External limiting membrane and visual outcome in macular hole repair: spectral domain OCT analysis.

PURPOSE: To investigate the relationship between postoperative visual acuity and integrity of the external limiting membrane (ELM) and inner segment-outer segment (IS-OS) junction layers, using spectral domain optical coherence tomography (SD-OCT), in eyes with macular holes (MHs) following surgical repair. METHODS: Medical charts of MH-operated cases were retrospectively identified and reviewed. The primary outcome measures were best-corrected visual acuity (BCVA) and the status of the ELM and IS-OS lines, using SD-OCT, at 6 weeks and 6 months postoperatively. RESULTS: Sixty-two eyes of 62 patients were included. At 6 weeks following surgery, out of 56 (90.3%) eyes with successful MH closure: 0 eyes showed the combination of disrupted ELM and continuous IS-OS layers; 7 eyes (12.5%) demonstrated continuity of both ELM and IS-OS (ELM(c)/IS-OS(c) group); 29 eyes (51.8%) had continuous ELM with discontinuous IS-OS layers (ELM(c)/IS-OS(d) group); and 20 eyes (35.7%) had discontinuities in both the layers (ELM(d)/IS-OS(d) group). The ELM(d)/IS-OS(d) group had the lowest visual gain at 6 months (P = 0.03). At 6 months, a restoration of the integrity of IS-OS layer was observed in 51.7% eyes in the ELM(c)/IS-OS(d) group and in 5% in the ELM(d)/IS-OS(d) group (P = 0.001). CONCLUSIONS: When both ELM and IS-OS layers showed disruptions 6 weeks postoperatively, a significantly worse BCVA was measured at 6 months, compared with the eyes with only IS-OS disruptions, detected 6 weeks following surgery. The integrity of the ELM layer appears to be a critical factor for the restoration of the photoreceptor layer and for predicting a successful visual outcome following MH repair.

Transscleral diode laser retinopexy in retinal detachment surgery: results of a multicenter trial.

PURPOSE: To evaluate the safety and efficacy of transscleral diode laser for retinopexy in rhegmatogenous retinal detachment surgery in a multicenter trial. METHODS: Seventy-two patients with primary rhegmatogenous retinal detachments were enrolled. No patient with chronic detachment, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy was enrolled. RESULTS: Information from follow-up of 6 months or longer was available on 65 eyes. Retinas were attached at 6 months with a single operation in 58 (89%) of these eyes. Complications included apparent pinpoint breaks in Bruch's membrane in 15 eyes, scleral-thermal effect in 14 eyes, and limited hemorrhage, which was intraretinal in 10 eyes and extended into the vitreous in 3 eyes. In one case, hemorrhage was judged perhaps to have contributed to initial surgical failure. The other complications had no known adverse effects. Complications were significantly associated with the physician's experience in using transscleral laser retinopexy. CONCLUSIONS: In this multicenter study, transscleral diode laser retinopexy served as a safe and effective means of creating chorioretinal adhesion during retinal reattachment surgery. Minor complications were minimized by increasing experience with the technique.

Comparison between extradural infusion of ropivacaine or bupivacaine for the prevention of postoperative pain after total knee arthroplasty.

We have compared the analgesia and motor block produced by extradural infusions of ropivacaine and bupivacaine after total knee arthroplasty. Fifty-two patients received 8 ml h1 of either 0.2% ropivacaine or 0.2% bupivacaine by extradural infusion for 24 h after operation. Analgesia was assessed by postoperative visual analogue scale (VAS) and morphine consumption. At rest these were low in both groups; median VAS was 0-13.3 mm for the ropivacaine group and 0-0.5 mm for the bupivacaine group. Over the 24 h of the infusion, the estimated (ropivacaine bupivacaine) difference in wound pain at rest was 5.6 mm (P = 0.017) and on passive movement 11.6 mm (P = 0.016). Median morphine consumption was 30.7 mg in the ropivacaine group and 20.5 mg in the bupivacaine group. In the ropivacaine group, 50% of patients compared with 19% in the bupivacaine group had no motor block 2 h after operation, increasing to 88% for ropivacaine and 56% for bupivacaine by 24 h. Bupivacaine produced significantly more frequent and intense motor block over the 24 h (P = 0.015).

Multicenter trial of transscleral diode laser retinopexy in retinal detachment surgery.

PURPOSE: To evaluate the safety and efficacy of transscleral diode laser for retinopexy in rhegmatogenous retinal detachment surgery in a multicenter trial. DESIGN: 67 patients with primary rhegmatogenous retinal detachment underwent scleral buckling surgery, using transscleral diode laser for retinopexy, at five study centers. STUDY PARTICIPANTS: 72 patients with primary rhegmatogenous retinal detachments were enrolled. No patient with chronic detachment, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy was enrolled. Five eyes were excluded because they required additional nonprotocol treatment at the time of surgery (vitrectomy or supplementary cryotherapy due to probe malfunction). MAIN OUTCOME MEASURES: Retinal reattachment at six months after one operation. Secondary measures: visual acuity and complications, including choroidal, retinal, and vitreous hemorrhage, inflammation, and scleral damage. RESULTS: Six months or greater follow-up information was available on 65 eyes. Retinas were attached at 6 months with a single operation in 58 (89%) of these eyes. Complications included apparent pinpoint breaks in Bruch is membrane in 15 eyes, scleral thermal effect in 14 eyes, and limited hemorrhage, which was intraretinal in 10 eyes, and extended into the vitreous in 3 eyes. In one case, hemorrhage was judged to have contributed possibly to initial surgical failure. The other complications had no known adverse effects. Complications were significantly associated with the physicians experience with transscleral laser retinopexy. CONCLUSION: In this multicenter series, transscleral diode laser retinopexy served as a safe and effective means of creating chorioretinal adhesion during retinal reattachment surgery. Minor complications were minimized by increasing experience with the technique.

Preoperative application of piroxicam gel compared to a local anaesthetic field block for postoperative analgesia.

The non-steroidal anti-inflammatory drugs inhibit prostaglandin synthesis and hence have an analgesic action. Following topical administration, the drug is concentrated in the tissues and so can have a local analgesic effect. This study investigated the effect of the preoperative application of topical piroxicam on postoperative analgesic requirement compared to a placebo group and a conventional local anaesthetic field block. Forty-two patients presenting for in-patient inguinal hernia repair were randomly allocated on a double-blind basis to have either piroxicam gel 15gm applied preoperatively, or an inguinal field block with 20 ml of 0.375% bupivacaine following induction of anaesthesia, or no treatment. Postoperative Visual Analogue Scores for pain on moving in group P, I or C on admission at 1h, 2h, and 4 h following surgery were: 2 vs 1 vs 6.5; 3 vs 3 vs 5; 3 v 2 vs 4.5; 3 vs 2 vs 5.0, respectively (P < 0.005). Median(range) time to first analgesia was 25.4(15-70) min in group I, 30.3(10-49) min in group P; this was not significantly different from group C21.5(7-70) min. Over the first 24 hours the postoperative morphine requirement was significantly less in the two treatment groups 30(20)mg in group I and 34(17) mg in group P and 71(15) in group C, P < 0.0001. There were no apparent NSAID-induced side-effects, or effects on wound healing. The preoperative administration of piroxicam (15gm) topically compared favourably with a preoperative local anaesthetic field block with respect to VAS scores, time to first analgesia and total morphine consumption. And both treatment groups provided significantly superior analgesia than the control group.

Improved postoperative analgesia with preoperative piroxicam.

PURPOSE: Piroxicam like other Non-Steroidal Anti-Inflammatory drugs can be used to provide postoperative analgesia. With a half-life of 50 hr given preoperatively its' analgesic effect should continue postoperatively. This study compared the effects of 20 mg piroxicam given at different times in the perioperative period on postoperative analgesic requirement. METHOD: Following ethical committee approval and written informed consent, 60 ASA I and II patients presenting for inpatient gynaecological laparoscopic surgery were given either 20 mg piroxicam or a placebo po two hours preoperatively, immediately before induction of anaesthesia or one hour postoperatively in a randomised double bind manner. RESULTS: Postoperative Visual Analogue Pain Scores were lower on admission to the recovery ward in patients given piroxicam preoperatively (Group 1), than in the other two treatment groups (groups 2 and 3). Pain scores were 2.72 vs 4.25 vs 6.67 respectively (P < 0.001). Pain scores did not differ at any other times. Time to first analgesic request was greater in the group 1 than in the other two treatment groups; 141 (61) min vs 115 (147) in Group 2 and 30 (36) min in Group 3. Nine patients in Group 1 requested further analgesia compared with 15 in Group 2 and 16 in Group 3. There were no piroxicam-induced side-effects. CONCLUSION: Piroxicam given two hours preoperatively reduced pain scores, time to first analgesia and postoperative analgesic requirements compared with administration prior to induction or one hour postoperatively.

The metabolic pathways for hormonal steroids appear to be reflected in the stereochemistry of DNA.

Computer graphics and energy calculations were employed to examine the relative fit of progesterone and its major biosynthetic precursors and inactive metabolites into partially unwound double stranded DNA. Progesterone was found to be the best fitting molecule; moreover, it was the only compound which exhibited full stereochemical complementarity by inserting completely between base pairs and forming optimal hydrogen bonds with both deoxyribose-phosphate backbones. Intermediates in each step of the biosynthetic and degradation pathways were progressively increasing and decreasing fits into DNA, respectively. When the fits of various possible stereoisomers were examined, the positions of functional groups manifest in the known biosynthetic precursors were found to provide the best possible fitting structures. Conversely, the positions of functional groups of known inactive metabolites provided the worst possible fitting structures. These findings coupled with previous reports showing that the specific biological function assigned to each class of steroid hormone correlates with the formation of a unique pattern of donor/acceptor linkages confirms that hormonal structures are indeed rare in their capacity to form "lock and key" complexes with DNA. Given that all possible linkages to DNA are not yet accounted for, the existence of other naturally occurring compounds with salient biological function is predicted.

3-phenylacetylamino-2,6-piperidinedione inhibition of rat Nb2 lymphoma cell mitogenesis.

3-Phenylacetylamino-2,6-piperidinedione (A10), an amino acid analog, has been reported to possess antineoplastic activity against certain neoplastic tissues. The antimitogenic properties of A10 were studied by determining its effect on prolactin (PRL)- and interleukin 2 (IL-2)-stimulated mitogenic responses in the rat Nb2 lymphoma cell line. The addition of A10 (1-12 mM) to PRL (0.4 ng/ml)-stimulated cells inhibited growth in a dose-dependent manner. DNA synthesis patterns studied by thymidine incorporation demonstrated that A10 was significantly inhibitory (25% at 20 hr; 50% at 40 hr, P less than 0.01). IL-2 stimulation of mitogenesis was also sensitive to A10 inhibition. The inhibition of PRL stimulated mitogenesis was reversible when A10 was removed after 24 hr of culture and A10 showed no toxicity in a chromium release assay. These data suggest that A10 effects may be cytostatic, rather than cytotoxic.

Effects of steroidal and non-steroidal antiandrogens on the androgen binding properties of the rat ventral prostate androgen receptor.

Steroidal (cyproterone acetate) and non-steroidal (RU23908 and hydroxyflutamide) antiandrogens are able to block testosterone-induced increases in nuclear androgen receptor (AR) in the prostate of 1-day orchidectomized rats, but when given alone, RU23908 and hydroxyflutamide increase nuclear AR (RU23908 greater than hydroxyflutamide) in the same animal model. The increases in nuclear AR induced by antiandrogen alone or with testosterone alone are blocked by cycloheximide 1 h after administration, suggesting that androgen or antiandrogens induce de novo AR synthesis. Concomitant to nuclear AR accumulation, testosterone is able to induce depletion of cytosol and microsomal AR. Blockade of testosterone-induced depletion of microsomal AR, but not of cytosol AR, occurs in the presence of antiandrogens. Cyproterone acetate has a higher relative binding affinity (RBA) for microsomal AR and cytosol AR than RU23908 or hydroxyflutamide. This phenomenon is in good agreement with the degree of inhibition by these compounds of the association rate of androgen for the microsomal AR. This correlation between RBA and inhibition of the initial rate of hormone binding to the receptor is not found for cytosol AR. The results show that antiandrogens are not 'pure' antagonists of androgen action and they are potent agonists in the absence of testosterone. Furthermore, testosterone alone or antiandrogens per se regulate AR levels acutely by protein-synthesis dependent mechanisms of action, in rat ventral prostate.

Characterization of estrogen-binding sites associated with the endoplasmic reticulum of rat uterus.

Microsomes prepared from rat uterine homogenates harbor high-affinity (Ka = 10(10) M-1), low-capacity binding sites for estrogens. Previous work from our laboratory has demonstrated that these estrophiles are located on endoplasmic reticulum and are not cytosolic contaminants of the membrane preparation. Subfractionation of microsomes into granular and agranular membranes and polysomes revealed approximately equal distribution of estrogen-binding activity among each of these constituents. These binding sites were fully extractable with 0.6 M KCl. Microsomal estrophiles solubilized under conditions of low ionic strength and complexed with estradiol migrated as 8S forms on continuous sucrose gradients. In the presence of 0.4 M KCl, the solubilized binding sites exhibit a sedimentation coefficient of 4S. Extracted binding sites do not undergo heat-induced transformation from a 4S to 5S species. The monoclonal antibody JS34/32 interacted with the endoplasmic reticulum-associated estrogen-binding sites when present in 50-fold molar excess, but not at lower antibody to binding site ratios. In comparison, the rat uterine cytosolic estrogen receptor formed complexes with JS34/32 at antibody to receptor ratios as low as 2:1. These results suggest that the endoplasmic reticulum possesses estrogen-binding sites with biochemical properties that differ from those of the classically described cytosolic (loosely associated nuclear) estrogen receptor.

Role of microsomal receptors in steroid hormone action.

Ventral prostate was used as a system to study the nature and properties of microsomal androgen receptor. The endoplasmic reticulum from rat ventral prostate contains high-affinity, low-capacity binding sites for androgen that are intrinsic to this intracellular compartment. Microsomal androgen receptors are not due to plasma membrane or cytosol contamination and they display a fast turnover, with depletion after 1 hour and complete replenishment 6 hours after androgen stimuli. Cycloheximide, but not actinomycin D, inhibits microsomal androgen receptor replenishment, indicating that testosterone may control microsomal receptor levels acutely by posttranscriptional mechanisms. Microsomal androgen receptor is a 5S protein that has a higher stability than its cytosolic counterpart, regardless of the presence of ligand. It does not become activated after heat or salt treatment. After extraction of binding sites, microsomes are capable of accepting cytosol mibolerone-receptor complexes to a level similar to the concentration of depleted binding sites; microsomes from nontarget tissues do not manifest such capability. The results indicate the coexistence of a non-DNA-binding form of androgen receptor in the microsomal membranes with the typical DNA-binding form of androgen receptor present in the cytosol of ventral prostate homogenates. Microsomal androgen receptor may represent an additional level of regulation of androgen action in the intact target cell.

Specific binding of androgen and androgen-receptor complex by microsomes from rat ventral prostate.

Microsomes from rat ventral prostate show the presence of a high affinity-low capacity population of androgen-binding sites with affinity for ionic exchange resin similar to that of cytosol androgen receptor (AR), as manifested by similar results obtained with hydroxylapatite. The affinity for mibolerone was similar for both forms (Ka = 0.5-2.9 x 10(10) M-1). The membrane-bound form can be extracted in hypotonic buffer, with retention of binding properties. Isotonic sucrose allowed higher degree of extractability of the microsomal AR than 10% (v/v) glycerol. The presence of hormone lends stability to the microsomal AR, while high salt or nonionic detergents have a deleterious effect on their longevity. The microsomal receptor form is not sensitive to serine-proteases as opposed to the cytosol AR. After exhaustive extraction of binding sites, microsomes are capable of accepting cytosol mibolerone-receptor complexes to a level corresponding to the concentration of depleted binding sites; microsomes from non-target tissue do not manifest such capability. Microsomal AR complexes do not bind DNA and they are not activated after heat treatment. Mixed preparations of extracted microsomal complexes with cytosol complexes showed heat-induced increased ability to bind DNA to the same level of diluted cytosol complex alone, indicating the absence of a microsomal inhibitor of DNA binding. The results indicate the co-existence of a non-DNA binding form of the AR in the microsomal membranes with the classical DNA binding form of the AR present in the cytosol of ventral prostate homogenates.

Role of 17 beta-hydroxysteroid dehydrogenase in the modulation of nuclear estradiol receptor binding by progesterone in the rat anterior pituitary gland and the uterus.

Progesterone has been shown to decrease occupied pituitary and uterine nuclear estradiol receptor (E2R) binding in mature and immature estrogen-primed rats. Progesterone has also been shown to stimulate pituitary but not uterine 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in the rat. The conversion of estradiol to its less active metabolite estrone by 17 beta-HSD and activation of phosphatase are among mechanisms considered to be involved in the reduction of E2R. To determine if 17 beta-HSD stimulation was a mechanism by which progesterone induced nuclear E2R decrease, the synthetic estrogen ethinylestradiol, which is not oxidized by 17 beta-HSD, was used instead of estradiol to prime adult ovariectomized rats. When ethinylestradiol-primed rats received 0.8, 2.0 or 4.0 mg/kg body wt of progesterone 2 h before sacrifice, the total and occupied nuclear E2R accumulation in the anterior pituitary by a subsequent ethinylestradiol injection 1 h later did not show any decrease. This response was different from that observed previously in estradiol-primed animals in which progesterone showed a multiphasic decrease of occupied form of nuclear E2R. However, in the uterus of ethinylestradiol-primed rats, a partial decrease of total and occupied nuclear E2R accumulation was observed in the presence of the three doses of progesterone used. The decrease of uterine nuclear E2R with the three progesterone doses was different from the dose-dependent effect of progesterone observed in the uterus of estradiol-primed rats. Affinity constants of the interaction between [3H]estradiol and the nuclear E2R were similar among groups treated with ethinylestradiol, estradiol and progesterone. These results demonstrate the involvement of 17 beta-HSD in the reduction of anterior pituitary gland E2R by progesterone in the estradiol-treated animals. Furthermore, the mechanism of decrease of E2R by progesterone in the uterus appears to be different from the pituitary gland.

Inhibitory effect of 5-alpha-dihydroprogesterone on nuclear estrogen receptor binding of the anterior pituitary and uterus in the rat.

Progesterone and its metabolite 5 alpha-dihydroprogesterone (5 alpha-DHP) have been shown to bring about gonadotropin release in the estrogen-primed ovariectomized rat. One of the actions of progesterone is the decrease in occupied estrogen receptors (E2Rs) in the anterior pituitary and uterus. This study attempted to determine if 5 alpha-DHP had a similar effect on pituitary and uterine E2Rs. Estrogen-primed ovariectomized mature female rats were injected with either vehicle, or 0.2, 0.8 or 2 mg/kg body weight (BW) of 5 alpha-DHP, 2 h before sacrifice and 1 h before the last estradiol injection (2 micrograms/rat). Nuclear E2Rs were determined by Scatchard analyses in the uterus and anterior pituitary. Total nuclear E2R levels of both tissues showed a 2-fold increase in the number of estradiol-binding sites after estradiol administration, as compared to control groups. In estradiol-primed rats, 5 alpha-DHP produced a significant decrease in total nuclear E2R levels in a tissue-specific manner. In the pituitary, there was a maximal and significant decrease in nuclear E2Rs with 0.2 and 2.0 mg/kg BW of 5 alpha-DHP as compared to estradiol alone; the intermediate dose of 0.8 mg/kg BW of 5 alpha-DHP induced a smaller nonsignificant change in nuclear E2Rs. In the uterus, 5 alpha-DHP showed a dose-dependent decrease in nuclear E2Rs. The 5 alpha-DHP effect in both tissues was due to a specific reduction in the occupied form of nuclear E2Rs levels. The unoccupied form of E2Rs was unaffected by 5 alpha-DHP administration. 5 alpha-DHP did not have any effect in the absence of estrogen priming.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of androgen binding sites with the endoplasmic reticulum of rat ventral prostate.

Microsomes from ventral prostate of 24-h castrated rats contain a single set of tissue-specific high-affinity, low-capacity androgen binding sites. These sites are indigenous to the endoplasmic reticulum, as shown by purification procedures associated with marker enzymes and electron microscopic analyses. When prostatic microsomal membranes are separated from plasma membranes using the nuclear or the mitochondrial pellets as the source of fractionation in sucrose gradients, the androgen binding activity is selectively associated with fractions rich in rough endoplasmic reticulum and ribosomes. Eighty-four percent of the total content of Na+/K+ adenosine triphosphatase (ATPase) and only 27% of the total binding capacity were concentrated in fractions rich in smooth-surfaced vesicular membranes, when nuclear suspensions constituted the membrane source. In contrast, the region of the same gradient when enriched in rough endoplasmic reticulum and deficient in plasma membrane content contained 73% of the androgen-binding capacity and only 14% of the ATPase. For fractions collected using mitochondrial suspensions as starting material, the ratio (total glucose-6-phosphatase/total binding capacity) was closer to 1.0 than similar ratios of ATPase/binding capacity, indicating co-sedimentation of binding sites with microsomal membranes and not with plasma membranes. Na+/K+ ATPase, but not 5' nucleotidase, is a valid plasma membrane marker for ventral prostate. Microsomal androgen receptors may constitute a new level of regulation of androgen action in target cells.

Inhibitory effect of progesterone on occupied estrogen receptors of anterior pituitary and uterus in adult rats.

Abstract The acute effects of a single progesterone injection on estradiol receptor (E(2)R) binding in the anterior pituitary and uterus were examined in the mature ovariectomized rat. Adult ovariectomized female rats receiving estradiol were injected with various doses of progesterone followed 1 h later by a final injection of 2 mug of estradiol. All animals were sacrificed 1 h after estradiol and the E(2)R binding in the nuclei and cytosol was determined. In the anterior pituitary, progesterone decreased total nuclear E(2)R in a biphasic inhibitory pattern, with maximal effects at 0.8 and 4 mg/kg body wt doses of progesterone and a smaller decrease with the 2 mg/kg body wt dose. This progesterone-induced decrease of nuclear E(2)R was due to a decrease in the occupied form of nuclear E(2)R. The unoccupied nuclear E(2)R and cytosol E(2)R binding were not altered by progesterone administration. In the uterus, progesterone caused a dose-dependent decrease in total nuclear E(2)R binding. This effect also occurred in the occupied form of E(2)R. The uterine unoccupied nuclear E(2)R and cytosol E(2)R were not altered by progesterone administration. These studies emphasize differences in the tissue specificity of progesterone action on occupied nuclear E(2)R which are presumably responsible for the mediation of estradiol action, and provide a biochemical basis for our previous observations of multiphasic effect of progesterone on gonadotropin secretion.

Relative binding properties of microsomal and cytosolic androgen receptor species of the ventral prostate.

A comparison between a microsomal and a cytosolic source of receptor-like androgen-binding activity was made in the rat ventral prostate. Microsomal binders remain in solution at 90% saturation with (NH4)2SO4 and display equal affinity for 5 alpha-dihydrotestosterone (DHT) and mibolerone. They have a half-life of dissociation of steroid-receptor complexes of 96 +/- 11 h and a 5S sedimentation coefficient for the untransformed moiety, with the appearance of a 3.5S species after incubation at 24 C for 30 min. They do not acquire DNA-binding capability after heat- or salt-attempted activation. Cytosol binders precipitate upon 90% saturation with (NH4)SO4 and have higher affinity for DHT than mibolerone. The half-life for dissociation of complexes is 85 +/- 14 h, and the complex sediments as an 8S moiety which is able to transform to a 4.4S form after heat activation correlated with increased DNA-binding ability of these species. Unactivated cytosol steroid-receptor complexes are also able to bind to DNA in the presence of molybdate. Salt-induced activation of cytosol moieties only occurred in the absence of molybdate. Microsomal androgen receptor is more stable than cytosol androgen receptor independently of the presence of hormone or partial purification of the moieties; the inactivation rates of the two forms of complexes differ 3-fold. Results indicate that androgen-binding sites associated with the microsomal and cytosolic fractions of the prostate are distinct entities.

Effect of progesterone on the activity of occupied nuclear estrogen receptor in vitro.

In previous studies, we have demonstrated that progesterone administration in vivo can selectively alter estrogen receptor levels and distribution in the rat anterior pituitary. The present study represents an attempt to extend these observations to an in vitro model. Cytosolic and nuclear preparations of uterine homogenates from ovariectomized adult rats were shown to be capable of temperature-dependent estrogen-mediated receptor activation and translocation from cytosol to nuclei upon recombination. Addition of progesterone to isolated cytosol did not diminish estrogen receptor binding capacity over at least a 2 h period at 22 degrees C. Preincubation of the subcellular fractions with progesterone, followed by removal of free progesterone prior to cytosol-nuclear recombination, resulted in dramatic reduction in nuclear estrogen receptor activity. This action was equally apparent whether progesterone was introduced to the cytosolic or nuclear fraction, and was confined to the steroid-occupied subpopulation of nuclear receptors. The ability of this in vitro system to mimic the estrogen receptor-suppressive effect of progesterone provides a good model in which to analyze the biochemical basis for a direct estrogen-inhibitory effect of progesterone on estrogen action.

A long Krupin-Denver valve implant attached to a 180 degrees scleral explant for glaucoma surgery.

A long glaucoma valve implant attached to an external scleral explant was used during filtration surgery in 72 eyes: 39 eyes with neovascular glaucoma and 33 eyes with other types of secondary glaucomas or with primary glaucoma in which prior filtration surgery had failed. The implant consisted of an open Silastic tube (outside diameter, 0.64 mm), which was placed into the anterior chamber. The external end of the tube contained a pressure-sensitive (opening pressure, 11 mmHg) and unidirectional slit-valve, and was sutured within the groove of a #220 Silastic explant. The 180 degree explant was placed beneath three rectus muscles and then sutured so that the grooved side was against the sclera, with the anterior edge 8 to 12 mm posterior to the limbus. The long glaucoma valve implant resulted in a large, posterior bleb extending over the area of the Silastic explant. The mean preoperative intraocular pressure (IOP) of 43.9 mmHg in the eyes with neovascular glaucoma was reduced to 17.4 mmHg after a mean follow-up of 20.2 months. The mean preoperative IOP of 38.1 mmHg in the eyes after failure of previous filtration surgery was reduced to 17.6 mmHg at a mean follow-up of 21.0 months. Postoperative IOP was less than 21 mmHg in 77% of eyes with neovascular glaucoma (47% required additional medication) and in 82% of eyes with previous failure of filtration surgery (56% required additional medication).