PubMed HealthSearch

Biomedical subjects

D Gozin

Publications and source records attributed to D Gozin.

At least 19 recordsLinked to original sources

Coagulation assays as diagnostic markers of hepatocellular carcinoma.

With the aim of improving the biological diagnosis of hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP) and factor V levels were assayed in 119 patients with HCC and 60 cirrhotic patients without HCC. Among the patients with HCC, increased levels of AFP (greater than 300 ng/ml) and of DCP (greater than 15 mU/ml) were observed in 36% and 69% of the cases, respectively. None of the 60 patients without HCC had increased AFP, and one had abnormal DCP; in this patient, DCP level returned to normal value after vitamin K1 injection. No significant correlation was found between increased AFP and DCP, thus indicating that the two tests complement each other for the diagnosis. A factor V level higher than expected from the reduced prothrombin time test of the patient was detected in 50% of patients with HCC and only 7% of those without HCC. No correlation was found between increased factor V and abnormal AFP or DCP. The thrombin time, fibrinogen activity to antigen ratio, and polymerization index failed to differentiate between cirrhosis and HCC. We conclude that AFP, DCP and factor V may give complementary informations in the diagnosis of HCC, one of these markers at least being positive in 88% of the patients.

Adult

Placental transfer of vitamin K1 and its implications in fetal hemostasis.

Vitamin K status was evaluated using coagulation studies and/or vitamin K1 assays in a total of 53 normal fetuses and 47 neonates. Second trimester fetal blood samples were obtained for prenatal diagnosis under ultrasound guidance. Endogenous vitamin K1 concentrations (determined by high performance liquid chromatography) were substantially lower than maternal levels. The mean maternal-fetal gradient was 14-fold at mid trimester and 18-fold at birth. Despite low vitamin K levels, descarboxy prothrombin, detected by a staphylocoagulase assay, was elevated in only a single fetus and a single neonate. After maternal oral supplementation with vitamin K1, cord vitamin K1 levels were boosted 30-fold at mid trimester and 60-fold at term, demonstrating placental transfer. However, these levels were substantially lower than corresponding supplemented maternal levels. Despite elevated vitamin K1 concentrations, supplemented fetuses and neonates showed no increase in total or coagulant prothrombin activity. These results suggest that the low prothrombin levels found during intrauterine life are not due to vitamin K deficiency.

Female

[Assay of decarboxy-prothrombin: its value in the diagnosis of hepatocellular carcinoma].

Serum decarboxy-prothrombin (DCP) was raised in 70.7% of histologically confirmed cases of hepatocellular carcinoma and, with alpha foetoprotein, constitutes a complementary biochemical marker for this disease. It is usually normal in other hepatic diseases but pathological values of DCP have been observed in a few cases of cirrhosis and in some pancreatic carcinomas with hepatic metastases. The differential diagnosis may be established by administering 20 mg of Vitamin K1 by slow intravenous injection: if the DCP remains pathological 15 days after Vitamin K1 the diagnosis of hepatocellular carcinoma is very probable. On the other hand, if the DCP is normal a Vitamin K deficiency may be diagnosed.

Biomarkers

Specificity of increased des-gamma-carboxyprothrombin in hepatocellular carcinoma after vitamin K1 injection.

The des-gamma-carboxyprothrombin (DCP) level was found to be increased in the majority of hepatocellular carcinomas (HCC). This increase has to be distinguished from an increased DCP level linked to a vitamin K deficiency. We studied the evolution of increased DCP level in 6 patients with histologically proven HCC and in 10 without HCC after slow injection of 20 mg of vitamin K1. The DCP assays performed subsequent to the vitamin K1 injection showed: first, a durable normalisation of the DCP level in the patients without HCC, suggesting that the increased DCP was linked, in them, to an underlying vitamin K deficiency; second, a transitory decrease followed by a return to the abnormal level in the patients with HCC. We can conclude that an increased DCP level which persists following vitamin K1 injection is specific for HCC. The minimal delay for the DCP assay after vitamin K1 injection seems to be 15 days.

Biomarkers

A new case of high-molecular-weight kininogen inherited deficiency.

A preoperative hemostasis study discovered a prolonged activated partial thromboplastin time in a 23-year-old Portuguese Caucasian woman without personal or past family history of hemorrhage or thrombosis. This was corrected by pooled plasma that excluded circulating anticoagulant. Activated partial thromboplastin time was prolonged whatever the activator, particularly ellagic acid, and was not corrected by prolonged kaolin incubation. Levels of factors VIII and XII were normal; factor XI and prekallikrein levels were either moderately low or normal according to activators and defective reagents used. High-molecular-weight kininogen (HMWK) level assessed by coagulation and immunological method was virtually nil. Fibrinolysis activity was normal before and after venous occlusion. The programmed operation was performed without any particular preparation and no complication arose. Family investigation found heterozygous HMWK deficiency in the proposita's father and three of her siblings.

Adult

A new method to assay des-gamma-carboxyprothrombin. Results obtained in 75 cases of hepatocellular carcinoma.

A new method for assaying the activity of des-gamma-carboxyprothrombin (DCP), using staphylocoagulase on undiluted adsorbed plasma, is described. The thrombin-coagulase formed is measured on a chromogenic substrate, and the results are expressed in milliunits per milliliter of increment of the optical density following the release of p-nitroaniline. Levels of DCP in 96 normal subjects were under 10 mU/ml (mean, 3.58 mU/ml). Of 70 nonhepatectomized patients with hepatocellular carcinomas, 74% had increased DCP levels of between 20 and 420 mU/ml (most of the values were between 20 and 100 mU/ml). Des-carboxyprothrombin and alpha-fetoprotein measurements gave complementary information, one marker or the other being positive in 87% of hepatocellular carcinoma. Fourteen of 15 patients with metastatic carcinoma of the liver had normal DCP levels, as did 95 patients with liver cirrhosis and 13 patients with chronic hepatitis. When the level of "total factor II" is below 40%, it is recommended that a second determination of DCP be performed 5 days after the injection of vitamin K, to exclude any vitamin K deficiency (in the case of hepatocellular carcinoma the DCP level will remain elevated). The DCP assay appears more sensitive and more specific than the alpha-fetoprotein assay for the diagnosis of hepatocellular carcinoma; furthermore, both tests are complementary.

Biomarkers

Assay of des-gamma-carboxyprothrombin using staphylocoagulase. Application to the diagnosis of cellular hepatocarcinoma.

A new clotting method is described to assay des-gamma-carboxyprothrombin (DCP), using staphylocoagulase and adsorbed undiluted citrated plasma. The thrombin-coagulase formed was tested with a chromogenic substrate. The results were expressed in milliunits (m.u.). All 96 normal plasmas had less than 15 m.u. (mean 3.58 m.u.). Out of 56 non-hepatectomized cellular hepatocarcinomas, 40 had DCP levels between 20 and 420 m.u. (average between 40 and 60 m.u.); 71.4% of cellular hepatocarcinoma had an increased DCP and 90% were positive either in alpha-foetoprotein or in DCP. Ten cases of non-cellular hepatocarcinomas had normal DCP levels. We found no cases of cirrhosis or chronic hepatitis, whether active or persistent, with abnormal level of DCP. Out of 127 patients tested, no case was found with a high DCP and a low level of "total factor II", which could be interpreted as a vitamin K deficiency. Only one case of hepatocarcinoma had 25 m.u. of DCP and a low total factor II (20%) and 2 had less than 10% total factor II with no detectable DCP.

Biomarkers

[A new method of functional assay of des-gamma-carboxyprothrombin using staphylocoagulase. Application to the diagnosis of hepatocellular carcinoma].

A new method to assay des-gamma-carboxyprothrombin (DCP) activity is described, using staphylocoagulase on undiluted citrated plasma after adsorption with bentonite (to remove fibrinogen), then with aluminium hydroxide. The thrombin-coagulase which is formed is measured by following the increase in optical density per minute of a chromogenic substrate. The results are expressed in milliunits (m.U.). The new method is sensitive and specific. It confirms the usefulness of the DCP assay for the diagnosis of hepatocellular carcinoma (Liebman et al.). Ninety-six normal subjects had levels of DCP ranging from 0 to 12 m.U. Out of 42 patients with hepatocarcinoma, 30 (71%) had DCP levels higher than 15 m.U. The increased DCP appears to be complementary to alpha-foetoprotein, since one or the other marker were positive in 37 out of 40 cases (92.5%) of hepatocellular carcinoma. Chronic hepatitis or cirrhosis (36 cases) and non-hepatocellular liver cancer (9 cases) gave normal DCP values.

Biomarkers

In vivo attempt to consume antithrombin III by i.v. injection of a thrombin-heparin mixture.

15 rabbits and 6 dogs were injected with a mixture of thrombin and heparin. Increasing amounts of thrombin, and various ratio of thrombin in relation to heparin, were used. It was found that huge amounts of thrombin could be perfused, under the protection of heparin, without untoward effects. But the high amount of thrombin needed to obtain a 50% reduction of the circulating AT III required a corresponding high amount of protective heparin. Since the secondary injection of protamin sulphate (after the end of the perfusion with the thrombin-heparin mixture) was precipitating the DIC syndrome, such attempts to decrease AT III in man are not feasible.

Animals

[New preparation method of C1 esterase for the dosage of its plasma inhibitor].

A purification method for C1 esterase is described. The final product significantly improved the sensitivity and the specificity of the enzymatic measurement of its plasma inhibitor C1-INH or alpha 2-neuraminoglycoprotein (alpha 2-NGP) by esterolysis of a synthetic substrate N-acetyl-L-tyrosine ethyl ester (ALTEe). A comparative study was done between the chromatographed C1 esterase and the native serum euglobulins: qualitative and quantitative determination of the serum contaminants, enzymatic activity measurement of C1-INH in normal subjects and in patients suffering from hereditary angioneurotic oedema (OANH) as well as in therapeutical C1-inhibitor concentrates.

Angioedema