Ralph M. Wynn

University of Arkansas at Little Rock, Little Rock, Arkansas, United States

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Publications (6)17.86 Total impact

  • K.-W. Schweppe · R.M. Wynn
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    ABSTRACT: Laparoscopy permits identification of endometriotic foci, but the evaluation is not closely correlated with the histological and ultrastructural findings, which include a wide spectrum of variations. Endometriotic implants have been studied extensively by light microscopy for many years. Early investigators thought that ectopic endometrium reacts in precisely the same manner as does the normal uterine mucosa, but this opinion has been modified. The first electron microscopic studies to compare the cyclic changes of ectopic and eutopic endometria showed that the functional changes in endometriotic glands do not proceed as clearly and uniformly as those in the uterine mucosa. Extension of this clinical research to include a larger group of patients and additional biopsies before and after treatment with danazol has led to a concept of individual treatment for endometriosis.In this study, 96 patients with laparoscopically diagnosed pelvic endometriosis had biopsies before oral treatment with danazol (600 mg/day). At the completion of 6 months of therapy, laparoscopic biopsy of residual endometriotic implants or scar tissue (63 in number) was repeated. Follow-up biopsies were performed also in six patients who discontinued therapy after 2-4 months because of severe side-effects. In 13 patients, the biopsies were performed 2-12 weeks after cessation of danazol.The morphological findings encompassed three groups: (1) patients with highly differentiated endometriotic foci with endocrine-dependent functional modulation. Some of these were in phase with the menstrual cycle, and others were delayed in comparison with the eutopic endometrium. (2) Patients with highly differentiated glands and stroma without apparent endocrine modulation. Some glands were dilated, and the epithelium in certain foci resembled endosalpinx or endocervix. (3) Patients with cystic glands lined by poorly differentiated cuboidal or low columnar epithelium. These structures underwent no morphological changes during the menstrual cycle, and portions of some glands resembled paraovarian cysts or cysts lined by germinal epithelium.In the first group of patients, a typical lesion was an endometriotic focus in the broad ligament. Here the endometrium was in the early proliferative phase. This tissue was uniformly modulated with homogeneously differentiated cells and nuclei. The lumina of the glands were lined by a single layered columnar epithelium, the apical membranes of which were generally straight with microvilli of 0.5-1.5 μm. The intercellular plasma membranes were connected by typical desmosomes, which were found predominantly in the apical third of the cell. The cell membranes, which were straight or slightly tortuous, were about 80 A thick, with an intercellular space of about 120 A. In the early proliferative phase, the basal membrane was about 300-400 Åthick. The nuclei were uniformly oval in the early proliferative phase and were surrounded by an electrondense doublelayered nuclear membrane with very few invaginations. In the early secretory phase, highly differentiated endometriotic foci underwent characteristic changes, but not as precisely or extensively as did eutopic endometrium. In the midsecretory and late secretory phases, the predominant ultrastructural pattern in endometriosis was mixed, variations occurring among adjacent glands and even within the same gland.The second group of patients was characterized by striking discrepancies in cellular differentiation and variation. The ultrastructural features of twothirds of these specimens resembled those of the proliferative endometrium and appeared to be unrelated to the specific cyclic changes in the eutopic endometrium. The extent of secretory activity exceeded by far that in the luteal phase of group 1.In group 3, the lumina of the glands were widened, with various diameters, and the lining epithelium consisted of cuboidal or low columnar cells. The apical surface had poorly developed, irregularly distributed microvilli. The poorly differentiated cytoplasm showed various degrees of electron density.Only about 50 per cent of the specimens obtained in the proliferative phase and only about 40 per cent of those from the secretory phase showed features of cyclic modulation. Only about 25 per cent of the endometriotic biopsies obtained during the proliferative phase and only about 10 per cent of those from the secretory phase corresponded closely to the eutopic endometrium.At the time of laparoscopic follow-up, on the last day of treatment with danazol, endometriosis had disappeared completely in 14 cases. In 32 patients, scarring persisted on the peritoneal surface without evidence of active endometriosis. In 46 (48 per cent) of the 96 patients, the endometriosis had healed laparoscopically. The disease persisted in 63 women.
    No preview · Article · Nov 1984
  • K W Schweppe · Ralph M. Wynn
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    ABSTRACT: The comparison of the ultrastructural features of endometriotic implants in 96 patients before and after suppressive therapy by danazol showed that the glands of the ectopic endometrium had a wide range of morphologic development. In about one-third of the pretreatment biopsies significantly different ultrastructural patterns were observed in the same specimen, ranging from poorly to highly differentiated endometrial glands. Adequate morphological changes during the menstrual cycle were found in implants only in 14 patients during the proliferative phase, but adequate, homogeneously performed secretory changes were completely missing during the luteal phase. Besides incomplete or delayed secretory changes the majority was proliferative rather than secretory. After 6 months of endocrine suppression laparoscopic biopsies of endometriosis were repeated, and the ultrastructural findings lead to three conclusions. 1. Poorly differentiated endometriotic foci do not respond to danazol. 2. Endometriotic implants consisting of highly differentiated epithelium with adequate cyclic variations respond well to danazol and disappear in nearly 80% of cases. 3. In endometriosis with mixed areas consisting of various degrees of glandular differentiation the hormonal suppression can eliminate endometriotic implants or arrest them at a proliferative stage. If the morphological appearance of the ectopic implants depends not simply upon the endocrine stimulus, but primarily on the degree of differentiation and maturity of the cell, then perhaps cyclic modulation is only a secondary phenomenon, and hormones play only a secondary role in therapy. If this hypothesis is correct, only complete elimination of endocrine influence can cure endometriosis. Transient or incomplete suppression may lead only to partial regression.
    No preview · Article · Jun 1984 · European Journal of Obstetrics & Gynecology and Reproductive Biology
  • K W Schweppe · Ralph M. Wynn · Fritz K. Beller
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    ABSTRACT: Ultrastructural features of endometriotic implants suggest an incomplete response to the prevalent hormonal milieu. The cyclic changes, especially in the secretory phase, appear to depend more on the morphologic differentiation of the ectopic implants than on the hormonal stimulus. The endometriotic tissue encompassed a wide range of morphologic development from poorly to highly differentiated glands. Variations occurred from gland to gland and even within the same gland. Complete proliferative development was found only in some of the patients and full secretory transformation was absent in all. The incomplete morphologic response to cyclic hormonal changes may explain the frequent failure of endocrine therapy.
    No preview · Article · May 1984 · American Journal of Obstetrics and Gynecology
  • K W Schweppe · R M Wynn
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    ABSTRACT: This report, the first ultrastructural study of endometriotic implants, compares the ectopic endometrium in 14 patients with that found in the uterus. The ultrastructural features of most of the glands of the ectopic endometrium resemble those of the corresponding glands lining the uterus. Specific ultrastructural characteristics associated with ovulation, such as giant mitochondria and nuclear channel systems, however, could not be detected in ectopic tissue. Although no pathognomonic electron microscopic characteristics were found in the ectopic endometrium, it was generally possible to assign each sample to a particular phase of the menstrual cycle.
    No preview · Article · Nov 1981 · Obstetrics and Gynecology
  • K W Schweppe · W P Dmowski · R M Wynn
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    ABSTRACT: Electron microscopic examinations were carried out on 29 representative endometriotic glands obtained from 16 biopsies. Patients with endometriosis diagnosed by laparoscopy and confirmed by laparoscopic biopsy prior to hormonal treatment received danazol, 800 mg daily. The tissue samples were obtained after 2, 4, and 6 months of usage of the drug to study the ultrastructural effect of this treatment. The glandular epithelium appeared to be arrested in what looked like the late proliferative stage of the normal menstrual cycle. The ciliated cells remained unchanged for the most part. The findings were correlated with possible effects of danazol on the target tissue, but caution is required in the interpretation of ultrastructural effects of steroids until detailed knowledge of the metabolic pathways is available.
    No preview · Article · Aug 1981 · Fertility and Sterility
  • K W Schweppe · Ralph M. Wynn
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    ABSTRACT: Transmission electron microscopy and ultracytochemical localization of alkaline phosphatase were employed to compare the glands of the isthmic mucosa with those of the fundal endometrium. Examination of 40 biopsies during various phases of the menstrual cycle and in the postmenopause have demonstrated the features of this transitional mucosa. The cyclic morphologic changes in the isthmus are almost identical with those of the glands of the basalis of the corpus. Alkaline phosphatase was demonstrated consistently on the plasma membranes of the isthmic mucosa but not on those of the glands of the basalis; technical considerations may in part explain these differences. Secretory activity was found in every phase of the cycle. The data from postmenopausal patients suggest the concept of migration of the isthmic mucosa toward the corpus uteri above the internal anatomical os.
    No preview · Article · Feb 1981 · Gynecologic and Obstetric Investigation