Systems for collaboration. Integrating multiple perspectives.

A number of suggestions have been offered for those who choose to collaborate with other professionals for comprehensive, interdisciplinary assessments of young children and their families. A systems perspective was used to emphasize the interrelatedness of different disciplines as well as the complex nature of relationships. (For a specific description of the professionals and their roles and responsibilities on early childhood assessment teams, please refer to the individual contributions by disciplinary representatives in this issue.) Whether long-established teams or loosely formed community coalitions, professionals working together can both improve and expand their services to children through collaboration. Although collaboration is not always easy and is certainly time-consuming, the rewards are great both for individual professionals and the young children and families served. Just like the long hours and often tedium of practicing for a musical performance, once the stage is set and the lights come on, a sort of magic occurs. Unlike an orchestra, however, at any time any member can take up the baton and lead a team to increased collaboration and improved patient services. Each member must excel not only on an individual instrument, but in integrating that skill with every other player. In this article, some strategies have been offered for professionals in conducting their interdisciplinary services and in leading collaborative efforts.

Development of a monoclonal antibody for use in radioimmunoassay of ethynylestradiol.

Production of monoclonal antibodies (MABs) to a 17 alpha-ethynyl-1,3,5 (10)-estratriene-3,17 beta-diol (ethynylestradiol, EE2) hapten is described. Culture antibodies generated by hybridized cells tested in enzyme-linked immunosorbent assay (ELISA) bound the 6-oxoethynyl-estradiol-6-(0-carboxymethyl) oxime-bovine serum albumin conjugate (EE2-6-0 CMO-BSA) but not BSA. On radioimmunoassay (RIA) with tritiated ethynylestradiol (3H-EE2), some of the antibodies demonstrated high binding affinity (Ka = 2.8 X 10(10) M-1) to EE2. Estradiol-17 beta, estrone and estriol did not show any displacement of 3H-EE2 from the MABs even at high concentration (1 X 10(4) ng/mL). Among the widely used progestins, norethynodrel and norethisterone exhibited considerable cross-reactivity (25.7-100% and 0.3-54.1%, respectively) but not levonor-gestrel with the MABs. The high affinity demonstrated by the MABs to EE2 3-sulfate but not to EE2 17-sulfate and EE2 3,17-disulfate suggests the dominant role of the 17 beta-hydroxyl group in immunogenicity.

Changes in urinary homocysteine following synthetic steroidal estrogen and progestogen administration to rats.

The present work involved the administration of both ethynyl estradiol and levonorgestrel to groups of rats, followed by determination of the homocysteine excretion rate in urine. The results indicate that a statistically significant difference exists between the excreted levels of homocysteine in the urine of both control and levonorgestrel-treated rats and the levels shown by rats treated with ethynyl estradiol. The implications of these results are discussed, especially with respect to observations which indicate that homocysteine may be a precipitating factor in the development of thrombosis. Also included in this paper is a study which confirms the identity of the HPLC peak as being homocysteine by forming a radioactive derivative of this particular sulphydryl-containing amino acid, and then analysing the resulting mixture by TLC.

Reversed-phase high-performance liquid chromatography for the determination of steroid hormones in oral contraceptives.

Reversed-phase high-performance liquid chromatography with UV detection is studied for the determination of both progestogenic and oestrogenic components of oral contraceptive formulations. The applicability of the assay is demonstrated for a number of different progestogen-oestrogen combinations in both conventional tablet and novel "paper" formulations. The results show that the method developed is a versatile technique for the routine assay of these pharmaceutical formulations.

Examination of some fragrance substances for mutagenic activity.

We tested 64 perfumes and aftershaves for mutagenicity in Salmonella typhimurium strains TA98 and TA100; most were tested both with and without metabolic activation. None of the test compounds gave a positive mutagenic response. The available amounts of some test samples were very small, however, and the possibility that larger samples might have produced positive results cannot be altogether discounted. Some tests indicated the presence of cytotoxic substances which require chemical analysis.

Trace elements in human milk.

Presented is a study, using multielement neutron activation analysis, of the elemental composition of blood plasma and milk in a group of lactating Australian women. Having established baseline values for nine elements, the authors studied factors affecting concentrations in milk and the partitioning of those elements between plasma and milk. Changes in this partitioning with the progression of lactation were demonstrated, and their nutritional implications for the exclusively breast-fed baby discussed. Progestogen-only oral contraceptives had no significant effect on levels of any of the trace elements in either blood or milk.

Changes in plasma vitamin A in lactating and non-lactating oral contraceptive users.

Plasma vitamin A and retinol-binding protein (RBP) concentrations have been studied in women using oral contraceptives (OC) for up to 4 years. In eight women taking an oestrogenic OC(1 mg of norethisterone acetate + 50 micrograms of ethinyloestradiol) values almost doubled within 6 months, but diminished somewhat after 4 years. Saturation of RBP with retinol remained fairly constant. Five lactating women who took progestogen-only OC (30 micrograms of levonorgestrel or 350 micrograms of norethisterone) showed no significant alteration in plasma vitamin A or RBP concentrations as compared with nine lactating non-OC users. All lactating women showed significant differences between the highest and lowest plasma vitamin A (P less than 0.005) and RBP (P less than 0.05) concentrations during the first 6 months of lactation. Highest values occurred 11-12 weeks postpartum and the lowest at 15-17 weeks. Percentage saturation of RBP with retinol was significantly higher (P less than 0.005) when vitamin A concentration was highest.

Choosing contraceptive steroids and doses.

PIP: The more than 145 pharmacologically different oral contraceptive (OC) products available throughout the world are based on a wide range of synthetic estrogens and progestogens. The active substance of all the estrogens is ethinyl estradiol, to which the other compounds are metabolized. Attempts to use natural estrogens have been unsuccessful. The more numerous synthetic progestogens are of 3 main types: pregnanes, used in OCs only in Eastern Europe and the People's Republic of China, and gonanes and estranes which are used worldwide. In the US only 2 estrogens are available, ethinyl estradiol (EE) and mestranol, which rapidly metabolizes to EE. The pharamacologic literature on the 2 is confusing, but the compound of 1st choice on theoretical grounds is EE, which is used by all the manufacturers of low-dose OCs. The choice of progestogens is between several estranes and 1 gonane, norgestrel, a totally synthetic steroid, unlike the estranes, which are commonly manufactured by chemical alteration of the plant steroid diosgenin. The original synthesis of norgestrel produces a racemate: an equal mixture of 2 enantiomers (2 molecules with identical composition but mirror images of each other). The naming of the enantiomers has caused much confusion. All the hormonal activity of norgestrel resides in the enantiomer named levonorgestrel by the World Health Organization but also correctly called d-norgestrel or d(-)-norgestrel by chemists. Although levonorgestrel replaced racemic norgestrel in OCs worldwide at least 5 years ago, it is only now being introduced in the US. OCs should be chosen according to the essential pharmacologic princple of exposing a person to the lowest effective dose of the drug. 3 obvious criteria for selecting among OCs are contraceptive efficacy, cycle control, and systemic risk effects and safety. A low dose OC should be chosen for general use whenever possible. The contraceptive efficacy of low-dose levongestrel/ethinyl estradiol is very high, cycle control is good and improves after the initial cycles, and laboratory tests have disclosed minimal systemic effects.^ieng

Synthetic sex hormone treatment during pregnancy and androgen receptors of male offspring.

Groups of 10 pregnant albino rats received a single subcutaneous injection of oil containing synthetic sex hormones on day 13 of pregnancy. Control rats received only oil. The steroid doses were ten times those used as oral hormonal pregnancy tests for humans. Norethisterone acetate (NEA) was given at 2 mg/kg, ethynylestradiol (EE) at 4 micrograms/kg, and NEA + EE together at these same doses. The concentration of penile total specific androgen-receptor binding sites in cytosol preparations was measured by means of in vitro uptake of tritiated methyltrienolone (3H-R 1881). No significant difference was observed between controls and treated groups for androgen-receptor concentrations in preparations from male offspring at birth, or in others reared to day 30. Rat penile androgen receptors showed high affinity for 5 alpha-dihydrotestosterone. Testosterone showed weaker binding (ca. 10%), while R 1881 showed much greater affinity (ca. 550%). Very weak binding was shown by progesterone, estradiol 17 beta, and the synthetic steroids investigated in this study.

A randomized prospective study of the metabolic effects of four low-estrogen oral contraceptives.

Healthy, nonsmoking, normotensive, well-motivated young women were assigned at random to one of four different commercial, low-estrogen oral contraceptives. Measurements of biochemical parameters were made on two blood specimens collected from fasting subjects late in the pretreatment cycle, then again late in each treatment cycle for 12 months. All the women assigned to one product (0.5 mg norethindrone + 35 micrograms ethinyl estradiol) dropped out of the study before the end of the fifth cycle, but discontinuations with the other three products were few. Though the numbers of subjects were small, the groups were closely matched, and most of the metabolic differences were statistically significant. Products containing ethynodiol diacetate and norethindrone were associated with increases in serum total cholesterol and triglycerides but decreases in high-density-lipoprotein-cholesterol. In contrast, the levonorgestrel-containing preparation produced significantly less of an effect on these tests. A similar pattern was seen with a range of blood coagulation and fibrinolytic factors. Minimal alterations were seen with the levonorgestrel preparation, whereas those containing norethindrone or ethynodiol diacetate showed marked increases in factors I, VII, VIII and X and plasminogen, associated with a decrease in antithrombin III. Differences in the metabolic impact of the various commercially available low-estrogen preparations, combined with their effects on intermenstrual bleeding, allow a choice of the progestogen component most suitable for general use.

Malonaldehyde production around copper IUDs.

Specimens of cervical mucus from 7 women fitted with copper IUDs were placed immediately after collection in liquid nitrogen. These specimens were shown by electron paramagnetic resonance measurements to contain statistically significantly higher concentrations of free radicals than similar specimens from 6 women fitted with plastic Lippes loops. Cervical mucus, collected from women immediately prior to elective removal of an IUD, was placed in 2M hydrochloricacid and later analyzed for malonaldehyde using a newly developed polarographic method. Positive results were obtained for 8 of 19 women fitted with copper IUDs, but for none of 21 women fitted with plastic devices. Cervical mucus was similarly collected from 10 women fitted with copper IUDs, 9 women fitted with plastic IUDs, and an additional 9 using other methods of contraception. Mucus was collected 3 times (early, middle, and late cycle). No malonaldehyde was detected in mucus from women with plastic IUDs, or other contraceptive methods. Positive results were obtained in 13 of 29 mucus specimens from those using copper IUDs. Stage of menstrual cycle did not influence the percentage of positive results. Malonaldehyde was detected in vitro in solutions of arachidonate or prostaglandin F2alpha in buffered saline incubated with sterile copper IUD, but not with the plastic. Rate of malonaldehyde production was markedly influenced by pH, temperature, agitation, substrate concentration, and size of gas-liquid interface. the rates of malonaldehyde production around the copper IUD in utero are unknown. The possible increased risk of carcinogenicity associated with the copper IUD is discussed.

Hypospadias, androgen biosynthesis, and synthetic progestogens during pregnancy.

Treatment of pregnant rats from days 13 through 19 with a synthetic steroid known to inhibit 3 beta-hydroxysteroid oxidoreductase was associated with a significant reduction in the capacity of fetal Wolffian ducts to metabolize dehydroepiandrosterone. In contrast, similar treatment with norethisterone acetate, alone or in combination with ethynylestradiol, or medroxyprogesterone acetate, at up to 100 times the human dose, was without effect on metabolism of dehydroepiandrosterone. It is suggested that the use of synthetic progestogens during pregnancy is unlikely to increase the risk of hypospadias due to inhibition of testosterone biosynthesis.