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Biomedical subjects

G F Schumacher

Publications and source records attributed to G F Schumacher.

At least 19 recordsLinked to original sources

Correlation of cervicovaginal fluid volume with serum estradiol levels and total follicular volume during human gonadotropin stimulation.

During the normal menstrual cycle the volume of cervicovaginal fluid (CVF), as determined by the patient at home using a simple volumetric aspirating pipette, increases significantly over several days prior to the luteinizing hormone (LH) surge and decreases characteristically shortly after ovulation. The present study was undertaken to test the hypothesis that self-determined measurements of CVF volume would correlate positively with serum estradiol (E2) levels and with total follicular volume (TFV) in cycles stimulated with exogenous gonadotropins. Consequently, 20 infertility patients, undergoing human menopausal gonadotropin (hMG)-stimulated cycles, were asked to measure daily CVF. Routine serum E2 determinations and vaginal follicular ultrasound studies were performed up to and including the day of human chorionic gonadotropin (hCG) administration (designated day 0). The mean daily CVF volume (+/- SD) increased from 0.1 +/- 0.01 ml on day -6 to 0.7 +/- 0.40 ml on day -1 and then decreased to 0.6 +/- 0.40 ml on day 0. On day 0, 7 of 20 cycles (35%) demonstrated a decrease in CVF, which ranged from 0.1 to 1.0 ml (mean, 0.42 ml). The mean daily CVF correlated positively (correlation coefficient = r) with the mean daily serum E2 (r = 0.89) and with the mean daily TFV (r = 0.88). The mean daily correlation of TFV for E2 was r = 0.98. The correlation between CVF and E2 of individuals ranged from r = 0.38 to r = 0.99 and the correlation between CVF and TFV ranged from r = 0.12 to r = 1.0, while the individual correlations of E2 to TFV ranged from r = 0.60 to r = 0.99.(ABSTRACT TRUNCATED AT 250 WORDS)

Cervix Mucus↗

IgG and IgA content of vaginal fluid during the menstrual cycle.

Immunoglobulin levels in cervicovaginal secretions during the menstrual cycle have not been well characterized biochemically. We determined the IgG and IgA concentrations in vaginal fluid obtained by patient self-sampling with an Ovu-Trac aspirator. Vaginal fluid IgG levels were less than 1-270 mg/dL. On the average the levels of IgG were relatively high after menstruation, declined during the ovulatory phase and remained relatively low during most of the luteal phase. The IgA levels were less than 10 mg/dL, and many samples contained IgA at our assay's lower limits of detection (microradial immunodiffusion). The preovulatory and luteal phase levels of IgG and IgA in vaginal fluid were generally lower than those reported for cervical mucus, but the ovulatory phase IgG and IgA composition was comparable between vaginal fluid and cervical mucus.

Body Fluids↗

Immunology of spermatozoa and cervical mucus.

Auto-immunization of the male and iso-immunization of the female with spermatozoal or testicular material can lead to a significant impairment of fertility. Interference of sperm antibodies with reproductive processes may occur by impairment of sperm migration through cervix, uterus and tubes and by blocking adherence of spermatozoa to the surface of the zona pellucida of the oocyte. A very important point to consider in this context is the immunological situation in the female genital tract which is a target organ for sex hormones. Observations in human and subhuman primates as well as in other mammalian species have shown that the levels of immunoglobulins and specific antibodies in secretions of the different compartments of the female reproductive tract are low compared to the serum in general and show typical cyclic changes under the influence of oestrogens and progesterone. Antibody levels appear to be especially low during the preovulatory period in cervical mucus and--according to observations in primates--in tubal fluid. Complement is present in borderline concentrations or not detectable. Data on levels of immunoglobulins or specific antibodies in endometrial fluid are scarce. However, their presence has been demonstrated. There are indications that a secretory immune system may be operational mainly in the cervical compartment of the female genital tract. Serum antibody levels do not reflect properly the immunological situation in secretions of the genital tract in most instances. This may be different in the male. Demonstrations of sperm antibodies in serum or even in genital secretions are not necessarily indicative of permanent sterility; the chances of conception may, however, be reduced. Antibody specificity, immunoglobulin class and quantitative relationships between spermatozoa and antibodies and hormonal influences have to be taken into consideration. Immunity to spermatozoa does not seem to be an all-or-nothing phenomenon and should be considered a relative rather than absolute cause of infertility.

Autoantibodies↗

Volumetric self-sampling of cervicovaginal fluid: a new approach to ovulation timing.

Cervicovaginal fluid that accumulates in the upper vagina and posterior fornix can be quantitatively correlated with the presumably fertile and infertile phases of the menstrual cycle. With a newly developed Volumetric Vaginal Aspirator that women self-administer, cervicovaginal fluid can be sampled on a daily basis and the sample volume or sample weight recorded. In a total of 18 cycles from 7 different subjects there was a striking 3- to 30-fold increase in sample volume or sample weight above early follicular phase levels that preceded the shift in basal body temperature (BBT) at midcycle. The maximum of sample volume or sample weight near midcycle was defined as "Volume Peak" or "Weight Peak." The magnitude of the Volume Peak or Weight Peak varied in the individual subjects and was between 400 and 1500 microliters or mg. The Volume Peak or Weight Peak generally occurred 1 to 2 days before or on the day of presumptive ovulation. With the BBT shift to luteal phase levels, the sample volume or sample weight sharply declined to early follicular phase levels. The results suggest that changes in sample volume or sample weight of cervicovaginal fluid measured with the self-applicable Volumetric Vaginal Aspirator can be used as an objective basis for approaches to natural family planning and for the assessment of optimal conditions for conception.

Adult↗

Specific antibodies and immunoglobulins in the oviductal fluid of the rhesus monkey.

Levels of specific antibodies against model antigens, immunoglobulins G and A and also albumin, in oviductal fluid were studied in the rhesus monkey during the periovulatory period. Animals were systemically or intravaginally immunized against T4 coliphages. Attempts to induce ovulation were made with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) monitored by radioimmunoassay of serum estrogen and progesterone. Collection of tubal fluid over 6 to 13 days was accomplished by surgical cannulation using a refrigerated extracorporeal collection device for each side. The results indicated the following: (1) The levels of specific antibodies against T4 coliphage and immunoglobulins (IgG, IgA) in the oviduct fluid averaged approximately one tenth of the serum values and showed a characteristic decrease and subsequent increase by a factor of 4 to 5 during and following treatment with hMG/hCG. The nadir was observed on the first or second day after hCG injection. (2) This pattern was similar in both ovulatory or nonovulatory cycles; therefore, these changes seem to be associated with the changes in serum estrogen levels. (3) There was a striking difference in serum and tubal fluid antibody levels after systemic versus after vaginal immunization by a factor of 10(3) and 10(4); however, the patterns in tubal fluid under treatment with hMG/hCG were very similar. (4) Specific antibodies in oviductal fluid and serum were mainly of the IgG class. (5) A concomitant change of total protein and albumin in oviduct fluid was also observed. The presence of sperm agglutination antibody in oviductal fluid was demonstrated in two monkeys after systemic immunization with homologous spermatozoa. The sperm antibody titers showed a similar pattern of change after hMG/hCG treatment.

Albumins↗

Sperm specific antigen(s) in detergent extract of rhesus monkey spermatozoa.

Sperm surface antigens were prepared by detergent extraction (Hyamine-Triton, Rohm and Haas Co., Philadelphia, PA) of spermatozoa from rhesus monkeys. Heterologous antisera against the extracts were produced in female New Zealand White (NZW) rabbits by hyperimmunization. The antiserum was absorbed initially with sperm-free monkey seminal plasma and then with lyophilized tissue homogenates of liver, kidney, spleen, and pancreas from male rhesus monkeys. The unabsorbed antiserum produced at least three precipitin lines against detergent extract in double immunodiffusion tests and possessed sperm immobilization and sperm agglutination antibody activity. The absorbed antiserum showed one precipitin line against the detergent extract and retained sperm agglutination antibody activity only. The sperm agglutination antibody in the absorbed antiserum was completely removed by either epididymal or washed ejaculated rhesus monkey spermatozoa. The same results were obtained with ammonium-sulfate-precipitated immunoglobulin preparations. Immunoelectrophoresis revealed only one precipitation line with the absorbed immunoglobulin preparation. It is concluded that Hyamine-Triton extract of rhesus monkey spermatozoa contains a component which can be characterized as sperm-specific by immunoabsorption techniques and is apparently associated with sperm agglutination but not with immobilization.

Animals↗

C-reactive protein in the evaluation of antibiotic therapy for pelvic infection.

C-reactive protein (CRP), an acute-phase reactant not found in normal serum, has previously been shown, by qualitative assay, to differentiate inflammatory from noninflammatory pelvic pathology. In this study, quantitative measures of serum CRP were obtained concomitantly with white blood counts (WBC) and erythrocyte sedimentation rates (ESR) in patients being treated for pelvic infection. CRP levels and their changes, which were not known to physicians treating the patients, accurately indicated those patients who would need supplementary antibiotics to achieve remission. WBC levels were misleading in over half the patients, and the ESR bore no relationship to the clinical situation. The data suggest that CRP may be used to assess the efficacy of antibiotic therapy in pelvic infection. Our successful use of single-agent therapy in most cases also suggests that the use of multiple antibiotics is unnecessary and that CRP levels can indicate when additional antibiotics are appropriate.

Anti-Bacterial Agents↗

Immune response after vaginal application of antigens in the rhesus monkey.

The immune response after vaginal application of antigens was investigated in six sexually mature female rhesus monkeys. Two model antigens, i.e., lipopolysaccharide (LPS) OF Salmonella typhosa and abortive type T-4 coliphages were applied with or without adjuvant. A plastic sponge used as the antigen carrier was introduced into the upper vagina and placed against the ectocervix. For primary immunization, each monkey received 18 vaginal antigen applications and 10 applications for each booster course. For comparison, three other female rhesus monkeys were immunized systemically. Alum or LPS was used as adjuvant. Blood was obtained two times and cervical mucus three times weekly from each monkey. Antibodies were only barely detectable in cervical mucus after the primary vaginal immunization. However, booster treatments resulted in definite antibody responses. Specific antibodies were also detected in the circulating blood after vaginal booster immunization. The antibody level in cervical secretion in three of four cases was higher than that in circulatin blood. Systemic immunization resulted in high levels of circulating antibodies, but less than 10% appeared in cervical secretions. A characteristic decrease in antibody levels in cervical mucus was usually observed at midcycle after local immunization as well as after systemic immunization. More than 90% of T-4 coliphages applied vaginally were absorbed within 48 hours. Although alum appeared to retard the absorption of antigens, it seemed to enhance the local response. More than 90% of the antibodies to the T-4 coliphages could be removed from the serum and cervial mucus by treatment with anti-immunoglobuin G antiserum. The lymphocyte response to antigens was studied by measuring the 3H-thymidine uptake by peripheral blood lymphocytes in culture. A positive response was observed in three of three systemically immunized and in only two of six locally immunized aminals. In general, the immune response was significantly weaker after local vaginal immunization than after systemic immunization.

Animals↗

Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia and semen abnormalities.

Epididymal cysts and/or hypoplastic testes have been found in 31.5 per cent of 308 men exposed to diethylstilbestrol in utero, compared to 7.8 per cent of 307 placebo-exposed controls. Analyses of the spermatozoa have revealed severe pathological changes (Eliasson score greater than 10) in 134 diethylstilbestrol-exposed men (18 per cent) and 87 placebo-exposed men (8 per cent). Further investigation of the 26 diethylstilbestrol-exposed men with testicular hypoplasia has revealed that 65 per cent had a history of cryptorchidism. Only 1 of the 6 placebo-exposed controls with testicular hypoplasia had a history of testicular maldescent. Although none of our Diekmann's lying-in study group has had carcinoma to date one must keep in mind the reported increased risk of testicular carcinoma in testes that are or were cryptorchid. A 25-year-old man who was not part of the study group was treated recently by us for a testicular carcinoma ( mixed anaplastic seminoma plus embryonal cell carcinoma) and he had a history of diethylstilbestrol exposure in utero and cryptorchidism.

Abnormalities, Drug-Induced↗

C-reactive protein in the differential diagnosis of gynecologic pathology.

A qualitative assay for the presence of C-reactive protein (CRP), with a threshold of approximately 1 mg per deciliter, was performed on 121 gynecologic patients who presented to the University of Chicago, Chicago Lying-In Hospital for various complaints. CRP results divided patients with inflammatory processes from those without inflammation or necrosis with an accuracy of over 98%. The method, which is quick and inexpensive, allows CRP to be a useful tool in the differential diagnosis of pelvic pain and masses and further may be useful in the assessment of the efficacy of antibiotic regimens in the treatment of pelvic inflammatory disease.

Adolescent↗

Purification of plasminogen activators from human seminal plasma.

Two plasminogen activators (1 and 2) were isolated from human seminal plasma by hiigh-speed centrifugation, Sephadex-gel filtration and ion-exchange chromatography. The activators were shown to be homogeneous by polyacrylamide-disc -gel electrophoresis at pH 8.3 and 4.5, and by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The molecular weights of activators 1 and 2 were estimated as 69 000 and 74 000. Their amino acid compositions are very similar, both being high in aspartic acid, glutamic acid, serine, glycine and leucine, and low in methionine, tryptophan, tyrosine, isoleucine and histidine. Activators 1 and 2 each possess 16 cysteine residues. Both activators have isoelectric points of approx. 7.0, are stable over a wide pH range at temperatures up to 60 degrees C, but lose activity at higher temperatures, particularly under very basic or acidic conditions. They are not inhibited by EDTA, Mg2+ and Ca2+ at 10 mM concentrations, but their activity decreases on addition of 10 mM-cysteine or Fe2+ and 6-aminohexanoate or sera from pregnant women. The precipitin band formed between urokinase and its antiserum is continuous with the precipitin bands formed between the seminal plasminogen activators and the urokinase antiserum. Antisera to urokinase inhibit both the activity of urokinase and the seminal plasminogen activators.

Amino Acids↗

Immunoglobulins, proteinase inhibitors, albumin, and lysozyme in human cervical mucus. I. Communication: hormonal profiles and cervical mucus changes--methods and results.

The serum levels of luteinizing hormone (LH), estradiol-17beta, and progesterone were determined simultaneously with the concentrations of immunoglobulin (Ig) G, IgA, C'3, alpha1-antitrypsin, inter-alpha-trypsin inhibitor, alpha1x-antichymotrypsin, albumin, and lysozyme in cervical mucus during nine ovulatory cycles. Spinnbarkeit and ferning were also assessed, and the basal body temperature was measured and recorded during these cycles. The profiles were synchronized according to the LH peak. The midcycle period, characterized by the rapid increase and decline of estrogen and the beginning rise of progesterone, shows a prounced minimum of immunoglobulins, C'3, proteinase inhibitors, albumin, and lysozyme in cervical mucus, which is known to be most receptive to sperm penetration at this time. Although the variation of cervical mucus values is considerable during the early proliferative and the luteal phases, the midcycle values appear to be constantly low, showing slight differences among the profiles of the different parameters. The statistical evaluation and the assessment of the significance of parameters for ovulation detection and the assessment of the fertile period as well as the correlation of these parameters with basal body temperature will be the subject of the second communication of this series.

Adult↗

Primate model for the evaluation of vaginal contraceptives.

A good animal model that simulates the human subject has not been available for the evaluation of the in vivo effectiveness of vaginal contraceptives. After careful consideration. The stumptailed macaque (Macaca arctoides) was studied for its applicability since it has a reproductive tract similar to that of the woman, is easy to handle, does not require tranquilization or anesthesia when the contraceptive is deposited, and breeds and conceives readily under caged conditions. The reported observations show the usefulness of this animal. Both postcoital sperm motility studies and breeding experiments were performed with the use of Delfen vaginal cream and K-Y jelly. K-Y jelly had no effect on the motility of vaginal spermatozoa or on the conception rate of the primates. Although Delfen vaginal cream consistently immobilized all spermatozoa in the postcoital test, half of the animals became pregnant within an average of 3.7 breeding cycles. These results illustrate the discrepancy between spermicidal tests and fertility measurements, and it is recommended that primate-breeding experiments be performed before a spermicide is evaluated in women as a contraceptive.

Animals↗