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Biomedical subjects

A F Haney

Publications and source records attributed to A F Haney.

At least 37 records · Page 2Linked to original sources

An elicited intraperitoneal inflammatory response has no effect on the establishment of pregnancy in the mouse.

OBJECTIVE: To determine the impact of intraperitoneal inflammation on reproduction in the mouse. DESIGN: The effect of an elicited sterile intraperitoneal inflammatory exudate and the passive intraperitoneal transfer of activated syngeneic leukocytes on mating efficiency and uterine implantations was evaluated in mice. SETTING: Research laboratory. INTERVENTIONS: Intraperitoneal injection of thioglycolate was used to elicit large numbers of activated peritoneal macrophages (mean 24.4 x 10(6) leukocytes/animal) in female CD-1 mice. The impact of this intraperitoneal exudate on mating efficiency and number of uterine horn implantations after gonadotropin-stimulated ovulation was determined. In separate experiments, the ovarian bursa present in this species was opened surgically to provide direct access of peritoneal constituents to the genital tract and the experiments repeated. Identical endpoints were evaluated in a third group of experiments using C3H/HEN syngeneic mice after passive transfer of 2, 5, and 10 x 10(6) similarly activated syngeneic peritoneal leukocytes. RESULTS: Neither the elicitation of a peritoneal inflammatory exudate nor the passive transfer of up to 10 x 10(6) activated syngeneic peritoneal macrophages reduced the mating efficiency or the number of uterine implantations. Furthermore, surgically opening the ovarian bursa did not alter these results, although it was associated with anatomic distortion and lowered the number of implantations in all groups. CONCLUSIONS: We could not confirm the previously published reports suggesting a profound adverse impact of intraperitoneal inflammation on reproduction in mice, even when providing direct continuity between the peritoneal cavity and the genital tract. Consequently, the usefulness of this model needs to be re-evaluated before considering it an adequate paradigm for evaluating potential mechanisms of infertility in women.

Adnexa Uteri↗

Does recommending timed intercourse really help the infertile couple?

Timed sexual intercourse is a frequently prescribed component in the treatment for infertile couples. This recommendation is based on a combination of intuition and data from studies often lacking in methodology. With increasingly sophisticated and expensive methods available to time coitus with the presumptive evidence of ovulation, such as the urinary LH kits, the already significant stress of timed intercourse is compounded by the expense of these timing modalities. There is a complete lack of data demonstrating an increased chance of pregnancy with use of such devices. Yet there is evidence that the stress of timed intercourse is a major problem for infertile couples and may even hinder normal reproductive functioning. Available data suggest that much of the period of peak fertility during the menstrual cycle is missed if coitus is timed with the menstrual calendar, basal body temperature thermometer, or LH kit. In addition, the recommendation of a coital frequency of at least a couple of times per week would not only help reduce stress, but also ensure coitus during the period of the menstrual cycle with the greatest chance of resulting in a pregnancy.

Adult↗

Serum and ascitic fluid levels of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in patients with ovarian epithelial cancer.

BACKGROUND: Recent studies have shown that multiple cytokines are secreted by ovarian epithelial cancer cells. Previous studies have shown that the cancer cell lines secrete macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-6 (IL-6), and transforming growth factor-alpha (TGF-alpha). Concomitantly, the serum levels of one of the growth factors (M-CSF) was found to be significantly elevated in patients with primary ovarian cancer and in second-look patients. The authors evaluated the serum levels of IL-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in patients with primary ovarian epithelial cancer. These levels were then compared with cytokine concentration found in normal peritoneal fluid. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of cytokines in normal peritoneal fluid, ascites, and serum. RESULTS: In serum, TNF-alpha and IL-6 were significantly increased in primary ovarian cancer patients when compared with control subjects (P < 0.0001 for both cytokines). TNF-alpha and IL-6 were also significantly higher than the levels found in second-look patients (P < 0.007 for TNF-alpha, and P = 0.0002 for IL-6). The levels of IL-1 alpha and beta were not elevated in ovarian cancer. TNF-alpha in the ascites was higher when compared with normal peritoneal fluid and was statistically significantly different when a cut-off point between 71-110 pg was selected (P < 0.005). The levels of IL-6 in ascites from patients with primary ovarian cancer also showed a marked increase (P < 0.0001) when compared with peritoneal fluid from control subjects. CONCLUSIONS: Levels of IL-1, IL-6, and TNF-alpha were determined in normal peritoneal fluid, ovarian malignant ascites, normal serum, and serum from patients with ovarian cancer. This study showed that the patients with ovarian cancer have elevated levels of IL-6 and TNF-alpha in serum and ascitic fluid. A larger study would help in evaluating the potential use of cytokines as tumor markers in ovarian cancer.

Ascitic Fluid↗

Unwanted pregnancies: understanding contraceptive use and benefits in adolescents and older women.

The highest percentages of unintended pregnancies and the largest increases in births reported in the United States in recent years were in adolescents and in women more than 35 years of age. Increasing numbers of these women will require contraception to avoid unintended pregnancy. In adolescents the combined oral contraceptive agents protect fertility indirectly and exert favorable actions on menstrual dysfunction and certain hormone-related disorders such as acne and hirsutism. To avoid sexually transmitted disease, barrier protection should be used along with oral contraceptives until mutually monogamous, stable relationships are established. Healthy older women who are nonsmokers may also safely use currently available contraceptives. These agents have little impact on metabolic parameters linked to the development of cardiovascular disease. In addition to providing reliable contraception, oral contraceptives offer noncontraceptive benefits to older reproductive-age women, including control of abnormal bleeding and a reduction in the incidence of ovarian and endometrial cancers and other gynecologic pathology. Intrauterine devices and progestin implants are safe, effective, and underused in the United States. Progestin implants may have an additional role in patients for whom estrogen preparations are contraindicated. Counseling is very important before insertion because of the high rate of nuisance side effects. The contraception selection process must consider the efficacy and acceptability of the specific method to avoid the probability of unintended pregnancy and the risk of sexually transmitted diseases.

Adolescent↗

The prognostic value of serum concentrations of progesterone, estradiol, and luteinizing hormone during superovulation with and without adjunctive leuprolide therapy.

OBJECTIVE: To determine the predictive value of preovulatory serum concentrations of P, E2, and LH for pregnancy achieved with IUI after superovulation with and without adjunctive leuprolide acetate (LA) therapy. DESIGN: Randomized, crossover study of superovulation with and without LA therapy. SETTING: Infertility clinic. PATIENTS: Subfertile patients referred for superovulation and IUI. MAIN OUTCOME MEASURES: Preovulatory serum concentrations of P, E2, and LH on the day of hCG administration; pregnancy. RESULTS: Preovulatory serum concentrations of P, E2, and LH had equivalent predictive value for pregnancy during cycles stimulated without LA therapy. No single parameter was particularly useful in clinical decision making. Threshold P concentrations proposed in other studies as useful in predicting pregnancy did not correlate with cycle fecundity. The predictive value of preovulatory concentrations of P during superovulation with adjunctive LA therapy was significantly worse than P concentrations during superovulation without LA therapy. CONCLUSIONS: Preovulatory serum P, E2, and LH concentrations in superovulation and IUI are not helpful in determining prognosis for pregnancy. The relative utility of predictive parameters may vary for different treatment regimens.

Chorionic Gonadotropin↗

Expanded-polytetrafluoroethylene but not oxidized regenerated cellulose prevents adhesion formation and reformation in a mouse uterine horn model of surgical injury.

OBJECTIVE: To evaluate the ability of the two currently available surgical barriers, oxidized regenerated cellulose and expanded-polytetrafluoroethylene (PTFE), to prevent postsurgical adhesions. DESIGN: Murine uterine horns were approximated in the midline and the contacting uterine surfaces injured by electrocautery, cutting, and scratching, with and without barriers interposed. Sham-operated and experimental animals had adhesions assessed visually and histologically 7 days postoperatively. In another group, adhesions were created and then lysed 7 days later with barriers interposed. Readhesion formation was assessed 14 days after lysis with the PTFE being removed 7 days after lysis. SETTING: Research laboratory RESULTS: Adhesions occurred at 58.5% of the electrocautery sites without barriers, 100% of the readhesion sites with recautery for hemostasis, and 92% of the recautery sites without hemostasis. None of the sham-operated sites developed adhesions. When oxidized regenerated cellulose was interposed, adhesions were observed at 36% of uninjured uterine horn sites, 62% with single and 92% with double electrocautery injuries and 90% of the reformation sites. The PTFE did not cause adhesions in uninjured controls and completely prevented adhesion formation and reformation, regardless of the type of injury or whether hemostasis was achieved. A thin cellular membrane, continuous with the uterine serosa, enveloped the PTFE. CONCLUSIONS: Expanded-polytetrafluoroethylene, but not oxidized regenerated cellulose, prevents adhesion formation and reformation in this murine uterine horn model. Additionally, oxidized regenerated cellulose was adhesiogenic even without surgical injury.

Animals↗

Endometriosis-associated infertility.

Despite intense clinical interest and increasingly sophisticated diagnostic techniques, we know surprisingly little of the relationship between endometriosis and infertility or the mechanism of infertility in these couples. No therapy specifically directed toward the ectopic endometrial implants, medical or surgical, has been demonstrated to improve the likelihood of pregnancy for couples with endometriosis-associated infertility. This is consistent with the observation that, in the absence of mechanical distortion of the pelvic viscera, no therapy directed against the implants improves the likelihood of pregnancy in these couples. The reason for this lack of progress is most probably that the mechanism of infertility in these couples remains to be determined. At present, it would be more accurate to say that these couples have unexplained infertility. The most promising therapeutic approach is to treat women with endometriosis-associated infertility with a non-specific cycle fecundity enhancing technique. Typically this is one of the newer assisted reproductive technologies such as controlled ovarian hyperstimulation with intrauterine insemination of capacitated sperm. Since the fecundity of many of the women with endometriosis in the later reproductive years is rapidly declining, this may represent their most cost-effective option for establishing a pregnancy. Only with further effort directed towards determining the mechanisms of infertility in these couples will a more effective therapy be forthcoming.

Causality↗

Endometriosis, macrophages, and adhesions.

In the judgement of most experienced clinicians, women with endometriosis are particularly prone to postoperative adhesion formation. Coincidently, a localized sterile PF inflammatory process is present in these women, although not exclusively confined to those with visible endometrial implants. This PF exudate contains numerous growth factors and cytokines, most secreted by the large population of activated macrophages, which have the potential to alter the tissue repair response. To further evaluate this possibility, attention will need to be focused on the nature of the PF immune system, changes in the PF immune response in various gynecologic disease states and the impact of surgery.

Ascitic Fluid↗

Prevention of adhesion formation/reformation with the Gore-Tex Surgical Membrane.

Eighteen patients with extensive adhesions and 10 undergoing myomectomy had GORE-TEX Surgical Membranes placed in order to prevent adhesion formation/reformation. At the time of second-look laparoscopy the membranes were removed easily and the extent of adhesion was minimal. Preliminary data from 10 additional patients undergoing adhesiolysis demonstrated that the GSM resulted in significantly fewer adhesions than did oxidized regenerated cellulose. The number of patients in this group will be expanded to insure that this difference is maintained.

Adnexal Diseases↗

Histologic features associated with hormonal responsiveness of ectopic endometrium.

OBJECTIVE: To correlate histologic parameters of endometriosis with hormonal responsiveness. DESIGN: Seven hundred sixty-eight unselected endometriotic implants and the corresponding intrauterine endometrium from 196 patients were classified by standard endometrial dating criteria. In addition, other histologic characteristics of endometriotic implants such as the amount of stroma, amount of fibrosis, the presence of surface epithelium, presence of focal hemorrhage, and gland characteristics were also noted. SETTING: Academic tertiary referral center. MAIN OUTCOME MEASURES: Comparison of histologic dating between endometriotic implants and the corresponding endometrium as a function of histologic parameters. RESULTS: Implants that were synchronous with the corresponding eutopic endometrium had more stroma than those that were out of phase. The amount of fibrosis was inversely related to hormonal responsiveness. The presence of surface epithelium in implants was also associated with an impaired response (28.0% versus 48.0% in phase). Endometriomas were found to be in phase with the corresponding endometrium less often than other types of implants (21.7% versus 43.3%). Although endometriomas had similar amounts of stroma when compared with other implants, they had significantly more fibrosis (850.2 microns versus 195.0 microns). CONCLUSIONS: These results suggest that the unpredictable response of endometriotic implants to cyclic endogenous hormones and hormonal therapy may be related to the architectural relationships between the cellular elements found in normal endometrium.

Endometriosis↗

Comparison of the peritoneal cells elicited by oxidized regenerated cellulose (Interceed) and expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane) in a murine model.

OBJECTIVE: The peritoneal fluid cell responses to the available barriers used to prevent postoperative adhesions, oxidized regenerated cellulose (interceed) and expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane), were compared. STUDY DESIGN: Oxidized regenerated cellulose and expanded polytetrafluoroethylene were inserted into the peritoneal cavity of mice and the peritoneal fluid cell number, differential cell count, morphologic type, adherence to plastic, and phorbol-12,13-myristate acetate-stimulated hydrogen peroxide production evaluated. Peritoneal fluid cell attachment to oxidized regenerated cellulose and expanded polytetrafluoroethylene was evaluated by electron microscopy. RESULTS: Oxidized regenerated cellulose promptly elicited increased numbers of large, morphologically activated peritoneal fluid macrophages that adhered more rapidly and produced more hydrogen peroxide than controls. Expanded polytetrafluoroethylene gradually increased the number of normal-appearing peritoneal fluid macrophages with increased hydrogen peroxide production but normal adherence. Macrophages rapidly attached to both materials in vivo, with oxidized regenerated cellulose being rapidly degraded. CONCLUSION: Oxidized regenerated cellulose, to a greater extent than expanded polytetrafluoroethylene, elicits an acute peritoneal fluid inflammatory exudate in the mouse, which may contribute to the oxidized regenerated cellulose-induced peritoneal injury and de novo adhesions observed in this model.

Animals↗

Murine peritoneal injury and de novo adhesion formation caused by oxidized-regenerated cellulose (Interceed [TC7]) but not expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane).

STUDY OBJECTIVE: To evaluate the impact of the materials contained in the available adhesion prevention barriers on the peritoneum. STUDY DESIGN, SETTING, PATIENTS: A murine paradigm was used, placing oxidized-regenerated cellulose (Interceed [TC7]) and expanded polytetrafluoroethylene (PTFE; Gore-Tex Surgical Membrane) in the peritoneal cavity for intervals up to 14 days. INTERVENTIONS AND MAIN OUTCOME MEASURES: The appearance of the peritoneum on scanning and transmission electron microscopy and the presence of de novo adhesions were the end-points used. RESULTS: Oxidized-regenerated cellulose caused localized sloughing of the mesothelial cell layer and leukocyte infiltration of the deeper tissue leading to the formation of adhesions to the bowel and liver in 58% of the animals. The surface of the oxidized-regenerated cellulose-injured peritoneum healed in 5 to 7 days. Neither peritoneal injury nor adhesions were noted in sham-operated animals or animals with PTFE. CONCLUSIONS: Oxidized-regenerated cellulose but not PTFE has a localized injurious effect on the peritoneum of the mouse, resulting in de novo adhesions. The impact of the barrier material itself on normal peritoneum may be an important consideration in designing surgical barriers for the prevention of postoperative adhesions.

Animals↗

Peritoneal fluid and plasma levels of human macrophage colony-stimulating factor in relation to peritoneal fluid macrophage content.

The peritoneal fluid (PF) of women with infertility (especially in the presence of endometriosis) contains increased numbers of leukocytes, 90% to 95% of which are macrophages. The high numbers of peritoneal macrophages presumably result from an influx of blood monocytes into the peritoneum, and/or from local proliferation of peritoneal macrophages. Once in the peritoneal cavity, monocytes differentiate into tissue macrophages. Mononuclear phagocyte proliferation and differentiation are influenced by different cytokines, including macrophage colony-stimulating factor (M-CSF). The purpose of this study was to determine the relationship of M-CSF levels in human PF and plasma to the macrophage content, and to the patient diagnoses. Mean concentrations of PF M-CSF were higher than plasma levels (2.44 +/- 0.13 v 0.95 +/- 0.06 ng/mL, respectively). The mean concentrations of plasma M-CSF did not differ in samples from women of different diagnostic groups (normal, peritoneal adhesions, endometriosis, inactive pelvic inflammatory disease, uterine fibroids, and idiopathic infertility), but the PF concentration was slightly higher in normal women. The absolute (total) amount of PF M-CSF in normal women was lower than in those of the other diagnostic groups. The total amount of PF M-CSF in all women correlated closely with the total number of peritoneal macrophages. The tubal patency status (open versus closed) did not influence the plasma and PF concentrations of M-CSF, nor the PF absolute amount of M-CSF. The PF M-CSF may have come from peritoneal macrophages, fibroblasts, mesothelial cells, or endothelial cells. PF M-CSF may play important roles in the proliferation and/or the differentiation of peritoneal mononuclear phagocytes.

Ascitic Fluid↗

Controlled ovarian hyperstimulation and intrauterine insemination for treatment of infertility.

Empirical therapy for subfertility using assisted reproductive technologies recently has gained popularity; however, the cost-effectiveness of these therapies, compared with an untreated control group, has not been established. Similarly, there has been no comparative cost analysis of the utility of controlled ovarian hyperstimulation and IUI in the management of the same condition. Significant PRs in untreated couples with subfertility mandate the design and execution of controlled trials to ascertain the role of controlled ovarian hyperstimulation and IUI in infertility therapy. Various disorders of subfertility have been treated with controlled ovarian hyperstimulation and IUI. The rationale for this therapy is the increase in gamete density at the site of fertilization, as with GIFT and IVF when used for management of the same problems. The live birth rate per initiated cycle and risk of complications are similar to results recently reported for GIFT and IVF. The utility of controlled ovarian hyperstimulation and IUI still remains controversial. When the relatively low direct and indirect costs of controlled ovarian hyperstimulation and IUI are considered, acknowledging the lack of prospective, controlled studies, this procedure appears to be at least as cost-effective as GIFT and IVF.

Adult↗

The stimulus responsible for the peritoneal fluid inflammation observed in infertile women with endometriosis.

OBJECTIVE: We tested the hypothesis that menstrual debris from ectopic endometrium is the stimulus responsible for eliciting the peritoneal fluid (PF) inflammation observed in infertile women with endometriosis. DESIGN, SETTING, PATIENTS: The extent of endometriosis was correlated with the PF volume and total PF cell count retrospectively in 135 infertile women with endometriosis. RESULTS: The volume and total cell count were positively correlated, whereas the total cell count was negatively correlated with the extent of endometriosis. Despite a similar negative trend, no statistically significant correlation was noted between the volume and the extent of endometriosis. These relationships did not change when the data were reanalyzed deleting those pathological features contributing to the endometriosis score but not capable of producing intraperitoneal menstrual debris, i.e., adhesions and encapsulated ovarian endometriomas. CONCLUSIONS: These findings indicate that menstrual debris from ectopic endometrium is probably not a major factor in the elicitation of the observed PF inflammation in infertile women with endometriosis and suggest an inverse relationship may exist between PF inflammation and the extent of endometriosis.

Ascitic Fluid↗

Lack of enhancing effect of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of human blood monocytes and peritoneal macrophages.

The influence of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of freshly isolated normal human peritoneal macrophages and blood monocytes was examined. Each of 14 HIV antibody-positive human serum samples was found to block the infection of four virus isolates (human T-cell lymphotropic virus type IIIBa-L [HTLV-IIIBa-L], HTLV-IIIB, D.U. 6587-7, and D.U. 7887-8) at serum dilutions ranging from 10(-1) to 10(-2). Three of these isolates (HTLV-IIIBa-L, D.U. 6587-7, and D.U. 7887-8) infected cultures of monocytes and macrophages rapidly and produced high levels of virus reverse transcriptase and p24 antigen. A fourth virus isolate (HTLV-IIIB) infected the monocytes and macrophages more slowly and produced low levels of viral protein. More dilute HIV antibody-positive sera had no significant effect on the overall level or rate of virus infection or expression. Complement did not appear to influence the course of infection by any combination of antisera or virus examined. Successful HIV-1 infection of the peritoneal macrophages and blood monocytes under the conditions tested showed strict dependence on CD4 since a recombinant CD4 polypeptide and an anti-CD4 monoclonal antibody effectively blocked the process.

Cells, Cultured↗

Serum human chorionic gonadotropin concentration for predicting multiple gestation in pregnancies conceived with superovulation and intrauterine insemination.

Assisted reproductive technologies are associated with an increased incidence of multiple gestation. Because they provide precise information on the time of ovulation, those technologies afford an opportunity to analyze the association between multiple gestation and maternal serum human chorionic gonadotropin (hCG) concentrations during early pregnancy. We retrospectively evaluated this association in 76 pregnancies (26 multiple) conceived with superovulation and intrauterine insemination. Using multiple linear regression, we discerned that the number of fetuses surviving the first trimester was directly proportional to the log of the hCG concentrations. The mean + 1 SD for the estimated hCG values of singleton pregnancies was selected a priori as the threshold for detecting multiple pregnancies. This threshold value provided a sensitivity of 73%, specificity of 80% and overall accuracy of 78%. Nine of 11 pregnancies with three or more fetuses had hCG concentrations above the threshold values. Although there is a positive correlation between the number of fetuses surviving the first trimester and the hCG concentration early in pregnancy, the predictive value of the hCG concentration is useful only for excluding most triplet and quadruplet pregnancies.

Chorionic Gonadotropin↗