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Biomedical subjects

J F O'Brien

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

At least 55 records · Page 3Linked to original sources

Insulin and glucose levels during CPR in the canine model.

Cardiopulmonary arrest and resuscitation produces tremendous physiological stress with resultant biochemical derangements. We undertook this study to determine insulin and glucose levels during cardiopulmonary arrest in the canine model. Baseline insulin and glucose levels were obtained from an ascending aortic arch catheter in six mongrel dogs. Ventricular fibrillation was induced by an electrical stimulus and ventilation was terminated. After five minutes of fibrillation, cardiopulmonary resuscitation (CPR) was initiated using external, mechanical CPR and a continuous epinephrine infusion at 5 micrograms/kg/min. Serum insulin and glucose levels were repeated 15 minutes after beginning CPR. Mean blood glucose 15 minutes after initiation of resuscitation (379 +/- 114 mg/dL) was significantly increased from prearrest levels (124 +/- 29 mg/dL, P less than .01). Mean serum insulin 15 minutes after initiation of resuscitation (11.3 +/- 3.3 microU/mL) was significantly decreased compared to prearrest levels (16.2 +/- 6.0 microU/mL, P less than .05). During ischemia, the myocardium becomes dependent primarily on glucose as a source of energy. Inappropriately low insulin levels during CPR may adversely affect an already compromised myocardial glucose metabolism. Further investigation is needed to determine the utility of insulin infusion during CPR.

Animals

Safe intubation in cervical spine injury.

Traumatic spinal injury is an ongoing community problem. Anatomical stability of the cervical spine depends on the integrity of the bony and ligamentous structures forming the cervical spine. Such stabilising structures are divided into two groups. These are designated anterior and posterior columns. One or both columns may be damaged during traumatic spinal injury. Not all spinal injuries are unstable. Instability may be predicted by viewing anterior-posterior and lateral X-rays of the cervical spine. C1 and C2 injury necessitates special through-mouth views. Instability of the neck requires a different intubation technique. A safe intubation technique is described, the essence of which is to stabilise the neck with longitudinal traction and avoid extension at the fracture site.

Anesthesia

Isolation and preliminary characterization of a monoclonal antibody that interacts preferentially with the liver isoenzyme of human alkaline phosphatase.

We have prepared murine monoclonal antibodies against isolated human bone alkaline phosphatase (ALP, EC 3.1.3.1). Hybridoma supernates were separately screened for reactivity against both human liver and bone ALP. Although most antibody-positive hybrids showed similar reactivity against both isoenzymes, one hybridoma produced an antibody that interacted preferentially with liver ALP. This antibody was purified and used to establish an immunoassay to differentiate liver ALP from bone ALP. When equal activities of the two isoenzymes (as determined by a conventional enzymic assay) were measured by the immunoassay, a fivefold greater response was obtained with liver than with bone ALP. The immunoassay can be used to measure the proportions of the bone and liver isoenzymes in mixtures of them. Cross reactivity with human placental and intestinal ALP is less than 3% relative to liver ALP. These findings support the feasibility of developing immunological methods to differentiate these isoenzymes in the clinical laboratory.

Alkaline Phosphatase

Duplication of part of chromosome 1q: clinical report and review of literature.

We report a male infant with a 47,XY, + der(22),t(1;22)(q32;q11)pat karyotype. Thus, he has duplication of chromosomes 1(q32----qter) and 22(pter----q11). Six patients with dup 1(q32----qter) and eight with dup 1(q42----qter) have been described. These two groups of patients share several manifestations, including postnatal growth retardation; relative macrocephaly with widely separated sutures or large fontanelles; prominent forehead; highly arched palate; micrognathia; downward slant of the palpebral fissures; broad, flat nasal bridge; and apparently low-set, malformed ears. Although many of these abnormalities are nonspecific, partial duplication of 1q should be considered in infants with relative macrocephaly, large fontanelles, and downward slant of the palpebral fissures. Our patient had duplication of the part of chromosome 22 that may be associated with the clinically variable cat-eye syndrome. Patients with dup 22(pter----q11) may also have downward slant of the palpebral fissures, micrognathia, and apparently low-set, malformed ears. The structural gene locus for beta-glucosidase has been mapped to chromosome 1. beta-Glucosidase activity in fibroblasts from our patient was normal, and his parents' activities were not significantly different from those of control individuals. Therefore, either the locus for this enzyme is not present on 1(q32----qter) or the enzyme does not consistently show a substantial gene-dose effect.

Abnormalities, Multiple

Selenium deficiency and fatal cardiomyopathy in a patient on home parenteral nutrition.

An adult patient with chronic idiopathic intestinal pseudo-obstruction maintained on home parenteral nutrition for 6 consecutive years died from cardiomyopathy and ventricular fibrillation. Postmortem examination of the heart revealed widespread myocytolysis and replacement fibrosis similar to that seen in the selenium deficient cardiomyopathy in China (Keshan disease) and animal models. Selenium deficiency in this patient was documented with extremely low concentrations of selenium and decreased activity of the selenoprotein, glutathione peroxidase, in blood, heart, liver, and skeletal muscle. Reports of selenium deficient diets causing myocardial damage in humans and animals and the findings in our patient strongly suggest that his fatal cardiomyopathy was caused by selenium deficiency.

Adult

Serum levels of creatine phosphokinase and its isoenzymes in normal and stressed neonates.

Twenty-six normal newborns (13 male, 13 female) with normal prenatal histories, no perinatal stress, and normal vaginal deliveries had creatine phosphokinase (CPK) activity and isoenzyme activities assayed in cord blood and in 24-hour postpartum serum. Total CPK activity was high in cord blood when compared with adult control values. Moreover, the total CPK was significantly higher in serum at 24 hours of age compared with cord blood. There was a significant increase in both the skeletal muscle isoenzyme and the cardiac muscle isoenzyme from birth to 24 hours of age. There was a decrease in the brain isoenzyme at 24 hours of age which was not statistically significant. These results were compared with values obtained in a group of 10 neonates with severe cardiac problems. Three of the ill neonates had significant elevation of total serum CPK and the skeletal muscle isoenzyme when compared with the normal newborns. There were no significant differences between the normal infants and the ill neonates for the cardiac isoenzyme and the brain isoenzyme. These data suggest that caution should be used in the diagnosis of certain neonatal cardiac syndromes based on serum CPK levels and isoenzyme alone.

Adult

Clinical and extraneural histologic diagnosis of neuronal ceroidlipofuscinosis.

Neuronal ceroid-lipofuscinosis is manifested by visual and intellectual deterioration and seizures. Autofluorescent lipopigments are found in neural and many nonneural tissues, with characteristic staining and ultrastructural properties. Presumptive diagnosis can usually be made on the basis of history, physical examination, and electrodiagnostic tests, but in the absence of a specific biochemical defect, histologic confirmation is essential. A 6-year-old boy with the clinical appearance of the juvenile form of the disease had sea-blue histiocytes in the bone marrow, and curvilinear profiles in ultrastructural inclusions in skin biopsy tissue, cultured skin fibroblasts, and bone marrow cells.

Ceroid

Sandhoff disease: impaired catabolism of sulfated glycosaminoglycans in cultured fibroblasts.

Fibroblasts cultured from the skin of patients with Sandhoff disease accumulate excessive amounts of sulfated glycosaminoglycans because of degradative inadequacy. Only a slight such abnormality in the metabolism of sulfated glycosaminoglycans was seen in fibroblasts from patients with Tay-Sachs disease. The defective glycosaminoglycan catabolism in Sandhoff fibroblasts is specifically corrected by intracellular replacement of beta-N-acetyl-hexosaminidase. Both beta-N-acetyl-hexosaminidase A and B are effective in bringing about such correction, although there seem to be differences in specificity. Our findings suggest that in Sandhoff disease there is an impaired catabolism of glycosaminoglycans in addition to the defect in the degradation of glycosphingolipids.

Acetamides