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Biomedical subjects

P M Atkinson

Publications and source records attributed to P M Atkinson.

33 records · Page 2Linked to original sources

Precursor prothrombin status in patients receiving anticonvulsant drugs.

Protein induced by vitamin K absence (PIVKA) is the circulating prothrombin precursor found in considerable concentrations when carboxylation of prothrombin is impaired. In this study PIVKA-positivity was assessed in adult epileptic patients receiving a variety of anticonvulsant drugs. Mean PIVKA (+/- SD) concentration was 4.6 +/- 2.3% in 16 epileptics vs 1.1 +/- 0.7% in 10 age-matched controls (p less than 0.001). 13 of the 16 (81%) epileptics had PIVKA values above the highest value recorded for the controls (Fisher exact test, p less than 0.001). Other indices of coagulation were normal. There was no correlation between PIVKA concentration and the particular anticonvulsant taken. This study therefore shows that most epileptics on anticonvulsant therapy have a subclinical coagulation defect. These data, together with previous findings of raised PIVKA concentrations in maternal-infant pairs exposed to gestational anticonvulsants and reports of neonatal haemorrhage in infants of epileptics, strengthen the case for antenatal vitamin K supplementation in pregnancies complicated by anticonvulsant therapy.

Adult↗

Homology of the NH2-terminal amino acid sequences of the heavy and light chains of human monoclonal lupus autoantibodies containing the dominant 16/6 idiotype.

The NH2-terminal amino acid sequences have been determined by automated Edman degradation for the heavy and light chains of five monoclonal IgM anti-DNA autoantibodies that were produced by human-human hybridomas derived from lymphocytes of two patients with systemic lupus erythematosus. Four of the antibodies were closely related to the idiotype system 16/6, whereas the fifth antibody was unrelated idiotypically. The light chains of the 16/6 idiotype-positive autoantibodies (HF2-1/13b, HF2-1/17, HF2-18/2, and HF3-16/6) had identical amino acid sequences from residues 1 to 40. Their framework structures were characteristic of VKI light chains. The light chain of the 16/6 idiotype-negative autoantibody HF6-21/28 was characteristic of the VKII subgroup. The heavy chains of the 16/6 idiotype-positive autoantibodies had nearly identical amino acid sequences from residues 1 to 40. The framework structures were characteristic of the VHIII subgroup. In contrast, the GM4672 fusion partner of the hybridoma produced small quantities of an IgG with a VHI heavy chain and a VKI light chain. The heavy chains of the lupus autoantibodies and the light chains of those autoantibodies that were idiotypically related to the 16/6 system had marked sequence homology with WEA, a Waldenstrom IgM that binds to Klebsiella polysaccharides and expresses the 16/6 idiotype. These results indicate a striking homology in the amino termini of the heavy and light chains of the lupus autoantibodies studied and suggest that the V regions of the heavy and light chains of the 16/6 idiotype-positive DNA-binding lupus auto-antibodies are each encoded by a single germ line gene.

Amino Acid Sequence↗

Acarboxy prothrombin in cord plasma from normal neonates.

Acarboxy prothrombin was detected in the plasma of 48 of 128 umbilical cord plasma samples and in all of 65 patients receiving coumadin. None was found in 20 normal adults. Although the prevalence was the same in blacks, whites, and neonates of mixed origin, levels were significantly higher in blacks. There was a negative correlation between the level of acarboxy prothrombin and the prothrombin index. There was no correlation between maternal age, birth weight, gestational age, obstetrical complications, race, socioeconomic status, albumen, or alpha-foetoprotein and the incidence of cord plasma acarboxy prothrombin.

Adult↗

Identification of a heparin activated amidolytic enzyme in carp (Cyprinus carpio) plasma.

A heparin activated amidolytic enzyme capable of cleaving synthetic thrombin sensitive chromogenic substrates was identified from the plasma of the carp (Cyprinus carpio). Activation was inhibited by KCl, protamine sulphate and human plasma. Heparin was not required for the continued action of the enzyme. Active enzyme was irreversibly inhibited by DFP. The pH and temperature optima was studied and the enzyme semi purified by Sephadex G100 superfine and Sephadex A50 chromatography. An approximate MW of 62,000 was found. Activity generated by as little as 0.002 units of heparin per ml carp plasma was detected. The trivial name carpamidase is proposed for the enzyme.

Animals↗

A rapid chromogenic method for the determination of prothrombin precursor in plasma.

A method was described for the quantitation of precursor prothrombin using a chromogenic substrate S2238 and Dispholidus typus venom. Prothrombin precursor was detected in the adsorbed plasma of all 65 patients on coumadin therapy tested, but was absent in 20 controls. The technic offered a rapid and sensitive method for determining if a prolonged prothrombin time is due to vitamin K antagonism or deficiency.

Adsorption↗

Clinical features of twig snake (Thelotornis capensis) envenomation.

A case of disseminated intravascular coagulation in a 13-year-old-boy caused by a bite from a twig snake (Thelatornis kirtlandii capensis) is described. The coagulant enzyme was found to be a single-chain mole-activate prothrombin and factor X as well as weakly accelerating fibrinolysis. Its action on synthetic chromogenic substrates is described. Boomslang antivenom was unable to block twig snake venom, and the implications of this as regards treatment are discussed.

Adolescent↗

The use of Dispholidus typus venom in elucidating the cause of a low prothrombin index.

A simple and rapid in vitro test was devised to detect the presence of the prothrombin precursor molecule circulating in the plasma of 55 out of 56 patients receiving oral vitamin K antagonists and in 4 out of 5 patients with obstructive jaundice, using either Dispholidus typus or Echis carinatus venoms. The absence of the molecule from the plasma of jaundiced patients was suggestive of hepatocellular rather than obstructive jaundice. The test is based on the clotting of aluminium hydroxide gel adsorbed plasma by the venoms. It is more sensitive and easier to perform than measuring antigenic prothrombin levels.

Adsorption↗

Plasma gonadotropins and androgens in surgically treated cryptorchid patients.

Plasma LH, FSH, and total 17betaOH androgen levels were measured in a group of 40 adult patients who underwent orchiopexy for either unilateral or bilateral cryptorchism during childhood. Gonadotropin abnormalities were found in 15 of 40 patients and thereby appeared to be a much more sensitive indicator of testicular malfunction than the androgens which were abnormal in only four patients. In the postpubertal phase, the estimation of gonadotropins and androgens appeared valuable, first, as an additional help in the prognosis of fertility, where combined raised levels of LH and FSH were found to indicate a poor prognosis; second, to detect in infertile patients gonadotropin deficiency which, if previously missed, can still be expected to respond to gonadotropin therapy; third, for the detection of the subclinically hypogonad group who may require follow-up, and finally for the detection of the low-androgen group who may require some form of hormonal therapy. As several patients in this study were found to have low gonadotropins, it is postulated that low levels of gonadotropin may play a role in the production of cryptorchism. The finding of high gonadotropin levels in another group may indicate a feedback mechanism sensitive to a damaged testis, but alternatively it is possible that there might be a primary resistance to the action of gonadotropins and it is postulated that such a resistance may be an additional factor of the causation of cryptorchism in some cases.

Adolescent↗

A follow-up study of surgically treated cryptorchid patients.

A group of 112 adult patients were traced who had had childhood orchiopexies at an average age of 9 yr at two childrens' hospitals. Sixty-seven per cent of all married patients had sired children although only 44% of the married bilateral cryptorchid patients had done so. The percentage paternity of the unilaterally cryptorchid patients was normal when compared with the general population. There appeared to be no difference in the eventual results of the two types of orchiopexy performed on this series of patients.

Adult↗

A comparison between des-gamma-carboxy prothrombin and alpha-fetoprotein as markers of hepatocellular carcinoma in southern African blacks.

Des-gamma-carboxy prothrombin (DCP), a precursor of prothrombin, has been reported recently to be as good a marker, or even better, of hepatocellular carcinoma than alpha-fetoprotein (alpha-FP). The sensitivity, specificity and predictive values of the two markers have been compared in 98 southern African Blacks with hepatocellular carcinoma and in 120 Black controls with various diseases which might be mistaken clinically for this tumour: 32 with hepatic metastases, 33 with amoebic hepatic abscesses, and 55 with chronic hepatic parenchymal disease. DCP levels were measured using a chromogenic assay with Dispholidus typus venom and staphylocoagulase. The agreement between the two methods was excellent (r = 0.995). alpha-FP concentrations were measured by radioimmunoassay. DCP levels were raised in 66 of 98 patients (67.3%) and alpha-FP levels in 82 of 98 patients (83.7%) with hepatocellular carcinoma (P = 0.006). The specificity of DCP was also less than that of alpha-FP, although the difference just failed to reach statistical significance (P = 0.085). The predictive values of both a positive and a negative test for DCP were significantly less than those for alpha-FP (P = 0.047 and 0.048, respectively). When, in an attempt to eliminate false positive results, the diagnostic cut-off level for DCP was increased from 1.5 to 5.0 mu/ml and that of alpha-FP from 20 to 400 ng/ml, the differences between the two markers remained the same. If the two tests were used together, the number of false negative alpha-FP results was reduced from 16.3% to 7.1% and the number of equivocal alpha-FP results was reduced from 11.2% to 5.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗