Cardiac troponin I serum concentrations in newborns: a study and review of the literature.

BACKGROUND: Serum cardiac troponin I (cTnI) is a specific marker of cardiac injury. The use of cTnI in neonates, especially in relation to perinatal asphyxia has not been extensively examined. We defined the range of normal values of cTnI in newborns, and study factors that may influence these concentrations. METHODS: Serum cTnI concentrations were measured on the third day of life in 179 normal newborns: 157 were term (after 37 weeks, mean: 39.7+/-1.1, range: 37-42) and 22 were premature infants (mean: 32.6+/-2.9, range: 27-36 weeks). RESULTS: Mean cTnI for the term infants was 0.63+/-0.58 ng/ml (median: 0.50, range: 0.00-4.30). The concentration of 1.80 ng/ml, can serve as the upper limit of normal values. There was a borderline significant trend for higher cTnI in preterm infants. The number of newborns with cTnI>1.80 ng/ml was significantly higher after delivery by caesarean section, compared to vaginal delivery (14.6% vs. 2.9%, p<0.02). No other significant associations were found between cTnI and perinatal or neonatal parameters. CONCLUSIONS: Normal reference values for cTnI in healthy term newborns were defined, but need to be addressed with caution due to the wide range of normal values.

Electron spin relaxation time of Fe(III) in high spin heme proteins.

The electron spin relaxation time of high spin Fe(III), taus, was determined from the frequency dependence (5-100 MHz) of the longitudinal proton relaxation rates of water in solutions of catalase, metmyoglobin and acid ferricytochrome c. In all three high-spin heme proteins the relaxation rates incrased below 25 MHz, while no frequency dependence was observed above that frequency. The results are interpreted by assuming that taus, which modulates the dipolar interaction between the unpaired electrons of the iron and the water protons, is frequently independent. Its value was determined to be (6 +/- 1) - 10(-11) s.

Liver preservation for transplant. Evaluation of hepatic energy metabolism by 31P NMR.

31P NMR spectroscopy proved to be an excellent, dynamic, nondestructive method for assessing the liver during cold flush and pulsatile perfusion experiments. 31P NMR spectroscopy was used to measure ATP decay, inorganic phosphate appearance, and phosphate chemical shift in the excised mouse livers subjected to cold and warm ischemia. Cold flush followed by cold preservation in saline, Krebs-Henseleit buffer, or Collins' solution showed that Collins' solution resulted in the slowest ATP decay. In temperature-controlled experiments (5 degrees -37 degrees C), ATP decay was much slower with lower temperature. In separate pulsatile perfusion experiments with oxygenated Krebs-Henseleit buffer, hepatic ATP was unchanged for at least 6 hr at 20 degrees C. At 37 degrees C, the NMR spectrum showed changes in the diphosphoesters region, but the ATP remained stable during the 6-hr perfusion. These studies suggest that for long periods of liver preservation, an adequate perfusion method should be developed.

Nuclear magnetic resonance proton imaging of bone pathology.

Thirty-two patients with diversified pathology were examined with a supraconductive NMR imager using spin echo with different TR and TE to obtain T1 and T2 weighted images. They included 20 tumors (12 primary, eight metastasis), six osteomyelitis, three fractures, two osteonecrosis, and one diffuse metabolic (Gaucher) disease. In all cases except for the stress fractures, the bone pathology was clearly visualized in spite of the normal lack of signal from the compact cortical bone. Nuclear magnetic resonance (NMR) imaging proved to be at least as sensitive as radionuclide scintigraphy but much more accurate than all other imaging procedures including computed tomography (CT) and angiography to assess the extension of the lesions, especially in tumors extended to soft tissue. This is due both to easy acquisition of sagittal and coronal sections and to different patterns of pathologic modifications of T1 and T2 which are beginning to be defined. It is hoped that more experience in clinical use of these patterns will help to discriminate between tumor extension and soft-tissue edema. We conclude that while radionuclide scintigraphy will probably remain the most sensitive and easy to perform screening test for bone pathology, NMR imaging, among noninvasive diagnostic procedures, appears to be at least as specific as CT. In addition, where the extension of the lesions is concerned, NMR imaging is much more informative than CT. In pathology of the spine, the easy visualization of the spinal cord should decrease the need for myelography.

Nuclear magnetic resonance imaging of liver hemangiomas.

Nine patients with cavernous hemangioma of the liver were examined by nuclear magnetic resonance imaging (MRI) with a 0.5 T superconductive magnet. Spin-echo technique was used with varying time to echo (TE) and repetition times (TR). Results were compared with 99mTc red blood cell (RBC) scintigraphy, computed tomography (CT), echography, and arteriography. Four illustrated cases are reported. It was possible to establish a pattern for MRI characteristics of cavernous hemangiomas; rounded or smooth lobulated shape, marked increase in T1 and T2 values as compared with normal liver values. It is concluded that, although more experience is necessary to compare the specificity with that of ultrasound and CT, MRI proved to be very sensitive for the diagnosis of liver hemangioma, especially in the case of small ones which may be missed by 99mTc-labeled RBC scintigraphy.

Effect of hyperoxia on uptake and metabolism of 5-hydroxytryptamine and beta-phenylethylamine in rat lung: a sex difference.

1 The uptake of 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (PEA) and their deamination by monoamine oxidase (MAO) were studied in perfused lung from male and female rats exposed to 100% O(2) at 1 ATA for up to 60 h.2 The uptake and metabolism of 5-HT in lungs from both male and female rats was not changed by exposure to O(2).3 The uptake and metabolism of PEA by lungs from male rats was unchanged. Uptake of PEA by lungs from female rats was inhibited 20% and 62% after 37 h and 50 h exposure respectively.4 MAO activity, both in vitro and in perfused lung, was increased towards PEA after 35 h of hyperoxia.5 Metabolism of PEA in perfused lung, measured over 30 min, was inhibited 52% after 50 h of O(2) hyperoxia.6 These results show that exposure to high concentrations of O(2) damages lung, resulting in inhibition of uptake of PEA and consequently in inhibition of metabolism of PEA.7 These results also indicate that, in lung from female rats, MAO-type B is more susceptible to changes in O(2) tension than MAO type A.

Liver adenine nucleotide metabolism during ischemia and reperfusion of mice livers studied by phosphorous-31 nuclear magnetic resonance.

Perfusion experiments were performed at 20 degrees C and 37 degrees C to study liver adenine nucleotide metabolism during ischemia and reperfusion of mouse livers using 31P NMR. Perfusing at 8 mL/min (Krebs-Henseleit buffer), ATP was shown to be stable for 6 hours. There was a progressive decrease in the phosphodiesters (glycerophosphorycholine and glycerophosphorylethanolamine) during the 6-hour period. Liver subjected to cold ischemia at 20 degrees C showed a slow decrease in the beta ATP peak during a 42 +/- 6-minute period with a rise in the inorganic phosphate accompanied by a shift of inorganic phosphate to the high field indicating intracellular acidosis. With reperfusion, the beta ATP returned to previous levels and the inorganic phosphate shifted to its original position. During warm ischemia (37 degrees C) the ATP peak disappeared within 5 +/- 1 minute and only returned to 34% of its original value after 30 minutes of ischemia, indicating damage to a certain percentage of liver cells. When the liver was subjected to multiple short periods of cold ischemia, there was complete recovery of the ATP after six cycles. Reperfusion after each period of cold ischemia resulted in an ATP recovery consistently greater than the initial amount, which gradually decreased to preischemic levels after a short period. This suggests that there is an as yet undelineated mechanism of ATP production during ischemia that attempts to protect the cell against ischemia.

Nuclear magnetic resonance assessment of adenosine triphosphate (ATP) dynamics in ischemic mouse livers perfused with adenine and ribose.

Hepatic energy stores are essential to liver viability. We used a mouse liver perfusion model and MR spectroscopy to study the effect of adding two precursors of ATP (adenine and ribose) on ATP dynamics during ischemia and reperfusion. Using Krebs-Henseleit buffer with or without added adenine and ribose made little difference in the ATP decay rate during ischemia, but the recovery of ATP during reperfusion was more complete when adenine and ribose were added to the buffer. These findings suggest that the addition of the precursors of ATP, adenine and ribose, to perfusate after ischemia can accelerate and enhance ATP recovery.

Treatment of severe, resistant familial combined hyperlipidemia with a bezafibrate-lovastatin combination.

Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by high levels of cholesterol, triglycerides, or both. The basic metabolic abnormality is overproduction of apolipoprotein B-100. High atherogenicity has been attributed to all forms of FCHL. We evaluated combined bezafibrate-lovastatin therapy in 10 patients (9 men and 1 woman) with FCHL and markedly high cholesterol and triglyceride levels who were at high risk of coronary artery disease and who had not responded to diet and bezafibrate treatment alone. Eight patients had coronary artery disease, 6 had hypertension, and 3 had noninsulin-dependent diabetes mellitus. Lovastatin 20 mg/day was added to the bezafibrate 600 mg/day regimen for 6 weeks; the lovastatin dosage was then doubled to 40 mg/day for an additional 6 weeks. The addition of 20 mg of lovastatin resulted in decreases of 15%, 20%, and 13% in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, respectively. Increasing the dose of lovastatin to 40 mg resulted in further moderate decreases of 4%, 3%, and 8% in total cholesterol, LDL cholesterol, and triglycerides, respectively, compared with the 20 mg/day dosage. Although previous reports have emphasized the potential side effects of combination treatment with lovastatin and fibric acid derivatives, our patients tolerated the regimen well, with no significant subjective complaints or laboratory abnormalities. The bezafibrate-lovastatin combination is a possible therapeutic option for severe, resistant FCHL, but close medical supervision is needed because of potential side effects.

Digoxin quinidine interaction: a pharmacokinetic study in the isolated perfused rat liver.

Digoxin-quinidine interaction was studied in the experimental model of isolated perfused rat liver. Neither digoxin nor quinidine were toxic to the isolated rat liver. The clearance of digoxin and quinidine by the liver was directly related to the rate of bile flow and the size of the initial dose of digoxin. In the presence of quinidine, after initial doses of digoxin of 0.5 and 1 micrograms, the concentration of digoxin in the perfusate was increased 2.5 and 3-fold. Its excretion in the bile was reduced by 45% and 20.5%, respectively (all comparisons, p less than 0.01). Digoxin concentration in the liver tissue was calculated and found to be appreciably elevated in the presence of quinidine. A reduction of about 30% (p less than 0.05) in the excretion of quinidine in the bile was observed in the presence of digoxin. Thus, a competition of digoxin and quinidine for biliary excretion was demonstrated as an underlying cause for digoxin-quinidine interaction in the isolated perfused rat liver.

Value of laboratory studies in assessment of dehydration in children.

BACKGROUND: Due to the lack of a reliable way of clinically measuring dehydration, laboratory tests are usually used to improve the accuracy of clinical assessment of dehydration in children. The purpose of this study was to compare the relationship between clinical and laboratory parameters in the assessment of dehydration and to evaluate the improvement of those parameters over time. METHODS: We conducted a retrospective study to assess the relationship between clinical assessment of dehydration and laboratory findings. RESULTS: Three hundred children were eligible for the study. Twenty-six per cent of those with mild dehydration had serum urea concentrations greater than 14.3 mmol/L, compared with 38% and 5% of those with moderate or no dehydration, respectively. Urea concentration showed a good specificity, 95%. Creatinine concentrations and mean pH were similar whether or not dehydration was present. Bicarbonate and base excess concentrations decreased with the increasing severity of dehydration and were significantly greater in subjects with moderate dehydration than in those without. The sensitivity (71%) and specificity (74%) of both tests were rather poor. All groups had an abnormal anion gap, which was significantly greater in those with mild or moderate dehydration. CONCLUSION: This study confirms that there is a discrepancy between clinical assessment and laboratory parameters of dehydration. Urea showed good specificity, and anion gap was the most sensitive laboratory parameter for assessment of dehydration. These findings need further validation.

The formation of genotoxic metabolites of benzo[a]pyrene by the isolated perfused rat liver, as detected by the bioluminescence test.

The kinetics of the formation of mutagenic metabolites of benzo[a]pyrene (BP) in an isolated perfused rat-liver system have been studied. No genotoxic activity was detected in the perfusate using either the Ames test or the new bioluminescence test for genotoxic agents (BLT). The bile excretion showed strong genotoxic activity especially in the presence of the deconjugation enzymes beta-glucuronidase and arylsulfatase. The BLT was 1000-fold more sensitive than the Ames test in detecting the genotoxic activity in the bile excretion.

Magnetic resonance imaging in orthopaedic surgery. A glimpse into the future.

Magnetic resonance images (MRI) were obtained of 10 healthy volunteers and 70 patients suffering from various orthopaedic disorders. Selected images of soft tissue, joint, bone and spinal abnormalities are presented and their interpretation is described. Although we have been using MRI for only a very short time, it is already possible to see its advantages: it provides good images of soft-tissues, detailed pictures of bone marrow, and excellent visualisation of the spine and spinal cord. The decision-making process in surgical procedures will in the future be influenced by this technique.

Anatomy of the normal knee as seen by magnetic resonance imaging.

Nuclear magnetic resonance imaging (MRI) was used to study the normal knee. As well as revealing bone quality, MRI provided useful information on intra-articular and extra-articular soft tissues. Midsagittal views gave clear images of the cruciate ligaments, and of the patellar and quadriceps tendons. Parasagittal views were the best for delineating the menisci which, like ligaments and tendons, are of low intensity; the semimembranosus tendon and its insertion to the proximal tibia were also seen clearly in these views. The cruciate ligaments and menisci, though visible in the coronal view also, were better seen in the sagittal view. Axial views provided information on the structure of the patella, its cartilage, the patellofemoral joint and posterior soft-tissue structures.

Alcohol-induced changes in urinary aminolevulinic acid and porphyrins: unrelated to liver disease.

Urinary porphyrins and their metabolites aminolevulinic acid (ALA) and porphobilinogen (PBG) were determined in 15 normal volunteers and in 45 alcoholics, subdivided into three groups according to their liver function tests and histology: alcoholics exhibiting no evidence of hepatocellular damage; alcoholics with fatty liver and impaired function of liver enzymes; and alcoholics with proven liver cirrhosis. The dominant trend observed in those alcoholics devoid of any evidence of liver disease was increased ALA, PBG, and uroporphyrin. Coproporphyrinuria was shared by the patients exhibiting liver damage. The data shown enabled us to differentiate between the direct, primary effect of alcohol on the heme biosynthetic pathway and the secondary indirect effect, which is probably related to liver damage that follows alcohol consumption. Evaluation of the results led to the suggestion that urinary ALA could possibly serve as a marker of alcoholism. The specificity and sensitivity of the test were found to be 87% and 80%, respectively.

The role of high-dose oral iron supplementation during erythropoietin therapy for anemia of prematurity.

OBJECTIVE: To assess whether a high intake of oral iron would increase the effect of recombinant human erythropoietin (rHuEPO) on hemoglobin synthesis. METHODS: We studied 30 preterm infants (gestational age 29+/-1.8 weeks, birth weight 1161+/-200 g, at age of 28+/-10 days) who were randomly assigned to receive either 8 mg/kg per day (n=15) or 16 mg/kg per day of oral iron during a course of rHuEPO therapy (900 microg/kg per week) for a duration of 4 weeks. Both groups were comparable in regard to clinical and laboratory data at the time of enrollment. RESULTS: rHuEPO caused a significant increase in reticulocyte count in the low- and high-dose iron groups, 17.1+/-5.3 to 34.7+/-9.2 and 16.3+/-3.3 to 42.5+/-5.6 (10(9)/l), respectively (p<0.05). However, in both groups, hematocrit values remained stable at the end of the study as compared to baseline (0.35+/-0.03% vs. 0.30+/-0.03%, 0.35+/-0.05% vs. 0.30+/-0.03%, NS) and in both groups there was a comparable and significant decrease in ferritin level (259+/-109 to 101+/-40 and 168+/-54 to 69+/-38 microg/l, respectively; p<0.01). The rates of bloody stools without any evidence of necrotizing enterocolitis were not significantly different between the two treatment groups (1/15 vs. 4/15, NS). CONCLUSION: We conclude that a higher dose (16 mg/kg per day) of oral iron is not more beneficial when compared to a lower dose (8 mg/kg per day) during rHuEPO therapy for anemia of prematurity. Further studies will define the optimal dosage and route of administration of iron supplementation during rHuEPO therapy.