Salpingographic demonstration of "cobblestone" mucosa of the distal tubes is indicative of irreversible mucosal damage.

OBJECTIVE: To establish the predictive value of the observation of a "cobblestone" pattern of the distal tube mucosa shown on the selective salpingogram as an indicator of significant and probably irreparable damage to the ciliated epithelium. DESIGN: Clinical study. SETTING: Fertility and Laser Center and Academic Radiology Department. PATIENT(S): Patients with primary or secondary infertility and obstruction of the fallopian tubes documented on hysterosalpingogram. INTERVENTION(S): Transcervical recanalization of obstructed tubes followed by reassessment by selective salpingogram. MAIN OUTCOME MEASURE(S): Progression of mucosal disease with resultant low likelihood of intrauterine pregnancies and high probability of ectopic pregnancy. RESULT(S): In 32 asymptomatic patients, there was progression to coalescence and agglutination of mucosal folds in 13, to a thick wall pyosalpinx in 4. Five thin wall and 8 thick wall hydrosalpinges in asymptomatic patients showed no significant progression of mucosal disease but increasing peritubular fibrosis. In 12 symptomatic patients, progressive fusion of mucosal folds with polypoid hyperplasia was observed in 11, a thin wall hydrosalpinx in 2. CONCLUSION(S): Cobblestone appearance of the distal tubes heralds significant mucosal damage, prone to progressive disease and hence, a poor chance for conception.

Efficacy of salpingography and transcervical recanalization in diagnosis, categorization, and treatment of fallopian tube obstruction.

PURPOSE: The efficacy of selective salpingography (SS) and transcervical recanalization (TCR) in diagnosis, categorization, and determination of optimal treatment modality for fallopian tube obstruction was investigated. METHODS: SS and, in some patients, TCR was performed in 430 patients with a diagnosis of obstruction of one or both fallopian tubes, as determined by hysterosalpingograms (HSG). All patients (age 21-46 years) had an infertility problem for at least 18 months. RESULTS: In 196 patients, 325 tubes were patent on SS. TCR recanalized 243 tubes in 176 patients. Disease of the distal tube was demonstrated in 66 patients. There were 39 live babies in a group of 176 patients with successful TCR. Best live birth rate was in 7 of 12 (58%) patients with underlying endometriosis, followed by postsurgical strictures in inflammatory disease, 6 of 31 (19%), and salpingitis isthmica nodosa in 25 of 168 (15%). There were no pregnancies in patients with cobblestone pattern of the distal tubes. CONCLUSIONS: SS and TCR were capable of correcting obstruction of the proximal tubes in 243 of 465 tubes in 176 of 234 patients (75%). With patency of the proximal tube restored, the distal tube could be assessed for changes indicative of damage to the ciliated epithelium which was likely to reduce the ability to become pregnant. This allowed for the triage of patients into groups benefiting from the relatively inexpensive and low complication TCR or patients in need of in vitro fertilization or similar assisted reproductive technologies.

Selective osteal salpingography and transvaginal catheter dilatation in the diagnosis and treatment of fallopian tube obstruction.

Selective salpingography and transvaginal catheter dilatation were performed in 157 women with infertility to diagnose, localize, and classify obstructive diseases of the fallopian tubes and to correct obstruction of the proximal (uterine-end) tube. In 61 (39%) of the patients, the selective salpingograms showed patent tubes despite the fact that two previous hysterosalpingograms showed obstruction of the proximal (uterine-end) tube. Transvaginal catheter dilatation successfully recanalized the proximal portion of the tubes in 79 (82%) of 96 patients with obstructed tubes. In 18 of 25 with successful transvaginal catheter dilatation and 6-month follow-up salpingography, the tubes remained patent. Coexisting disease of the distal (ovarian-end) tubes was diagnosed in 29 (18%) of the patients. Pregnancy was achieved in 11 of the 157 patients (six in whom obstructions were corrected by transvaginal catheter dilatation and five in whom selective salpingograms showed patent tubes). There were no complications due to the procedure. The excellent diagnostic and therapeutic yield, lack of complications, and low cost justify the use of these percutaneous techniques to investigate female infertility and to treat obstruction of the uterine end of the fallopian tube.

Isolation of unliganded steroid receptor proteins by high-performance size-exclusion chromatography. An investigation of steroid-dependent structural alterations.

The physicochemical properties of unliganded steroid receptor proteins remain largely unknown primarily due to receptor lability in the absence of specific ligand, especially during prolonged biochemical analyses. We have utilized high-performance size-exclusion chromatography (HPSEC) as a rapid means of investigating the structural properties of cytosolic estrogen receptor proteins in both the presence and absence of [3H]estradiol-17 beta. Cytosols prepared from immature calf uteri were analyzed by HPSEC on an Altex TSK-3000 SW column (600 mm X 7.5 mm I.D.) either before or after incubation with 10 nM [3H]estradiol-17 beta. Postcolumn detection of previously unliganded receptor was accomplished by incubation of fractions (0.38 ml) with 10 nM [3H]estradiol-17 beta for 2-18 h at 0 degrees C. Receptor-bound steroid was separated from free steroid by incubation with small pellets of hydroxylapatite. Nonspecific binding of [3H]estradiol-17 beta in parallel fractions was estimated using an unlabelled competitor (diethylstilbestrol) specific for the estrogen receptor. In low ionic strengths the receptor exists as a single, relatively stable, large form (retention time 34 min). The elution properties of this receptor configuration do not depend on bound steroid ligand. Analysis of receptor at elevated ionic strengths in the presence and absence of steroid ligand suggests that the salt-induced dissociation of receptor components to smaller forms (retention time 47 min) may be partially steroid-dependent. Characterization of receptor in 6 M urea demonstrates the presence of intermediate-sized receptor components (retention time 36-38 min). Analyses of receptor in 6 M urea-0.4 M potassium chloride suggests an inhibition of the more extensive salt-induced dissociation event seen in 0.4 M potassium chloride alone. Furthermore, the intermediate-sized receptor forms seen under these conditions (retention time 41-42 min) are generated in a steroid-dependent manner. The preparation of different molecular forms of biologically active, unliganded estrogen receptor by HPSEC should help further our investigations into the molecular mechanism(s) by which steroid hormones exert their receptor-mediated effects on target cells.

High-performance chromatofocusing of steroid receptor proteins in the presence and absence of steroid. Investigation of steroid-dependent alterations in surface charge heterogeneity.

We have previously reported the development of high-performance chromatofocusing (HPCF) systems for rapid evaluation of the surface charge heterogeneity of steroid receptor proteins, each in the presence of its specific steroid ligand. However, the surface charge properties of ligand-free receptor proteins remain largely unknown. We have now employed HPCF to rapidly evaluate the surface charge properties of cytosolic estrogen receptor proteins in both the presence and absence of the ligand ([3H]estradiol-17 beta). All operations were performed at 0-4 degrees C. Cytosols prepared from immature calf uteri were preparatively analyzed by HPCF on a SynChropak AX-500 column (25 cm X 4.6 mm I.D.) either before or after incubation with 5-10 nM [3H]estradiol-17 beta. Elution of receptor was by generation of internal pH gradients (pH 8.1 to 3.2) using Pharmacia Polybuffers 96 and 74. Postcolumn detection of previously unliganded receptor was accomplished by incubation of pH-neutralized (pH 7.4) fractions with 5 nM [3H]estradiol-17 beta in the presence and absence of unlabelled competitor. Specifically bound steroid was determined in each fraction using an hydroxylapatite adsorption assay. Significant surface charge heterogeneity was observed for both unliganded receptor and the steroid-receptor complex. The heterodisperse pattern of receptor surface charge appeared to vary in a steroid-dependent manner. Preformed steroid-receptor complexes eluted primarily between pH 6.5-7 and between pH 5-6, with indications for heterogeneity within both regions. The surface charge distribution of unliganded receptor routinely revealed additional, more acidic eluting (pH 3.8-4.6) receptor forms. Sodium molybdate, a commonly used receptor-stabilizing agent, maintains receptors during HPCF as relatively acidic eluting forms (pH 3.8-5.0). The specific elution profile of molybdate-stabilized receptor also appears steroid-dependent. These data demonstrate that HPCF can be used preparatively to rapidly isolate unliganded receptor forms in a biologically active state.