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Biomedical subjects

J F O'Brien

Publications and source records attributed to J F O'Brien.

At least 19 recordsLinked to original sources
PubMed1992

Fluid resuscitation in traumatic hemorrhagic shock.

Fluid resuscitation from traumatic hemorrhagic shock is a critical component of therapy for the critically injured patient. Therapy is aimed at restoring hemodynamic stability and oxygen delivery to tissues. The route and rate of fluid infusion, the temperature of the fluid infused, the type of asanguineous fluids chosen, and the timing of red cell transfusion may all impact substantially on the patient outcome. Complications of fluid therapy, especially edema, may be related to the choice of fluid infused. Identification of hypovolemia and methods to monitor tissue are important aspects of patient care.

Animals↗
PubMed1991

Clinical evaluation of high-performance affinity chromatography for the separation of bone and liver alkaline phosphatase isoenzymes.

The newly described high-performance (HPLC) affinity chromatography method for the separation of human bone and liver alkaline phosphatase (ALP, EC 3.1.3.1) isoenzymes was clinically evaluated. The improved resolution of bone from liver isoenzyme and lower detection limit was achieved by conjugation of wheat-germ lectin (WGL) to a diol-bonded silica gel column, stepwise elution with N-acetylglucosamine (NAG) and post column derivatization using para-nitrophenyl phosphate substrate. To establish a reference interval, we measured bone ALP in 86 healthy women, ages 33 to 95 years. The normal reference interval is described by a piecewise linear regression on age (R2 = 0.20, P less than 0.01). For women less than or equal to 45 years, bone ALP, U/l = 8.495. For normal women between ages of 45 to 55 years, bone ALP, U/l = -12.765 + 0.472* age. If age greater than or equal to 55 years, then bone ALP, U/l 13.219. In all 10 patients with primary biliary cirrhosis, serum bone ALP levels were elevated. In addition, sera from 43 patients with diverse metabolic bone diseases were evaluated. As expected, the sera from all 6 patients with Paget's disease and 2 with osteolytic metastasis had bone ALP activity which was greater than 3 standard deviations (SD) from the mean. In all 10 patients with hypoparathyroidism, bone ALP levels were depressed. Only 1 of the 9 patients with glucocorticoid excess and 2 of the 7 patients with primary hyperparathyroidism had elevated bone ALP when compared to the 95% confidence interval for the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Significance of mildly elevated creatine kinase (myocardial band) activity after elective abdominal aortic aneurysmectomy.

The clinical significance of mildly elevated creatine kinase (CK) myocardial band (MB) enzyme levels in patients undergoing elective repair of an abdominal aortic aneurysm was evaluated retrospectively in 348 patients. For each patient, preoperative and postoperative electrocardiograms (ECGs) were interpreted blindly for left ventricular hypertrophy, ST segment abnormality, left bundle branch block, right bundle branch block, left axis deviation, atrial fibrillation, T wave abnormality, and Q waves. A total of 107 patients (31%) had postoperative CK-MB elevations of trace or greater; 37 had trace, 35 had 1% to 4%, and 35 had greater than or equal to 5% elevation. There was no difference in survival between those with trace and no CK-MB elevation. Patients with increased CK-MB (greater than or equal to 1%) values were more likely to have ECG abnormalities. The following ECG (either preoperative or postoperative) abnormalities were univariately related to decreased postoperative survival: left ventricular hypertrophy (P less than 0.001), ST segment abnormalities (P less than 0.001), left bundle branch block (P less than 0.001), the combination of right bundle branch block and left axis deviation (P = 0.006), Q wave infarction (P less than 0.001), and atrial fibrillation (P less than 0.001). There were 15 in-hospital deaths, and 333 patients were discharged and followed-up for a median of 4.6 years. There were 97 posthospitalization deaths, 61% of which were due to cardiac causes. Overall survival was associated with the degree of CK-MB elevation; the higher the CK-MB, the worse the survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Rectal thiopental compared with intramuscular meperidine, promethazine, and chlorpromazine for pediatric sedation.

STUDY OBJECTIVES: We studied the hypothesis that rectal thiopental is an effective agent for emergency department pediatric sedation and may have advantages over a more traditional regimen. DESIGN: Rectal thiopental 25 mg/kg was compared with the combination of meperidine 2 mg/kg, promethazine 1 mg/kg, and chlorpromazine 1 mg/kg in a prospective, randomized, double-blinded study. TYPE OF PARTICIPANTS: Children between 18 months and 6 years of age presenting to our teaching hospital ED for laceration repair were entered after the clinical decision was made to sedate. Patients with altered sensorium, medical contraindications to sedation, or medication allergy were excluded. INTERVENTIONS: After informed consent, each patient received IM injection (drug combination or placebo) and rectal suspension (rectal thiopental or placebo) simultaneously. MEASUREMENTS AND MAIN RESULTS: Vital signs, pulse oximetry, and pediatric Glasgow Coma Scores were recorded before and every 15 minutes after sedation until discharge. Intradermal lidocaine and suturing began when the patient appeared adequately sedated, and response was numerically scored. Patients were discharged when able to stand. Twenty-nine patients 34 +/- 13 months old were studied. Fifteen patients received rectal thiopental, and 14 received the drug combination. Analysis using the Wilcoxon two-sample test revealed no differences in age, sex, weight, or wound location between groups. The time course of sedation was different for the two treatment regimens. At 15 and 30 minutes after administration, patients who received rectal thiopental were more deeply sedated than those who received the drug combination, as evidenced by significantly lower Glasgow Coma Scores (P less than .05). Accordingly, time from medication administration to suturing was 29 +/- 12 minutes in the thiopental group and 54 +/- 33 minutes (P less than .01) in the drug combination group. Patients in the thiopental group also recovered more quickly and were discharged approximately one-half hour earlier than those in the drug combination group (89 +/- 25 vs 120 +/- 44 minutes, P less than .05). No difference in response to lidocaine injection or suturing was demonstrated between the groups. Laceration repair time was comparable between the groups. There were eight sedation failures (three of 15 in thiopental group and five of 14 in drug combination group, P = NS). Vital signs remained stable, no adverse reactions occurred, and no patient had decreased oxygen saturation to less than 95%. CONCLUSION: Rectal thiopental is superior to this drug combination for pediatric sedation because it can be administered painlessly, has a more rapid onset and offset of action, and is of equal safety and efficacy at the dosage studied.

Administration, Rectal↗
PubMed1991

Screening for biotinidase deficiency in children with unexplained neurologic or developmental abnormalities.

To test the hypothesis that the frequency of biotinidase deficiency is greater in children with unexplained developmental delay or neurologic abnormalities than in the general population, we studied children seen at a large outpatient clinic over a four-year period who had one or more of these neurologic abnormalities and for whom no specific cause for their abnormalities could be found. The group totaled 274 children (163 boys; 111 girls) whose ages ranged from 2 weeks to 17 years. Characteristics were IQ/DQ, 30 to 70 in the 115 for whom scores were available; 41% had seizures; 15% had sensorineural hearing loss; 54% showed gross motor delay or ataxia; and 27% had decreased muscle tone. One patient with a classical clinical picture of biotinidase deficiency was diagnosed during the study period and was not included in the study. None of the patients with nonclassic findings had a deficiency of biotinidase activity. Our results suggest that biotinidase deficiency does not account for a large proportion of children with unexplained neurologic abnormalities or developmental delay. This does not negate the importance of biotinidase testing in children with clinical patterns specifically suggestive of the deficiency.

Adolescent↗
PubMed1991

Quantifying bone and liver alkaline phosphatase by the resolution of two-component inactivation data obtained with a centrifugal analyzer.

In this method we use a linear equation to resolve two-component decay data from the urea inactivation of mixtures of alkaline phosphatase (EC 3.1.3.1) of liver and bone origin. The specificity for the bone/liver isoenzyme is enhanced by including L-phenylalanine in the urea reaction to inhibit the intestinal and placental forms. Bone and liver fractions are each quantified from results of a single run on the centrifugal analyzer. Total activity and the L-phenylalanine-inhibited fraction are measured on separate runs. A simplification of this method has been used in our laboratory for 14 years in performing greater than 80,000 analyses of clinical specimens. Speed, accuracy, and precision are improved over previous methods by this mathematical solution. Data reduction is automated through the use of a personal computer interfaced to the analyzer. With such systems generally available, this method can now be suggested as suitable for routine use to separate these and perhaps other isoenzyme mixtures.

Alkaline Phosphatase↗
PubMed1990

Isolated aspartate aminotransferase elevation due to macroenzyme formation with liver biopsy correlation.

Serum aspartate aminotransferase (AST) has rarely been reported to complex with immunoglobulins, resulting in abnormally elevated serum activity. A similar phenomenon occurs with serum amylase, resulting in the more common entity of macroamylasemia. AST macroenzyme formation can occur in the presence or absence of liver disease and, at times, can lead to a false suspicion of liver disease. We describe the abnormal liver histology found in a healthy patient with isolated AST elevation due to AST macroenzyme formation.

Aspartate Aminotransferases↗
PubMed1990

Liver- and bone-derived isoenzymes of alkaline phosphatase in serum as determined by high-performance affinity chromatography.

To separate liver and bone alkaline phosphatase (ALP) isoenzymes in human serum, we used high-performance affinity chromatography (HPAC) on a column of wheat-germ lectin conjugated to 7-microns-diameter silica particles and an eluent containing N-acetyl-D-glucosamine (NAG). On-line spectrophotometric detection of ALP involved pumping diethanolamine-buffered p-nitrophenyl phosphate solution post-column. Bone and liver isoenzymes could be separated into two peaks with only 10% overlap when an exponential gradient was used. A linear-step gradient separated 80.9% of liver ALP and 91.6% of bone ALP in two distinct peaks. True bone and liver ALP peak areas for the linear-step gradient were determined by using correction factors, because each peak contained a co-eluted portion of the other ALP isoenzyme. The detection limit improved 10-fold over those of other techniques for ALP isoenzymes, owing to the relatively large sample that could be applied to the column. Correlation with a urea-inactivation procedure was reasonable for patients' serum samples (r = 0.98 and 0.79 for liver ALP and bone ALP, respectively).

Alkaline Phosphatase↗
PubMed1989

Effect of long-term freezer storage, thawing, and refreezing on selected constituents of serum.

We determined the effect of long-term freezer storage and repeated thawing and freezing of serum on concentrations of electrolytes (sodium, potassium, calcium, and phosphate), enzymes (aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatine kinase), total protein, tumor markers (carcinoembryonic antigen and alpha-fetoprotein), and other substances. Vials (1 ml) of frozen serum from a single blood drawing from 40 women with no breast disease and 70 with benign breast disease were analyzed annually from 1983 to 1987. Blood had been obtained from 40 subjects in 1978, 40 in 1980, and 30 in 1983. Thawing and refreezing studies were done in two ways: (1) serum samples from 30 subjects with benign breast disease were thawed at weekly intervals for 6 weeks and (2) serum samples from 30 patients with stage IV breast cancer were analyzed for alpha-fetoprotein and carcinoembryonic antigen, and serum specimens from 23 patients with benign breast disease and 7 control subjects were analyzed for lactate dehydrogenase and creatine kinase after thawing and keeping the samples at room temperature for up to 4 hours and then refreezing them. For measuring laboratory variability, duplicate samples were processed. Long-term storage (up to 10 years) and repeated thawing and refreezing did not affect the results of any tested constituents of serum. Although most measurements showed statistically significant variability over test cycles, these differences were thought to be due to laboratory variability.

Biomarkers, Tumor↗
PubMed1989

Does exercise training alter myocardial creatine kinase MB isoenzyme content?

Skeletal muscle biopsies from highly trained endurance athletes have been shown to contain an increased percentage of the creatine kinase MB (CK-MB) isoenzyme, which has been attributed to continuous regeneration of the skeletal muscle fibers in response to exercise-induced injury. The purpose of this study was to determine whether myocardium undergoes a similar degenerative-regenerative process as a result of exercise training. Fifteen mongrel dogs underwent a 12-wk period of training (N = 8) or cage confinement (N = 7). The animals were then sacrificed, and samples of left and right ventricular myocardium were analyzed for total CK activity and CK-MB isoenzyme content. Percentages of CK-MB were slightly but insignificantly higher from both ventricles of exercise-trained as compared with cage-confined dogs: left ventricle, 4.6 +/- 0.6% vs 3.3 +/- 0.6%, respectively (P = 0.15); right ventricle, 4.0 +/- 0.4% vs 3.0 +/- 0.8%, respectively (P = 0.29). We conclude that chronic exercise training does not induce physiologically important degenerative changes in myocardium.

Animals↗
PubMed1989

Alkaline phosphatase isoenzymes of liver and bone origin are incompletely resolved by wheat-germ-lectin affinity chromatography.

We used wheat-germ-lectin affinity chromatography as a tool to investigate the structure of alkaline phosphatase (ALP, EC 3.1.3.1) and to obtain fractions enriched in either bone or liver ALP activity. Liver and bone isoenzymes in serum samples were incompletely resolved except that the activity in the nonretained fraction (fraction 1) always represented pure liver isoenzyme and constituted a larger percentage of total activity in pooled sera with increased liver ALP activity than in pooled sera with increased bone activity. In contrast, a more avidly retained ALP activity, presumably with high glycosylation, was found in human serum with high activity of bone ALP. Using a solid-phase immunoassay, we examined the fractions obtained from the wheat-germ-lectin-Sepharose 4B column to determine whether the isoenzyme preference of the monoclonal antibody was markedly influenced by the degree of glycosylation. Whether samples contained high proportions of liver or of bone isoenzyme activity, the nonretained fraction contained a higher percentage of liver ALP, whereas the more strongly bound fraction contained a higher percentage of bone ALP. Except for eluted fractions that either contained no detectable N-acetylglucosamine or the highest percentage of it, the avidity of the liver-isoenzyme-specific monoclonal antibody for ALP seemed to be independent of the degree of glycosylation, suggesting that the epitope for monoclonal antibody may be expressed in some structure other than the carbohydrate moieties.

Acetylglucosamine↗
PubMed1988

Does low-energy helium-neon laser irradiation alter "in vitro" replication of human fibroblasts?

Cultured human fibroblasts were treated in a controlled, randomized manner to assess the effect of low-energy (0.9 mW) helium-neon (HeNe) laser irradiation on cellular proliferation. Two trials were performed: one with fibroblasts in the third to fourth passage and the other with fibroblasts in the 13th to 14th passage. In each trial, separate plastic petri dishes were inoculated with the cells, maintained in a 5% CO2-95% air atmosphere, and nourished with HB 102 media. Treatment began 48 h after inoculation with daily 60-s irradiations of the "treated" cultures over a 5-d period. Control cultures underwent the same handling but were not irradiated. A significant stimulative, or inhibitive, effect on replication was not found in either trial.

Cell Division↗
PubMed1988

Concurrent assays of circulating bone Gla-protein and bone alkaline phosphatase: effects of sex, age, and metabolic bone disease.

We measured the serum concentrations of 2 biochemical markers of bone formation, bone Gla-protein (BGP) and bone alkaline phosphatase (BAP), in 164 normal subjects and 164 patients with metabolic bone disorders. The data were reported as Z scores (deviation in SDs from the sex-specific age regression in normal subjects). Both serum BGP and BAP distinguished abnormalities well (mean Z scores for BGP and BAP, respectively) and gave concordant results in patients with hypoparathyroidism (-1.7, -1.4), hyperthyroidism (+1.1, +1.8), primary hyperparathyroidism (+3.6, +2.5), acromegaly (+1.2, +2.8), and postmenopausal osteoporosis (+0.4, +1.9). The 2 markers gave discordant results, however, in patients with glucocorticoid excess (-2.4, +0.9), Paget's disease (+1.8, +41.8), chronic renal failure (+16.3, +0.4), and osteolytic metastases (-1.4, +5.9). These discrepancies may have occurred because serum BGP and BAP concentrations reflect different aspects of osteoblast function or because there are differences in their clearance from the circulation. Consequently, more information is derived about the level of bone formation across the wide range of metabolic bone disorders when both biochemical markers are assayed.

Adult↗
PubMed1988

Effect of two anticoagulants on leukocyte yield and function, and on lysosomal enzyme activity.

We compared acid citrate-dextrose (ACD-B) and heparin to determine which anticoagulant better preserves leukocytes for lysosomal enzyme assays if processing was done immediately or delayed for 24 h or more. Twenty normal subjects had blood drawn into tubes containing either ACD-B or heparin. The leukocytes were isolated by sedimentation in dextran (50 g/L) less than 2, 24, 48, and 72 h later. The most apparent difference was that cell counts indicated a 30% reduction in the number of leukocytes for ACD-B and a 95% reduction for heparin-treated cells at 48 h. The neutrophil function assay indicated that leukocyte processing must be done in less than 24 h regardless of the anticoagulant used, and that heparin is to be preferred. A comparison of heparin and ACD-B for maintenance of the activity of arylsulfatase A (EC 3.2.6.1) and hexosaminidase (EC 3.2.1.50) indicates that there is no effect of anticoagulant. However, at 48 h after venipuncture, there is an 80% reduction in the number of heparin-treated samples that are suitable for use in the assay. Those laboratories doing lysosomal enzyme tests on mailed specimens, which are most often greater than 24 h old, should use ACD-B as anticoagulant.

Anticoagulants↗
PubMed1987

Macroenzyme as a cause of unexplained elevation of aspartate aminotransferase.

Aspartate aminotransferase (AST) can exist as a macroenzyme by forming a complex with an immunoglobulin. This immunoglobulin-complexed macromolecule can cause an elevation in serum AST activity, which may be detected on routine blood chemistry analysis and erroneously considered to indicate the presence of liver disease. Clinicians should be aware of this phenomenon so patients are not subjected to unnecessary procedures. In patients with unexplained AST elevation, liver and muscle disease can be biochemically excluded by the finding of normal serum levels of alanine aminotransferase and creatine kinase. The presence of macro-AST can be determined by exclusion chromatography, electrophoresis, and activation assays with pyridoxal 5-phosphate. The elevated AST values can persist for many years.

Aged↗
PubMed1987

The rib deformity in adolescent idiopathic scoliosis. A prospective study to evaluate changes after Harrington distraction and posterior fusion.

A prospective study to investigate changes in the rib hump or rib deformity after correction of the lateral curvature in adolescent idiopathic scoliosis is reported. The operative treatment for 47 patients was by a Harrington distraction rod and posterior fusion. Before operation and at follow-up, measurements of the Cobb angle, of vertebral rotation, and of the rib deformity were taken. Despite operative correction of the lateral curve, there was a progression of the rib deformity in 64% of the cases after four years. Correction of the lateral curve may thus have no effect on vertebral rotation and cannot be guaranteed to effect a permanent reduction of the rib hump.

Adolescent↗