Search PubMed⌕ Search

Biomedical subjects

W P Dmowski

Publications and source records attributed to W P Dmowski.

At least 19 recordsLinked to original sources
PubMed1996

Urinary N-telopeptides to monitor bone resorption while on GnRH agonist therapy.

OBJECTIVES: To assess the utility of urinary cross-linked N-telopeptides in monitoring bone resorption and predicting bone loss during GnRH agonist administration. METHODS: Ninety patients who were prescribed GnRH agonist therapy for 3-6 months for treatment of endometriosis, leiomyomas or other gynecologic disorders participated in this prospective multicenter study. N-telopeptides, serum estradiol (E2), and bone mineral density were monitored before, during and up to 3 months after the course of GnRH agonist therapy. RESULTS: N-telopeptide levels increased significantly throughout GnRH agonist therapy and returned to baseline levels by 3 months after treatment was completed. A significant negative correlation was seen between N-telopeptide and E2 measurements after 3 months (r=-0.23, P<.05), 4 months (r=-0.32, P < .05), and 5 months (r=-0.41, P<.005) of GnRH agonist therapy. The percent change in bone mineral density at L1-L4 at 6 months of GnRH agonist treatment correlated inversely with the percent change in N-telopeptides from baseline to 2,3,4, and 5 months of treatment; the percent change of bone mineral density at the femoral neck at 6 months correlated inversely with the percent change of N-telopeptides from baseline to month 4. CONCLUSIONS: Urinary N-telopeptide determinations provide a quantitative measure of bone resorption, due to GnRH agonist-induced hypoestrogenism. Increases in resorption as measured by N-telopeptides parallel decreases in in E2 levels. Increases in N-telopeptides on GnRH agonist therapy may provide a tool to predict decreases in bone mineral density.

Adult↗
PubMed1996

Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis.

OBJECTIVE: To evaluate basal (constitutive) and stimulated synthesis of tumor necrosis factor alpha (TNF alpha), interleukin (IL)-8, IL-10 by peritoneal macrophages (PM) in women with endometriosis. DESIGN: Peritoneal macrophages were cultured in the presence or absence of lipopolysaccharide (LPS) for 24 hours. Peritoneal fluids (PF) and PM supernatants were assayed for cytokines using ELISA. SETTING: Institute for the Study and Treatment of Endometriosis and university-based research laboratories. SUBJECTS: Fertile controls undergoing tubal ligation (n = 8) and women with endometriosis (n = 17). INTERVENTION: Peritoneal fluid samples were obtained at the time of diagnostic laparoscopy (endometriosis group) or laparoscopy for tubal ligation; both were performed in the midluteal phase of the cycle. RESULTS: Both basal and LPS stimulated production of TNF alpha, IL-8, and IL-10 by the PM were elevated significantly in women with endometriosis as compared with the fertile controls. CONCLUSIONS: This study demonstrated that cytokines TNF alpha, IL-8, and IL-10 are synthesized at greater than normal levels by basal and stimulated PM from women with endometriosis. The levels of TNF alpha and IL-8 correlated with the levels in the PF, suggesting that PM are the principal source of these cytokines in the PF.

Ascitic Fluid↗
PubMed1995

Immunological aspects of endometriosis.

During the past decade, evidence has accumulated indicating an association between endometriosis and changes in humoral and cell-mediated immunity. However, it is not clear whether immune changes are the sequelae or play a role in the etiopathogenesis of the disease. The latter concept is supported by the observation that exposure of rhesus monkeys to radiation or immunotoxicants leads several years later to an increase in frequency and severity of endometriosis. Studies from our laboratories support the theory that endometrial cells misplaced during menses can implant in ectopic locations only in women with genetically or environmentally altered cell-mediated immune function. Development of endometriosis may then prompt a humoral response in some women, which results in the production of autoantibodies to endometrial cells or cell-derived antigens. These autoantibodies may cross-react with the uterine endometrium, interfere with implantation, and cause infertility or early spontaneous abortions. We recently observed that the presence of autoantibodies in endometriosis was associated with significantly lower in vitro fertilization/embryo transfer pregnancy rates. Interestingly, in about 30% of women with unexplained infertility, immune changes characteristic of endometriosis were also present, suggesting a subclinical form of this disease. We conclude that: (1) women with unexplained infertility should have studies of the immune function to rule out subclinical form of endometriosis; (2) evaluation of infertility in women with endometriosis should include an assessment of autoantibody status; and (3) treatment methods involving autoantibody suppression should be considered in women with endometriosis positive for autoantibodies.

Endometriosis↗
PubMed1995

The effect of endometriosis, its stage and activity, and of autoantibodies on in vitro fertilization and embryo transfer success rates.

OBJECTIVES: To analyze IVF cycle parameters, including pregnancy rates (PR), in women with and without endometriosis and to evaluate the effect of the stage and activity of endometriosis and of autoantibodies. DESIGN: A retrospective analysis of 237 consecutive IVF cycles (193 patients), 119 in women with and 118 without endometriosis. The endometriosis group was further subdivided according to the stage and activity of the disease and autoantibody positivity. SETTING: Hospital-based and freestanding IVF programs with the same IVF team. PATIENTS: One hundred ninety-three women of reproductive age undergoing IVF; 84 had prior diagnosis of endometriosis, and 109 had other indications for IVF. Within the endometriosis group, 40 did and 44 did not have evidence of active disease. Autoantibodies were measured in 50 patients. INTERVENTIONS: The IVF protocol was standard with GnRH agonist administered from the midluteal phase of the preceding cycle. Variables included the method of ET and the use of corticosteroids. MAIN OUTCOME MEASURES: Number of follicles produced, number of eggs retrieved, fertilization rates, number of embryos transferred, and PR per transfer. RESULTS: There was no difference between groups in the response to stimulation, number of oocytes retrieved, number fertilized, and number cleaved. The overall PR was 27% per transfer; it was similar in women with and without endometriosis (29% and 25%, respectively). There was also no difference in PR according to the stage or activity of the disease. However, PR in autoantibody-positive and -negative patients were significantly different (22.9% and 45.7%, respectively). Among autoantibody-positive patients treated with corticosteroids, 8 of 10 conceived. CONCLUSIONS: This study confirms previous reports that IVF success rates are comparable in women with and without endometriosis regardless of the activity and stage of the disease. However, our study also indicates that autoantibodies may affect adversely implantation of embryos and that this effect can be overcome by administration of corticosteroids.

Adult↗
PubMed1995

Differential expression of VLA beta 1 (CD29) on monocytes from patients with endometriosis.

PROBLEM: Previous studies have established that in vitro proliferation of endometrial cells is enhanced by peripheral blood monocytes (PBM) and suppressed by peritoneal macrophages (PM) from patients with endometriosis but only suppressed by PBM and PM obtained from normal subjects. The functional activity of PBM and PM is influenced by the engagement of numerous cell surface receptors with their respective physiological ligands. METHOD: In this study, PBM and PM from fertile women (Group 1), women with unexplained infertility (Group 2), and women with limited (Group 3) or severe (Group 4) endometriosis were isolated in order to analyze these cells for the expression of CD54, CD58 and HLA-DR (immunoglobulin supergene antigens) CD18 and CD29 (integrins) and CD44 (an addresin). These cell surface antigens are involved in monocyte/macrophage trafficking, activation, signal transduction and/or adhesion. RESULTS: No differences were detected in the percentage of PBM expressing CD18, CD44, CD54, CD58, or HLA-DR among the four groups of subjects. Furthermore, the density of these antigens expressed on PBM was identical in patients and control subjects. In contrast, the percentage of PBM expressing CD29 (also known as VLA beta 1) and the density of CD29 expressed per cell were significantly reduced (P < 0.01) in patients with limited endometriosis compared to controls and patients with severe disease. Interestingly, although the percentage of CD29+ PBM from women with severe endometriosis was not statistically different from the percentage of CD29+ PBM from controls, the density of CD29 expressed per cell was significantly elevated among patients with severe disease. Analysis of PM from the four subject groups revealed no differences in CD29 expression or density. However, the percentage of PM expressing CD18 was significantly decreased in patients with limited (but not severe) endometriosis. CONCLUSION: Since both CD18 and CD29 play a role in cell trafficking and/or adhesion, alterations in their expression among patients with endometriosis suggest that these integrin beta chains may play a role in the pathogenesis of the disease.

Endometriosis↗
PubMed1994

Monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis.

OBJECTIVE: To investigate the capacity of monocytes from women with endometriosis to influence endometrial cell proliferation. DESIGN: Uterine endometrial cells were cultured in the presence and absence of autologous blood monocytes for 72 hours before assessment of endometrial cell proliferation by thymidine incorporation. SETTING: Patients were tested at initial presentation for evaluation of infertility and/or endometriosis. PATIENTS, PARTICIPANTS: Fertile controls, n = 17; infertile controls, n = 9; untreated endometriosis, n = 29. INTERVENTIONS: None. RESULTS: Endometrial cell proliferation was enhanced significantly by blood monocytes in patients with endometriosis but was suppressed significantly by blood monocytes in fertile controls. Endometrial cell proliferation was not affected significantly by blood monocytes in infertile controls analyzed as a group, but a subset of infertile patients also showed enhancement of endometrial cell proliferation by blood monocytes. CONCLUSIONS: Blood monocytes from patients with endometriosis and a subset of patients with unexplained infertility enhance autologous endometrial cell proliferation, whereas blood monocytes from fertile patients suppress endometrial cell proliferation. The capacity of monocytes to enhance endometrial cell proliferation appears to require both monocyte-derived factors that stimulate endometrial cell proliferation and endometrial cells capable of responding to those stimulatory factors. If either of these factors is absent, monocytes either suppress or have no effect on endometrial cell proliferation.

Adult↗
PubMed1994

Effect of danazol in vitro and in vivo on monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis.

OBJECTIVE: To investigate danazol's effect in vitro and in vivo on the ability of peripheral blood monocytes (PBM) from women with endometriosis to stimulate endometrial cell proliferation. DESIGN: Uterine endometrial cells from untreated or danazol-treated patients with endometriosis were cultured with or without autologous or heterologous PBM in the presence of different concentrations of danazol for 72 hours before assessment of endometrial cell proliferation by thymidine incorporation. SETTING: Not for profit clinical research institute and academic cell culture laboratory. PATIENTS: Women of reproductive age undergoing laparoscopy for endometriosis, 19 untreated patients and 17 danazol-treated patients. INTERVENTIONS: Peripheral blood monocytes and endometrial biopsies obtained at laparoscopy. Danazol (800 mg/d) administered for 2 to 6 months (treated group) or added to cell cultures in concentrations of 10(-6), 10(-7), or 10(-9) M. RESULTS: Endometrial cell proliferation was enhanced by autologous or heterologous PBM from untreated patients with endometriosis but was unaffected or suppressed by PBM from danazol-treated patients. Danazol in vitro reduced PBM-enhanced endometrial cell proliferation. Endometrial cell proliferation from danazol-treated patients was not enhanced by PBM from untreated patients with endometriosis. CONCLUSIONS: Danazol treatment in vitro or in vivo suppresses PBM-mediated enhancement of endometrial cell proliferation. The effects are against both PBM and endometrial cells, suggesting that danazol affects monocyte-derived growth-stimulating factors and endometrial cell response to growth-stimulating factors.

Adult↗
PubMed1994

The role of cell-mediated immunity in pathogenesis of endometriosis.

It is well recognized that cell-mediated immune responses contribute to the elimination of foreign antigens and cells from the invading organism. It is also likely that the immune system can recognize and eliminate altered or misplaced autologous cells such as ectopic endometrial cells. This mechanism may be operative in most women, preventing the development of endometriosis. Recent studies in women with endometriosis demonstrate functional changes in cells of the immune system including monocytes/macrophages, natural killer cells, cytotoxic T-lymphocytes and B cells. These changes suggest decreased surveillance, recognition and destruction of the misplaced endometrial cells and possible facilitation of their implantation and development of endometriosis. Peripheral blood monocytes (PBM) and peritoneal macrophages (PM) may play a key role in this respect, and may control the function of other immune cells. We have demonstrated that in normal fertile women without endometriosis, PBM and PM suppress endometrial cell proliferation in vitro. In endometriosis, PBM stimulate and PM inhibit endometrial cell proliferation and the cytotoxic effect of PM is inversely correlated with the stage of the disease. The decrease in PM cytotoxic function is controlled by prostaglandin synthesis. In infertile women without endometriosis, the effects of PM and PBM are variable. In about one third of patients, the effects of PM and PBM suggest subclinical endometriosis; in the remaining two thirds of patients the effects of PM and PBM are similar to those of fertile controls. Interestingly, endometrial cells in women with endometriosis are more sensitive to the stimulatory effect of PBM, and more resistant to the cytotoxicity of the immune cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1993

Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The incidence of the reproductive disease endometriosis was determined in a colony of rhesus monkeys chronically exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) for a period of 4 years. Ten years after termination of dioxin treatment, the presence of endometriosis was documented by surgical laparoscopy and the severity of disease was assessed. The incidence of endometriosis was directly correlated with dioxin exposure and the severity of disease was dependent upon the dose administered (p < 0.001). Three of 7 animals exposed to 5 ppt dioxin (43%) and 5 of 7 animals exposed to 25 ppt dioxin (71%) had moderate to severe endometriosis. In contrast, the frequency of disease in the control group was 33%, similar to an overall prevalence of 30% in 304 rhesus monkeys housed at The Harlow Primate Center with no dioxin exposure. This 15-year study indicates that latent female reproductive abnormalities may be associated with dioxin exposure in the rhesus. Therefore, the effects of this toxin may be more diverse than previously recognized.

Animals↗
PubMed1993

Correlation between fetal heart rate, crown-rump length, and beta-human chorionic gonadotropin levels during the first trimester of well-timed conceptions resulting from infertility treatment.

OBJECTIVES: To evaluate sequential changes in fetal heart rate (FHR) during the first trimester of well-timed pregnancies resulting from infertility treatment and to correlate the data with fetal growth curve and beta-hCG levels. DESIGN: Serial measurements of FHR, crown-rump length (CRL) and beta-hCG at weekly intervals throughout the first trimester in 67 consecutive conceptions, resulting from infertility treatment. The day of preovulatory LH surge or of exogenous hCG administration was known in each case. SETTING: Hospital based and private assisted reproductive technology centers. RESULTS: Mean FHR was 108 +/- 12, 26 to 30 days after LH/hCG (5 weeks, 4 days from last menstrual period [LMP]) in embryos 3 +/- 0.3 mm in size; the FHR gradually increased, reaching a peak of 177 +/- 10 on days 51 to 55 (9 weeks from LMP) in embryos of 23 +/- 5.5 mm; it decreased to 156 +/- 5 on days 76 to 80 (12 weeks, 5 days from LMP) in embryos of 62 +/- 5.7 mm. There was, previously not reported, high level correlation between beta-hCG and FHR during the entire first trimester and positive correlation between FHR and CRL during the first 55 days from conception. CONCLUSIONS: During the first trimester of pregnancy, FHR closely follows beta-hCG pattern. Correlation between beta-hCG and FHR is an interesting phenomenon that needs further investigation.

Chorionic Gonadotropin↗
PubMed1993

Mitogen induced production of polyclonal IgG is decreased in women with severe endometriosis.

PROBLEM: The etiology and/or pathogenesis of endometriosis may involve aspects of both humoral and cellular immunity. METHOD: In this investigation, we analyzed the ability of B lymphocytes from distinct patient groups for production of IgG1, IgG2, and IgG3 following in vitro stimulation with polyclonal B-cell mitogens (pokeweed mitogen and Staphylococcus aureus Cowan strain I) after in vitro stimulation with polyclonal B-cell activators. RESULTS: We observed that the in vitro production of IgG1, IgG2, and IgG3 was identical among fertile controls (no endometriosis; N = 22), infertile women without endometriosis (N = 22), infertile women without endometriosis (N = 20) and patients with stage 1 or 2 endometriosis (N = 31). In contrast, in vitro IgG2 production was significantly reduced among women with stage 3 or 4 endometriosis (N = 11) compared to controls (P < 0.001). CONCLUSION: Since the number of circulating B cells was similar in each patient group studied, the reduced production of IgG2 in patients with stage 3 or 4 disease was not merely due to fewer antibody producing cells in those subjects, and we speculate that the observed decrease in polyclonal IgG2 production among these patients is due to a primary defect. In additional studies, we observed that polyclonal IgG2 production was normal among stage 3 or 4 patients treated with danazol (N = 11), but significantly reduced in patients treated with gonadotropin releasing hormone agonists (N = 8). Although not conclusive, these data suggest that danazol may have the capacity to correct the defective production of polyclonal IgG2 in patients with severe endometriosis.

Antibody Formation↗
PubMed1993

Sex preselection through albumin separation of sperm.

OBJECTIVE: To determine if passage of sperm through columns of liquid albumin before their use in artificial insemination could affect the sex ratio at birth. DESIGN: Sperm were isolated by layering over columns of liquid albumin. The isolated fractions were inseminated into the uterus on the presumptive day of ovulation. SETTING: Patients were treated in 65 clinical practices (Sperm Centers) located both in this country (57) and abroad (8). PATIENTS: Individuals were self-selected by their desire to have a child of a specified sex. MAIN OUTCOME MEASURE: The sex of offspring resulting from the insemination of isolated sperm. RESULTS: Insemination with sperm isolated to enhance male sex preselection produced 71% and 76% males depending on the technique. Use of isolated sperm in women who were taking clomiphene citrate was associated with a 69% birth of females. CONCLUSIONS: Separation of sperm on columns of liquid albumin can affect the sex ratio at birth.

Cell Separation↗
PubMed1992

Laparoscopic myomectomy.

Fifty-six patients presenting with infertility (17); bleeding, pain, and pressure symptoms (32); and pelvic mass (seven) associated with leiomyomas were managed with laparoscopic myomectomy. Twenty-four second-look procedures were performed to evaluate healing and adhesion formation. Operative time ranged between 45-443 minutes (mean 157), estimated blood loss varied from 10-400 mL (mean 75), and the mean length of hospital stay was 1 day. Traditional morcellation was used initially but was abandoned because of long operating time; vaginal or abdominal removal (depending on size) proved more satisfactory. Three patients developed subcutaneous emphysema and one had febrile morbidity due to upper respiratory tract infection. There were no other complications. In 24 second-look procedures, adhesions were present in 16 subjects (66%). Twelve of 17 in the infertility group conceived (71%); all 39 patients with other complaints experienced satisfactory relief. There were no reoperations. When myomectomy is indicated, the laparoscopic approach appears to offer an alternative to abdominal surgery in selected patients.

Adult↗
PubMed1992

The development of cytotoxicity in peritoneal macrophages from women with endometriosis.

OBJECTIVE: To assess the activation status of peritoneal macrophages from women with endometriosis. DESIGN: Peritoneal macrophages from patients undergoing laparoscopy were tested for cytotoxic activity against a cultured hepatoma cell line. SETTING: Patients were tested at initial laparoscopy or at the completion of therapy. PATIENTS AND PARTICIPANTS: Fertile controls (n = 27), infertile controls (n = 20), untreated endometriosis (n = 43), danazol-treated endometriosis (n = 22), and gonadotropin-releasing hormone agonist (GnRH-a)-treated endometriosis (n = 13) were tested. INTERVENTIONS: Danazol (800 mg/d) or GnRH-a therapy for 6 months. RESULTS: Cytotoxicity was elevated in stage I and II endometriosis (P less than 0.02) and in infertile controls (P less than 0.05) compared with fertile controls. Cytotoxicity in stage III and IV endometriosis was lower (P less than 0.02) than in stage I and II endometriosis. Indomethacin in vitro increased cytotoxicity (P less than 0.05) in stage III and IV endometriosis but not in the other groups tested. Cytotoxicity in danazol or GnRH-a-treated patients was increased (P less than 0.05 or greater) compared with untreated patients with comparable stage of disease. CONCLUSIONS: Peritoneal macrophage cytotoxicity in women with endometriosis is affected by (1) the extent of endometriosis, (2) prostaglandin metabolism, and (3) treatment with danazol or GnRH-a.

Cytotoxicity, Immunologic↗
PubMed1990

Progesterone:estradiol ratios at implantation in ongoing pregnancies, abortions, and nonconception cycles resulting from ovulation induction.

UNLABELLED: The purpose of this study was to compare progesterone (P):estradiol (E2) ratios after ovulation induction at the time of implantation in cycles resulting in ongoing pregnancies or abortions and in nonconception cycles. Material included 43 stimulated conception cycles, 29 with human menopausal gonadotropins (hMG) and human chorionic gonadotropins (hCG), 14 with clomiphene citrate (CC) with or without hCG, and 28 nonconception cycles (13 hMG and hCG, 15 CC with or without hCG). Midluteal P and E2 were measured and expressed in ng/mL. There were no differences in P:E2 ratios (mean +/- SE) for ongoing pregnancies after hMG and hCG (n = 20, 112.6 +/- 14.9), CC and hCG (n = 6, 97.0 +/- 15.9), or CC alone (n = 5, 96.2 +/- 25.5), and the data were pooled. Progesterone:estradiol ratios in 31 ongoing pregnancies and 28 nonconception cycles were 107.0 +/- 10.7 and 115.2 +/- 12.5, respectively, both significantly higher than in 12 abortions (64.5 +/- 13.2). IN CONCLUSION: (1) P:E2 ratios at the time of implantation were similar after CC with or without hCG and hMG and hCG treatment; (2) high luteal P:E2 ratio was associated with ongoing pregnancies; and (3) lower P:E2 ratio was seen in cycles leading to spontaneous abortion.

Abortion, Spontaneous↗
PubMed1990

Danazol. A synthetic steroid with diverse biologic effects.

Danocrine (danazol) is a synthetic steroid with multiple and diverse biologic effects. It exerts these effects by binding to steroid transport proteins in the circulation and to specific receptors in target tissues. Centrally, danazol inhibits gonadotropins, suppressing gametogenesis and steroidogenesis. Gonadal and adrenal steroidogenesis are suppressed further through danazol's direct effect on specific enzyme systems. Danazol also displays immunoregulatory effects both in vivo and in vitro. In endometriosis, danazol induces amenorrhea and a hypoestrogenic state, resulting in endometrial atrophy. The drug's direct binding to androgen and progesterone receptors in endometriotic tissue may contribute further to the suppression of endometriosis. In women with endometriosis who produce autoantibodies against endometrial cells and endometrial cell-derived phospholipids, histones and nucleotides, danazol may improve reproductive performance through the suppression of abnormal autoantibody levels. In several other autoimmune and genetic disorders danazol brings about a clinical improvement by lowering abnormal autoantibody production or by increasing the concentration of genetically deficient protein. In order to explore the full clinical potential of the drug and to better understand danazol's mechanism of action and especially its immunoregulatory effects in autoimmune diseases and endometriosis, further investigation is necessary.

Animals↗