Outcome of long benign esophageal strictures undergoing endoscopictherapy: a tertiary center experience.

COMPLEX BENIGN ESOPHAGEAL STRICTURES ARE DEFINED BY LENGTH (≥2 CM), SMALL DIAMETER, AND STRICTURE ANGULATION OR TORTUOSITY. THE LONG-TERM COURSE OF COMPLEX ESOPHAGEAL STRICTURES BASED ON LENGTH IS CURRENTLY UNCLEAR. WE SUSPECT THAT THE ESOPHAGEAL STRICTURE LENGTH MIGHT IMPACT THE EFFECTIVENESS OF ENDOSCOPIC DILATION THERAPY. WE PERFORMED A RETROSPECTIVE STUDY OF ALL BENIGN ESOPHAGEAL STRICTURES OF 2 CM OR LONGER TREATED AT A SINGLE CENTER BETWEEN JULY 1, 2010, AND MAY 31, 2014. PRIMARY OUTCOMES WERE CHANGED IN DYSPHAGIA SCORE AT THE END OF FOLLOW-UP COMPARED TO FIRST DILATION AT OUR FACILITY AND THE NEED FOR GASTROSTOMY PLACEMENT OR ESOPHAGECTOMY DURING FOLLOW-UP. DATA WERE STRATIFIED INTO FOUR SUBGROUPS ACCORDING TO STRICTURE LENGTH 20­29, 30­49, 50­99, AND 100 MM OR LONGER. EIGHTY-SEVEN PATIENTS (MEAN AGE 66 YEARS, 54% WOMEN) WERE FOLLOWED OVER A MEDIAN OF 40 MONTHS. PATIENTS UNDERWENT A MEDIAN OF 6 DILATIONS, AVERAGING 0.3 DILATIONS PER MONTH. MEDIAN DYSPHAGIA SCORE REMAINED UNCHANGED AT 2; 37 (43%) PATIENTS REPORTED RESOLUTION OR IMPROVED DYSPHAGIA AND 50 (57%) PATIENTS REPORTED NO IMPROVEMENT OR WORSENED DYSPHAGIA. GASTROSTOMY PLACEMENT OR ESOPHAGECTOMY WAS NEEDED FOR 23 (26%) AND 3 (3%) PATIENTS, RESPECTIVELY. MEDIAN DEGREE OF DYSPHAGIA AT THE END OF FOLLOW-UP DID NOT DIFFER BETWEEN THE FOUR STRICTURE LENGTH SUBGROUPS, YET NO PATIENT HAD IMPROVEMENT IN THE 100 MM OR LONGER SUBGROUP. MORE THAN HALF OF PATIENTS WITH LONG BENIGN ESOPHAGEAL STRICTURES HAD UNCHANGED DYSPHAGIA OR DEVELOPED WORSE DYSPHAGIA DURING FOLLOW-UP. LONG-TERM OUTCOMES DID NOT DIFFER BETWEEN DIFFERENT STRICTURE LENGTHS: .

Discrepancy between the effects of desialylation of human chorionic gonadotrophin on in vitro ovarian biological activity and on receptor binding.

An in vitro bioassay based on progesterone production by enzymatically-dispersed immature rat ovary cells, was used to investigate the effect of sialidase treatment on the biological activity of human chorionic gonadotrophin (hCG). The potency in this bioassay system and in an ovarian receptor assay were compared, to substantiate possible discrepancies between the effect of this treatment on biological activity and on receptor binding. Ovarian cells responded dose-dependently to the addition of hCG as well as sialidase treated hCG (asialo-hCG). Dose-response curves of hCG and asialo-hCG were parallel and the maximal stimulation levels reached were the same. Sub-maximal doses of hCG and asialo-hCG were additive. The potency of asialo-hCG was 65% of the original preparation. Addition of low concentrations of phosphodiesterase inhibitor resulted in a greatly enhanced sensitivity of the bioassay, but had no effect on the potencies of asialo-hCG and hCG. In contrast to intact gonadotrophins, the receptor assay potency of asialo-hCG was more than three times the bioassay potency. In agreement with this, it was found that when equal amounts of 125I-labelled hCG and asialo-hCG were specifically bound to the ovarian cells, the latter stimulated progesterone production less effectively. It is concluded that there is a discrepancy between the effect of desialylation on the biological activity and on the receptor-binding ability of hCG.

The effect of galactose oxidase treatment on the hepatic binding and biological activity of desialylated human chorionic gonadotrophin.

125I labelled desialylated hCG (asialo-hCG) was treated with galactose oxidase, in order to find out whether oxidation of the terminal galactosyl residues would diminish the hepatic uptake of asialo-hCG. Specific binding to the hepatic asialo-glycoprotein receptor was monitored in vitro by a rat liver radioligand receptor assay (RRA). Hormonal activities were compared by ovarian RRA and by in vitro bioassay. Uptake studies were done in superovulated immature rats. Galactose oxidase treatment had hardly any influence on the in vitro ovarian binding and biological activity of [125I]asialo-hCG. Binding in the liver RRA was virtually abolished. In vivo hepatic uptake, however, was considerably above the level of [125I]hCG, as was the uptake in the kidneys. The hepatic uptake was inhibited by the administration of a high dose of asialo-fetuin. It is concluded that oxidation of the terminal galactosyl residues reduces the binding of asialo-hCG to the hepatic asialo-glycoprotein receptor, without affecting its hormonal properties. The ovarian uptake in vivo, however, is still limited by the high hepatic and renal clearance.

A pitfall in the ovarian ascorbic acid depletion assay (OAAD): effect of unilateral ovariectomy, hCG and asialo-hCG.

The estimation of the effect of desialylation on the biological activity of human chorionic gonadotrophin (hCG), as determined in the ovarian ascorbic acid depletion assay (OAAD), according to the modification in which the animals are used twice, appeared to be dependent on the assay conditions. Animals which received hCG in the first assay (OAAD-1) gave higher potency estimates for hCG and asialo-hCG in OAAD-1. The results of the experiments indicate that the ovarian sensitivity for hCG and asialo-hCG is increased after administration of hCG and unilateral ovariectomy and decreased after administration of asialo-hCG.

The "treatment" of unexplained infertility with danazol.

In order to investigate the possible stimulating effect of danazol on fertility, a randomized clinical trial was performed on 40 women with unexplained infertility. Of these 40 women, 21 received 200 mg of danazol daily for 100 days and 19 received a placebo treatment during the same period. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, estrone, estradiol, progesterone, and testosterone were followed before, during, and after treatment. Danazol administration induced anovulation in all women, with prompt resumption of normal ovulatory function after discontinuation of the drug. No influence was seen on serum LH, FSH, and testosterone levels, but serum estrone, estradiol, and progesterone levels decreased significantly during treatment. Serum prolactin levels also decreased, but not significantly. No pregnancies occurred in the placebo group during a 6-month follow-up period. In the danazol group, five pregnancies occurred, of which two were ectopic and three went to term. The difference in pregnancy rate between both groups was statistically significant (P less than 0.05).

Ovarian binding and intrinsic biological activity of desialylated human chorionic gonadothrophin (ASIALO-hCG).

The present study was undertaken to investigate the effect of desialylation on the intrinsic in vivo biological activity of hCG. To block the hepatic uptake of asialo-hCG we investigated asialo-orosomucoid. The biological activity of hCG and asialo-hCG was estimated with the ovarian ascorbic acid depletion assay (OAAD). The uptake studies were performed with [125I]hCG and [125I]asialo-hCG. Desialylation of hCG increased its hepatic uptake, almost completely abolished its ovarian uptake, and reduced its in vivo biological activity to less than 1%. Administration of asialo-orosomucoid caused a reduction of the hepatic uptake of asialo-hCG to the level observed for hCG. The ovarian uptake increased, but was lower than observed for hCG, due to a considerably higher renal accumulation of asialo-hCG. The in vivo biological activity of asialo-hCG was approximately 1/5 of the activity of hCG when both were tested in the presence of asialo-orosomucoid. To exclude the interference of renal accumulation, binding and biological activity were also investigated after bilateral nephrectomy. The uptake of radioactivity in the ovaries following injection of [512I]asialo-hCG and asialo-orosomucoid was then almost the same as observed after injection of [125I]hCG alone. When both preparations were now tested in the presence of asialo-orosomucoid, the in vivo biological activity of asialo-hCG appeared to be approximately 1/3 of the value obtained for hCG. It is concluded that the intrinsic in vivo biological activity of hCG is lowered by desialylation.

Treatment of unexplained infertility with danazol.

In order to investigate the possible stimulatory effect of danazol on fertility, a randomized clinical trial was performed on 40 women with unexplained infertility. Twenty-one women received 200 mg danazol daily for 100 days and 19 women received a placebo for the same period. No pregnancies occurred in the placebo group during a 6 month follow-up period. In the danazol group, 5 pregnancies occurred of which 1 were ectopic and 3 went to term.

Sex hormone binding globulin: binding capacity and studies on the binding of cyproterone acetate and other steroids.

Sex hormone binding globulin in blood is quantitated by ammonium sulphate precipitation technique with two radioactive ligands, [3H]testosterone and [3H5dihydrotestosterone. Plasma levels in normal men, normal women, women taking oral contraceptives containing oestrogens, and pregnant women are presented, measured with both ligands. Binding experiments with these ligands and several competing steroids show marked differences in displacement ability. For cyproterone acetate 100-500 ng per tube is required to obtain even a slight displacement of the radioactive ligands.

A radioligand receptorassay for serum HCG.

A radioligand receptorassay system is described for the measurement of human choriogonadotrophin (HCG) in serum, using 600-1600 X g fractions of homogenates of superovulating rat ovaries. The method is specific for HCG and lutrophin (LH), with a detection limit of 3.5 mIU HCG. The values obtained in the dilutions of pregnancy sera paralleled the standard curve up to 20 microliter, and no non-specific effects were found with this amount of serum. The potency ratio R/I, measured in normal pregnancy sera by radioligand receptorassay and radioimmunoassay, varied between 1.1 and 3.2. No relationship was found between the stage of pregnancy and the R/I ratio.

Serum levels of unconjugated aetiocholanolone androstenedione, testosterone, dehydroepiandrosterone, aldosterone, progesterone and oestrogens during the normal menstrual cycle.

The results of daily determination of the levels of gonadotrophins, oestradiol, oestrone, progesterone, aldosterone, dehydroepiandrosterone, androstenedione, testosterone, and aetiocholanolone in the serum of 6 normal, ovulating women are reported and discussed. A pre-ovulatory aldosterone peak and rising values in the luteal phase of the cycle were found. Androstenedione, testosterone, and aetiocholanolone levels were significantly elevated from 3 days before until 3 days after ovulation. Since the mean androstenedione/aetiocholanolone ratio in the individual cycles in this period was similar to the ratio found during the rest of the cycle, we think it unlikely that aetiocholanolone is produced by the ovaries. No correlation was found between the aetiocholanolone patterns and the basal body temperature. In a case of conception followed for 20 days after ovulation, the steroid patterns remained unchanged until the presumed day of implantation, after which the aldosterone, androstenedione, testosterone, and aetiocholanolone levels started to rise. The mean androstenedione/aetiocholanolone ratio during the 10 days after implantation did not differ from the values obtained in the foregoing periods, so direct aetiocholanolone production by the ovaries after implantation seems unlikely.