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Biomedical subjects

R S Schenken

Publications and source records attributed to R S Schenken.

At least 37 records · Page 2Linked to original sources
PubMed1997

Pathogenesis.

There are many hypotheses concerning the pathogenesis of endometriosis, though no single theory can explain all cases. It is likely that several mechanisms are involved. Early studies concentrated on the histogenesis of the endometriotic lesion. Recent evidence has implicated components of the immune system in the pathogenesis of endometriosis. This review considers the evidence for different theories of the histogenesis of endometriosis and discusses possible immune factors that may be involved in the pathophysiology of the disease.

Ascitic Fluid↗
PubMed1996

Regulation of rat granulosa cell alpha-inhibin expression by luteinizing hormone, estradiol, and progesterone.

OBJECTIVE: Our purpose was to assess the effects of follicle-stimulating hormone, luteinizing hormone, forskolin (an adenylyl cyclase activator), estradiol, and progesterone on alpha-inhibin promoter activity in an in vitro fusion gene-transfection system. STUDY DESIGN: A fusion gene consisting of the alpha-inhibin 5' flanking and promoter regions linked to the chloramphenicol acetyl transferase reporter gene was constructed. A granulosa cell line originally derived from an inbred strain of Berlin Duckrey rats was transiently transfected with the fusion gene. Fusion gene activity was determined by measuring chloramphenicol acetyl transferase activity in transfected cells. RESULTS: Both follicle-stimulating hormone and luteinizing hormone activated the alpha-inhibin promoter. Activity in response to combined luteinizing hormone-forskolin treatment was greater than the summation of the activities of the two treatments individually, suggesting that the effects of luteinizing hormone might be partially mediated by second messengers other than cyclic adenosine monophosphate. Gonadotropin-stimulated activity was diminished by estradiol and combined estradiol-progesterone treatments. CONCLUSIONS: The stimulatory effects of follicle-stimulating hormone and luteinizing hormone on alpha-inhibin production are mediated at least in part by stimulation of the alpha-inhibin promoter. The stimulatory effects are blunted by estradiol-progesterone. These observations may partially explain how alpha-inhibin is down-regulated in vivo in response to the preovulatory luteinizing hormone surge.

Animals↗
PubMed1996

Phase I prehysterectomy studies of the transcervical administration of quinacrine pellets.

To determine the safety of transcervical administration of quinacrine pellets as a method of voluntary female sterilization, three noncomparative Phase I clinical trials of the administration of 250 mg quinacrine were carried out in 21 women who were scheduled to undergo hysterectomy 24 h or one month later. Detailed results are presented for one of the trials using 10-min pellets. Six of 10 women had minor transitory complaints during the postinsertion 24-h follow-up period. Five women reported pelvic/abdominal cramping, one experienced headache, and one experienced dizziness. Blood chemistry values were not adversely influenced by the quinacrine. The average plasma level of quinacrine peaked at 3 h, 36.1 ng/ml, slightly lower than the value observed 4 h after oral administration of 200 mg in a previous study. An average of 27% of the administered dose was recovered in tampons. Quinacrine was detected in the plasma of two women at the four/six-week visit. Selected results are presented from two other trials that were halted because of slow recruitment. The transcervical administration of 250 mg of 10-min quinacrine pellets was well tolerated. However, based on recent mutagenicity testing and meetings with regulatory officials, it appears unlikely that the use of quinacrine for nonsurgical sterilization could be approved in the United States or Europe.

Abdominal Pain↗
PubMed1996

Diminished alpha-inhibin messenger ribonucleic acid in in vitro fertilization-embryo transfer poor responders reflects declining follicle reserve.

OBJECTIVES: To quantitate and compare granulosa cell alpha-inhibin messenger RNA (mRNA) levels in IVF-ET poor and good responders and thereby learn how alpha-inhibin mRNA levels change in states of diminished ovarian responsiveness. DESIGN: Ribonucleic acid analysis of stored luteinized granulosa cell samples. SETTING: Academic tertiary care institution. PATIENTS: Fifty-three women undergoing follicle aspiration for IVF-ET were studied. Patients were classified as poor responders (n = 16) or good responders (n = 37) according to their E2 concentration on the day of hCG; the E2 of poor responders was < 1,000 pg/mL (3,671 pmol/L) and that of good responders was > or = 1,000 pg/mL (3,671 pmol/L). MAIN OUTCOME MEASURES: Messenger RNA levels were measured using dot blot RNA analysis. The following parameters were determined or derived: total mRNA levels, total alpha-inhibin mRNA levels, alpha-inhibin mRNA per follicle, and proportional alpha-inhibin mRNA as the ratio of alpha-inhibin mRNA:total mRNA. RESULTS: Proportional alpha-inhibin mRNA and alpha-inhibin mRNA per follicle were not significantly different between poor responders and good responders. Total mRNA and total alpha-inhibin mRNA levels, however, were diminished significantly in poor responders. CONCLUSIONS: The observations that proportional alpha-inhibin mRNA and alpha-inhibin mRNA per follicle do not significantly change in poor responders, whereas total alpha-inhibin mRNA does, indicate that the decrease in total alpha-inhibin mRNA in poor responders reflects a decreased pool of total mRNA, likely because of a reduction in follicle number. These findings are in contrast to other recent reports that describe a change in granulosa cell function accompanying states of decreased ovarian responsiveness.

Adolescent↗
PubMed1995

Partial characterization of K(+)-induced increase in [Ca2+]cyt and GnRH release in GT1-7 neurons.

Secretion of pituitary gonadotropins is regulated centrally by the hypothalamic decapeptide gonadotropin releasing hormone (GnRH). Using the immortalized hypothalamic GT1-7 neuron, we characterized pharmacologically the dynamics of cytosolic Ca2+ and GnRH release in response to K+-induced depolarization of GT1-7 neurons. Our results showed that K+ concentrations from 7.5 to 60 mM increased [Ca2+]cyt in a concentration-dependent manner. Resting [Ca2+]cyt in GT1 -7 cells was determined to be 69.7 +/- 4.0 nM (mean +/- S.E.M.; n = 69). K+-induced increases in [Ca2+]cyt ranged from 58.2 nM at 7.5 mM [K+] to 347 nM at 60 mM [K+]. K+-induced GnRH release ranged from about 10 pg/ml at 7.5 mM [K+] to about 60 pg/ml at 45 mM [K+]. K+-induced increases in (Ca2+]cyt and GnRH release were enhanced by 1 microM BayK 8644, an L-type Ca2+ channel agonist. The BayK enhancement was completely inhibited by 1 microM nimodipine, an L-type Ca2+ channel antagonist. Nimodipine (1 microM) alone partially inhibited K+-induced increases in [Ca2+]cyt and GnRH release. Conotoxin (1 microM) alone had no effect on K+-induced GnRH release or [Ca2+]cyt, but the combination of conotoxin (1 microM) and nimodipine (1 microM) inhibited K+-induced increase in [Ca2+]cyt significantly more (p < 0.02) than nimodipine alone, suggesting that N-type Ca2+ channels exist in GT1-7 neurons and may be part of the response to K+. The response of [Ca2+]cyt to K+ was linear with increasing [K+] whereas the response of GnRH release to increasing [K+] appeared to be saturable. K+-induced increase in [Ca2+]cyt and GnRH release required extracellular [Ca2+]. These experiments suggest that voltage dependent N- and L-type Ca2+ channels are present in immortalized GT1-7 neurons and that GnRH release is, at least in part, dependent on these channels for release of GnRH.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Proliferating cell nuclear antigen marks the initiation of follicular growth in the rat.

Despite expanding knowledge on the kinetic aspects of folliculogenesis, the question of what initiates follicle growth remains unanswered. Efforts to solve this problem have been thwarted by the absence of sensitive markers to identify the onset of follicular growth. In this study, we determined whether increased proliferating cell nuclear antigen (PCNA) correlates with initiation of follicle growth and might therefore be useful for studying early events in this process. Paraffin sections of ovaries from cycling adult rats, prepubertal eCG+hCG-primed rats, and prepubertal control rats were processed for immunocytochemistry by use of a PCNA primary antibody. In primordial follicles, neither granulosa cells nor oocytes stained for PCNA. PCNA immunoreactivity coincided with the earliest sign of follicle growth, appearing in pregranulosa cells of early primary follicles just beginning to grow. In all primary follicles, some granulosa cells were PCNA-positive. PCNA immunoreactivity in oocytes first appeared in primary follicles, preceding oocyte enlargement. In preantral and antral follicles, granulosa cell PCNA staining was uniform throughout the granulosa cell layers. Oocytes were positive for PCNA in both preantral and antral follicles. PCNA expression diminished in atretic follicles. In CL, granulosa cell PCNA expression was also decreased. Theca cell PCNA expression was first evident in the transitional follicle (1-2-layer granulosa cells) and was present in all stages thereafter. The pattern of PCNA expression did not differ among adult cycling, prepubertal eCG+hCG-stimulated, and control rat ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Cytokine regulation of cellular proliferation in endometriosis.

OBJECTIVE: This study was designed (1) to characterize the resident leukocyte population in ectopic endometrium (EE), (2) to assess proliferative activity of cellular components in EE, (3) to assess whether resident leukocytes in EE express IFN gamma mRNA and (4) to demonstrate endometrial epithelial cell IFN gamma receptors in EE. STUDY DESIGN: Biopsies of EE and normal eutopic endometrium (UE) were studied immunocytochemically using monoclonal antibodies specific for CD45 leukocyte common antigen, CD3 (a T cell marker), CD11c (a macrophage marker), and Ki67 (proliferation marker). Leukocyte types were identified immunocytochemically, followed by in situ hybridization to assess expression of IFN gamma mRNA. IFN gamma receptor expression was assessed by immunocytochemistry. RESULTS: The percentage of scattered stromal cells staining for each CD marker was greater in EE than in UE. The proliferative activity of endometrial stromal cells and epithelial cells was significantly less in EE than in UE. The overall concentration of T cells and macrophages expressing IFN gamma mRNA was significantly greater in EE than in UE. The percentage of each leukocyte type expressing IFN gamma mRNA was also greater in EE than in UE, and IFN gamma receptors were present in glandular epithelium of EE. CONCLUSIONS: These findings support a possible paracrine role for resident leukocytes and IFN gamma in regulating cell proliferation in endometriosis.

Adult↗
PubMed1994

Serum progesterone concentrations on the day after human chorionic gonadotropin administration and progesterone/oocyte ratios predict in vitro fertilization/embryo transfer outcome.

PURPOSE: In gonadotropin-releasing hormone analogue-pretreated in vitro fertilization-embryo transfer cycles, pregnancy rates are inversely related to serum progesterone levels on the day of administration of human chorionic gonadotropin. The relationship of the progesterone concentration on other days in the periovulatory period to pregnancy rates in such cycles is little studied. We therefore retrospectively analyzed the relationship between progesterone concentrations on the day after human chorionic gonadotropin and pregnancy in 114 cycles, 28 and 23 of which produced clinical and ongoing/delivered pregnancies, respectively. To assess the effect of the extent of follicular luteinization on success, we also studied the relationship between the progesterone concentration per oocyte retrieved and pregnancy for the day of and day after human chorionic gonadotropin. RESULTS: Progesterone concentrations on the day after human chorionic gonadotropin were inversely associated with clinical pregnancy by multiple logistic regression analysis (P < 0.05). Progesterone/oocyte ratios were inversely associated with clinical pregnancy (P < 0.05) and ongoing/delivered pregnancy (P < 0.02) for both the day of and the day after human chorionic gonadotropin. CONCLUSION: The study results extend the window of time during which elevated progesterone concentration is associated with poor outcome to at least 2 days. This finding is consistent with hypothetical mechanisms attributing the link between progesterone concentration and outcome to either endometrial or follicle/oocyte events. The association of lack of follicular luteinization (low progesterone per oocyte ratios) and favorable outcome suggests a predominant effect of progesterone on follicle/oocyte quality. Further studies are needed to clarify the mechanisms underlying the association between progesterone and in vitro fertilization-embryo transfer outcome.

Adult↗
PubMed1994

Elevated serum progesterone levels on the day of human chorionic gonadotropin administration in in vitro fertilization cycles do not adversely affect embryo quality.

OBJECTIVE: To assess the effect of an elevated serum P level on the day of hCG administration in an IVF cycle on resulting embryos by evaluating their performance at subsequent frozen ET. DESIGN: A retrospective study. PARTICIPANTS: Ninety-six consecutive patients undergoing frozen ET cycles were studied in a tertiary care center. MAIN OUTCOME MEASURES: Serum obtained on the day of hCG administration in an IVF cycle was assayed for E2 and P by RIA. The main outcome measured was the development of a clinical pregnancy in a subsequent frozen ET cycle. RESULTS: Using a previously described breakpoint in serum P concentration of 0.9 ng/mL (2.86 nmol/L), 8 of 69 (11.6%) frozen ETs in which embryos from low P level IVF cycles were transferred and 7 of 27 (25.9%) frozen ETs of embryos from elevated P level IVF cycles were transferred resulted in the development of clinical pregnancies. Although this does not clearly demonstrate superiority of embryos obtained from elevated P cycles, employing a power calculation, the probability that the pregnancy rate in the elevated serum P group is at least equal to the observed rate in the low P group is 92.8%. CONCLUSION: These data suggest that an elevated serum P level on the day of hCG administration does not adversely affect the quality of oocytes or resulting embryos.

Chorionic Gonadotropin↗
PubMed1994

Transfer of dideoxyinosine across the human isolated placenta.

1. Dideoxyinosine (ddI) has recently been approved for the treatment of patients with HIV infection. As increasing numbers of such patients are pregnant, we wished to define the rate and mechanism(s) of ddI transfer by the placenta to the foetus. Using isolated single perfused human term placental cotyledons, the drug was shown to cross the placenta from mother to foetus at a rate of 25% that of a freely diffusible marker, antipyrine, and at about half the rate of zidovudine (AZT). The transfer of ddI was similar in both directions (maternal to foetal and the reverse), equal to that of L-glucose, a passively transported sugar, and was not inhibited by excess inosine or uric acid (structural analogues of ddI). ddI did not cross to the foetus against a concentration gradient. The transport process appeared to be passive and it was not altered by AZT. 2. ddI was not metabolized in the Krebs Ringer buffer/albumin perfusate, and placental homogenates converted only 4% of ddI to hypoxanthine over the 4 h incubation. However, when maternal term or cord blood was incubated with ddI for 3 h, 50% of the drug was converted to hypoxanthine in maternal blood and to hypoxanthine and uric acid in cord blood. 3. Thus, ddI metabolism in maternal blood should decrease its net transfer to the foetus in vivo. In the foetal circulation, ddI will be further metabolized by erythrocytes to hypoxanthine and possibly to uric acid. Hence, the fraction of administered ddI delivered to foetal tissues should be much lower than that of AZT.

Antipyrine↗
PubMed1994

Characterization of lymphocyte subpopulations and T cell activation in endometriosis.

PROBLEM: Numerous studies have characterized the lymphocyte subpopulations in normal eutopic endometrium and suggested a role for the cytokine secretory products of these lymphocytes in regulating endometrial cell proliferation and differentiation. Recent studies have shown that ectopic endometrium contains a greater concentration of scattered stromal lymphocytes than does eutopic endometrium. However, the lymphocyte subpopulations and their activation status have not been characterized in ectopic endometrium. METHODS: We performed immunohistochemical studies on serial sections of proliferative and secretory phase eutopic endometrium and ectopic endometrium obtained during the proliferative phase using monoclonal antibodies to CD4 (T helper-inducer cells), CD8 (T cytolytic-suppressor cells), CD22 (B-cells), CD56 (natural killer cells), and VLA-1 (T-cell activation marker). RESULTS: Ectopic endometrium contained significantly more scattered stromal CD4, CD8, and activated T cells than did proliferative and secretory eutopic endometrium. There were more activated T-cells in proliferative than in secretory eutopic endometrium. Ectopic endometrium contained significantly fewer NK cells than proliferative and secretory endometrium. CONCLUSIONS: These results demonstrate that (1) the increased lymphocyte population in ectopic endometrium is due to increased numbers of CD4 and CD8 cells, and (2) a greater number of activated T cells are present in ectopic endometrium as compared to eutopic endometrium. Increased concentration of stromal T cells and enhanced VLA-1 expression in ectopic endometrium suggest that cytokine products of the activated T-cells may be involved in regulating cellular processes of endometriosis tissue.

B-Lymphocytes↗
PubMed1994

Endometriosis classification for infertility.

The American Fertility Society (AFS) classification for endometriosis is a widely-used system for categorizing the severity of pelvic endometriosis. Although this classification represents a detailed description of the location and extent of disease, it has limitations when used to predict fecundity following treatment of the different stages of endometriosis. Concern regarding the inability of the AFS classification to discriminate between mild, moderate and severe disease in terms of pregnancy outcome is related to arbitrary assignment of point scores for each pathologic observation, and to arbitrary assignment of total scores to patients divided into severity categories. Establishment of empirically-derived scores for individual pathologic observations and identification of cut-off scores based on pregnancy outcome for each category would offer a reliable, clinically useful classification system for endometriosis in infertile women.

Endometriosis↗
PubMed1993

Complications associated with the absorption of hysteroscopic fluid media.

OBJECTIVES: To review the literature concerning complications resulting from absorption of hysteroscopic fluid distension media and to describe methods to treat and prevent these complications. DESIGN: All pertinent literature on fluid distension media used for endoscopy, as well as relevant reports concerning the management of fluid and electrolyte imbalance, was reviewed. RESULTS: The absorption of large volumes of electrolyte-free, low-viscosity fluid may result in volume overload with water intoxication. Volume overload may cause pulmonary edema, and water intoxication may lead to hyponatremia, hypo-osmolarity, and cerebral edema. In contrast, the absorption of dextran-70 may cause volume overload secondary to the oncotic effect of intravascular dextran. Dextran-70 has been associated with anaphylaxis and coagulation disorders. TREATMENT: The use of diuretics is advocated. Urine output must be closely monitored. Judicious correction of electrolyte imbalance will prevent morbidity. PREVENTION: Meticulous attention to intraoperative fluid balance is imperative. A multichannel hysteroscope is necessary to keep intrauterine pressure low. Extensive surgical procedures may need to be performed in stages. CONCLUSIONS: Severe volume overload and electrolyte imbalance may result from fluid absorption during operative hysteroscopy. Most complications may be avoided by closely monitoring fluid balance intraoperatively.

Absorption↗
PubMed1993

The transfer of cocaine and its metabolites across the term human placenta.

This study defines human placental transport of cocaine and its two minor, but pharmacologically active, metabolites--norcocaine and cocaethylene. The experimental system was the single, isolated perfused cotyledon of a normal term human placenta, and antipyrine served as a freely diffusible marker. Cocaine was transferred rapidly by the placenta at a rate about 80% that of antipyrine. The transfer had characteristics of passive transport consistent with the high lipid solubility of the drug. We found no evidence of significant placental metabolism of cocaine during its rapid placental transfer. Ethanol did not alter the cocaine transfer rate. Norcocaine and cocaethylene were equally as rapidly transferred. Thus the placenta is no barrier to the transfer of cocaine and its derivatives to the fetus.

Biological Transport↗
PubMed1993

Chronic cocaine disruption of estrous cyclicity in the rat: dose-dependent effects.

The effects of cocaine on cyclic reproductive function in females remain largely unknown. In this study, we sought to define the range of doses of cocaine effective in disrupting estrous cyclicity and inhibiting ovulation. Estrous cyclicity was monitored daily by vaginal cytology. Group 1 consisted of rats receiving no treatment. Group 2 consisted of rats injected daily with saline s.c. Groups 3 to 6 consisted of rats injected with 1, 5, 10 and 20 mg/kg/day of cocaine HCl s.c., respectively. Group 7 consisted of rats that were food-restricted to allow weight gains comparable to those of group 6. Our results indicate a dose-dependent effect of cocaine on estrous cyclicity with an estimated IC50 of 8.5 mg/kg/day (i.e., the dose of cocaine required to inhibit the number of proestrus: estrus events per 3-week period of analysis by 50%). Over 50% of the rats with cycle disruption on 10 mg/kg/day of cocaine, but almost none of those with cycle disruption on 20 mg/kg/day, returned to normal cyclic patterns after cessation of cocaine treatment. Serum luteinizing hormone levels were reduced 53 and 74% by 10 and 20 mg/kg/day of cocaine, respectively, with an IC50 of 8.9 mg/kg/day. In contrast, cocaine had no significant effect at any of the tested dosages on serum follicle-stimulating hormone or prolactin levels. Ovulation rates were significantly reduced at both 10 and 20 mg/kg/day of cocaine (IC50 = 11 mg/kg/day of cocaine).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Interleukin-6 in experimental endometriosis.

OBJECTIVE: To measure the concentration of interleukin-6 (IL-6) in peripheral serum and conditioned media (CM) of macrophages collected from the peritoneal cavity in rats before and after surgically inducing endometriosis. DESIGN: Adult female rats (n = 50) underwent autotransplantation of adipose tissue or uterine squares. Peritoneal cavity macrophages were collected at the initial laparotomy. Rats were killed 4 or 8 weeks later, and peripheral serum and peritoneal cavity macrophages were collected. Macrophages were cultured for 48 hours, and the IL-6 concentrations in CM and serum were measured using the B9 hybridoma cell line bioassay. RESULTS: Serum IL-6 levels were significantly increased at 4 weeks but not at 8 weeks in rats receiving endometrial implants. Interleukin-6 production by macrophages from rats with endometrial implants at 4 or 8 weeks was not significantly different from baseline or from rats receiving adipose tissue implants. CONCLUSION: The increased serum IL-6 levels at 4 but not 8 weeks after surgical induction of endometriosis suggest that IL-6 may be involved in the initial development of endometriosis in this experimental model.

Animals↗