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Biomedical subjects

A Duncan

Publications and source records attributed to A Duncan.

At least 127 records · Page 7Linked to original sources

A hypercoagulable state follows orthotopic liver transplantation.

Orthotopic liver transplantation may be associated during the postoperative period with hepatic artery thrombosis, a catastrophic occurrence generally necessitating emergency retransplantation. To assess the contribution of the coagulation mechanism to this complication, the levels of procoagulant and anticoagulant proteins were followed in 41 liver transplant patients during the first 10 postoperative days. The mean activities of all procoagulant factors reach normal values on day 1 except for factors V and VII, which achieve normal activity by day 3. Supernormal levels of factor VIII activity and antigen are noted (peak values on day 5 of 334% +/- 113% and 481% +/- 260%, respectively). The anticoagulant proteins show delayed recovery, with deficient antithrombin III levels seen in 81% of patients on day 3 and 57% on day 5. Similarly, proteins C and S are subnormal in 24% and 21%, respectively on day 3, and 20% and 10%, respectively, on day 5. During this period, elevated levels of thrombin/antithrombin complexes are encountered, reflecting in vivo activation of the coagulation mechanism. Activated thrombin is, therefore, being generated at a time when a decrease in the major regulatory anticoagulant proteins exists. These data suggest an imbalance between the hemostatic and thrombotic mechanisms and indicate a sustained prothrombotic state that may contribute to the risk for hepatic artery thrombosis. Using a regimen of low-dose heparin and fresh frozen plasma infusion, no thromboses have been seen in 65 consecutive liver transplants.

Blood Coagulation Disorders↗

The effect of variation in dietary protein or mineral supply on calcium and phosphorus metabolism in lactating ewes.

Two experiments are described in which changes in both nitrogen and mineral balance were monitored in ewes during lactation. In Expt 1, two groups (n 6) of ewes were fed on diets that were either high (15 g crude protein (N X 6.25; CP)/MJ metabolizable energy (ME)) or low (10 g CP/MJ ME) in protein content, and concurrent N and mineral balance studies were made at intervals during lactation with 45Ca and 32P being used to monitor faecal endogenous calcium and phosphorus losses. Ewes fed on the high-protein diet maintained a positive N balance during early lactation, whereas those fed on the low-protein diet were in negative N balance. Both groups, however, showed the same degree of negative Ca and P balance, with the amounts lost being directly related to milk yield. This indicates that loss of mineral from the skeleton at this time is not secondary to a loss of bone matrix due to a shortfall in dietary protein supply. In Expt 2, two groups of ewes (n 4) were fed on diets in late pregnancy that were either just adequate or generous in Ca and P supply relative to requirement (TCORN, 1990). After parturition both groups were fed on a diet which was formulated to meet their estimated Ca and P requirements for lactation. As in the previous experiment both groups were in negative Ca and P balance in early lactation and variation in dietary Ca and P supply during pregnancy had no effect on the extent of this loss. Alternative explanations for the cause of this loss of mineral from the skeleton are discussed.

Amino Acids↗

99Tcm-nanocolloid imaging in inflammatory bowel disease.

We have used 99Tcm-labelled nanocolloid in an attempt to locate areas of inflamed bowel wall or abscesses in five patients with ulcerative colitis and nine with Crohn's disease. The scintigraphic findings were evaluated by comparison with those of recent barium studies and, in three patients, with surgical findings at laparotomy. It proved difficult to localize segments of inflamed bowel accurately with 99Tcm-nanocolloid because of the accumulation of radioactivity in the gut lumen, especially 2 or more hours after injection. However, there was little uptake of the labelled nanocolloid by areas of inflamed gut wall in the period before 2 h. When 99Tcm-nanocolloid scans were compared with 111In-WBC scans in eight patients who had both investigations, 99Tcm-nanocolloid scintigraphy was considerably less sensitive than 111In-WBC scintigraphy. One abscess was located correctly; the other was obscured by nearby bladder and bone marrow radioactivity. We conclude that 99Tcm-nanocolloid scanning is neither sensitive nor reliable enough for assessing the location of inflamed bowel wall or the presence of abscess in patients with inflammatory bowel disease.

Adult↗

Chromogenic assay for equine plasminogen.

A functional assay for equine plasminogen was established, using urokinase as the activator, a synthetic chromogenic substrate, a computer-assisted centrifugal analyzer, and acidified/neutralized plasma. One documented effect of plasma acidification appears to be inactivation of alpha-2-antiplasmin. Intra- and interassay precision testing yielded coefficients of variation of 4.1% (n = 10) and 5.6% (n = 26), respectively. Plasminogen was stable in equine plasma stored up to 1 week at 4 C and up to 5 months at -70 C. Plasminogen in nonacidified equine plasma was not activated by urokinase, streptokinase, tissue plasminogen activator, or tissue plasminogen activator plus soluble fibrin. Streptokinase also failed to activate plasminogen in acidified/neutralized equine plasma.

Animals↗

Evaluation of coagulation and fibrinolysis during the prodromal stages of carbohydrate-induced acute laminitis in horses.

The balance of coagulation and fibrinolysis was studied in 15 horses during the prodromal stages of acute laminitis induced by carbohydrate overload. Progression of the disease was stopped 12 to 24 hours before the expected onset of lameness in trial 1 (8 horses) and at the onset of lameness in trial 2 (7 horses). The end points in each trial were identified by specific changes in blood pressures (trial 1) and by changes in pulse, rectal temperature, and arterial pressure (trial 2) that were anticipated on the basis of original description of the experimental model. Blood samples for hemostasis evaluation were collected before and after carbohydrate overload in trial 1 and after carbohydrate overload in trial 2. Significant changes were not detected in platelet count, mean platelet volume, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, plasminogen concentration, alpha-2-antiplasmin, antithrombin III, protein C, thromboxane B2, or fibrin(ogen) degradation product concentration. We concluded that an imbalance in coagulation and fibrinolysis is not pathogenic in the onset of experimentally induced equine acute laminitis. Because several test methods used to evaluate hemostasis in these horses were new, reference values for 34 healthy adult horses were established.

Animals↗

Hypolactasia and Crohn's disease: a myth.

A retrospective analysis was made of jejunal biopsies performed on 62 patients with Crohn's disease for disaccharidase levels and routine histology. Thirteen patients with irritable bowel syndrome acted as a control group. Two patients with Crohn's disease had hypolactasia. Two patients had marginally low sucrase levels, but all patients had normal maltase levels. Only one patient with irritable bowel syndrome had hypolactasia with normal histology. There were no significant differences between the two groups. Four patients with Crohn's disease had abnormal jejunal histology. The prevalence of hypolactasia in patients with Crohn's disease is not increased. Ideally lactase deficiency in patients with Crohn's disease should be confirmed before starting a lactose-free diet which can produce further restrictions on dietary intake.

Adult↗

Glioblastoma multiforme in adults: results of treatment.

One hundred and thirty adult patients with brain tumors were treated in the Department of Radiation Oncology, Brown Cancer Center, University of Louisville School of Medicine from 1973 to 1980. Forty-one patients (39%) were diagnosed with glioblastoma multiforme. Forty-two percent of the patients were in the age group of 51-60 years. There were 24 males and 27 females. Forty-seven percent of the patients had partial resection, 27% had total excision and 26% had biopsy only. The radiation dose ranged from 4400 to 6600 rad with a median dose of 5500 rad. The median survival was 8.5 months, (range 3 to 120 months), 38% of patients survived one year or more and 10% survived 2 years or more. A detailed review of the current policy of treatment and of the ongoing clinical trials is done in this paper.

Adult↗

Antigenic assay for protein C determination in horses.

An antigenic assay was developed for determination of protein C in horses. Protein C, a natural, vitamin K-dependent anticoagulant component in blood, was isolated from equine plasma, a specific antibody was produced in goats, and a rocket electroimmunophoresis assay was established. Tests were performed to verify the identity of the isolated protein C and to determine the purity of the antibody. Protein C antigen was measured in plasma from 34 clinically normal horses, and values were compared with amidolytic function values. The mean (+/- SD) values for the 2 test methods were similar (antigen content, 104.5 +/- 13.8%; amidolytic activity, 104.6 +/- 17.5%), but the correlation coefficient was 0.1. Four horses given Na coumarin had markedly decreased plasma protein C amidolytic activity and minimal decrease in protein C antigen content.

Animals↗

Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy.

We measured serum alkaline phosphatase isoenzymes and osteocalcin levels in 40 healthy women at 4-week intervals throughout uncomplicated pregnancies and 6 weeks after delivery in 17 women. Serum bone alkaline phosphatase was significantly higher in the third trimester than in early pregnancy (P less than 0.001), and this elevation was still apparent at the end of the puerperium, suggesting increased bone turnover. Serum osteocalcin was not detected (less than 0.2 micrograms/L) after the first trimester in the majority of women, and it reappeared within 48 h after delivery. The disappearance of osteocalcin after the first trimester and its rapid reappearance after delivery suggest placental clearance of this peptide. We conclude that serum osteocalcin measurements cannot be used as a marker of bone metabolism during pregnancy.

Adult↗

The effects of copper deficiency on the pyridinium crosslinks of mature collagen in the rat skeleton and cardiovascular system.

The 3-hydroxypyridinium crosslinks of collagen were quantified in tissues of the skeleton and cardiovascular system of normal and copper-deficient rats. The copper-deficient rats used in this study displayed retarded growth, cardiac hypertrophy, anemia, and lowered liver copper concentrations. Quantification of the crosslinks by high performance liquid chromatography indicated that there were lower concentrations of collagen crosslinks in the hearts of copper-deficient animals, a finding that was manifest in both right and left ventricles. This was in contrast to the collagen of the aorta where no alteration in crosslink concentration was observed. The femoral diaphysis of copper-deficient rats also had lower amounts of collagen crosslinks than copper-supplemented animals, whereas crosslinking in the tibial diaphysis and articular cartilage was relatively unaffected by copper deficiency. These results are discussed with reference to the cardiac and skeletal abnormalities that occur in copper-deficient animals.

Animals↗

Medulloblastoma: results of treatment.

Fourteen patients with a diagnosis of medulloblastoma were treated in the Department of Radiation Oncology, University of Louisville School of Medicine from 1973 to 1979. The age of these patients ranged from 2 to 47 years with a median of 9 years. Twelve of them were 15 years or younger. All patients received craniospinal radiation after surgery, with a boost to the primary site by reduced field. The median dose to the primary was 4736 rads (range 3600 to 5600 rad). The median follow-up was 29.5 months. Six patients have died, and four of those six patients lived more than two years. Eight patients are alive to the last follow-up with a median survival of 29 months. Eight of 14 patients had local control and one patient developed distant metastasis. A brief review of the literature is done in this paper.

Adolescent↗

Urinary hydroxy-pyridinium crosslinks provide indices of cartilage and bone involvement in arthritic diseases.

The urinary concentrations relative to creatinine of the collagen crosslinks, pyridinoline (PYD) and an analogue derived specifically from bone collagen, deoxy-pyridinoline (DPD), were measured using a high performance liquid chromatography (HPLC) technique in 41 patients with rheumatoid arthritis (RA) and 45 patients with osteoarthritis (OA), and were compared with values of 118 healthy control individuals. The levels of DPD were increased significantly in both RA and OA suggesting accelerated bone degradation in both disease groups. PYD concentrations were also significantly increased in both diseases, but larger increases were detected in patients with RA, for which this index correlated with clinical measures of joint involvement and biochemical variables of inflammatory activity. Cross-sectional studies showed that treatment with disease modifying drugs (gold and D-penicillamine) led to decreased crosslink levels but longterm corticosteroids resulted in increased urinary crosslinks, probably due to the induction of bone resorption. Measurement of both pyridinium crosslinks in urine may therefore provide information on the stage, activity, level of bone involvement and efficacy of drug therapy in arthritic diseases.

Amino Acids↗

Quantitative analysis of the pyridinium crosslinks of collagen in urine using ion-paired reversed-phase high-performance liquid chromatography.

A method has been developed for the simultaneous and rapid analysis of the 3-hydroxypyridinium crosslinks of mature collagen, pyridinoline and deoxypyridinoline, in samples of urine and tissue. After hydrolysis in 6 M HCl, samples were prefractionated by partition chromatography using columns packed with cellulose CF1. The appropriate fractions were freeze-dried and then subjected to high-performance liquid chromatography using a gradient system with 20 mM NH4Cl, pH 3.5, and acetonitrile, incorporating 1-octanesulfonic acid as an ion-pairing agent; the pyridinium crosslinks were detected fluorometrically. The limit of detection of both crosslinks was 1 pmol. The mean recoveries of added standard to samples ranged between 94.2 and 97.2%, and the reproducibility of the complete procedure was between 12 and 16%. An application of the method in the study of degenerative disorders of bone and connective tissue is illustrated.

Adult↗