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Biomedical subjects

J Bonnar

Publications and source records attributed to J Bonnar.

At least 19 recordsLinked to original sources
PubMed1992

The plasminogen activator urokinase and its inhibitor PAI-2 in endometrial cancer.

Invasion and metastasis of malignant cells require the disruption of the extracellular matrix, degradation of basement membranes, and intrusion into connective tissue and vascular and lymphatic spaces. Several studies have indicated a role for urokinase (u-PA) in proteolysis of the extracellular matrix and hence in stromal invasion and metastasis. Many malignant cells are known to secrete u-PA. Plasminogen activator inhibitor-type 2 (PAI-2) is an inhibitor of u-PA and is present in several neoplastic cell lines and malignant ascites. We measured u-PA and PAI-2 antigen in tissue homogenates of normal and malignant endometrium from 21 postmenopausal patients. Enzyme-linked immunoassays which measure the bound and unbound, single-and two-chain form of the activator and bound and unbound form of the inhibitor were used. Urokinase was present in four of seven normal (range, 0.15-0.5; median, 0.15 ng/mg protein) and in significantly higher concentrations in all malignant endometrial homogenates (range, 0.41-9.2; median, 3.4 ng/mg protein), P < 0.001. PAI-2 was detectable in four of seven normal endometrial homogenates at low concentrations (range, 1.1-3.1; median, 1.1 ng/mg protein) and in all malignant tissue homogenates at significantly higher levels (range, 1.6-27.3; median, 4.9 ng/mg protein), P < 0.01. Levels of endometrial PAI-2 were higher in stages IC or greater compared to those in stages IA and 1B cancers (P < 0.05). PAI-2 may be useful as a prognostic marker in endometrial cancer.

Aged↗
PubMed1992

Increased whole blood platelet aggregation in normal pregnancy can be prevented in vitro by aspirin and dazmegrel (UK38485).

OBJECTIVE: To determine the effect of normal pregnancy and the early puerperium on whole blood platelet aggregation and to assess the role of thromboxane A2 (TXA2) in platelet aggregation in pregnancy. DESIGN: A prospective descriptive study. SETTING: TCD Medical School, St James's Hospital, Dublin. SUBJECTS: Twenty healthy primigravidae who remained normotensive during pregnancy and the puerperium. INTERVENTIONS: 20 ml blood samples were obtained serially at 12, 20, 28, 32 and 36 weeks gestation, during established labour and at 1 h, 24 h, 48 h and 6 weeks after delivery. MAIN OUTCOME MEASURES: Whole blood platelet aggregation in response to aggregating agents ADP, PAF (platelet aggregating factor) collagen, adrenaline and arachidonic acid (AA) at each stage of pregnancy and peuerperium was measured using a particle counting technique. The in vitro effect of aspirin and dazmegrel (thromboxane synthetase inhibitor UK38485) on platelet aggregation in pregnancy was also investigated. RESULTS: Platelet aggregation in response to collagen, adrenaline, ADP and AA were increased in the last trimester, during labour and at 1 h after delivery but decreased 24-48 h after delivery. Platelet aggregation in response to AA, collagen and adrenalin was reduced by both aspirin and dazmegrel. CONCLUSIONS: The earliest and most marked increases in platelet aggregation during normal pregnancy were found in response to AA and collagen. These platelet changes were prevented when whole blood was pre-incubated with either aspirin or dazmegrel. This suggests that enhanced production of TXA2 is responsible for increased platelet reactivity in normal pregnancy.

Adenosine Diphosphate↗
PubMed1991

The mast cell and histamine concentration of the human post-menopausal uterus.

Mast cells and histamine concentrations have been studied in uteri removed by hysterectomy from women in their post-menopausal years. Mast cell numbers were expressed as mean numbers/mm2 following fixation in 10% formalin and staining with Azure B. The majority of mast cells, in both the endometrium and myometrium, were very densely stained. Mast cells in the myometrium showed a significant negative correlation with years post-menopausal (rs = -0.52, P less than 0.05). Extracted histamine from uterine tissue was condensed with o-phthaldialdehyde to form a fluorophore and its fluorescence was measured at 450 microns using a spectrofluorometer. No significant correlation was found between histamine concentrations in the uterine wall and years post-menopausal.

Aged↗
PubMed1991

Mast cells in the normal uterus and in dysfunctional uterine bleeding.

Mast cells in the human uterus were examined following fixation in 10% formalin and staining with Azure B. Mast cells were present in all parts of the corpus uteri. Cyclical changes were observed by light microscopy for mast cell numbers/mm2 in the functional endometrium, basal endometrium and the endometrial/myometrial border throughout the menstrual cycle. No significant differences were found for mast cell numbers in the menstrual, proliferative or secretory phases of the menstrual cycle in dysfunctional uterine bleeding (DUB). No correlation was found between mast cell numbers in the uterine wall in the secretory phase of the menstrual cycle and average menstrual blood loss for patients with DUB.

Cell Count↗
PubMed1991

A multicentre study of coagulation and haemostatic variables during oral contraception: variations with geographical location and ethnicity. Task Force on Oral Contraceptives--WHO Special Programme of Research, Development and Research Training in Human Reproduction.

A comparative study of the effects of combined oral contraceptives (OC) on coagulation and fibrinolytic variables using standardized laboratory technique and methodology has been performed in Dublin (Ireland), Salvador (Brazil), Santiago (Chile) and Singapore. Of 777 entrants to the study, 622 were randomly allocated to receive one of four different OC formulations. The remainder did not opt for OC. The progestogenic component was levonorgestrel (LNG) in three of the OC formulations and norethisterone acetate (NEA) in the fourth. Results for the three LNG user groups were pooled. The changes in haematological variables observed over 12 months in the LNG and NEA users were examined in relation to the changes seen in the women not on OC. Women in Salvador differed markedly from those in the other three centres, in showing no acceleration of the prothrombin time and no increase in either fibrin plate lysis or plasminogen following the use of OC. After adjusting the findings in OC users for those in non-users, significant differences in response between centres were also detected for activated partial thromboplastin time (accelerated only in Dublin and Santiago), factor VII activity (increased mainly in Salvador and Santiago) and fibrinogen (for which the most marked changes were an increase in Dublin and a decrease in Salvador). This variability between centres in the effects of OC on coagulation and fibrinolysis suggests that OC administration in different populations may not carry equal thrombotic risks.

Adult↗
PubMed1991

The ultrastructure of mast cells in the uterus throughout the normal menstrual cycle and the postmenopause.

During the menstrual cycle a gradation in mast cell granule ultrastructure was observed from the functional endometrium towards the myometrium of the uterus. Mast cells with particulate granules were present in the functional endometrium and those with granules containing identifiable scrolls in the basal layer of the endometrium and in the myometrium; mast cells containing very electron-dense granules were present in the deeper layers of the myometrium. The secretory activity of mast cells throughout the menstrual cycle is described. Mast cell secretion was observed to a lesser extent in the postmenopausal uterus. Mast cells with particulate granules were absent in the postmenopausal uterus and many very electron-dense granules were observed in mast cells in the myometrium.

Adult↗
PubMed1990

Comparative studies of 30 micrograms ethinyl estradiol combined with gestodene and desogestrel on blood coagulation, fibrinolysis, and platelets.

An association between an increase in the incidence of thromboembolic disease and the use of combined oral contraceptives has been shown by several epidemiologic studies. Evidence of the vascular complications of oral contraceptives suggests that venous thromboembolism correlates with estrogen dosage and arterial complications with both estrogen and progestogen components. In 60 healthy, randomly allocated women, the effects of ethinyl estradiol, 30 micrograms, combined with gestodene, 75 micrograms, and desogestrel, 150 micrograms, on blood coagulation, fibrinolysis, and platelet function were compared. Subjects were studied before oral contraceptive use, at 12, 24, 36, and 48 weeks of treatment, and at 6 and 12 weeks after treatment. Both oral contraceptives affected the hemostatic system, but our results indicate that the ethinyl estradiol/gestodene combination causes changes in the hemostatic system similar to those in the ethinyl estradiol/desogestrel combination. Factors VII and X activity were slightly higher with the ethinyl estradiol/desogestrel combination than with the ethinyl estradiol/gestodene combination, possibly reflecting a greater estrogenic effect.

Adolescent↗
PubMed1990

Effect of radiation and other cytotoxic agents on the growth of cells cultured from normal and tumor tissues from the female genital tract.

A technique is presented which allows the response of human gynecological tissue to radiation and cytotoxic drugs to be assessed using a tissue culture explant system. The technique is simple to use and gives results in line with those obtained for human tissues by more complex culture methods. Data are presented showing how the explant technique developed by the group for other tissues can be adapted to yield acceptable results for normal tissue response to radiation. The potential of the technique for use in predictive testing of individual tumor response is then assessed in five cases of gynecological malignancy. It is clear that variations in sensitivity to different radio- and chemotherapy agents and combinations can be detected. The results obtained require clinical validation and it is hoped that this will come over the next few years from evaluation of patient response to treatment using individually optimized, rather empirical therapy.

Adenocarcinoma↗
PubMed1989

The morphologic characteristics of menstrual hemostasis in patients with unexplained menorrhagia.

The endometrium in uteri removed by hysterectomy in patients with unexplained menorrhagia was compared with the endometrium in patients with normal menstruation who had a hysterectomy for uterine prolapse. The vascular ultrastructure and hemostatic plug formation were examined from the late secretory phase throughout menstruation to day 9 of the proliferative phase of the menstrual cycle. Endothelial defects, with and without hemostatic plugs, were more common and were present longer in the endometrial blood vessels of patients with unexplained menorrhagia than in patients with normal menstruation. In normal menstruation, no vascular defects were observed after day 3 of the cycle, whereas vascular defects were observed up to day 9 in the blood vessels of patients with unexplained menorrhagia. These morphologic features are likely to play a major role in the increased menstrual bleeding in such patients without uterine pathologic findings.

Adult↗
PubMed1989

Comparison between mefenamic acid and danazol in the treatment of established menorrhagia.

Forty women with established menorrhagia were treated with either mefenamic acid (500 mg thrice daily for 3-5 days in two cycles) or danazol (100 mg twice daily for 60 days) in an open parallel group randomized study. Mefenamic acid reduced mean menstrual blood loss from 160 ml to 127 ml (20%, P less than 0.01). Danazol reduced mean menstrual loss from 163 ml to 65 ml (60%, P less than 0.001). The percentage reduction in menstrual blood loss was significantly greater in the danazol group than in the mefenamic acid group, but the adverse side-effects occurred significantly more often in the danazol group (75%) than in the mefenamic acid group (30%, P less than 0.005). Overall, approximately half the women in each group were prepared to continue with the treatment they received to reduce their menstrual bleeding.

Adult↗
PubMed1989

Inhibitors and activators of fibrinolysis during and after childbirth in maternal and cord blood.

During normal childbirth profound changes in the fibrinolytic system take place. Tissue plasminogen activator (t-PA), the antigen and its biological activity and, the activity of plasminogen activator inhibitor (PAI): were measured in twenty-two healthy women during and shortly after spontaneous delivery (2nd stage and 3rd stage of labour, 48 and 72 hours post partum). Significant increases of plasma t-PA antigen and activity occurred during childbirth and before delivery of the placenta, while the inhibitor remained unchanged. After delivery the PA inhibitor and t-PA antigen showed a steep decline. The activity of t-PA remained largely unchanged during labour and after delivery. The comparison between the activity levels of PAI in infant cord blood and in maternal peripheral blood, taken simultaneously during the process of placental separation, showed significantly higher PAI activity in the mother. In contrast the levels of t-PA activity were found to be significantly higher in cord blood. Our results demonstrate that during the process of child-birth and separation of the placenta distinct alterations in the fibrinolytic system occur most likely due to placental effects.

Adolescent↗
PubMed1987

The fibrinolytic enzyme system in normal menstruation and excessive uterine bleeding and the effect of tranexamic acid.

The fibrinolytic enzyme system of menstrual and peripheral blood was studied in three groups of women: Group 1, 20 subjects (mean age 37.2 years) with normal menstrual loss; Group 2, 20 patients (mean age 39 years) with dysfunctional uterine bleeding studied before treatment, and Group 3, during treatment with a fibrinolytic inhibitor, tranexamic acid (AMCA) (1 g 8-hourly). The fibrinolytic activity (plasminogen activator and plasmin) of menstrual blood was significantly higher than that of peripheral blood in the three groups (p less than 0.001). Both plasminogen activator and plasmin were higher in the menstrual blood of patients with menorrhagia (Group 2) compared with the control subjects (Group 1) (p less than 0.001 and p less than 0.1 respectively). Treatment with AMCA significantly reduced both plasminogen activator (p less than 0.01) and plasmin (p less than 0.05) in the menstrual blood of patients with menorrhagia (Group 3). No significant differences in fibrinolytic activity were found in peripheral blood between Groups 1 and 2; however, both plasminogen activator and plasmin were significantly lower (p less than 0.01) in Group 3 than in Group 2. Plasmin activity was also significantly lower (p less than 0.05) in Group 3 compared to Group 1. These findings confirm the presence of increased fibrinolytic activity in the uterus in excessive (dysfunctional) bleeding.

Administration, Oral↗
PubMed1987

Coagulation effects of oral contraception.

In Europe and North America, estrogen/progestogen oral contraception has been associated with an increase in venous thromboembolism, myocardial infarction, and stroke. These hazards are found mainly in smokers and in women over the age of 35. Venous thromboembolism appears to correlate with the estrogen dosage, and the arterial complications with both the estrogen and progestogen components. Blood coagulation and vascular thrombosis are intimately related. Estrogen/progestogen oral contraception affects blood clotting by increasing plasma fibrinogen and the activity of coagulation factors, especially factors VII and X; antithrombin III, the inhibitor of coagulation, is usually decreased. Platelet activity is also enhanced with acceleration of aggregation. These changes create a state of hypercoagulability that, to a large extent, appears to be counterbalanced by increased fibrinolytic activity. Studies of the oral contraceptives in current use show that the coagulation effects depend on the dosage of estrogen and the type of progestogen used in combination. Current research is aimed at finding the estrogen/progestogen formulations that induce the least changes in the coagulation system and other physiologic processes. In this respect, the new low-dose formulations are a major step forward and should reduce the risk of vascular thrombotic complications.

Blood Coagulation↗
PubMed1987

Blood coagulation with a combination pill containing gestodene and ethinyl estradiol.

The coagulation effects of oral contraceptives are determined by the interaction of the estrogen and the progestogen components. Serial studies on the coagulation system were carried out in 120 randomly allocated healthy women to compare the effects of (1) triphasic gestodene/ethinyl estradiol and triphasic levonorgestrel/ethinyl estradiol and (2) monophasic gestodene/ethinyl estradiol and monophasic desogestrel/ethinyl estradiol. The triphasic study showed significant increases in factor VII, factor X, fibrinogen, plasminogen, and fibrinolytic activity. No significant differences were noted between levonorgestrel and gestodene except for factor VII, which was higher with gestodene. Antithrombin III and anti-Xa were unchanged, and platelet aggregation was slightly accelerated with gestodene. The monophasic study is still in progress: Significant increases of factor VII, factor X, plasminogen, and fibrinolytic activity and no changes in antithrombin III, anti-Xa, and platelet aggregation have been found with both monophasic gestodene and desogestrel. The results of the triphasic study indicate that the effect of gestodene on the blood coagulation system is similar to that of levonorgestrel and that both formulations increase fibrinolytic activity. The increased coagulation activity would appear to be counteracted by enhanced fibrinolysis, so protecting the dynamic balance between coagulation and fibrinolysis. Further data are required in the monophasic gestodene and desogestrel study before any conclusions can be drawn.

Adolescent↗
PubMed1986

A morphometric study of the effect of oral norethisterone or levonorgestrel on endometrial blood vessels.

A morphometric study was undertaken to quantitate vessel numbers in uterine biopsies from a control group of patients, patients with dysfunctional uterine bleeding and patients taking low dose norethisterone or levonorgestrel. Vessels were counted at the endometrial/myometrial junction and in the functional endometrium just below the surface epithelium. The number of arteries at the endometrial/myometrial junction was found to be decreased in patients taking norethisterone and levonorgestrel. An increase was found in the total number of veins and in the number of dilated veins in the functional endometrium of the progestogen-treated specimens. Dilated veins were frequently found close to the endometrial surface and it is possible that they may be the major cause of the irregular bleeding associated with low dose oral progestogens.

Administration, Oral↗
PubMed1986

Oral contraceptives and blood coagulation.

In discussing the possible vascular complications of oral contraception, one must differentiate between venous and arterial effects. Different estrogen-progestogen combinations have different effects on the hemostatic system.

Age Factors↗