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Biomedical subjects

B D Cowan

Publications and source records attributed to B D Cowan.

At least 19 recordsLinked to original sources

Receiver-operator characteristic, efficiency analysis, and predictive value of serum progesterone concentration as a test for abnormal gestations.

OBJECTIVE: Our objective was to determine if a discriminatory progesterone concentration could be established that confidently predicted abnormal early gestations. STUDY DESIGN: We analyzed differences in progesterone concentrations between normal (n = 40) and abnormal (n = 34) pregnancies during the first 49 days of gestation. The receiver-operator characteristic curve, test efficiency, and predictive value of serum progesterone to discriminate between an abnormal and normal first-trimester gestation were calculated for progesterone concentrations between 5 and 25 ng/ml. RESULTS: Receiver-operator characteristic curve analysis indicated that the best discriminatory progesterone concentration was 10 ng/ml. Test efficiency was maximum between serum progesterone concentration of 9 to 14 ng/ml (80%). When progesterone was less than 10 ng/ml, the predictive value of the abnormal test result was greater than 90%. CONCLUSION: Receiver-operator characteristic analysis, test efficiency, and the predictive value of an abnormal test result suggest that the best progesterone cut off point that predicts abnormal early pregnancies is 10 ng/ml.

Abortion, Spontaneous

Treatment of unruptured ectopic pregnancy with methotrexate.

Medical treatment is appropriate for patients with an unruptured tubal pregnancy who wish to preserve fertility or have medical problems associated with increased risk of anesthesia. Patients with persistent trophoblast after conservative surgery should be treated with methotrexate rather than undergo a repeat surgery. All nine of our patients with ectopic pregnancies who were treated with MTX were cured with one course of therapy. Little toxicity was observed and subsequent reproductive performance after medical treatment was comparable to that reported in the literature. Direct injection of MTX into an ectopic pregnancy under sonographic control provided an option for treatment which required little anesthesia, reduced the amount of drug and allowed the treatment of a gestation which would otherwise not be considered a candidate for the 3 dose intramuscular injection protocol (see Table 3).

Female

Benign symptomatic hyperandrogenism in a postmenopausal woman.

Hyperandrogenemia in postmenopausal women requires an evaluation to exclude pathologic ovarian or adrenal causes. Our patient exhibited no signs of hypercortisolism, congenital adrenal hyperplasia, or adrenal or ovarian neoplasia based on biochemical testing and pelvic sonography. We hypothesized that unexplained androgen excess in our patient was due to the development of gonadotropin-dependent excess ovarian stromal androgen production. This syndrome may be comparable to gestational hyperreactio luteinalis where elevated gonadotropins stimulate ovarian stromal androgen production. If tumor can confidently be excluded, such women may benefit from gonadotropin suppression with long-acting GnRH-a.

Aged

Hydatidiform mole pregnancy trophoblast extracts differentially suppress interleukin-2-induced proliferation of human T-lymphocytes and PHA-blasts.

Immunoregulatory factors of trophoblast origin may partially abrogate maternal immune responses to the fetus during pregnancy. We have previously shown that soluble factors extracted from hydatidiform mole trophoblast suppress interleukin-2 (IL-2)-dependent proliferation of a cloned murine cytotoxic T cell line (CTLL-2). To characterize human T cell responses to this trophoblast extract, we measured the effects of molar tissue extracts (HME) on IL-2-stimulated proliferation of human T-lymphocytes and mitogen (PHA) transformed T-cell blasts (PHA-blasts). HME significantly (P less than 0.05) suppressed T-lymphocyte proliferation in response to 5 and 10 units/ml of IL-2 at 500 and 250 micrograms/ml, while no effect was observed at the 100 micrograms/ml concentration. Suppression by HME of IL-2-stimulated T-cell proliferation was partially overcome by the addition of excess IL-2. HME also suppressed (P less than 0.05) IL-2-stimulated proliferation of PHA-blasts at 500 and 250 micrograms/well at both 5 and 10 units/ml of IL-2. As observed with resting T-cell responses, no suppression of PHA-blast proliferation was observed using 100 micrograms/ml of HME. In contrast to the response of the resting T-cells to excess IL-2, HME suppression of IL-2-stimulated blast proliferation was not affected by increasing the concentration of IL-2. These results indicate that extracts from hydatidiform mole trophoblast contain immunosuppressive factors that block human T-cell clonal expansion by inhibiting the utilization and/or production of IL-2. Furthermore, the effects of HME are not reversed by excess IL-2 when PHA-blasts are reacted compared to resting T-cell responses, which are partially reversed in the presence of excess IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Survival

Biochemical assessment and prediction of gestational well-being.

It is apparent from this brief review of serum markers that there is no ideal biochemical screen available to either assure fetal well-being or reliably predict fetal compromise. At present, MSAFP has become the dominant serum marker, but much work needs to be done to refine its usefulness as a screen and its utility in association with other measurements of fetoplacental well-being. The trend in modern obstetric management is toward an array of biophysical tests of fetal well-being, particularly in the last trimester of pregnancy. Biochemical screening in early gestation is used increasingly to assess future fetoplacental status and to predict risk for later pregnancy complications. Combinations of these biochemical and biophysical modalities will likely achieve the greatest predictive success in assessing fetal and placental well-being.

Atrial Natriuretic Factor

Abnormal bleeding in the climacteric.

In the perimenopausal years, we encounter a situation where the normal diminution in reproductive capacity, with its resulting disruption of the normal menstrual hormonal pattern, coincides with a very real risk of pelvic pathology. Limitation in the ability to diagnose and to treat these patients conservatively has in the past resulted in a high rate of hysterectomy. With increased understanding of the normal physiology of this stage of transition and with improved diagnostic tools, we are now able to come to a definitive diagnosis in most patients. This ability to assure the diagnosis has made it much easier to counsel the patient confidently about the appropriate course of action. We will continue to encounter the problem of hysterectomy for bleeding with no histologic lesion being found. Although reviewers' letters may be considered an unnecessary thorn in the side, the improved practice that has resulted from these efforts gives strong support to their continued activities. We can have confidence that our treatment plan evolved in a logical manner and offers our patients a high probability of benefit at justifiable risk.

Climacteric

Suppression of lymphocyte proliferation in vitro by macromolecules in the vesicle fluid and tissue extracts of hydatidiform mole.

This study examines the effects of vesicle fluid and tissue extracts from hydatidiform mole trophoblast on lymphocyte proliferation in vitro. Samples were obtained by direct aspiration of vesicles (hydatidiform mole vesicle fluid (HMF] or homogenization of molar tissues (hydatidiform mole extract (HME] following therapeutic uterine evacuation of hydatidiform mole. Dialyzed and lyophylized HMF pooled from two patients exhibited a 30% suppression (P less than 0.05) of mitogen-induced lymphocyte proliferation at a concentration of 12.5 micrograms protein/ml. Similarly, lymphocyte transformation was significantly suppressed (P less than 0.05) by HME at concentrations of 500 and 250 micrograms/ml. Molecular weight chromatography of HME resolved 4 protein fractions. Fraction 3 (35--50 kDa) and fraction 4 (less than 35 kDa) significantly suppressed mitogen-induced lymphocyte transformation while fractions 1 and 2 demonstrated no immunosuppression. Heat treatment (56 degrees C, 30 min) abolished the immunosuppressive activity of HME as well as fractions 3 and 4. These results suggest that hydatidiform mole trophoblast contains heat-labile macromolecules which suppress mitogen-mediated lymphocyte transformation. Such trophoblast-derived factors may interfere with maternal rejection of the allograft.

Female

Bromocriptine inhibition of anesthesia-induced hyperprolactinemia: effect on serum and follicular fluid hormones, oocyte fertilization, and embryo cleavage rates during in vitro fertilization.

Thirty-two patients undergoing in vitro fertilization (IVF) were given bromocriptine either 1 or 12 hours before anesthesia or received no drug to determine what effect suppression of transient, anesthesia-induced hyperprolactinemia would have on peripheral and follicular fluid hormones, fertilization and cleavage rates, and pregnancy. Thirty minutes after anesthesia, there was a 120-ng/mL rise in serum prolactin (PRL) in control patients versus an insignificant change in women given bromocriptine. Levels of PRL in follicular fluid were significantly less, and estradiol (E2) levels were higher (P less than 0.05) in all bromocriptine-treated patients compared with controls, whereas follicular fluid levels of progesterone (P), inhibin activity, and midluteal serum P were unaffected. Although fertilization and pregnancy rates were similar, a greater proportion of fertilized oocytes from bromocriptine-treated patients advanced to cleaving embryos compared with controls (95% versus 63%, respectively; P less than 0.001). We conclude that bromocriptine, given before anesthesia, can suppress transient, anesthesia-induced hyperprolactinemia and dramatically alter follicular fluid concentrations of PRL and E2. Although these changes in hormonal milieu affected neither oocyte fertilization nor pregnancy rate in our IVF patients, they seemed to have a positive influence on embryonic development after IVF.

Adult

Conservative management of Cushing's syndrome in pregnancy. A case report.

A woman with clinical and laboratory findings of Cushing's syndrome was managed during pregnancy without the use of surgery or drugs to lower her serum cortisol. A good maternal and infant outcome was achieved with conservative measures, and surgical removal of an adrenal adenoma was delayed until the postpartum period.

Adenoma

Transcervical resection of submucous uterine fibroids: an alternative approach to management.

Transcervical resection of submucous uterine fibroids can be an effective alternative to laparotomy and transuterine myomectomy in selected women. To date the authors have performed this procedure in three patients in an ambulatory environment. In two patients, transcervical resection was performed for giant intrauterine myomas which caused pathologic uterine bleeding and infertility. In a third patient the procedure was performed to resect multiple small submucous myomas causing infertility.

Adult

Failed fertilization during an in vitro fertilization cycle after oral ingestion of amantadine hydrochloride.

Oocyte fertilization occurred during three in vitro fertilization/embryo transfer (IVF/ET) treatment cycles of an infertile couple but failed during an IVF cycle when the husband took amantadine for prophylaxis against viral infection. Semen parameters were similar to those of other cycles attempted by this couple as well as to those of other IVF couples treated concurrently. We circumstantially suggest that amantadine, and potentially other ingestible medications or foods, while not spermicidal, may impair gamete function during IVF/ET.

Adult

Hydatidiform mole macromolecules inhibit interleukin-2-mediated murine lymphocyte proliferation in vitro.

Macromolecules extracted from hydatidiform mole trophoblast inhibit mitogen-induced lymphocyte proliferation. To characterize the mechanism of this immunomodulation, we determined the effects of hydatidiform mole vesicle fluid (HMF) and tissue extracts (HME) on lymphokine function in vitro. Utilization of interleukin-1 (IL-1) and interleukin-2 (IL-2) were determined by using a lymphoma cell line (LBRM-33-1A5) and a murine T cell line (CTLL2), respectively. HMF suppressed (P less than .05) IL-2-dependent CTLL2 cell proliferation at 500 (36.4% of controls) and 50 (74.9% of controls) micrograms/ml. HME also suppressed CTLL2 proliferation (P less than .05) at 500 (46.0% of controls), 100 (67.2% of controls), 50 (71.5% of controls), and 10 (85.4% of controls) micrograms/culture ml. In contrast, HMF exhibited no effect on IL-1-stimulated LBRM-33-1A5 production of IL-2. However, 500 micrograms/ml of HME inhibited (P less than .05) IL-2 production (63.0% of controls) in the IL-1 utilization assay. This suppressive effect was probably due to a carry over of HME from the LBRM-33-1A5 culture to the target cells (CTLL2) used to measure IL-2 production. Molecular weight chromatography of an HME sample eluted an IL-2 inhibitor in a low molecular weight (35-50 kd) and high molecular weight (greater than 250 kd) fraction. These data suggest that one way in which macromolecules derived from hydatidiform mole could interfere with in vitro immunologic responses is by modulating interleukin-2 function.

Animals

Partial characterization of a uteroglobin-like protein in the human uterus and its temporal relationship to prostaglandin levels in this organ.

During the past decade several corticosteroid-dependent, low mol wt proteins with phospholipase-A2 (PLA2) inhibitory activity have been described. This family of proteins is collectively known as lipocortins. Blastokinin or uteroglobin (utg), a progesterone-induced protein, first discovered in the pregnant rabbit uterus, is also a potent PLA2 inhibitor, but genetically distinct from lipocortins. Although utg has been found in rabbits, its presence in humans has not been well established. Here, we present biochemical, immunological, and immunohistological evidence for the detection of a utg-like protein in the human uterus. Since inhibition of PLA2 may modulate tissue eicosanoid levels and since rabbit utg has been reported to be a potent PLA2 inhibitor, we also studied the temporal relationship between utg and tissue prostaglandin E2 and F2 alpha levels in estrogen- and progesterone-dominated endometrial tissue. We found an inverse temporal relationship between utg-like protein and eicosanoid levels in this organ. Since some eicosanoids (e.g. prostaglandins, leukotrienes, etc.) are known to be involved in smooth muscle contractility and inflammatory processes, our findings may help to understand the pathogenesis of some human disorders in which abnormal eicosanoid production occurs.

Adult