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Biomedical subjects

R A Wild

Publications and source records attributed to R A Wild.

At least 37 records · Page 2Linked to original sources
PubMed1993

Antigenic similarities between respiratory and reproductive tract mucins: heterogeneity of mucin expression by human endocervix and endometrium.

OBJECTIVES: To determine whether common epitopes are shared by respiratory and reproductive tract mucins and to compare the expression of cross-reactive mucin subtypes in human endocervix and endometrium. DESIGN: An immunohistochemical study of mucin expression using a panel of monoclonal and polyclonal antimucin antibodies and timed endocervical and endometrial biopsies. SETTING: University of Oklahoma Health Sciences Center, a tertiary care referral center. PATIENTS: Twenty-eight women who underwent laparoscopy, laparotomy, or hysterectomy. MAIN OUTCOME MEASURES: The expression of human tracheal mucin subspecies (types I to V) in endocervix (n = 3) and endometria (n = 25). RESULTS: Of the five mucin subspecies, type I mucin was localized to the squamous epithelium of endocervix and both glands and stroma of endometrium. Both tissues failed to react with type II mucin. Type III mucin was localized to differentiated cells of the squamous epithelium of endocervix and the glandular endometrium. Type IV mucin was specific to endometrium and was localized both in endometrial glands and stroma with no reactivity with endocervix. Type V mucin was expressed in both cervical and endometrial stroma and glands. CONCLUSIONS: Human respiratory and reproductive tract mucins share common peptide and carbohydrate epitopes. Human endocervix and endometria express a unique pattern of mucin antigens. Because of their restricted specificity, these monoclonal antibodies could provide new tools to investigate normal and aberrant expression of reproductive tract mucin subtypes in tissues and secretions.

Adult↗
PubMed1993

Vulvar acanthosis nigricans: a marker for insulin resistance in hirsute women.

OBJECTIVE: To determine the frequency of acanthosis nigricans (AN) in a group of hirsute, hyperandrogenic women and to determine the body site most frequently affected. DESIGN: Cross-sectional observational study. SETTING: University teaching hospital. PATIENTS, PARTICIPANTS: Reproductive age, nonhypertensive, nondiabetic women referred for evaluation of hirsutism, documented to have hyperandrogenism, without medications known to influence lipid, carbohydrate, or hormonal metabolism. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Presence of AN. Insulin resistance was assessed by measuring fasting glucose, fasting insulin, and nadir glucose after a 0.1 U/kg i.v. insulin bolus in both obese and nonobese, hirsute, hyperandrogenic women. RESULTS: Twenty-four of 43 women were found to have AN. Although AN was identified at several body sites including the axilla (n = 14), on the nape of the neck (n = 13), below the breasts (n = 7), and on the inner thigh (n = 7), it was always present on the vulva in women who displayed one or more lesions. Acanthosis nigricans was found only in the obese, hirsute, hyperandrogenic women. These women were the most insulin resistant. CONCLUSIONS: Acanthosis nigricans and insulin resistance are found frequently in obese, hirsute, hyperandrogenic women. The vulva is the most likely place to find this marker.

Acanthosis Nigricans↗
PubMed1992

Lipoprotein abnormalities in hirsute women. II. Compensatory responses of insulin resistance and dehydroepiandrosterone sulfate with obesity.

OBJECTIVE: The purpose of our study was to further understand interrelationships between insulin, androgens, obesity, and apolipoprotein metabolism. STUDY DESIGN: In this University cross-sectional observational study for hypothesis generation, 53 women with hirsutism-hyperandrogenism were ternately divided according to body mass index into the following groups: 22 to 28 (n = 17), 29 to 36 (n = 19), 37 to 61 (n = 17), and 16 controls. Mean hormone and clinical parameters were compared by using the Student t test, analysis of variance, and Pearson correlation. RESULTS: Dehydroepiandrosterone sulfate correlated negatively with fasting insulin (r = 0.4, p < 0.05) and reached significance in those most obese. Unbound testosterone concentrations were 24.7, 38.9, and 31.9 ng/dl, respectively. Dehydroepiandrosterone sulfate concentrations were 2.8, 2.3, and 2.3 micrograms/dl, respectively; their ratios were 13.4, 18.6, and 20.4, respectively, even though mean fasting insulin concentrations (reflecting insulin resistance) were 13.0, 20.4, and 42.6 microU/ml, respectively. Although more atherogenic apolipoprotein profiles and higher fasting insulin concentrations were found with greater body weight, lipid-insulin interrelationships may reflect dehydroepiandrosterone sulfate interaction. CONCLUSIONS: We hypothesize that dehydroepiandrosterone sulfate dampens the effect of insulin resistance, which in turn is reflected in apolipoprotein profiles in women with hirsutism/hyperandrogenism.

Adaptation, Physiological↗
PubMed1992

Lipid and apolipoprotein abnormalities in hirsute women. I. The association with insulin resistance.

OBJECTIVE: We attempted to evaluate apolipoprotein lipid levels in hirsute hyperandrogenic women and to clarify the influence of insulin resistance versus endogenous sex steroids on these profiles. STUDY DESIGN: Forty-seven women seen for evaluation of hirsutism in the Reproductive Endocrine Clinic were contrasted with 15 normal women. Thirty-one patients were treated with the gonadotropin-releasing hormone analog, leuprolide acetate, 7.5 mg intramuscularly monthly for 3 months. Insulin resistance was assessed before and after GnRH analog administration. Mean concentrations were compared with the Student t test and analysis of variance. RESULTS: Hirsute women were heavier and had higher systolic and diastolic blood pressures, more menstrual irregularities (all p less than 0.01), and higher waist/hip ratios (p less than 0.05). They had higher triglyceride, very-low-density lipoprotein C-III levels and lower high-density lipoprotein cholesterol concentrations (all p less than 0.01). They had lower apolipoprotein A-I/A-II ratios (p less than 0.01). After administration of GnRH analog, androgen and estrogens were suppressed and insulin resistance was unaltered. Insulin correlated with apolipoprotein lipid abnormalities. CONCLUSION: Lipid and apolipoprotein abnormalities in these hirsute women seem to be associated more with insulin resistance than with endogenous androgens or estrogens.

Adult↗
PubMed1992

Detection of antiendometrial antibodies in patients with endometriosis: methodological issues.

OBJECTIVE: To determine if methodological reasons explain previous inability of a single investigator to detect antiendometrial antibodies in patients with endometriosis by indirect immunofluorescence (IIF). DESIGN: Sera of selected patients were tested by standard IIF and recently reported methodology. Alternate diluent experiments were conducted to explain discordant results. SETTING: Sera were obtained preoperatively, and testing was completed in an institutional research laboratory. Results are compared with surgical findings. PATIENTS/PARTICIPANTS: Patients, seven with endometriosis and six without endometriosis, 40 years of age or less who are presenting for gynecological surgery. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Indirect immunofluorescence was graded according to the presence or absence of cytoplasmic staining, intensity of the staining, and the lowest dilution at which staining was observed. RESULTS: The standard IIF method repeatedly demonstrated the presence of cytoplasmic staining for the presence of antiendometrial antibodies in patients with endometriosis, whereas modified methods did not produce similar positive staining results. During the alternate dilution experiments, when fluorescein isothiocyanate conjugate (FITC) was diluted in animal sera, negative results were obtained. CONCLUSIONS: The variations used in alternate methodology and failure to titrate FITC reported by other investigators are possible reasons for false-negative results reported.

Adult↗
PubMed1992

Amniotic fluid levels of substance P.

The presence of substance P (SP) in the amniotic fluid (AF) from 88 obstetric patients was determined with a radioimmunoassay. AF was collected from each patient in EDTA-coated tubes. Cross-reactivity of anti-SP antibody with methionine, met-enkephalin, leu-enkephalin, beta-endorphin, eledoisen and physalemin was less than 1%. The SP levels during the midtrimester were not significantly lower than those of late gestation. Data on the late-gestation group were evaluated further as per the clinical problem. The only statistically significant finding was between the diabetics with fetal maturity and the non-diabetic group. This preliminary study identified the presence of SP in AF in mid and late gestation.

Amniotic Fluid↗
PubMed1992

Evaluation of endometrial tissue specific complement activation in women with endometriosis.

OBJECTIVE: To determine if endometrial tissue specific complement (C) activation occurs in patients with endometriosis. DESIGN: Prospective. SETTING: University of Oklahoma Health Sciences Center, a tertiary care referral center. PATIENTS: Twenty-six women, 9 with endometriosis and 17 without endometriosis. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Uterine and ectopic endometria were evaluated by the immunofluorescence assay for the presence of activated products of the initial (C3d) and terminal (C5b-9) C pathway, C3 regulatory proteins (decay-accelerating factor and membrane cofactor protein), and terminal C regulatory proteins (clusterin and vitronectin). RESULTS: The initial (C3d) and terminal (C5b-9) C components were deposited on blood vessel walls in uterine and/or ectopic endometria of women with and without endometriosis. In the stromal compartment at both sites, C deposition was colocalized with terminal C inhibitors/cell-cell attachment factors, clusterin and vitronectin on elastic fibers. No specific staining for C proteins was detected on the glandular epithelium of uterine and ectopic endometrial tissues examined. Furthermore, intense staining of endometrial epithelium for C3 regulatory proteins, decay-accelerating factor, and membrane cofactor protein was noted on endometrial glands from women with and without endometriosis. CONCLUSIONS: Our findings demonstrate a lack of specific deposition of C in the glandular epithelial cells of endometria of women with endometriosis. The localization of C3 regulatory proteins, decay-accelerating factor, and membrane cofactor protein on glandular epithelium may suggest the involvement of intrinsic protective mechanisms on these cells from autologous C attack in vivo.

Adult↗
PubMed1992

Hyperandrogenism in the adolescent.

Problems of hyperandrogenism are becoming increasingly recognized in the female adolescent. Manifestations of androgen excess can have both far-reaching metabolic implications and significant effects on body image. At a crucial time in personality development, these problems should not be taken lightly. A common pathophysiology associated with androgen excess is PCOS. Awareness of this fascinating syndrome and its metabolic implications can alert health-care professionals so that the adolescent's metabolic, physical, and psychological needs are best addressed. Individualization of treatment is the rule. Team approaches to the diagnosis and treatment of the disorder have proven effective in reversing pathophysiology that has led to hirsutism.

Adolescent↗
PubMed1991

Effects of peritoneal macrophages from patients with endometriosis on the proliferation of endometrial carcinoma cell line ECC-1.

Endometriosis has been shown to be associated with increased number and activity of peritoneal macrophages. The peritoneal macrophage-conditioned media from 33 women with or without endometriosis were studied for their effects on an endometrial carcinoma cell line, ECC-1. The media from six of six stage III/IV cases demonstrated a mitogenic effect, which was blocked by an antibody to epidermal growth factor receptor. However, the conditioned media from seven of nine stage I/II cases and 14 of 18 normal women did not show a mitogenic effect. The difference between stage III/IV and the other two groups was significant (p less than 0.01). The incorporation of tritium-thymidine was three times higher with the media from stage III/IV cases, as compared with that of controls. When purified cytokines were tested in the tritium-thymidine uptake assay, only epidermal growth factor-transforming growth factor-alpha was mitogenic on ECC-1, whereas tumor necrosis factor, interleukin-1, and platelet-derived growth factor had no effect. Thus peritoneal macrophages in patients with endometriosis may play an important role in the progression of endometriosis, and the noted effects could be mediated by epidermal growth factor or a related growth factor.

Cell Division↗
PubMed1991

Hirsutism: metabolic effects of two commonly used oral contraceptives and spironolactone.

Fifty-one hirsute women were randomly treated for nine months with ethinyl estradiol 35 ug plus norethindrone 0.4 mg or 30 ug ethinyl estradiol plus 1.5 mg norethindrone acetate if they needed contraception or spironolactone 200 mg daily if they did not. Metabolic evaluations in response to therapy demonstrated triglyceride elevations with the two oral contraceptives but not with spironolactone. While systolic blood pressure was lower with spironolactone, fasting insulin levels were higher as opposed to either low-dose oral contraceptive preparation. Ethinyl estradiol 30 ug plus 1.5 mg norethindrone acetate lowered 3-alpha-diol glucuronide levels, yet ethinyl estradiol 35 ug plus norethindrone 0.4 mg and spironolactone were more effective in lowering Ferriman-Gallwey Scores. Treatment strategies for hirsute women need to consider metabolic consequences as well as efficacy.

Analysis of Variance↗
PubMed1991

Lipid metabolism and hyperandrogenism.

Hyperandrogenism and lipid metabolism were shown to be related intimately. Any discussion of the nature of their relationship must include other clinical and metabolic variables such as hyperinsulinemia and UBO. Despite the many correlations among each of these factors, the appropriate sequence in the pathogenesis of these conditions has not been defined. Do conditions that result in insulin resistance (e.g., genetic defects, insulin receptor antibodies, and obesity) also lead to the development of hyperandrogenemia by direct or indirect ovarian stimulation by insulin? Does hyperandrogenism of ovarian or adrenal origin cause abnormal upper body fat distribution, in turn leading to lipid abnormalities and insulin resistance? Regardless of the issue of mechanism of causality, women with hyperandrogenism are thought to be at greater risk for cardiovascular morbidity and mortality than their normoandrogenic counterparts. These women often are obese, hypertensive, and sedentary; ingest diets high in saturated fats; and have glucose intolerance and/or insulin resistance. All these abnormalities are well known independent risk factors for the development of lipid abnormalities and cardiovascular disease. Whether hyperandrogenism is a secondary consequence of any of these or whether it is an independent contributor to lipid aberrations requires future study. Treatment strategies for hyperandrogenic women, however, should not only be directed toward alleviation of the cosmetic problem of hirsutism but also toward the prevention and treatment of cardiovascular morbidity using modalities aimed at eradicating hyperinsulinemia, hypertension, and dyslipidemia. These modalities should include modifications in diet, exercise, and weight in addition to pharmacologic and/or surgical manipulation. Weight reduction will reduce many cardiovascular risk factors. Obesity is easier to target because of the many risk factors that result in it.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1991

F(ab')2 segment is the active component of immunoglobulin G autoantibody generation in patients with endometriosis.

OBJECTIVE: To determine if the low titer antiendometrial antibody detection by indirect immunofluorescence (IIF) in the sera of patients with endometriosis is because of specific antigen-antibody interactions. DESIGN: Sera of selected patients subjected to separation of immunoglobulin fragments by ammonium sulfate precipitation and pepsin digestion and tested by IIF. In a comparative method, a fragment, crystallizable (Fc) flooding technique was used to determine the active component. SETTING: Sera obtained preoperatively in the outpatient and results matched with surgical findings. PATIENTS/PARTICIPANTS: Patients 45 years of age or less presenting for gynecological surgery who had signed an informed consent for the drawing of preoperative blood. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Indirect immunofluorescence was graded according to the intensity of staining and the lowest dilution at which staining occurred. RESULTS: All of the sera of the 11 patients with endometriosis exhibited F(ab')2 specific staining but none exhibited Fc fragment staining. None of the 7 control patients displayed F(ab')2 or Fc fragment staining. CONCLUSIONS: F(ab')2 fragment is the active component of an immunologically specific interaction when antiendometrial antibodies are detected in the sera of patients with endometriosis.

Antibody Formation↗
PubMed1991

Endometrial antibodies versus CA-125 for the detection of endometriosis.

Detection of endometrial antibodies using an indirect immunofluorescence method along with a well-established human endometrial carcinoma cell line was evaluated and compared with CA-125 for detecting endometriosis. Two hundred two patient sera from the infertility, gynecological, and gynecological oncology services were evaluated. The sensitivity for antibody testing was 83.1% with a specificity of 78.8%, in contrast to a sensitivity of 27.3% and a specificity of 82.6% for CA-125. These preliminary findings offer promise that antibody detection methods may be a useful adjunct in the diagnosis of endometriosis.

Adult↗
PubMed1991

Autoantibodies associated with endometriosis: can their detection predict presence of the disease?

To evaluate the usefulness of autoantibody detection as a nonoperative method of diagnosing endometriosis, we tested 221 sera from 215 patients from the infertility, gynecology, and gynecologic oncology services by an indirect immunofluorescence assay using monolayer cultures of an endometrial carcinoma cell line. The assay showed positive cytoplasmic staining, demonstrating a sensitivity of 83% in the patients with laparoscopically confirmed endometriosis. The specificity of the assay was 65% for the infertility patients and 76% for the infertility and gynecology patients combined. Several gynecologic cancer patients showed either nuclear or nuclear and cytoplasmic staining, but few showed exclusive cytoplasmic staining. These initial results suggest that detection of antibodies might be useful for the diagnosis of endometriosis.

Adult↗
PubMed1990

Evidence of heterogeneous mechanisms in lipoprotein lipid alterations in hyperandrogenic women.

Fifty-one hyperandrogenic women had their lipoprotein lipid profiles determined. Free and albumin-bound testosterone was associated with triglycerides and with high-density lipoprotein cholesterol independent of fasting insulin levels, percent ideal body weight, and waist/hip ratio. To gain insight into mechanisms of these lipid alterations, the women were subgrouped according to apparent source of androgen excess. Whereas all groups had low levels of high-density lipoprotein-2 cholesterol and high triglyceride concentrations, only in those with high luteinizing hormone-to-follicle-stimulating hormone ratios was free and albumin-bound testosterone associated with triglycerides and high-density lipoprotein cholesterol independent of fasting insulin levels. Relationships between percent ideal body weight and waist/hip ratios, free and albumin-bound testosterone, sex hormone binding globulin, fasting insulin and 2-hour insulin levels and blood pressure are not significant in all subgroups, suggesting differing endocrinological influences and differing mechanisms for lipoprotein lipid alterations.

Adult↗
PubMed1990

Clinical signs of androgen excess as risk factors for coronary artery disease.

Women with androgen excess have been found to have higher triglycerides and lower high-density lipoprotein cholesterol concentrations than nonhirsute women and are presumed to be at increased risk of coronary artery disease. However, definitive data linking androgen excess with coronary artery disease is lacking. We evaluated 102 women coming to coronary artery catheterization for signs and symptoms of androgen excess. Hirsutism was found more commonly in those women with confirmed coronary artery disease (chi 2 = 10.11). Waist:hip ratio (an index of android fat distribution) was associated with hirsutism (by ANOVA, F-test) and with coronary artery disease (t-test). The strongest associations were found in older women (aged greater than or equal to 60). Androgen excess in women may signal risk for coronary artery disease.

Acne Vulgaris↗
PubMed1990

Basal body temperature and endometriosis.

This investigation examined the association between pelvic endometriosis and altered basal body temperature (BBT). The study population consisted of infertile women who have been diagnosed as having endometriosis. A significant association was found between the presence of pelvic endometriosis (without previous treatment) and the appearance of a late decline in BBT during the early follicular phase of the menstrual cycle. A temperature greater than 97.8 degrees F on the first 3 days of menses is associated with pelvic endometriosis. The findings of this study support the early clinical diagnosis of endometriosis in infertile women. Basal body temperature chart analysis may be useful as a clinical adjunct when endometriosis is suspected.

Adult↗