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Biomedical subjects

C A Winkel

Publications and source records attributed to C A Winkel.

At least 19 recordsLinked to original sources
PubMed2001

Medical and surgical therapies for pain associated with endometriosis.

Endometriosis is a common condition for which a number of treatments have been proposed. Medical treatments are based on the hormonal responsiveness of endometriosis implants. These therapies include progestins (with or without estrogens), androgens, and gonadotropin-releasing hormone (GnRH) analogs. Surgical treatments may include hysterectomy with oophorectomy or organ-sparing surgery involving ablation or resection of visible lesions of endometriosis and restoration of pelvic anatomy. There are no studies that directly compare the effectiveness or adverse effects of medical therapy and surgical therapy. Studies on medical therapy compare different treatments with placebo or with other active treatments. Hormone-based therapies for endometriosis show 80%-100% effectiveness in relief of pelvic pain over a 6-month course of therapy. Serious adverse outcomes after medical therapy are unusual. Studies on surgical therapy are largely anecdotal, with noncomparative reports on a variety of surgical methods. A few comparative surgical studies have been reported. Because of the noncomparative nature of many of the surgical studies, the use of combinations of surgical procedures and techniques in the reported studies, and the reporting of results from surgeons with an unusually high level of technical skill, the gynecological practitioner has little basis in the literature for assessing the optimum surgical approach. Surgical complications are believed to be underreported and may be related to how aggressive a surgical procedure is undertaken.

Androgens↗
PubMed2001

Role of a symptom-based algorithmic approach to chronic pelvic pain.

OBJECTIVE: Chronic pelvic pain (CPP) is a disorder that has a significant impact on the patient's quality of life. Laparoscopic diagnosis can be disappointing, and recurrence is common after surgical treatment. A symptom-based algorithmic approach to treatment of CPP is presented that is safe and cost-effective. METHODS: This approach is oriented towards making a potential clinical diagnosis of endometriosis. It relies on a structured evaluation of the patient and administration of medical therapy including GnRH agonists to selected patients. Evaluation begins with a history and physical examination; selected cases receive specific therapy. Non-responders undergo appropriate laboratory and imaging studies. If results remain negative, it is possible to make a clinical diagnosis of endometriosis and begin empiric treatment. RESULTS: Early results strongly indicate that using this approach allowed clinicians to make highly accurate diagnoses (correct in 85-90% of cases). CONCLUSION: Use of this approach will minimize the need for surgery.

Algorithms↗
PubMed2000

A cost-effective approach to the management of endometriosis.

Endometriosis is a common disease that affects a large number of women throughout the world. Whereas in the past laparoscopy was commonly used for the diagnosis and treatment of women with endometriosis and pelvic pain, recent studies have demonstrated that surgical therapy offers no better results in terms of pain relief than medical therapy with a gonadotrophin-releasing hormone agonist. Surgical therapy requires considerable experience and expertise on the part of the surgeon and the results are likely to be operator dependent. The results of the very best surgeons, as published in the medical literature, often cannot be replicated by the average gynecologist. Medical treatment, on the other hand, is not operator dependent. The efficacy of clinical diagnosis given a thorough evaluation has been proved, and the outcomes of empiric medical therapy with a gonadotrophin-releasing hormone agonist are substantial. Given the similar results obtained with a gonadotrophin-releasing hormone agonist and surgical intervention and the fact that medical treatment is less expensive, primary therapy with a gonadotrophin-releasing hormone agonist appears to be the most cost-effective approach to the management of endometriosis and pelvic pain. Because of the limited information currently available, a statement regarding endometriosis and infertility would probably be inappropriate at this time.

Cost-Benefit Analysis↗
PubMed1999

Modeling of medical and surgical treatment costs of chronic pelvic pain: new paradigms for making clinical decisions.

Additional complexity has been added to the healthcare decision-making process by the socioeconomic constraints of the industry and a population that is increasingly educated about healthcare. As a result, decisions balanced on the basis of outcomes and economic realities are needed. This modeling of surgical versus medical treatment costs for chronic pelvic pain and endometriosis factors in the large number of women with chronic pelvic pain, direct and indirect costs of the condition, and clinical benefits, projected costs, and savings of the therapies. This process of calculation becomes an aid for decision making in the current healthcare system.

Algorithms↗
PubMed1995

The regulation of plasminogen activators and plasminogen activator inhibitor type 1 in endothelial cells by sex hormones.

OBJECTIVE: The purpose of this study was to assess the effect of 17 beta-estradiol, progesterone, and testosterone on secretion of plasminogen activators and plasminogen activator inhibitor type 1 by cultured endothelial cells. STUDY DESIGN: Bovine aortic endothelial cells were cultured in medium that contained 17 beta-estradiol, progesterone, or testosterone at various concentrations (10(-13) to 10(-6) mol/L). Plasminogen activator activity in culture medium in the presence of cells was assayed after a 36-hour incubation using chromogenic substrate and iodine 125-labeled fibrin plate assays. Plasminogen activator inhibitor type 1 antigen was detected in conditioned media of bovine aortic endothelial cells by Western blotting analysis. RESULTS: All three steroid hormones exhibited biphasic dose-response effects, characterized by stimulation of plasminogen activator secretion at lower concentrations and inhibition of plasminogen activator secretion at higher concentrations. A significant stimulatory effect on plasminogen activator secretion (74% over control) was observed at a 17 beta-estradiol concentration of 10(-12) mol/L (p < 0.03). At higher concentrations of 17 beta-estradiol, progesterone, and testosterone, inhibition of plasminogen activator secretion was observed (p < 0.05). Decreased levels of plasminogen activator inhibitor type 1 antigen were detected in supernatants treated with either 17 beta-estradiol or progesterone at a concentration of 10(-12) mol/L and were maximal at 10(-7) mol/L 17 beta-estradiol, progesterone, and testosterone. CONCLUSION: The secretion of plasminogen activators and plasminogen activator inhibitor type 1 is regulated in a biphasic dose-dependent manner by sex hormones in bovine aortic endothelial cells.

Animals↗
PubMed1995

Laparoscopic gray-scale and color Doppler US: preliminary animal and clinical studies.

PURPOSE: To evaluate a semiflexible ultrasound (US) transducer inserted through a laparoscopic port to image abdominal structures. MATERIALS AND METHODS: Laparoscopic US with a 9.6-mm-diameter, 5.0-7.5-MHz semiflexible transducer with gray-scale, color, and spectral Doppler capabilities was performed in three miniature swine and in 25 patients with a variety of abdominal abnormalities. RESULTS: This miniature US probe was used to locate normal structures such as blood vessels, allowing the surgeon to decide the best approach for dissection. Color and spectral Doppler US proved especially useful in differentiating vascular from nonvascular structures. The presence or absence of stones in the gallbladder and common bile duct was readily determined. It was possible to detect masses and to provide guidance for their aspiration or biopsy within abdominal organs. In 10 cases (40%), laparoscopic US helped the surgeon make the decision for clinical management and altered the surgical procedures. CONCLUSION: Laparoscopic US was useful in assisting laparoscopic evaluation of abnormalities in the abdomen.

Abdomen↗
PubMed1994

Gonadotropin-releasing hormone agonists. Current uses for these increasingly important drugs.

Use of gonadotropin-releasing hormone (GnRH) agonists produces a transient increase and subsequent long-term reduction in concentrations of pituitary hormones, resulting in gonadal hormone suppression. This reversible suppression is useful in treating diseases dependent on these hormones. GnRH agonists have been approved for use in patients with endometriosis, advanced prostate cancer, and precocious puberty. As research continues, GnRH agonists are expected to change the clinical approach to the treatment of many other reproductive and nonreproductive diseases.

Endometriosis↗
PubMed1993

Sonographically guided laparoscopy and mediastinoscopy using miniature catheter-based transducers.

Miniature ultrasound transducers (12.5 MHz) housed in 9 Fr catheters were passed through a laparoscope or mediastinoscope to image a variety of normal and abnormal structures within the peritoneal cavity and mediastinum in 20 patients. These transducers made it possible to visualize the gallbladder and bile ducts and evaluate for the presence of stones, to detect masses and provide guidance for their aspiration or biopsy, and to image the internal structures of the ovary and fallopian tube. In addition, these miniature transducers were used to locate such normal vital structures as blood vessels, thereby allowing the surgeon to decide on the best approach for dissection during mediastinoscopy. During conventional surgery, the surgeon or gynecologist can palpate an area of abnormality not directly visualized. However, during laparoscopy and mediastinoscopy direct palpation is not possible. Therefore, it is important to find another method to determine what structures lie beneath the visualized surface. These miniature ultrasound transducers appear to offer a means for making such determinations.

Adult↗
PubMed1993

Current reproductive technology: considerations for the oncologist.

Advances in reproductive technology now afford options for certain cancer patients that the oncologist must consider when planning treatment. For men undergoing treatment likely to destroy testicular function, the development of sperm banks to store cryopreserved sperm offers the hope of future fatherhood. Cryopreserved sperm can be held indefinitely, with pregnancies via artificial insemination reported up to 15 years after freezing. For female cancer patients who will lose ovarian function but likely retain a viable womb, in vitro fertilization techniques hold the promise of pregnancy with the use of donated ova. In some cases, it may even be possible to extract the woman's own eggs before surgery and fertilize them with her husband's sperm. The resulting embryos, like sperm, can be frozen for indefinite future use. In the future, with new technological advances, extraction of ova for freezing at the time of ovarian extirpation may be a possibility.

Cryopreservation↗
PubMed1990

Serum CA 125 levels in early pregnancy and subsequent spontaneous abortion.

CA 125 has been found in high concentrations in human amniotic fluid throughout gestation, with significant quantities seen in the decidua and chorion. Because disruption of the epithelial basement membrane of the fetal membrane or the decidua could theoretically lead to a rise in maternal CA 125 levels, this increase may be a predictor of subsequent spontaneous abortion of the fetus. A study was initiated to investigate whether a sudden rise in the serum CA 125 level might predict spontaneous first-trimester abortions. CA 125 levels of 101 pregnant women were evaluated 18-22 days from conception and 6 weeks from conception (a frequent time for spontaneous abortion) to determine whether there is a sudden increase (from baseline or early trimester levels) during the middle or late first trimester immediately before or at the time of abortion. The results indicated that although there was a definite correlation found between elevation of CA 125 and spontaneous abortion, the higher levels occurred early in the first trimester whereas the majority of abortions did not occur until much later, after fetal viability was established. Six of ten women with CA 125 levels of 150 U/mL or greater aborted, compared with four of 92 women with CA 125 levels less than 150 U/mL. One of 11 women pregnant after in vitro fertilization had a CA 125 level above 150 U/mL, and she aborted.

Abortion, Spontaneous↗
PubMed1989

Efficacy of a gonadotropin-releasing hormone agonist in the treatment of uterine leiomyomata: long-term follow-up.

The authors employed a gonadotropin-releasing hormone agonist (GnRH-a) (D-His6-pro9-NET-GnRH) to treat 19 patients with symptomatic uterine leiomyomata, by daily subcutaneous injections (4 micrograms/kg) for 6 months. After therapy, patients were followed for 6 months without any therapy. Uterine volumes were measured by serial pelvic examinations and pelvic sonography. Measurements of serum estradiol, luteinizing hormone, and follicle-stimulating hormone were used to assess treatment response. Pituitary desensitization and hypoestrogenemia were achieved in all within 8 weeks, and in 18 of 19, hypoestrogenemia was maintained for the duration. Uterine volume at the conclusion of therapy (207.5 +/- 152.7 ml) was significantly reduced in all patients when compared with pretreatment sizes (420.8 +/- 276.4, P less than 0.05). Side effects included hot flashes (78%), vaginal dryness (32%), and transient frontal headaches (55%). All patients reported partial or complete relief from their symptomatic leiomyomata. Uterine volume at the conclusion of follow-up (345.4 +/- 195.7 ml) was greater than at the conclusion of therapy. Menses resumed in all patients within 4 to 8 weeks. In conclusion, GnRH-a therapy does not provide definitive therapy for symptomatic uterine leiomyomata but is effective in reducing the size of leiomyomata as a temporary measure. Gonadotropin-releasing hormone agonist therapy may be useful as an adjunct before myomectomy or hysterectomy and deserves further investigation.

Adult↗
PubMed1989

The effect of therapy initiation day on clomiphene citrate therapy.

Eighty-seven anovulatory patients were treated with clomiphene citrate (CC) to induce ovulation in 414 cycles. Clomiphene citrate was initiated randomly on the 2nd, 3rd, 4th, or 5th day of the menstrual cycle to evaluate the effectiveness of therapy. The results of therapy were assessed in terms of ovarian response and pregnancy outcome. Ovarian response was evaluated employing basal body temperature (BBT) to define follicular, luteal, and cycle lengths, and a midluteal serum progesterone (P) level and the integrated luteal P to define luteal adequacy. Pregnancy outcome was evaluated in the categories of total pregnancy, live birth, first trimester abortion, and fecundity rates. There were no significant differences noted between the groups who started CC on the 2nd, 3rd, 4th, or 5th day of cycle in terms of anovulation rates (12% to 21%), luteal dysfunction (28% to 39%), and normal ovulation rates (42% to 57%). Pregnancy was achieved in 31% (n = 27/87) of patients with a spontaneous abortion rate of 19% (n = 5/27). The fecundity rates ranged between 5.7% and 9.4%. Pregnancy outcomes also were not significantly different between the groups. Significantly shorter luteal phase length and longer follicular phase length were observed in the cycles with luteal dysfunction. The luteal progesterone parameters, including midluteal serum P concentration, the integrated luteal P, and the luteal P amplitude were significantly lower in the cycles with luteal dysfunction.

Abortion, Spontaneous↗
PubMed1989

Physiologic characterization of transformed and cloned rat granulosa cells.

Properties of a clonal line of SV40-transformed rat granulosa cells (DC3 cells) were elucidated. DC3 cells were maintained in vitro in Iscove Modified Dulbecco Medium that contained 20% fetal bovine serum. The cells had a logarithmic growth phase doubling time of approximately 18 h and produced detectable quantities of estrone, estradiol, and progesterone. Steroidogenesis was increased by supplementation with either steroidogenic substrates or agents that stimulated activity of adenylate cyclase. Production of progesterone and estrogens was enhanced when medium was supplemented with 25-hydroxycholesterol, and production of estradiol was enhanced by medium supplementation with androstenedione. Treatments with forskolin and cholera toxin resulted in marked increases of cyclic adenosine 3',5'-monophosphate (cAMP) in medium and cells and enhanced steroidogenesis. Isoproterenol and vasoactive intestinal peptide, but not follicle-stimulating hormone (FSH), luteinizing hormone (LH), insulin or prolactin, stimulated cAMP secretion by suspended cells. DC3 cells had small but detectable levels of binding to FSH, but binding of LH and epidermal growth factor could not be detected. DC3 cells possess characteristics expected of granulosa cells arrested in an early stage of differentiation and may provide a useful model for studies of "immature" granulosa cell functions.

Animals↗
PubMed1988

Luteal-phase support in stimulated cycles in an in vitro fertilization/embryo transfer program: progesterone versus human chorionic gonadotropin.

A study was undertaken to compare the hormonal parameters [serum concentrations of estradiol (E2), and progesterone (P) and P/E2 ratios] of patients undergoing in vitro fertilization/embryo transfer to whom either progesterone in oil or human chorionic gonadotropin (hCG) was administered as luteal support. Seventeen patients were studied in 20 cycles. In 10 randomly assigned cycles 25 mg of intramuscular progesterone in oil was administered daily from the day of embryo transfer (day +4) until day +18. In the other 10 cycles, 1500 IU of hCG was given intramuscularly on days +4, +7, +10, and +13. Even when accounting for the differences in recruitment in the two groups, the hCG-treated group had significantly higher concentrations of serum P (P less than 0.01) and E2 (P less than 0.05) during the luteal phase. The luteal P/E2 ratios were higher in the progesterone-treated group because of the lower E2 levels in that group, although the difference was not statistically significant. The ratio of the mean luteal P to the preovulatory serum E2 was significantly higher in the hCG-treated group (P less than 0.01). There were three clinical pregnancies in the hCG-treated group. We conclude that (1) higher P concentrations are achieved with hCG treatment than with progesterone treatment during the luteal phase; (2) high luteal P/E2 ratios per se may not be an important determinant of implantation; (3) progesterone production by the corpus luteum is not maximal in progesterone-treated cycles; and (4) the usefulness of hCG as a luteal support agent should be further evaluated.

Chorionic Gonadotropin↗
PubMed1988

Adnexal mass occurring with intrauterine pregnancy: report of fifty-four patients requiring laparotomy for definitive management.

Fifty-four cases in which surgical intervention during pregnancy was required for definitive therapy of adnexal masses were reviewed. The calculated incidence of adnexal masses that required surgical intervention during pregnancy in our primary population (patients who were not referred for evaluation of an already identified mass) was one case per 1300 live births. A malignant tumor was found in 5.9% of the pregnant patients who underwent exploratory celiotomy for therapy of an adnexal mass. Those pregnant women who underwent emergency celiotomy because of hemorrhage or torsion as a complication of an adnexal mass spontaneously aborted or underwent premature delivery more frequently than those patients who underwent elective celiotomy for removal of the mass (p less than 0.001). On the basis of this review, we recommend that pregnant women with persistent adnexal masses undergo elective extirpation of the mass in the second trimester of pregnancy.

Adnexal Diseases↗