall mortality (+/-SE) after acute myocardial infarction among 34,189 patients on long-term dialysis was 59.3+/-0.3 percent at one year, 73.0+/-0.3 percent at two years, and 89.9+/-0.2 percent at five years. The mortality from cardiac causes was 40.8+/-0.3 percent at one year, 51.8+/-0.3 percent at two years, and 70.2+/-0.4 percent at five years. Patients who were older or had diabetes had higher mortality than patients without these characteristics. Adverse outcomes occurred even in patients who had acute myocardial infarction in 1990 through 1995. Also, the mortality rate after myocardial infarction was considerably higher for patients on long-term dialysis than for renal-transplant recipients. CONCLUSIONS: Patients on dialysis who have acute myocardial infarction have high mortality from cardiac causes and poor long-term survival.     

Apolipoprotein A, fibrinogen, age, and history of stroke are predictors of death in dialysed diabetic patients: a prospective study in 412 subjects

BACKGROUND: Diabetic patients with end-stage renal failure (ESRD) have a high cardiovascular morbidity and mortality. The underlying mechanisms are not completely elucidated. The aim of our study was to define predictors of death in diabetic patients with end-stage renal disease. PATIENTS AND METHODS: We performed a prospective study in 35 dialysis centres in Germany between 1985 and 1994. To evaluate predictors and risk factors in this population we examined 412 diabetic patients at the time of admission to dialysis treatment (peritoneal dialysis (PD) or haemodialysis (HD)). Classification of the type of diabetes was done according the criteria of the National Diabetes Data Group [1,2]. Items assessed at the time of admission were coronary artery disease (CAD), peripheral occlusive disease (POD), and stroke. CAD was defined as a history of myocardial infarction with the corresponding changes in the ECG or luminal narrowing by more than 50% in at least one coronary artery upon coronarangiography; POD was defined as claudication and/or brachial-tibial ratio (BTR) less than 0.9 or a history of amputation. Assessment of the nutritional state comprised body mass index, skinfold thickness of the upper arm and lateral thorax area, and urea concentration. Cholesterol, HDL, LDL, apolipoprotein A (ApoA-I) and B (ApoB), triglycerides, lipoprotein(a) (Lp(a)), and fibrinogen were measured. As an index of disturbed cardiac innervation beat-to-beat variation was measured. Outcome measurements were causes of death (i.e. cardiac and non-cardiac) and time of survival. RESULTS: One hundred and eighty of 412 (44%) patients died during the observation period. Patients who died were older (61 +/- 12 versus 53 +/- 15 years P < 0.0001), had lower skin fold thickness (13.1 +/- 6.0 versus 15.1 +/- 7.3 mm P < 0.04), lower ApoA-I (100 +/- 35 versus 111 +/- 32 mg/dl P < 0.005) and higher fibrinogen (515 +/- 146 versus 451 +/- 155 mg/dl P < 0.02). Type II diabetic patients had a lower mean survival time than type I (34 versus 66 months P < 0.0006). The mode of renal replacement therapy (PD or HD) had no adverse effect on survival time. Survivors less frequently had a history of CAD, POD and stroke than non-survivors. In multivariate analysis ApoA-I, fibrinogen, age and stroke were independent predictors of cardiac and non-cardiac death in diabetic patients with end-stage renal failure. Lipid values and nutritional state did not independently predict the overall and cardiovascular mortality. CONCLUSION: This study in dialysed diabetic patients identifies several predictors of death, some of which are susceptible to intervention.     

Protein catabolic rate over lean body mass ratio: a more rational approach to normalize the protein catabolic rate in dialysis patients

Protein catabolic rate (PCR), equivalent to dietary protein intake in "stable" dialysis patients, is widely accepted as a marker of their protein nutritional status. PCR is usually established from urea generation rate using urea kinetic modeling (UKM), but the normalizing factor is still a matter of controversy. By convention, PCR is expressed in grams of protein degraded daily divided by the dry body weight (BW) (nPCRBW). To be valid, this implies that dry BW is close to ideal BW and that body composition is preserved with a lean body mass (LBM) over BW ratio near 0.73. Such conditions being infrequently found in dialysis patients, it has been proposed to normalize PCR to ideal BW or to total body water, but these correction factors are not really appropriate. A more rational approach would be to express PCR as the ratio of protein degraded to the kilograms of LBM (nPCRLBM), thus offering the main advantage of directly coupling PCR to changes in protein or nitrogen reserve. In this study, we developed a combined kinetic model of urea and creatinine applied to the midweek dialysis cycle in 66 end-stage renal disease (ESRD) patients. UKM provided Kt/V and PCR, whereas creatinine kinetic modeling (CKM) was used to calculate LBM. Thirty-four patients with a preserved LBM (LBM/dry BW ratio equal to or greater than 0.70; mean ratio, 0.81 +/- 0.11) and with a dry/ideal BW ratio of 1.01 +/- 0.16 had a mean PCR of 1.14 +/- 0.30 g/kg/24 h when normalized to BW (nPCRBW) and of 1.40 +/- 0.30 g/kg/24 h when normalized to LBM (nPCRLBM). In the 32 patients with a reduced LBM (LBM/dry BW ratio, below 0.70; mean ratio, 0.60 +/- 0.09) and dry/ideal BW ratio of 1.11 +/- 0.23, the mean nPCRBW was 0.99 +/- 0.31 g/kg/24 h, whereas nPCRLBM was 1.62 +/- 0.32 g/kg/24 h. For both subgroups, Kt/V was similar, with mean values of 1.76 +/- 0.34 and 1.69 +/- 0.27. Normalizing PCR to LBM offers a double benefit: it compensates for the error induced by abnormal body composition (eg, obese patients) and permits PCR to be adjusted for the decrease in LBM that occurs with age. We propose nPCRLBM as a more rational index to express PCR in dialysis patients.     

A decision tree for the early diagnosis of acute myocardial infarction in nontraumatic chest pain patients at hospital admission

STUDY OBJECTIVE: To find an accurate algorithm for the diagnosis of acute myocardial infarction in nontraumatic chest pain patients on presentation to the emergency department. DESIGN: In a prospective clinical study, we compared the diagnostic performances of clinical symptoms, presenting ECG, creatinine kinase, creatine kinase MB activity and mass concentration, myoglobin, and cardiac troponin T test results of hospital admission blood samples. By classification and regression trees, a decision tree for the diagnosis of acute myocardial infarction was developed. SETTING: Emergency room of a Department of Internal Medicine (University Hospital). PATIENTS: One hundred fourteen nontraumatic chest pain patients (median delay from onset of chest pain to hospital admission, 3 h; range, 0.33 to 22): 26 Q-wave and 19 non-Q-wave myocardial infarctions, 49 patients with unstable angina pectoris, and 20 patients with chest pain caused by other diseases. MEASUREMENTS AND RESULTS: Of each parameter taken by itself, the ECG was tendentiously most informative (areas under receiver operating characteristic plots: 0.87 +/- 0.04 [ECG], 0.80 +/- 0.08 [myoglobin], 0.80 +/- 0.04 [creatine kinase MB mass], 0.77 +/- 0.04 [creatine kinase activity], 0.69 +/- 0.06 [clinical symptoms] 0.67 +/- 0.06 [creatine kinase MB activity], 0.67 +/- 0.05 [troponin T]). In patients presenting 3 h or less after the onset of chest pain, ECG signs of acute transmural myocardial ischemia were the best discriminator between patients with and without myocardial infarction. In patients presenting more than 3 h, however, creatine kinase MB mass concentrations (discriminator value, 6.7 micrograms/L) were superior to the ECG, clinical symptoms, and all other biochemical markers tested. This algorithm for diagnosing acute myocardial infarction was superior to each parameter by itself and was characterized by 0.91 sensitivity, a 0.90 specificity, a 0.90 positive and negative predictive value, and a 0.90 efficiency. CONCLUSIONS: We found an algorithm that could accurately separate the myocardial infarction patients from the others on admission to the emergency department. Therefore, this classifier could be a valuable diagnostic aid for rapid confirmation of a suspected myocardial infarction.     

Analytical evaluation and comparison of Dupont aca lactate dehydrogenase-1 (LD1) isoenzyme assay diagnostic efficiency for acute myocardial infarction detection with other LD1 methods and aca CK-MB. A two-site study

The purpose of this study was to examine the analytical characteristics of a rapid new assay for lactate dehydrogenase 1 (LD1) isoenzyme on the Dupont aca analyzer and the diagnostic efficiency of LD1 for detection of acute myocardial infarction (AMI) when used alone and with creatine kinase MB (CKMB). Total aca LD1 assay precision, with percent coefficients of variation (%CVs) of less than 3.2% from 56 U/L to 469 U/L LD1, across fifty assay days was excellent. Linearity was confirmed from 0 to 332 U/L and no detectable calibration drift was noted from 5 to 489 U/L over a ninety-day period. The aca LD1 results compared well with Roche Isomune-LD1, Abbott Spectrum A-Gent, Helena electrophoresis, and Beckman electrophoresis LD1 methods, giving r's from 0.987 to 0.994, slopes from 0.94 to 1.65, and y-intercepts from -2.95 to 6.94 U/L. Examination of 450 ambulatory subjects, about equally distributed by sex, yielded a 43 +/- 14 U/L aca LD1 patient reference interval. Serum samples from 159 consecutive patients at the University of Tennessee Memorial Hospital and 96 patients at Allentown Hospital, submitted for AMI detection assistance, were assayed in a single-blind study for LD1 and ion-exchange CKMB by Dupont aca methods, which provide automated results in ten minutes whenever needed. The aca LD1 assay yielded a clinical sensitivity of 89% and specificity of 95% for AMI with a decision threshold of 120 U/L. The diagnostic efficiency of the aca LD1 assay was 94% at 120 U/L, which equaled or exceeded that of the three comparative LD1 methods. The predictive value of positive (PV+) and negative (PV-) results on the first sample collected were 80% and 85% for aca LD1, 65% and 90% for aca ion-exchange CKMB, and 83% and 90% when both tests were combined. Significantly, the PV+ and PV- results when two or more samples were assayed was improved to 88% and 95% for aca LD1, relatively constant at 65% and 97% for aca ion-exchange CKMB, and dramatically improved to 95% and 100% when both CKMB and LD1 tests were combined. The results from these two medical centers show that the aca LD1 assay provides useful clinical information for AMI diagnosis when employed alone or in combination with aca CKMB. These results also suggest that LD1 should be included in biochemical evaluations for AMI to attain optimal predictive values of results.     

Three cases of near-tetraploid acute myeloid leukemias originating in pluripotent myeloid progenitors

The kinetics of peritoneal transport of insulin-like growth factor (IGF) system-related proteins during dialysis is not well characterized. We studied temporal changes in dialysate and serum concentrations of IGF-I and IGF-II as well as IGF binding protein (BP)-1, -2, and -3 in ten children with end-stage renal disease (ESRD) undergoing continuous cycling peritoneal dialysis (CCPD) during a 4-h peritoneal equilibration test (PET). Dialysate concentrations of IGF-I, IGF-II, and all three IGFBPs demonstrated a time-dependent increase during PET. Despite their transport, the serum concentrations of these proteins did not change significantly during the PET. Dialysate/serum ratios for IGF-I, IGF-II, and IGFBP-1, -2, and -3 were significantly increased at 2 h and increased further at 4 h, at which time values averaged 1.3+/-0.2%, 3.1+/-0.5%, 6.2+/-1.0%, 2.4+/-0.2%, and 1.3+/-0.2% of serum levels, respectively. The transperitoneal clearance (microl/min per 1.73 m2) of the three IGFBPs was inversely related to both their molecular weight and plasma concentration. However, peritoneal clearance of IGF-I and -II was similar to that of the larger and more-abundant IGFBP-3. Mass transfer rates (microg/h per 1.73 m2) for the IGFs and their binding proteins were directly proportional to their prevailing plasma concentration. Based on estimates of mass transfer, only a small molar excess of IGFBPs was removed from the circulation relative to the combined molar concentration of IGF-I and IGF-II. Hence, it seems unlikely that any beneficial effect of CCPD on growth in children with ESRD is mediated via a preferential loss of IGFBPs into the dialysate fluid.     

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.     

Levels of CK MB mass in patients with acute myocardial infarct treatedwith fibrinolysis. Comparison with levels of CK, CKMB, CKMB mass and troponin T in the diagnosis of coronary ischemia]

In a group of 26 patients with AIM the CKMB value was raised above the discrimination level already on admission--on average 2.7 +/- 1.4 hours after development of ischaemic pain--in 46% patients. The maximal value of CKMB mass was achieved in the group with probable reperfusion 12.1 +/- 3.8 hours after the development of ischaemic pain and this value was elevated in relation to the discrimination value 41.5 +/- 17x and in relation to the so-called basal value 145 +/- 117x. In the group without probable reperfusion the maximal value was achieved significantly later, after 19.8 +/- hours and was elevated in relation to the discrimination value 31 +/- 17x and in relation to the final value 84 +/- 42 times. The value of CKMB mass increased above the discrimination limit from the onset of ischaemic pain after 4.0 +/- 1.5 and after 5.7 +/- 3 hours in the group with probable and without probable reperfusion and declined below the discrimination limit after 00 +/- 60 and 119 +/- 98.0 hours in the same groups. On comparison of CK, CKBM, CKBM mass and troponin T on admission the CKMB mass value was elevated in 46% patients, the value of CK in 23%, of CKMB in 27% and the troponin T value in 96% patients. With regard to the assembled experience that haemolytic serum raises false troponin T values, the percentage of elevated troponin T values on admission declines from the original 96% to 81% when all haemolytic samples are eliminated. The time of reaching maximal values of CKMB mass in patients with AIM and probable reperfusion was significantly shorter than in CK values and is similar as in CKMB values. The time taken to raise the CKBMB mass value above the discrimination value is significantly shorter than the time taken by CK levels, but significantly longer than the time before troponin T levels are raised. The time of total elevation of CKMB mass levels above the discrimination limit does not differ from the time taken to raise CK values, it is however shorter than the increase of troponin T values, although the exact time of persistence of raised levels of troponin T was not assessed in our work. The time of increase above and decrease below the discrimination limit was not assessed in CKMB values. Based on mutual comparison of the impact of indicators for assessment of the diagnosis of ischaemic heart attacks the authors consider it best regardless of financial costs--to assess troponin T, possibly along with levels of CKMB mass.     

Blocking of classical complement pathway inhibits endothelial adhesion molecule expression and preserves ischemic myocardium from reperfusion injury

Myocardial injury after ischemia (I) and reperfusion (R) is related to leukocyte activation with subsequent release of cytokines and oxygen-derived free radicals as well as complement activation. In our study, the cardioprotective effects of exogenous C1 esterase inhibitor (C1 INH) were examined in a rat model of myocardial I + R (i.e., 20 min + 24 hr or 48 hr). The C1 INH (10, 50 and 100 U/kg) administered 2 min before reperfusion significantly attenuated myocardial injury after 24 hr of R compared to vehicle treated rats (P < .001). Further, cardiac myeloperoxidase activity (i.e., a marker of PMN [polymorphonuclear leukocyte] accumulation) in the ischemic area was significantly reduced after C1 INH treatment compared to vehicle treated animals (0.81 +/- 0.1, 0.34 +/- 0.13, 0.13 +/- 0.1 vs. 1.44 +/- 0.3 U/100 mg tissue, P < .001). In addition, C1 INH (100 U/kg) significantly attenuated myocardial injury and neutrophil infiltration even after 48 hr of reperfusion compared to vehicle treatment. Immunohistochemical analysis of ischemic-reperfused myocardial tissue demonstrated activation of classical complement pathway by deposition of C1q on cardiac myocytes and cardiac vessels. In addition, expression of the endothelial adhesion molecules P-selectin and intercellular adhesion molecule 1 (ICAM-1) was observed after reperfusion of the ischemic myocardium. In this regard, C1 INH administration abolished expression of P-selectin and ICAM-1 on the cardiac vasculature after myocardial ischemia and reperfusion. Blocking the classical complement pathway by exogenous C1 INH appears to be an effective means to preserve ischemic myocardium from injury after 24 and 48 hr of reperfusion. The mechanisms of this cardioprotective effect appears to be due to blocking of complement activation and reduced endothelial adhesion molecule expression with subsequent reduced PMN-endothelium interaction, resulting in diminished cardiac necrosis.     

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.     

Anatomy and embryology of the lateral sellar compartment (cavernous sinus) medial wall

The protease inhibitor cystatin C is a non-glycosylated low molecular weight protein (Mr=13359) which is produced by all nucleated cells at a constant rate, freely filtered by the renal glomeruli, and catabolized in the tubuli. The aim of the study was to elucidate the applicability of serum cystatin C as a marker of glomerular filtration rate (GFR) in patients with various kidney diseases with a wide range of renal function and in dialysis patients. Seventy-six patients with various kidney diseases (aged 20 to 79 years) and 61 dialysis patients (aged 21 to 82 years) were included. Serum cystatin C was measured by automated particle-enhanced immunoturbidimetry, serum and urine creatinine by an enzymatic method, and GFR by 99mTc-DTPA-clearance using a single plasma sample method. Serum cystatin C in patients with various kidney diseases was 1.90+/-0.98 mg/L (mean+/-SD) and in dialysis patients 7.14+/-1.91 mg/L. In the non-dialysis patients a linear relationship was found between 99mTc-DTPA-clearance and 1/serum cystatin C (r=0.91, p-value<0.0001), 1/serum creatinine (r=0.89, p-value<0.0001), and creatinine-clearance (r=0.88, p-value<0.0001). Comparison of the non-parametric ROC plots for serum cystatin C (area under the curve (AUC)=0.9665; SE=0.0169), serum creatinine (AUC=0.9554; SE=0.0205), and creatinine-clearance (AUC=0.9731; SE=0.0160) revealed no significant differences (p-values: 0.50, 0.78, and 0.49). In conclusion, cystatin C may be a likewise good marker of the GFR as serum creatinine and creatinine-clearance, cystatin C having the advantage being independent of gender and muscle mass.     

Oral ganciclovir dosing in transplant recipients and dialysis patients based on renal function

BACKGROUND: An oral formulation of ganciclovir (GCV) was recently approved for the prevention of cytomegalovirus disease in solid organ transplant recipients. This study was designed to determine the bioavailability of GCV and to test a dosing algorithm in transplant and dialysis patients with different levels of renal function. METHODS: Pharmacokinetic studies were carried out in 23 patients who were either a recipient of an organ transplant or on hemodialysis. Drug dosing was established by the following algorithm based on calculated creatinine clearance (CrCl): CrCl = [(140-age) x body weight]/(72 x Cr) x 0.85 for women that is, CrCl >50 ml/min, 1000 mg every 8 hr; CrCl of 25-50 ml/min, 1000 mg every 24 hr; CrCl of 10-24 ml/ min, 500 mg every day; CrCl < 10 ml/min (or on dialysis), 500 mg every other day after dialysis. GCV was taken within 30 min after a meal. The patients received oral GCV for between 12 days and 14 weeks. Serum specimens (or plasma from patients on hemodialysis) obtained at steady state were analyzed for GCV concentrations by high-performance liquid chromatography. In nine of the transplant recipients, absolute bioavailability was determined by comparing GCV levels after single oral and intravenous doses of GCV. RESULTS: The following GCV concentrations (mean +/-SD) were determined: with CrCl of > or =70 ml/min, the minimum steady-state concentration (Cmin) and maximum concentration (Cmax) were 0.78+/-0.46 microg/ml and 1.42+/-0.37 microg/ml, respectively, with a 24-hr area under the concentration time curve (AUC0-24) of 24.7+/-7.8 microg x hr/ml; with CrCl of 50-69 ml/min, the Cmin and Cmax were 1.93+/-0.48 and 2.57+/-0.39 microg/ml, respectively, with an AUC0-24 of 52.1+/-10.1 microg x hr/ml; with CrCl of 25-50 ml/min, the Cmin and Cmax were 0.41+/-0.27 and 1.17+/-0.32 microg/ml, respectively, with an AUC0-24 of 14.6+/-7.4 microg x hr/ml. For one patient with a CrCl of 23.8 ml/min, the Cmin and Cmax were 0.32 and 0.7 microg/ml, respectively, with an AUC0-24 of 10.7 microg x hr/ml. With CrCl of <10 ml/min, the mean Cmin and Cmax were 0.75+/-0.42 and 1.59+/-0.55 microg/ml, respectively, with a mean AUC0-24 of 64.6+/-18.8 microg x hr/ml. Absolute bioavailability, for the nine patients so analyzed, was 7.2+/-2.4%. For those patients with end-stage renal failure, GCV concentrations fell during dialysis from a mean of 1.47+/-0.48 microg/ml before dialysis to 0.69+/-0.38 microg/ml after dialysis. CONCLUSIONS: The bioavailability of oral GCV in transplant patients was similar to that observed in human immunodeficiency virus-infected patients. However, levels between 0.5 and 1 microg/ml (within the IC50 of most cytomegalovirus isolates) could be achieved with tolerable oral doses. The proposed dosing algorithm resulted in adequate levels for patients with CrCl greater than 50 ml/min and for patients on dialysis. For patients with CrCl between 10 and 50 ml/min, the levels achieved were low and these patients would likely benefit from increased doses.