Transcobalamin II in human seminal plasma.

Study of cobalamin-binding proteins revealed seminal plasma to be the most concentrated site of transcobalamin II in man. The next richest normal fluid, blood, has approximately one-tenth its concentration. Normal seminal unsaturated cobalamin-binding capacity averaged 15,030 +/- 7,290 pg/ml, of which 11,550 +/- 6,660 pg/ml was transcobalamin II. Transcobalamin II levels were markedly diminished in subjects lacking seminal vesicles (1520-1660 pg/ml), but not after vasectomy. This suggests that seminal vesicles are the chief source of this protein in semen. R binder concentration was increased in postvasectomy subjects (9,970 +/- 4,900 pg/ml vs. 2,980 +/- 1,370 pg/ml in normals) and varied in other patients. The endogenous cobalamin content of semen was only 88-699 pg/ml, and was carried largely by R binder rather than by transcobalamin II. The function of the unusually large seminal transcobalamin II pool in reproduction is unknown, but seems unlikely to be related solely to cobalamin transport needs, at least within the male reproductive tract itself.

Accidental insertion of multiple IUDs.

Data are presented for 7 women, each having two IUDs in utero. Five of these patients developed symptoms of abnormal bleeding and/or pelvic pain and 2 were asymptomatic. Three women had received the second IUD because it was assumed the first one had been expelled when the filaments were no longer palpable or visible. Other causes, as well as the prevention, diagnosis, and potential danger of this complication, are discussed.

Effect of human endometrial secretions on the metabolism of human spermatozoa.

The interaction between human uterine secretions and human spermatozoa was studied. Secretions were obtained by washing the endometrial surfaces of normal uteri removed at surgery and collecting uterine fluid by incubating Millipore chambers in the uteri of volunteers. A microtechnique was devised for conducting metabolic studies with the small volumes (50 microliters) of fluid obtained in the chamber. The uterine secretions obtained by these two methods reduced the formation of CO2 by sperm from labeled glucose without affecting the accumulation of lactic acid. Sperm motility was not affected during a 3-hour incubation period. Uterine washings also reduced the rate of oxygen uptake of treated sperm. The metabolic alteration may have the effect of prolonging the life-span of spermatozoa within the female tract.

Presence of soluble b-type cytochrome in human seminal fluid.

In 1951 it was shown that human spermatozoa contained cytochromes a, b, and c. It was noted that the cytochromes were confined to the sperm and were not found in seminal fluid. More recently we have observed in seminal plasma a soluble component that has a typical spectrum of a reduced cytochrome b, but can be distinguished from the b-type cytochromes in other mammalian tissue. This substance, seminal plasma cytochrome (SPC) has not been described before. The spectrum of reduced SPC has peaks of 4290 A and 5620 A. The reduction can be induced chemically with sodium dithionite or enzymatically using reduced nicotinamide adenine dinucleotide as electron donor. The reduced SPC can bind carbon monoxide, giving an absorption peak in the range of 4140 A to 4250 A. SPC was present in semen from vasectomized men and infertility patients with azoospermia, as well as in the seminal plasma of normal donors. This indicates that the enzyme is not present as an artifact caused by leakage from spermatozoa. The possible function of SPC in seminal plasma is unknown at the present time.

Inhibition of the oxidative metabolism of human spermatozoa by a heat-labile factor in seminal plasma.

The effect of different media on the oxidative and glycolytic metabolism and on the motility of human spermatozoa has been investigated. Sperm resuspended in Ringer's solution produce more carbon dioxide than sperm in the original seminal plasma. In addition, sperm resuspended in heated seminal plasma have a higher carbon dioxide production and higher oxygen uptake than sperm in untreated seminal plasma. The mean lactic acid production was not significantly affected by different media. The motility of sperm in heated seminal plasma was poorer than that in untreated seminal plasma, although the percentage of cells that stained with eosin did not differ in the two media. After being heated, seminal plasma not only continued to take up oxygen but did so at a higher rate. The results of the present study suggest that seminal plasma contains a heat-labile component that inhibits the oxidative metabolism of human sperm but does not significantly alter sperm glycolysis.

Idiopathic oligospermia and peripheral androgen metabolism.

3 alpha, 17 beta-Androstanediol glucuronide (3 alpha-diol G), a marker of peripheral androgen action, known to be decreased in states of androgen insensitivity, was measured along with testosterone (T) and dihydrotestosterone (DHT) in both serum and seminal plasma of men with idiopathic oligospermia (IO). Seminal plasma T and DHT values were decreased in IO, compared with control values. The values of seminal plasma DHT correlated with the sperm count (r = 0.42, P less than 0.05). Serum 3 alpha-diol G was unaltered in IO as compared with controls. Levels of 3 alpha-diol G in seminal plasma were also similar. Seminal plasma 3 alpha-diol G, averaging 161 ng/dl (95% confidence limits, 33 to 320 ng/dl), represented a three- to fourfold decrease from levels in serum. This, in comparison with the 20-fold difference between seminal plasma and serum T, implies a different metabolic and/or secretory pattern for 3 alpha-diol G. We conclude that 3 alpha-diol G is not a useful marker of IO and suggest that, given the limitations of our measurements, androgen resistance may not be a common finding in this disorder.

Physiological aspects of vaginal contraception.

PIP: Since the introduction of oral contraceptives and IUDs there has been a decline in the use of other methods. In 1961 contraceptive aerosol foam was introduced and has become widely used. Vaginal contraceptives are reasonably effective; no systemic side-effects are produced; there are no medical contraindications and they can be used without medical supervision. Results of in vitro tests do not necessarily correlate with clinical effectiveness. To be effective a spermicide must be able to immobilize sperm immediately. It has been shown that aerosol foam and vaginal cream are quickly dispersed over the walls of the vagina and external cervical os. Jelly was not as well distributed. Material from vaginal suppositories was also poorly distributed. Pregnancy rates for the various preparations have ranged from 1.3 to 30 per 100 women years. The higher rates were usually associated with less reliable groups of patients. A great number of substances have been tested; of these phenylmercuric acetate and the surface acting agents (long-chain compounds, detergents, and soaps) are most widely used today. Urea in sodium carboxymethyl cellulose has been found to be effective and has been used in India. A number of chelating agents have spermicidal properties. For some compounds chelation with various metals reduces the spermicidal effect while for others the resulting chelates are more toxic than either substance alone. Heavy metals have not been used clinically in recent years. Metallic copper and metallic iron immobilize spermatozoa in vitro but a relatively large amount of the metals or their salts are needed. Patient acceptability is an important factor. Vaginal foam has been widely acceptable. All the preparations of vaginal spermicides have to be used near the time of coitus. Silastic rings have been intended only for the absorption of the steroid into the general circulation. To warrant commercial development, any new spermicides would have to have advantage over agents already in clinical use. A particular area of interest is vaginal preparations for both contraception and prophylaxis against veneral infections. No single product has yet been approved for both purposes although those currently used have varying degrees of activity in vitro against sexually transmitted pathogens. Irreversible inhibition of acrosomal protease (acrosin) has been investigated in the rabbit and 1 compound, tosyllysine chloromethyl ketone (TLCK), has an antifertility effect when applied vaginally in rabbits. Local immunization against sperm-coating protein or a sperm fraction has been tried in animals. The efficacy of non-spermicidal agents in humans would need to be determined entirely by results of clinical trials.^ieng

Effect of steroid hormones on the metabolism of human spermatozoa.

Information relating to the effect of steroids on the metabolism and motility of human spermatozoa is limited despite the increasing interest in the use of these hormones for the purpose of contraception. In the present study it was shown that progesterone, testosterone, and 11-beta-OH-progesterone significantly inhibit the CO2 production of human spermatozoa. Estrone was ineffective. Progesterone and testosterone, but not estrone, also significantly depressed O2 uptake. In contrast to CO2 production and O2 uptake, lactic acid production was not significantly affected by any of the steroids studied. The inability of estrone to inhibit sperm metabolism was not due to its lower solubility relative to the other steroids tested. The data indicate that the effective steroids inhibit sperm respiration, but not the sperm glycolytic pathway.

PIP: Some steroids have been studied as part of a general evaluation of the influence of biological fluids on human spermatozoa. The effect of various androgens, progesterones and estrogens on the oxidative and glycolytic metabolism and on the motility and viability of washed sperm are reported. Semen specimens were provided by 4 healthy volunteers with normal semen analysis and were used within 2 hours after collection. Each experiment was conducted with a single ejaculate and not with sperm pooled from several donors. A portion of the sample was used as the control; the remainder was divided for treatment with various steroids. Progesterone, testosterone, and 11-B-OH-progesterone significantly inhibited the carbon dioxide production of human spermatozoa. Estrone was ineffective. Progesterone and testosterone also significantly depressed oxygen uptake. Lactic acid production was not significantly affected by any of the steroids studied. The inability of estrone to inhibit sperm metabolism was not because of its lower solubility relative to the other steroids tested. The data indicated that although the effective steroids inhibited sperm respiration they did not inhibit the sperm glycolytic pathway.

Daily chlormadinone acetate as an oral contraceptive.

PIP: 267 fertile women less than 40 years old took .5 mg of chlormadinone daily for a total of 3199 months to assess its effectiveness as an oral contraceptive. The total pregnancy rate, calculated by the Pearl Formula, was 4.5 pregnancies per 100 women years and the rate for method failure was 3.7 pregnancies per women years. The rates calculated by the life-table method were 2.5 pregnancies per 100 women for the first year and 4.1 pregnancies per 100 women for the first 24 months. All births were normal. Other disadvantages were abnormal and irregular bleeding, experienced by 107 women including 40% of all patients with histories of regular menses. Side effects other than abnormal bleeding were infrequent, with headaches as the most common (7.9%). Chlormadinone acetate was not recommended for contraceptive use at this time due to a high pregnancy rate and abnormal bleeding.^ieng

Analysis of 100 cases of missing IUD strings.

In a study of 100 patients with missing IUD strings 69 women had their IUD in utero (4 were pregnant) and 17 had unnoticed expulsions (4 pregnancies); 9 devices were in the peritoneal cavity and one had perforated the cervix. Since the IUD was in the uterine cavity in the majority of these cases, most contraceptors whose IUD strings disappear can be managed in the office or clinic with relatively simple techniques to locate and remove the device.

Clinical experience with the Cu-7 intrauterine device.

PIP: 186 women ranging in age from 18-40 years were selected from the Los angeles Planned Parenthood Clinic and used the Cu-7 intrauterine device for 1693 woman-months. 110 of these women had never been pregnant or had aborted their only pregnancy. There were 1.1 pregnancies/100 women for the first year of use, calculated by the life-table method. 7 women expelled the Cu-7 device during the first year of the study, while 20 other women had it removed for medical reasons, 18 of these for excessive bleeding and/or cramping. The device was effective and well tolerated.^ieng

Study of medroxyprogesterone acetate and testosterone enanthate as a male contraceptive.

PIP: The effect of im injections of medroxyprogesterone acetate (100 or 150 mg) and testosterone enanthate (200 mg) over a 4-month period on spermatogenesis and serum testosterone levels was studied in 14 healthy, normal men. Treatment reduced sperm counts and suppressed gonadotropin levels in all subjects. 10 subjects showed sperm counts of less than 5 million/ml, though only 2 became azoospermic. A return to pretreatment sperm concentrations was not observed until 16-41 weeks after the last injection. Testosterone enanthate did not maintain serum testosterone levels at pretreatment values, though none of the subjects reported a decrease in libido. 1 subject developed unilateral gynecostamia during treatment. It is concluded that the doses used in this study are probably insufficient to provide effective contraception in males.^ieng

Mineral oil lubricants cause rapid deterioration of latex condoms.

As little as sixty seconds' exposure of commercial latex condoms to mineral oil, a common component of hand lotions and other lubricants used during sexual intercourse, caused approximately 90% decrease in the strength of the condoms, as measured by their burst volumes in the standard ISO (International Standards Organization) Air Burst Test. Burst pressures were also reduced, although less dramatically. Lubricants such as Vaseline Intensive Care and Johnson's Baby Oil, each containing mineral oil, also affected condom integrity. Five min. exposure of condoms to glycerol, a frequent component of hand lotions and 'personal lubricants', did not significantly affect burst volume or pressure. Aqueous nonoxynol-9 spermicide did not affect either burst index. The implications of these results for contraception and protection from sexually transmitted diseases, including AIDS, are discussed.

PIP: Prolonged exposure of latex goods to mineral oil has long been known to cause deterioration. In order to determine whether mineral oil-lubricated condoms were subject to breakage during the average duration of sexual intercourse, condoms lubricated with 7 common lubricants were subjected to International Standards Organization Air Burst Tests for periods ranging from 60 seconds to 1 hour. The lubricants used were: water, light mineral oil, Squibb Mineral Oil, Johnson's Baby Oil, Vaseline Intensive Care Lotion, glycerol, and an aqueous solution of the spermicidal agent nonoxynol-9. 2 lots of condoms were tested, one of 1-month old condoms and one of 9-months old condoms. The tests demonstrated that mineral oil damaged the latex condoms within 60 seconds. Interviews with 1275 American males indicated that Vaseline Intensive Care Lotion was used by 61%. Johnson's Baby Oil was the choice of over 1/2 of 145 British males. Johnson's Baby Oil is almost pure mineral oil, and Vaseline Intensive Care Lotion contains mineral oil. Mineral oil-lubricated condoms are risky; however, the nonoxynol gel-treated condom, recommended as an AIDS prevention measure, is water-based and therefore safe.

Effect of prophylactic antibiotics on morbidity associated with IUD insertion: results of a pilot randomized controlled trial. IUD Study Group.

The efficacy of administering an antibiotic prior to IUD insertion to reduce the risk of introducing an upper genital tract infection during the procedure has not yet been established. Two double-blind randomized studies conducted in Africa comparing a 200 mg prophylactic dose of doxycycline with a placebo did not conclusively identify a reduced risk of post-insertion pelvic inflammatory disease (PID). A clinical trial of comparable design is currently under way in the US. This multi-site trial will evaluate whether use of an antibiotic prior to insertion reduces the risk of IUD removal for all medical reasons, including upper genital tract infection, within the first three months after insertion. This paper reports on the pilot phase of this study, which was designed to test the protocols and data collection instruments in advance of the full-scale clinical trial. A total of 447 prospective IUD (TCu-380A) users were randomly assigned to receive either a 200 mg dose of doxycycline or a placebo one hour before IUD insertion. 3.6% (8/219) of participants who received the antibiotic had the device removed for medical reasons (infection, bleeding, cramping, etc.) within three months post-insertion compared to 4.5% (10/223) of participants who received the placebo. This reduction in the removal rate was not statistically significant given the limited size of the pilot study (RR = 0.81; 95% CI 0.28-2.29). Only two subjects, one from each treatment group, met the diagnostic criteria for acute PID. The overall three-month retention rate was 91.8% for the antibiotic group and 89.7% for the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration of norethandrolone and testosterone as a contraceptive agent for men.

PIP: A study of norethandrolone as a male oral contraceptive is presented. 4 subjects received 20 mg/day of the drug for 3 months concurrent with 2 or 3 subdermal capsule implants containing 20-mg testosterone. A considerable variation in sperm counts was observed during the cycle, though an azoospermic condition was not realized. Sperm counts in all subjects were markedly lower at some time during the treatment. Circulating levels of serum androgens, follicle-stimulating hormone, dihydrotestosterone, and testosterone were more consistently suppressed than were luteinizing hormone levels. Libido was slightly decreased in all subjects during treatment. All hormone levels returned to pretreatment values within 3 months of discontinued treatment. The amount of testosterone released from the capsules was between 32.2-36.4 mcg/cm/day. It is concluded that the dosage administered was inadequate for contraceptive purposes.^ieng

Studies of cervical caps: I. Vaginal lesions associated with use of the Vimule cap.

Prior to investigating the contraceptive efficacy of cervical caps, we undertook a preliminary study to evaluate potential side effects of these devices. Women who had not previously used a cap were randomly assigned to wear either a Vimule or Cavity Rim Cap (CRC) for as long as seven days. The Vimule cap caused lesions of the portio vaginalis ranging from erythematous impressions to abrasions and frank lacerations. There was variation in the degree of trauma depending, in part, on the size of the cap and duration of wear. Disruption of the epithelium occurred in eight of twelve Vimule users, but the lesions were sometimes difficult to see owing to their location. CRCs were worn by 20 women. This device sometimes left a "suction ring" on the cervix but did not disrupt the epithelium. Two of three long-term users of the Vimule cap who were also studied had unusual formations of the vaginal mucosa suggesting a proliferative reaction to chronic irritation. It is recommended that all women using a Vimule Cap be carefully re-examined and counseled about further use of the device according to the findings of the examination.

PIP: Prior to investigating the contraceptive efficacy of cervical caps, we undertook a preliminary study to evaluate the potential side effects of these devices. Women who had not previously used a cap were randomly assigned to wear either a Vimule or Cavity Rim Cap (CRC) for as long as 7 days. The Vimule Cap caused lesions of the portio vaginalis ranging from erythematous impressions to abrasions and frank lacerations. There was variation in the degree of trauma depending, in part, on the size of the cap and duration of wear. Disruption of the epithelium occurred in 8 of 12 Vimule users, but the lesions were sometimes difficult to see owing to their location. CRCs were worn by 20 women. This device sometimes left a "suction ring" on the cervix but did not disrupt the epithelium. 2 of 3 longterm users of the Vimule cap who were also studied had unusual formations of the vaginal mucosa suggesting a proliferative reaction to chronic irritation. It is recommended that all women using a Vimule cap be carefully reexamined and counseled about further use of the device according to the examination findings.

Cytodiagnosis of Candida organisms in cervical smears.

Cervical smears and cervical scrapings cultured on Sabouraud agar from 31 women suspected of having Candida genital infections were examined in a study of the cytomorphology of this fungal infection in cervical smears. Of the 31 samples, 20 (64.5%) grew C. albicans in culture. One sample (3.2%) grew C. paratropicalis, 2 (6.4%) grew mixed C. albicans and Torulopsis glabrata and 2 (6.4%) grew T. glabrata alone. Of the 25 fungus-positive samples, 20 (80%) had fungus-positive cervical smears and 5 (20%) had fungus-negative smears. There was no instance in which the cervical smear was positive but the culture was negative. Among the cases positive for C. albicans, organisms occurred in two forms: pseudohyphae without blastospores (29.4%) and pseudohyphae with blastospores (70.6%). T. glabrata was present in the smears as budding and nonbudding yeasts. Although the sensitivity of the cervical smear in detecting fungus in culture-positive patients was only 80%, the cervical smear can still be a useful means of rapid identification of C. albicans when blastospores and pseudomycelium are present. The presence of budding or nonbudding yeast without pseudohyphae should strongly suggest a T. glabrata infection.

Behavior analysis and public policy.

The Task Force on Public Policy was created to examine ways for behavior analysts to be more functional citizen scientists in the policymaking arena. This report informs readers about the contexts and processes of policymaking; and it outlines issues regarding the roles of behavior analysts in crating policy-relevant conceptual analyses, generating research data, and communicating policy-relevant information. We also discuss a possible role for the professional association in enhancing analysis, research, and advocacy on policies relevant to the public interest.