"Sweet" hydrothorax complicating chronic peritoneal dialysis.

Massive pleural effusion occurring during continuous peritoneal dialysis (PD) is a rare, life-endangering complication of this procedure. We describe a case of a patient with type 2 diabetic end-stage renal disease (ESRD) treated by PD who had new-onset dyspnea, right pleural effusion, and uncontrolled hyperglycemia. Respiratory distress and pleural effusion progressed quickly during the course of dialysis. A large volume of a "sweet" fluid with a high glucose content was evacuated from the pleural space. Immediate improvement in the patient's condition and glucose control followed discontinuation of PD and initiation of hemodialysis.

JC polyomavirus reactivation is common following allogeneic stem cell transplantation and its preemptive detection may prevent lethal complications.

Extended application of allogeneic stem cell transplantation (alloSCT) is expected to increase the frequency of JC polyomavirus (JCPyV)-related progressive multifocal leukoencephalopathy (PML). The aim of this study was to assess frequency, risk factors and course of JCPyV reactivation in allografted hematology patients. This retrospective study included consecutive adult patients, treated with alloSCT between January 2008 and December 2011. Quantitative JCPyV-PCR analysis was performed on whole blood DNA samples, originally drawn for cytomegalovirus detection since transplant date. The study included 164 patients diagnosed with hematological malignancies. Patients received reduced-intensity conditioning (n=74) or myeloablative conditioning (n=90), followed by alloSCT. Twenty patients developed transient and 20 had persistent JCPyV reactivation. Two of the patients with persistent reactivation showed a gradual increase in JCPyV levels, preceding PML development by 96 and 127 days. Cessation of immunosuppression resulted in complete resolution of neurological symptoms in one patient, while the other died of PML. Seventy percent of the 'persistently reactivating' patients died. Multivariate analysis confirmed age to be the only significant predictive factor for JCPyV reactivation. In conclusion, JCPyV reactivation occurs in a quarter of allografted patients. Preemptive detection of JCPyV reactivation in high-risk subjects and early discontinuation of immunosuppressive therapy may prevent development of lethal PML.

Effects of danazol, gonadotropin-releasing hormone agonist, and estrogen/progestogen combination on experimental endometriosis in the ovariectomized rat.

Direct effects of a gonadotropin-releasing hormone agonist (GnRHa), danazol, or estrogen/progestogen (E/P) on experimental endometriosis were evaluated in castrated female rats. Endometrial explants decreased in size following castration, but there was no further change in the treatment groups. Histologic examination indicated atrophy and regression of experimental endometriosis in all groups of castrated animals. As expected, following castration, serum estradiol (E2) became undetectable, serum progesterone (P4) decreased, and cytosolic E2 and P4 binding capacity in the endometrial explants was lower. However, in danazol-treated animals, serum P4 and E2 receptor concentrations were significantly higher than in all other castrated groups, and in both danazol and E/P treated animals, concentrations of P4 receptor were significantly higher than in castrated controls. In contrast, GnRHa treatment had no effect on serum E2 and P4 levels nor on E2 or P4 receptors. The authors conclude that danazol and E/P preparations may have a direct effect on the ectopic endometrium through interaction with steroid receptors.

Persistent ovarian cysts following administration of human menopausal and chorionic gonadotropins: an attenuated form of ovarian hyperstimulation syndrome.

Ovarian cysts persisting after the onset of menses were demonstrated by ultrasound (US) in 40 of 71 (56%) nonconception cycles following ovulation induction with human menopausal gonadotropins (hMG) and human chorionic gonadotropin (hCG). Persistent cysts were self-limited and all resolved spontaneously within two cycles. They developed more frequently during stimulation cycles with (1) higher mean pre-hCG serum estradiol (E2), (2) a greater number of medium and large follicles at peak pre-hCG E2, and (3) a larger leading follicle diameter at peak pre-hCG E2. Persistent ovarian cysts frequently occurred despite a peak pre-hCG E2 lower than 1000 pg/ml. Although ovarian enlargement in the presence of cysts exceeded 5 X 5 cm in 25% of cases, no patient developed clinical symptoms of ovarian hyperstimulation syndrome (OHSS). Repeated induction of ovulation with hMG/hCG in the presence of nonfunctional, persistent cysts resulted in pregnancies in 6 of 15 cases (40%). Asymptomatic persistent ovarian cysts frequently follow an hMG/hCG regimen and, when nonfunctional, are not a contraindication to repeated ovarian stimulation. Persistent ovarian cysts appear to be an attenuated form of OHSS.

High progesterone/estradiol ratio in follicular fluid at oocyte aspiration for in vitro fertilization as a predictor of possible pregnancy.

Eighteen women undergoing in vitro fertilization (IVF) procedures were studied. All had optimal (900 to 1600 pg/ml) peak serum estradiol (E2) response to the same stimulation regimen with clomiphene citrate and menotropins; fertilization rate was above 64%; and two to four embryos in two to eight cell stages were replaced in each patient. All were considered to have optimal chances for conception. The authors compared progesterone (P), E2, and P/E2 ratio in serum and follicular fluid (FF) at the time of oocyte aspiration in eight patients who conceived (group I) and ten who did not (group II). Mean serum P and E2 levels and serum P/E2 ratio were not significantly different between the groups. In contrast, mean FF P concentrations (ng/ml) were significantly (P less than 0.05) higher in group I (9721 versus 5385), as was FF P/E2 ratio (19.0 versus 11.8; P less than 0.02). There was no significant difference in mean FF E2 concentrations between the groups. These data indicate that in IVF cycles with optimal serum E2 response to the stimulation protocol, FF P and P/E2 ratio at the time of oocyte aspiration may be predictive of subsequent implantation and pregnancy.

Enhancement of human monocyte and peritoneal macrophage chemiluminescence activities in women with endometriosis.

Preliminary reports indicate that products of human mononuclear phagocytes may contribute to the infertility associated with endometriosis. To determine whether the generation of reactive oxygen metabolites by blood monocytes and peritoneal macrophages is altered in women with endometriosis, the present study evaluated luminol-enhanced chemiluminescence (CL) in cells at rest and following stimulation with phorbol myristate acetate (PMA) or serum-opsonized zymosan (SOZ). Peripheral venous blood and peritoneal fluid samples were collected from 60 infertile women undergoing diagnostic laparoscopy at midluteal phase and mononuclear phagocytic cell fractions were obtained by density gradient centrifugation. Whereas there was no significant difference between resting CL values in peripheral blood monocytes collected from women with and without endometriosis, PMA- and SOZ-stimulated monocyte CL was significantly greater in endometriosis patients. In contrast, there was a significant elevation in resting CL values when peritoneal macrophages from endometriosis patients were compared with macrophages obtained from patients with normal pelvic organs. It appears that chronic stimulation of macrophages in the peritoneal cavity provokes constitutive release of large quantities of reactive oxygen products in women with endometriosis. This may occur secondary to the accumulation of activated monocytes into the peritoneal cavity.

Inhibition of implantation in vitro of frozen-thawed mouse embryos by the signal molecule diadenosine tetraphosphate.

The dinucleotide polyphosphate, diadenosine 5', 5'''-P(1), P(4)-tetraphosphate (Ap4A), has been identified in mammalian and non-mammalian cells as a signal molecule that initiates the process of DNA replication and cell division. The objective of this study was to determine the function of this messenger molecule in preimplantation mouse embryonic cells. Frozenthawed two-cell mouse embryos were incubated in the presence of 0, 0.1 and 1.0 mM Ap4A at 37 degrees C in moist 5% CO(2) in air mixture for 5 d. The developmental stages of the embryos in terms of hatching and implantation were evaluated. The data showed dose-dependent inhibition of blastocyst implantation; however, there were no differences observed in the number of embryos developing to the blastocyst stage. The results suggest that Ap4A neither promotes nor inhibits the development of early stage embryos except at the implantation stage, where it exerts inhibitory control.

Nocturnal prolactin levels in infertile women with endometriosis.

Both hyperprolactinemia and endometriosis are associated with infertility. A study was performed to ascertain whether sleep-related prolactin (PRL) hypersecretion was present in endometriosis. Fifty-five consecutive infertile women with regular menstrual cycles and admitted for diagnostic laparoscopy were studied. Blood samples were drawn throughout the night preceding surgery. Serum PRL, estradiol and progesterone levels were measured with radioimmunoassays. Nocturnal patterns of PRL secretion may be altered in infertile women with endometriosis, with an exaggerated and prolonged nocturnal peak. This alteration in PRL dynamics may contribute to infertility in women with endometriosis and may be a part of the pathophysiology of this disease.

Hysterosalpingography, laparoscopy and hysteroscopy in infertility. A comparative study.

The accuracy and significance of hysterosalpingography (HSG) during an infertility evaluation were assessed by comparing the radiologic findings on HSG to the operative findings during laparoscopy and hysteroscopy. One hundred ninety-three patients underwent a complete infertility evaluation at our center. HSG was performed during the proliferative phase and was followed by laparoscopy and hysteroscopy, when indicated, during the same or next cycle. False-positive findings on HSG were noted in 5.1% of the patients. In 21%, adnexal adhesions and pelvic endometriosis were identified during surgery in spite of normal HSG. HSG is as accurate as laparoscopy in the diagnosis of tubal disease. However, laparoscopy excels HSG in the diagnosis of pelvic pathology. HSG should remain an integral part of the female infertility investigation and must be performed before laparoscopy and hysteroscopy.

Effectiveness of stimulated menstrual cycles and Percoll sperm preparation in intrauterine insemination.

To examine the usefulness of intrauterine insemination in women with various fertility factors, we retrospectively analyzed data from women treated during 1986 and 1987. Ninety-three patients underwent 1-11 cycles of single or double procedures, for a total of 423 inseminations in 263 treatment cycles. Twenty-six patients (28%) conceived, for a 10% total pregnancy rate per cycle, with 58% of the pregnancies resulting from double inseminations per cycle. An average of two treatment cycles was required to achieve pregnancy. Eight pregnancies (31%) occurred in spontaneous cycles, while 18 (69%) occurred in stimulated cycles. While clomiphene citrate therapy was useful in anovulatory patients, it was of no benefit in ovulatory patients being treated with intrauterine insemination. Human menopausal gonadotropin therapy was of benefit in both ovulatory and anovulatory patients when combined with intrauterine insemination. The live birth rate was higher (75%) in spontaneous cycles than in stimulated cycles (44%). Semen preparation was accomplished by sperm washing in 61% of the pregnancies and by Percoll preparation in 39%. The effectiveness of the discontinuous Percoll gradient for semen preparation for insemination was suggested by a pregnancy rate of 9% per cycle. While the mean sperm count in the pregnant group was 44 million, successful pregnancy was accomplished with a double insemination of 880,000 and 1.16 million rapidly progressive sperm in the first and second inseminate, respectively. The data confirm the important role of intrauterine insemination for the treatment of infertility.

Evaluation of the Pipelle curette for endometrial biopsy.

The Pipelle endometrial suction curette was evaluated, and its application and effectiveness were compared to those of the Novak curette for endometrial sampling during the midluteal phase. Fifty women underwent an endometrial biopsy with the Pipelle and Novak curettes. Ninety percent of the women preferred the biopsy with the Pipelle. Histologically, tissue obtained with the Pipelle was satisfactory and similar to that with the Novak. The Pipelle curette appears to be an excellent device for midluteal endometrial biopsy during an infertility evaluation.

Novel peptides that inhibit heparanase activation of the coagulation system.

Heparanase is implicated in cell invasion, tumour metastasis and angiogenesis. It forms a complex and enhances the activity of the blood coagulation initiator - tissue factor (TF). We describe new peptides derived from the solvent accessible surface of TF pathway inhibitor 2 (TFPI-2) that inhibit the heparanase procoagulant activity. Peptides were evaluated in vitro by measuring activated coagulation factor X levels and co-immunoprecipitation. Heparanase protein and/or lipopolysaccharide (LPS) were injected intra-peritoneally and inhibitory peptides were injected subcutaneously in mouse models. Plasma was analysed by ELISA for thrombin-antithrombin complex (TAT), D-dimer as markers of coagulation activation, and interleukin 6 as marker of sepsis severity. Peptides 5, 6, 7, 21 and 22, at the length of 11-14 amino acids, inhibited heparanase procoagulant activity but did not affect TF activity. Injection of newly identified peptides 5, 6 and 7 significantly decreased or abolished TAT plasma levels when heparanase or LPS were pre-injected, and inhibited clot formation in an inferior vena cava thrombosis model. To conclude, the solvent accessible surface of TFPI-2 first Kunitz domain is involved in TF/heparanase complex inhibition. The newly identified peptides potentially attenuate activation of the coagulation system induced by heparanase or LPS without predisposing to significant bleeding tendency.

Regulation of mouse trophoblast giant cell nucleus development in hatched mouse blastocysts by cyclic cytidine 3',5'-monophosphate (cCMP).

The dibutyryl analog of cCMP enlarged the nuclei of trophoblast giant cells and promoted blastocyst development. The result suggests that cCMP has a trophic effect on embryonic development, specifically by altering the size of the trophoblast cell nucleus but does not enhance trophoblast cell proliferation processes.

Effectiveness of short pituitary suppression with gonadotropin-releasing hormone agonist leuprolide during induction of ovulation for in vitro fertilization.

A short suppression regimen with daily 0.5 mg leuprolide commencing the first day of in vitro fertilization (IVF) cycles was evaluated in 10 women who previously underwent similar IVF cycle without suppression. Induction of ovulation, oocyte retrieval, incubation, and embryo transfer were similar in all the cycles. Assessment included the amount of human menopausal gonadotropin (hMG) used, length of stimulation, serum estradiol and luteinizing hormone (LH) levels, number of oocytes retrieved and their quality, cleavage rate, and number of embryos. The results showed that when leuprolide was used, no endogenous LH surge was detected, and there was a significant increase in hMG injected, from 19.0 +/- 5.8 to 34.4 +/- 17 ampoules, and in estradiol levels, from 1276 +/- 470 to 2618 +/- 1084 pg/ml (mean +/- SD). In addition, there was an increase in the total oocytes retrieved from 54 to 94, their cleavage rate from 59 to 86%, and the number of embryos from 24 to 70 in the suppressed cycle. No deleterious effects were observed and there were two pregnancies in this group.

Predictive value of sperm hyperactivation measurements based on the dilution effect method in clinical in vitro fertilization.

Sperm hyperactivation motility characterized by wide oscillatory movements of the sperm head, nonlinear directions, and rapid motility with occasional star-shaped pattern of movement was measured during routine semen analyses prior to an in vitro fertilization procedure. The method consisted of diluting liquefied semen 1:20 with Ham's F-10 supplemented with processed human cord sera followed by incubation at 37 degrees C for 30 minutes. At the end of the incubation period, aliquots of semen samples were evaluated by phase contrast microscopy for sperm hyperactivation. The results indicated that (1) sperm samples exhibiting 15% or more hyperactive motility were associated with a significantly higher percent fertilization of oocytes during the IVF procedure; (2) sperm hyperactive motility was correlated to sperm fertilizability during IVF treatment cycles.

Early endocrine events in induced pregnancies.

Progesterone (P) and human chorionic gonadotropin (beta-hCG) levels were measured randomly or serially in 141 single clinical intrauterine pregnancies resulting from treatment of infertility. Seventy (group I) were conceived during spontaneous cycles, 36 (group II) with clomiphene citrate, and 35 (group III) with menotropins (hMG). Each group was subdivided into subgroup A (normal pregnancies) and B (pregnancies ending in abortion). Thirteen percent of patients in group I aborted, 19% in group II, and 31% in group III (P less than .05). The overall mean (+/- SD) P level in group IA was 25.8 +/- 10.3 ng/mL and in group IB, 16.6 +/- 9.9 ng/mL (significantly lower, P less than .001); in group IIA the mean P level was 37.8 +/- 21.9 ng/mL and in group IIB, 22.9 +/- 17.9 ng/mL, again significantly lower (P less than .01). In subgroups IB and IIB, 11 of 16 patients showed early abnormal beta-hCG patterns; these findings suggest defective embryonic development and/or deficient corpus luteum function as the cause of abortion. There was no significant difference between mean P in group IIIA (71.1 +/- 43.7 ng/mL) and IIIB (75.7 +/- 55.9 ng/mL). In group IIIB, the mean "peak" P level of 101.1 +/- 73.6 ng/mL was followed by a mean "nadir" of 35.4 +/- 24.8 ng/mL at 6-9 weeks. In group IIIB, 7 of 11 patients showed normal beta-hCG patterns. Three patients with precipitous P decline aborted karyotypically normal fetuses in spite of normally rising beta-hCG levels and the presence of fetal cardiac activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic CMP (cytidine 3',5'-monophosphate) suppresses changes in human sperm amplitude of lateral head displacement and hyperactivation.

The dibutyryl analog of cCMP suppressed sperm amplitude of lateral head displacement and hyperactivation. Sperm motility was inhibited by dibutyryl cCMP with a shift toward less linear trajectory sperm movements. The results suggest a role of cCMP as an inhibitory signal on sperm motility patterns related to sperm capacitation.

Cryopreservation of in vitro-fertilized human embryos: histologic and cytogenetic analysis of an ectopic conceptus.

In this study, 39 embryos from 17 patients were cryopreserved in a Planer R204 cell freezer using the protocol of Mohr et al. (J Vitro Fert Embryo Transfer 2:1-10, 1985). The procedure was modified by supplementing the cryoprotectant with 10% heat-inactivated and filtered (0.22 micron) maternal serum instead of fetal calf serum, and embryos were frozen in 500-microliter plastic straws instead of glass ampoules. After 12-25 weeks of storage in liquid nitrogen, 12 embryos from six patients were thawed at 8.0 degrees C min to room temperature, incubated in 75% maternal serum with Ham's F-10, and replaced in utero. One pregnancy occurred. The patient was a 34-year-old nulligravida with occluded fallopian tubes. A year prior, she conceived triplets from three embryos during an in vitro fertilization (IVF) cycle, but she delivered at 21 weeks and the infants did not survive. The second IVF attempt produced four embryos. Two were replaced during the IVF cycle, but they did not implant. Two were cryopreserved and replaced 25 weeks later. On day 28 after replacement, beta human chorionic gonadotropin (beta-hCG) was 4126 IU, but there was no gestational sac in utero on ultrasonographic examination. Laparoscopy disclosed a right tubal pregnancy which was removed with the fallopian tube. Histological examination demonstrated normal chorionic villi. The chromosomal pattern was 46 XX by direct analysis and cell culture.

Follicular phase hormonal profiles during administration of leuprolide for in vitro fertilization.

Hormonal changes induced during short-term administration of leuprolide were evaluated during the follicular phase in 57 patients who completed an IVF cycle. They were compared with those of 14 patients who were placed on long-term suppression. There was an unexpected abnormal increase in serum progesterone during the first week of the cycle in nine of the 57, with no significant change in the fertilization and cleavage rate; however, no pregnancy was achieved in this group. Transient mild elevation of progesterone was also detected in 16 patients with no adverse effect on fertilization and the outcome of the IVF. In the long protocol, the tonic levels of LH, FSH, and progesterone remained low throughout the follicular phase. The total number of pregnancies was higher in the short suppression regimen, but the full-term pregnancy rates were similar in both protocols.