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D Shander

Publications and source records attributed to D Shander.

16 recordsLinked to original sources

Hypothesis: warfarin administered simultaneously with heparin infusion will prevent heparin-discontinuance associated coronary thrombosis.

Recent studies have evidenced an association between the time of heparin discontinuance and coronary artery reocclusion. Some investigators have concluded that inadequate heparinization was responsible, and further heparin infusion or an increase in dose would have been indicated. However, several investigators (Rao: Thrombosis Research 24:181-186, 1981; Marciniak and Gockerman: Lancet September 17:581-584, 1977; Fisken et al.: Lancet December 10: 1231, 1977; Conard et al.: Thrombosis Research 22:507-511, 1981; Kakkar et al.: Lancet January 12:103-104; Green: Lancet February 16:374, 375; Harborne and Nicolaides: Thrombosis Research 43:657-662, 1986; Bonen et al.: Thrombosis Research 27:123-124, 1982; Blomback et al.: Acta Physiologica Scandinavica 58:306-318, 1963; Holm et al.: Scandinavian Journal of Haematology 35:564-569, 1985; Andersson et al.: Thrombosis Research 34:333-340, 1984) have demonstrated that antithrombin III levels are reduced in patients on intravenous heparin. Both reduced antithrombin III levels and reduced rate of antithrombin inhibition of thrombin at the time of heparin discontinuance may increase the risk of coronary rethrombosis. If this theory is correct, increasing heparin infusion may exacerbate this risk. We propose an investigation that will provide evidence for or against the decreased antithrombin III theory, and in doing so, test an experimental therapy designed to prevent coronary reocclusion upon heparin discontinuance. In a randomized, placebo-controlled double-blinded study, we will determine whether simultaneous administration of warfarin with heparin initiation provides more time to increase antithrombin III levels and prevent coronary reocclusion upon heparin discontinuance, compared to heparin without warfarin therapy.

Antithrombin III

Ovarian steroid modulation of gonadotropin secretion and pituitary responsiveness to luteinizing hormone-releasing hormone in the female hamster.

The significance of ovarian estradiol (E2) and progesterone secretion in the regulation of pituitary LH and FSH secretion and pituitary responses to LHRH was investigated in the hamster. Cycling females showed increased LH and FSH responses to LHRH on the morning of proestrus as compared to the responses observed on diestrus day 2. Pituitary responsiveness to LHRH declined on the evening of proestrus, after the preovulatory LH/FSH release. The secondary increase in serum FSH concentration on the morning of estrus was accompanied by a selective increase in the pituitary FHS response to exogenous LHRH. Hamsters ovariectomized (ovx) on diestrus day 2 exhibited daily afternoon LH surges but not FSH surges for at least 10 days after ovx. The magnitude of the LH surges in ovx hamsters was approximately 30-50% of that observed in proestrous females. The pituitary LH response to exogenous LHRH in ovx animals was about 25% as great as in proestrus hamsters. Serum FSH concentrations in ovx females increased by only 30% after LHRH injection, while similar treatment with LHRH resulted in 3- to 4-fold increments in serum FSH in proestrous hamsters. Implantation of E2 capsules in ovx hamsters resulted in increased gonadotropin responses to exogenous LHRH. Serum LH concentrations in the E2-implanted, LHRH-injected animals were as great as those observed after LHRH injection in proestrous females. Administration of LHRH, LH, or progesterone on the morning of proestrus failed to detectably alter the timing or magnitude of the proestrus afternoon FSH surge. The present results suggest that the increasing serum titers of estrogen on diestrus and early proestrus result in increased pituitary sensitivity to LHRH, and this increased sensitivity probably contributes to the magnitude of the preovulatory LH surge. The increases in LH and progesterone which occur during the afternoon do not seem to be responsible for triggering the proestrous FSH surge.

Animals

Systemic embolization of the disk occluder of the Wada-Cutter prosthetic valve. A late complication.

The results in 22 patients in the Denver area with Wada-Cutter prostheses were reviewed. There were 14 late deaths, with an average follow-up of six years. Four cases of valve malfunction not related to thrombosis were documented. There were three cases of embolization of the occluder. A survivor is reported. Clinical evaluation of the group suggested new mitral regurgitation to be a sensitive indicator of impending embolization of the occluder. Documentation of valve malfunction warrants valvular replacement.

Embolism