Correlation of cystatin-C with glomerular filtration rate by inulin clearance in pregnancy.

OBJECTIVE: To test utility of cystatin-C as a marker of glomerular filtration rate during pregnancy, we performed serial correlations with inulin clearance during pregnancy and postpartum. METHODS: Twelve subjects received inulin infusions and serum cystatin-C at three time points. Pearson's correlation coefficient was calculated. RESULTS: Cystatin-C levels ranged 0.66-1.48 mg/L during pregnancy, and 0.72-1.26 mg/L postpartum. Inulin clearance ranged 130-188 mL/min during pregnancy, and 110-167 mL/min postpartum. Cystatin-C did not correlate with inulin clearance at any time point. CONCLUSION: Serum cystatin-C did not correlate with inulin clearance during pregnancy or postpartum.

Beneficial effects of felodipine on myocardial and coronary function during low-flow ischemia and reperfusion.

An acute coronary occlusion causes severe low-flow ischemia in the occluded region. Calcium antagonists have the potential to reduce the rate of ischemic injury by decreasing myocardial oxygen demand, as well as by other mechanisms, especially when given prior to the onset of ischemia. However, their clinical use may be limited by their negative inotropic effects. The purpose of this study was to assess the effects of felodipine as a potentially protective agent against myocardial ischemia and reperfusion injury, independent of any negative inotropic actions, when given after the onset of low-flow ischemia. Isolated isovolumic (balloon-in-LV), blood-perfused rabbit hearts, paced at a constant heart rate, were subjected to 90 minutes of low-flow ischemia at a coronary perfusion pressure of 10 mmHg, which reduced coronary blood flow to 22-24% of baseline. After 15 minutes of low-flow ischemia, hearts received 2 x 10(-6) M felodipine (n = 7) or no drug (controls, n = 8). Felodipine was given until 15 minutes of reperfusion. During low-flow ischemia both groups of hearts had identical coronary blood flow, heart rate, left ventricular (LV) developed pressure, lactate production, and O2 consumption. However, felodipine markedly protected against ischemic diastolic dysfunction. At the end of low-flow ischemia, LV end-diastolic pressure (LVEDP) had increased from 10 +/- 1 to 28 +/- 5 mmHg in the felodipine group, while in the controls LVEDP increased to 48 +/- 8 mmHg (p < 0.05). During 30 minutes of reperfusion, felodipine had a beneficial effect upon coronary blood flow (initial postischemic hyperemia 245 +/- 38% of baseline in the felodipine group vs. 124 +/- 18% in the controls; p < 0.01) Felodipine markedly improved the recovery of contractile function [LV developed pressure recovered from a baseline of 104 +/- 4 to 75 +/- 6 mmHg (72%) in the felodipine group vs. 34 +/- 10 mmHg (32%) in the control group; p < 0.01], as well as diastolic function (LVEDP = 25 +/- 4 mmHg in the felodipine group vs. 61 +/- 10 mmHg in the controls; p < 0.05), and ATP levels (8.5 +/- 1.4 mumoles/g d.w. in the felodipine group vs. 3.9 +/- 1.4 mumoles/g d.w. in the control group, p < 0.05). Felodipine, given after the onset of low-flow ischemia, protects the myocardium during both ischemia and reperfusion by mechanisms other than reducing myocardial oxygen demand.

Can ischemic preconditioning protect against hypoxia-induced damage? Studies of contractile function in isolated perfused rat hearts.

Ischemic preconditioning in the rat significantly improves functional recovery following global ischemia by undefined mechanisms. It has been suggested that preconditioning protects by altering the tissue metabolic milieu during ischemia, either by increasing ischemic tissue accumulation of a beneficial substance (e.g. adenosine), or inhibiting tissue accumulation of a malefic component (e.g. protons). If this is the case, we hypothesized that no protection should be afforded by preconditioning against a prolonged period of hypoxia, since the continued coronary flow would prevent the accumulation of any metabolic products in the myocardium. To test this hypothesis, isolated buffer-perfused rat hearts were preconditioned by 5 min of ischemia + 5 min of reperfusion and then subjected to 30 min of ischemia, or 25 min of substrate-free hypoxia, or 60 or 90 min of hypoxia with substrate. Function was re-assessed after reperfusion/reoxygenation for a further 30 min and compared to non-preconditioned controls. Ischemic preconditioning improved functional recovery following 30 min of global ischemia (% recovery of developed pressure (LVDP) in control v preconditioned hearts was 31 +/- 4 v 66 +/- 6%; P < 0.05). Importantly, this protection was achieved almost entirely via a better preservation of diastolic function (end diastolic pressure = 78 +/- 3 mmHg in control and 40 +/- 5 mmHg in preconditioned hearts following 30 min of reperfusion; P < 0.05). However, no preconditioning-induced protection was observed following either substrate-free hypoxia or hypoxia with substrate (% recovery of LVDP in control v preconditioned hearts was 31 +/- 4 v 34 +/- 4% after 25 min of substrate-free hypoxia, 48 +/- 3 v 53 +/- 6% after 60 min of hypoxia + substrate and 25 +/- 5 v 30 +/- 6% after 90 min of hypoxia + substrate respectively). Furthermore, no protection by preconditioning against hypoxia-induced diastolic dysfunction was observed. We conclude that preconditioning protects against ischemic injury, but not hypoxic injury. Although hypoxia-induced injury may differ from that induced by ischemia, the results are consistent with the hypothesis that the continued presence of flow with hypoxia abolishes the protective effect of preconditioning. Furthermore, the results support the concept that preconditioning of the ischemic myocardium requires the accumulation of a factor in the ischemic myocardium, either to exert the preconditioning protective effect, or as a factor of injury against which preconditioning affords protection.

Antibiotic-loaded biodegradable bone cement for prophylaxis and treatment of experimental osteomyelitis in rats.

A biodegradable, particulate composite bone cement containing gentamicin and vancomycin was used for both treatment and prophylaxis of Staphylococcus aureus osteomyelitis in rats. Osteomyelitis was established by inoculating S. aureus into holes that were drilled in the proximal tibiae and were filled with polymethylmethacrylate (PMMA) cylinders. The cylinders were left in place for 3 weeks. The infections were serially evaluated by clinical and radiographic examination and by quantitative culture for colony forming units (CFUs) at the time the rats were killed. For treatment, cements containing antibiotic were implanted in animals that had established osteomyelitis and were left in place for an additional 3 weeks. Sites treated with biodegradable cement containing antibiotics exhibited significantly fewer CFUs in comparison with controls (p < 0.01). Sites treated prophylactically with the biodegradable cement developed no infections as evaluated by clinical or radiographic criteria or by quantitative culture. At this relatively early time, no significant difference in therapeutic effectiveness was found when either the biodegradable cement or PMMA was used as a carrier for antibiotics.

Protective effect of increased glycolytic substrate against systolic and diastolic dysfunction and increased coronary resistance from prolonged global underperfusion and reperfusion in isolated rabbit hearts perfused with erythrocyte suspensions.

Current therapy of myocardial infarction may include early reperfusion. We simulated myocardial perfusion conditions during evolving myocardial infarction in isolated, normothermic, isovolumic rabbit hearts perfused with buffer containing bovine red blood cells (hematocrit of 40%), and we assessed the effects of high levels of glucose and insulin as "therapy" during prolonged (150-minute) severe underperfusion and reperfusion. Protocol 1 consisted of underperfusion at a constant coronary perfusion pressure of 8 mm Hg. The control group (n = 8) received 5.5 mmol/l glucose and 15 microunits/ml insulin; the group treated with high levels of glucose and insulin (G + I) (n = 8) received 19.5 mmol/l glucose and 250 microunits/ml insulin during both underperfusion and reperfusion. Relative to the control group, the G + I group experienced 1) greater developed pressure during underperfusion and increased recovery during reperfusion, 2) preserved diastolic function during underperfusion and reperfusion, 3) lower coronary resistance and greater coronary flow during the underperfusion period, 4) increased glycolytic flux and preserved glycogen stores and high energy phosphate levels, and 5) less loss of myocyte enzymes (creatine kinase and alanine aminotransferase). In protocol 2, coronary flow was kept identical in control (n = 8) and G + I hearts (n = 8) during the underperfusion period, and left ventricular end-diastolic pressure was kept below 10 mm Hg in both groups to minimize subendocardial damage and vascular compression. In this protocol, the effect of the G + I intervention in the prevention of an increase in coronary resistance during the underperfusion period was distinguished from its myocellular metabolic effects; the high G + I substrate had protective effects on mechanical and metabolic function that were less marked than, but similar to, those in protocol 1, indicating that its mechanisms of protection during underperfusion affected both cardiac function and coronary resistance. We conclude that the G + I intervention, in clinically relevant concentrations, markedly protected severely underperfused myocardium for 150 minutes and may be a beneficial intervention in combination with reperfusion therapy in acute myocardial infarction.

Effects of two types of fish oil supplements on serum lipids and plasma phospholipid fatty acids in coronary artery disease.

Fish oil has consistently been shown to lower triglyceride levels, but its effects on low-density lipoprotein (LDL) cholesterol remain controversial. The current study compares the long-term effects of 2 different fish oil preparations (ethyl ester and triglyceride) versus olive oil in patients with coronary artery disease. Eighty-nine subjects were randomly assigned to receive capsules containing 6 g/day (triglyceride group) or 7 g/day (ethyl ester group) of n-3 fatty acids, or capsules containing 12 g/day of olive oil for 6 months. Mean triglyceride levels decreased by 28% in the ester and 32% in the triglyceride fish oil groups (p less than 0.05 for both). LDL cholesterol levels increased by 3% (difference not significant) in the ester and 12% (p less than 0.05) in the triglyceride fish oil groups; in hypertriglyceridemic subjects the increase was 23% (p less than 0.01) and 14% (difference not significant), respectively. Plasma phospholipid fatty acid analysis showed a fivefold increase in eicosapentaenoic acid levels in both fish oil groups (p less than 0.001), and a long-term decrease in arachidonic acid levels (p less than 0.001). Achieved eicosapentaenoic acid level correlated with the degree of increase in LDL cholesterol (r = 0.38, p less than 0.05). These data suggest that fish oil administration is associated with an increase in LDL cholesterol levels in a diverse group of patients with coronary artery disease; this change appears to be correlated with n-3 fatty acid absorption. The impact of this increase in LDL is unknown, but should be considered as potentially adverse.

Calibration as a source of imprecision in cholesterol testing. Ramifications for patient risk classification.

Routine calibration of a cholesterol assay system may compromise rather than improve precision. We compared an enzymatic assay on a centrifugal analyzer using a fixed factor with a factor recalculated from the response of standards assayed with each run. Over 36 batch runs, using three quality control materials, we found no statistically significant difference between the two methods in mean value, but in every case the fixed factor values were significantly more precise. With the risk classification system in effect at the time of the study, 32 (9.4%) of 342 patient serum specimens assayed for cholesterol were classified differently based solely on the method of data reduction. Thus, recalibration of our cholesterol assay system contributed to greater imprecision and to discrepancies in classification of patients' risk levels.

Clinical performance of the EMIT vancomycin assay.

In evaluating the EMIT system for vancomycin used in the Cobas Bio centrifugal analyzer, we found two potential problems, each of which may have important clinical ramifications. First, precision, though acceptable in concentrations up to 30 mg/L, was marginal in the range above 30 mg/L. Second, when EMIT values were compared with those by fluorescent polarization immunoassay (TDx), we found a good correlation but a significant proportional bias: [EMIT] = (0.877)[TDx] + 0.435 mg/L (r = 0.971). The proportional bias was much more pronounced in specimens with high creatinine values than in specimens with normal values for creatinine. It remains to be determined which method is more nearly accurate. This imprecision and proportional bias in specimens with increased creatinines lead us to conclude that the EMIT vancomycin system should be used with caution.

Reducing adult phlebotomy blood loss with the use of pediatric-sized blood collection tubes.

The feasibility of collecting smaller blood volumes during phlebotomy for diagnostic laboratory testing was evaluated by substituting pediatric-size for adult-size blood collection tubes. The volume of blood drawn with the use of pediatric-size tubes from 41 patients in an intensive care unit (120.2 mL total; 32.2 mL/day) was 46.8% lower than in that of a control population for which adult-size tubes were used (226.1 mL total; 55.6 mL/day). Sufficient blood was available for performance of all laboratory tests ordered at the time of the phlebotomy. Although substituting pediatric-size tubes does not address the problem of excessive use of laboratory tests, smaller tubes may reduce the severity of phlebotomy-induced anemia in adults without compromising laboratory test procedures.

Usefulness of lactate dehydrogenase and lactate dehydrogenase isoenzymes for diagnosis of acute myocardial infarction.

The usefulness of lactate dehydrogenase (LD) and LD isoenzymes in the diagnosis of acute myocardial infarction (AMI) is controversial. The present study reviewed 507 consecutive patients in whom creatine kinase, creatine kinase isoenzymes, LD and LD isoenzymes were ordered over a 1-month period. Of these, 249 had an insufficient number of serial enzyme determinations to establish a laboratory diagnosis of AMI. After excluding an additional 11 patients for other reasons, 247 patients remained for analysis. Of these, only 2 (0.8%) had myocardial infarction by standard clinical criteria with normal creatine kinase and creatine kinase-MB but elevated LD and abnormal LD isoenzymes. Seven patients (7 of 247, 2.8%) had false-positive LD isoenzymes. Thus, the routine use of LD and LD isoenzymes was of no use in most patients (96%) and led to the incorrect diagnosis of AMI more than 3 times as often as it helped with a correct diagnosis. Total 1-month charges for all the LD and LD isoenzymes obtained equalled +42,450. Therefore, it appears that LD and LD isoenzymes are not routinely useful in the diagnosis of AMI and may result in considerable unnecessary expense. It is suggested that LD and LD isoenzymes be ordered only under suspicion of late presentation (greater than 48 hours) of AMI.

The abbreviated Burn-Specific Health Scale.

We have developed and validated an abbreviated Burn-Specific Health Scale. The scale is self-administered by the patient, easy to score, and divided for purposes of analysis into several domains of life function. This scale has potential usefulness in many areas of burn care.

Clinical computing in a teaching hospital.

This report describes a hospital-wide clinical computing system that permits physicians, nurses, medical students, and other health workers to retrieve data from the clinical laboratories; to look up reports from the departments of radiology and pathology; to look up demographic data and outpatient visits; to look up prescriptions filled in the outpatient pharmacy; to perform bibliographic retrieval of the MEDLINE data base; to read, write, retract, edit, and forward electronic mail; and to request delivery of a patient's chart. During a one-week study period, from 300 video display terminals located throughout the hospital, 818 patient care providers used a common registry of 539,000 patients to look up clinical and laboratory data 16,768 times; 477 other hospital workers used the patient registry 46,579 times. In a separate study of 586 health care providers, 470 (80 per cent) indicated that they used computer terminals "most of the time" to look up laboratory results; in contrast, 48 (8 per cent) preferred printed reports. Of 545 hospital workers, 440 (81 per cent) indicated that the computer terminals definitely or probably made their work more accurate, and 452 (83 per cent) indicated that terminals enabled them to work faster. The large amount of use by clinicians and their judgment that the computer has been so helpful to them suggests that a reliable, comprehensive, and easy-to-use computer system can contribute substantially to the quality of patient care.

PaperChase. Self-service bibliographic retrieval.

During the past three years, from terminals within Beth Israel Hospital, Boston, 3,654 persons used a computer program called PaperChase to search the medical literature. While performing 39,022 searches, these persons had 1,976,421 references displayed and selected 449,690 of them for printing. Throughout this period, the program underwent continual modification. Each year the number of searches increased--from 10,678 to 11,541 to 16,803. Each year the percentage of new users who were unsuccessful decreased--from 16 to 13 to 11. By the end of the third year, 549 people had completed 20 or more searches. PaperChase enables people to search the medical literature themselves, and thus provides a new experience in computerized bibliographic retrieval. When made available without charge in a teaching hospital, PaperChase is widely used.

PaperChase: a computer program to search the medical literature.

This report describes PaperChase, a computer program that permits users to search medical literature by author's name, journal of publication, title word, or medical subject heading (MeSH term), as indexed by the National Library of Medicine. PaperChase was installed in the medical library of Beth Israel Hospital in Boston, with a data base of 400,000 references--nearly all the articles shelved there. During the first year of operation, 1032 medical students, house officers, practicing physicians, and other library users, without formal instruction or user's manual, conducted 8459 searches and displayed 399,821 references, 97,769 of which they selected for printing. Among users who conducted an initial search, 49 per cent returned to complete five or more searches, and 14 per cent returned to complete 20 or more. The large number of satisfied users and the low installation and operating costs suggest that PaperChase could be a valuable means of providing widespread computerized bibliographic retrieval.

A redefinition of normal acid-base equilibrium in man: carbon dioxide tension as a key determinant of normal plasma bicarbonate concentration.

It has been shown recently that normal acid-base equilibrium in the dog is characterized by a strong positive correlation between plasma bicarbonate concentration and PCO2. The present study was undertaken to examine the possibility that a similar relationship between normal levels of PCO2 and plasma bicarbonate might be present in man. The results indicate that values for bicarbonate within the normal range are highly dependent upon the prevailing level of PCO2 ([HCO3-] = 0.36 PaVCO2 + 10.4; r = 0.73). Thus, approximately 50% of the normal variance in bicarbonate concentration is explained simply by the variance in PCO2. The joint confidence region for bicarbonate concentration and PCO2, that can be derived from these data provides a new and more rigorous definition of normal acid-base equilibrium in man.

Advances in radiologic reporting with Computerized Language Information Processing (CLIP).

Computerized Language Information Processing (CLIP) is a system of radiologic reporting in which the user interacts with a computer keyboard and cathode-ray tube terminal to generate coded reports. The hierarchical medical classification on which the code is based permits rapid on-line compilation of reports of any degree of complexity. The system provides organized sets of pre-assembled statements that are rapidly accessed and modified for each examination. Although the reports are printed in English, they are held in the computer as a succinct code that is eminently suited for permanent storage and rapid retrieval.