An updated unified pharmacophore model of the benzodiazepine binding site on gamma-aminobutyric acid(a) receptors: correlation with comparative models.

A successful unified pharmacophore/receptor model which has guided the synthesis of subtype selective compounds is reviewed in light of recent developments both in ligand synthesis and structural studies of the binding site itself. The evaluation of experimental data in combination with a comparative model of the alpha1beta2gamma2 GABA(A) receptor leads to an orientation of the pharmacophore model within the Bz BS. Results not only are important for the rational design of selective ligands, but also for the identification and evaluation of possible roles which specific residues may have within the benzodiazepine binding pocket.

Formation in vivo, purification and crystallization of a complex of the gamma and epsilon subunits of the F0F1-ATPase of Escherichia coli.

A complex comprising the epsilon subunit of Escherichia coli F1-ATPase (ECF1-ATPase) and a glutathione-S-transferase gamma subunit (of ECF1-ATPase) fusion protein was formed in vivo and purified from cell extracts by binding to glutathione-agarose beads. The glutathione-S-transferase was released from the complex by digestion with thrombin and the gamma/epsilon complex purified by cation-exchange chromatography. Crystals of the complex were grown by vapour diffusion using PEG8000 as precipitant. The crystals are orthorhombic, space-group P2(1)2(1)2 with a = 161.9 A, b = 44.1 A and c = 63.4 A. The volume of the asymmetric unit is consistent with the presence of a complex of one gamma subunit and one epsilon subunit.

A prospective study of adolescents who choose among levonorgestrel implant (Norplant), medroxyprogesterone acetate (Depo-Provera), or the combined oral contraceptive pill as contraception.

OBJECTIVES: Levonorgestrel implants (Norplant) and medroxyprogesterone acetate injections (Depo-Provera) represent additional contraception options for adolescents. The purpose of this study was to examine prospectively clinical profiles among adolescents who chose one of the two long-term contraceptives compared with profiles among those who chose the combined oral contraceptive pill (OCP). METHODS: Girls who needed contraception and did not require confidentiality were presented with a contraceptive menu consisting of Norplant (n = 58), Depo-Provera (n = 66), or OCP (n = 75). At baseline and follow-up visits over 6 months, patients were interviewed regarding gynecologic history, side effect symptoms, and satisfaction. The average age of subjects was 15.5 years (range 11 to 20 years); 66% were African-American and 34% white. RESULTS: Significantly more teens who chose Depo-Provera (73%) reported having used some method of birth control previously than those selecting either Norplant (30%) or OCP (26%). Adolescents who chose either Norplant (34%) or Depo-Provera (43%) were significantly more likely to have been pregnant previously than those choosing OCP (12%). Those selecting Depo-Provera were significantly more likely to report a history of genital infection with Chlamydia trachomatis (42%) than those in the other two contraceptive groups (22%). Prevalences of reported recent depression and fatigue before initiation of treatment were high, exceeding 35% across the three groups. A total of 105 and 40 adolescents were assessed at 3 and 6 months, respectively. At follow-up, more than 80% of OCP users maintained regular menstrual cycles, whereas over 80% of those choosing Norplant or Depo-Provera had disrupted cycles. Complaints of nausea and dizziness among Norplant users and fatigue among Depo-Provera and OCP users increased significantly between the baseline and follow-up visits. Reports of local reactions to the Norplant device were common but not clinically significant. Blood pressure readings, facial acne, and body mass index did not change over time in any treatment group. Subjects in the Norplant and Depo-Provera groups appreciated freedom from daily compliance to maintain contraceptive effectiveness and the "hidden" nature of the method. Appointment compliance at the end of 6 months was 78% for Depo-Provera, 40% for Norplant, and 46% for OCP. CONCLUSIONS: The implant and injection forms of contraception appear to be especially popular among girls with previous pregnancies or birth control use. The common occurrences of medical symptoms and sexually transmitted diseases before initiation of therapy underscore the importance of baseline evaluation. Norplant users may be warned about nausea and dizziness as well as minor local symptoms around the insertion site and unpredictable uterine bleeding patterns. Adolescent patients choosing Depo-Provera may expect amenorrhea by the end of 6 months of therapy along with possible fatigue. Early intervention may be needed with adolescents who choose Norplant or OCP to encourage better compliance with follow-up appointments.

Pharyngeal gonorrhea screening in adolescents: is it necessary?

A prospective study was performed to examine the prevalence of pharyngeal gonorrhea in two urban female adolescent populations and to compare pharyngeal infection with a history of orogenital activity and concurrent genital gonorrhea. Group I was drawn from a children's hospital adolescent clinic and group II was drawn from a public health clinic for sexually transmitted diseases. None of the 240 adolescents in group I had a pharyngeal culture positive for Neisseria gonorrhoeae compared with 3.4% in group II. Only 2.5% of group I had genital gonorrhea, but 33% of group II had positive genital cultures. In only two of the 20 patients with pharyngeal gonococcal infection was the pharynx the only infected site. The addition of routine pharyngeal culturing for gonorrhea yielded only 1% additional gonorrhea cases. There was a significant relationship between concurrent genital and pharyngeal gonorrhea. These findings indicate that routine screening for pharyngeal gonorrhea is not productive in some adolescent populations. A more economic approach would be to use gonorrhea treatment that is effective against both genital and pharyngeal gonorrhea or to obtain pharyngeal cultures in those adolescents returning for test-of-cure cultures after antibiotic treatment for genital gonorrhea.

Different 1,4-dihydropyridines exhibit discriminating effects on passive calcium uptake in rat liver plasma membrane vesicles.

The effects of a number of calcium channel effectors on Ca2+ uptake by rat liver plasma membrane vesicles was examined. Nifedipine, verapamil and diltiazem had to be present at 1 mM in order to produce > 50% inhibition of Ca2+ uptake. The two structurally similar 1,4-dihydropyridines, nicardipine and nisoldipine exhibited opposite effects; nicardipine inhibited while nisoldipine stimulated Ca2+ uptake. The results show that low concentrations (microM) of calcium channel blockers of excitable cells have little effect on Ca2+ uptake by liver plasma membrane vesicles consistent with earlier findings of others that voltage-gated calcium channels are absent in hepatocytes. However, the opposite effects of higher concentrations (ca. 1 mM) of nicardipine and nisoldipine on Ca2+ uptake suggest a discriminatory action that might be useful in studying further the mechanism of passive Ca2+ uptake by these membrane vesicles.

Effects of hormonal contraceptives on bone mineral density.

The clinical research to date on the effects of 3 types of hormonal contraceptives, i.e. depot medroxyprogesterone acetate ('Depo-Provera'), levonorgestrel subdermal implants ('Norplant'), and oral contraceptives, on bone mineral density in premenopausal women is reviewed. The large variance in results across studies for each method is in part due to differences in research design, techniques for measuring bone mineral density, age of the study participants and type of oral contraceptive preparation. However, the balance of the evidence leans toward a positive effect of oral contraceptives on bone mineral density in women of all age. On the other hand, few observations have yet been published on the effects of the new progestin oral contraceptives on bone mineral density. The few extant data suggest a positive impact of levonorgestrel subdermal implants on bone mineral density in women of all ages. Although the findings are preliminary, it appears that depot medroxyprogesterone acetate may exert a negative effect on bone mineral density. More specifically, caution should be exercised in prescribing long term depot medroxyprogesterone acetate (e.g. > 5 years) especially in young adolescents (e.g. < 16 years old) who may not have yet reached peak bone mass.

Abortion in adolescence: a four-country comparison.

The purpose of this study was to conduct a comparison, using qualitative analytic methodology, of perceptions concerning abortion among health care providers and administrators, along with politicians and anti-abortion activists (total n = 75) in Great Britain, Sweden, The Netherlands, and the United States. In none of these countries was there consensus about abortion prior to legalization, and, in all countries, public discussion continues to be present. In general, after legalization of abortion has no longer made it a volatile issue European countries have refocused their energy into providing family planning services, education, and more straightforward access to abortion compared with similar activities in the United States.

Research articles published in the Journal of Adolescent Health: a two-decade comparison.

PURPOSE: To examine changes in subject contents and study designs of research articles published in the Journal of Adolescent Health since its inception. METHODS: A retrospective review of all research articles was conducted from selected years, ranging from 1980 through 1998. The study sample was composed of the following: original articles, case reports, brief scientific reports, international articles, fellowship forum, and health briefs. RESULTS: A total of 582 articles were evaluated. The total percentage of medical topics in research articles published in the Journal decreased from 61% in 1980-1981 to 38% in 1997-1998 (p <.01). This finding was in contrast to topics related to psychosocial issues, which increased from 23% to 50% (p <.01) over the same period. This change was largely accounted for by studies focusing on high-risk behavior. Retrospective designs, including case reports/series and chart reviews, decreased from 25% of all research articles in 1980-1981 to 9% in 1997-1998 (p <.01). The percentage of observational studies, i.e., those using cross-sectional and longitudinal designs, increased from 62% to 79% over the same period (p <.01). No changes were observed in the percentage of experimental designs, never exceeding >5% of total study designs. Finally, over the 20 years, professional background and academic departments of first authors of research broadened, with increasing contributions from nonphysicians and from non-pediatric disciplines such as psychology, public health, and nutrition. CONCLUSION: A shift in subject content of research articles from medical to psychosocial topics was observed over the past 2 decades. A shift in research designs from retrospective to cross-sectional and longitudinal was observed over the same period. The pool of authors has diversified.

Scientific abstracts at the Society for Adolescent Medicine meetings: a 3-decade comparison.

PURPOSE: The purpose of this study was to review abstracts accepted for presentation at the annual national meeting of the Society for Adolescent Medicine (SAM) over the past 3 decades for subject content and research design. METHODS: Retrospective review was conducted of research abstracts for 3 years, selected at random, for the 1990s and then matched at 10-year intervals for the previous 2 decades. The major categories for subject content were: medical, psychosocial, health services, and miscellaneous; for research design categories were: retrospective, observational, experimental, and miscellaneous. Subsequent publication was also assessed. RESULTS: The most notable change over the 3 decades in subject content was a shift from medical topics (58% to 19%) to psychosocial topics [20% to 52% (p < .001)] of abstracts, the latter largely accounted for by increases in topics pertaining to high-risk behaviors. There was a substantial decrease in abstracts concerning medical aspects of chronic illness (p < .001), well-adolescent care, growth and development, and psychosocial aspects of chronic illness (p < .02). Regarding research design, the proportion of retrospective studies decreased over the 3 decades (p < .02); the most prevalent design was observational, with an increase in studies using established databases (p < .02). Less than 15% represented an experimental design. Studies using qualitative analysis appeared for the first time in the 1990s. The percentage of presentations which eventuated in published reports increased from 35% to 63% over the 3 decades (p < .02). CONCLUSION: A significant shift occurred in subject content of scientific abstracts from a medical to a psychosocial emphasis. The proportion of retrospective designs decreased, and qualitative analyses emerged. The likelihood of later publication of the studies increased.

Depot medroxyprogesterone acetate (Depo-Provera) and levonorgestrel (Norplant) use in adolescents among clinicians in Northern Europe and the United States.

PURPOSE: To compare attitudes and practices related to clinicians' use of depot medroxyprogesterone acetate [Depo-Provera (DMPA)] and levonorgestrel implants in adolescents in three northern European countries and the United States. METHODS: Between the fall of 1993 and the winter of 1995, surveys eliciting clinician attitudes and practices with the two contraceptive methods were collected from practitioners who provide contraceptive care to teens in Sweden (n = 282), The Netherlands (n = 197), Great Britain (n = 108), and the United States (n = 548). RESULTS: Clinicians in Great Britain and the United States reported prescribing of DMPA, selected DMPA in their top three choices for contraception in teens, and had patients ask about DMPA more frequently than clinicians in Sweden or The Netherlands (p < 0.0001). U.S. clinicians were more likely to report prescribing of the implants, list them as a top choice, and have patients ask for it more frequently than were providers in the other three countries (p < 0.0001). Noncompliance with previous contraceptives was the most common indication for use of either method in this age group. "Worst fears" with DMPA use included infertility, particularly among Swedish clinicians (p < 0.0001), as was pregnancy and loss to follow-up, particularly among British clinicians (p < 0.0001). Condom nonuse was a concern associated with both methods. Breakthrough uterine bleeding was a concern related to implant use, particularly among Swedish practitioners (p < 0.0001). CONCLUSION: Clinicians in the United States and Great Britain display more enthusiasm toward the use of the long-term progestins in adolescents than do clinicians in Sweden or The Netherlands. Continuing education programs could be designed to educate clinicians to allay their concerns about these contraceptives in countries where teen pregnancy is considered a problem.

The use of long-acting contraceptives in adolescents.

DMPA and implants have played an important role in the attempt to prevent teenage pregnancies. Adolescent health care providers should provide continued counseling to girls using DMPA or implants and should promptly address any concern associated with these methods. Future studies are warranted to explore ways to prevent or reduce the side effects of DMPA and implants, as well as to develop new, optimal, long-acting contraceptives. Detailed baseline information should be obtained in every future study that explores the presence of side effects during the use of long-acting contraceptives.

The pediatrician and the sexually active adolescent. Sexual activity and contraception.

Sexuality and its resultant consequences continue to be major issues for adolescents and for those who provide their health care. This article discusses current sexual behavior in adolescents and describes the various forms of hormonal contraception that sexually active adolescents should use.

PIP: Adolescence, especially early adolescence, is a period of development during which individuals are more physically mature than they are cognitively mature. That is, while the average girl becomes capable of conceiving a child as early as age 10 or 12 years, she is still cognitively a child who is incapable of perceiving the future consequences of current behavior and who is not capable of being an effective parent. Available data indicate that more US adolescents are sexually active than ever before. While surveys suggest that more than half of high school-aged teens have ever had sexual intercourse, adolescent sexual activity tends to be sporadic, with adolescents typically experiencing prolonged periods of abstinence between episodes of sexual intercourse. Naturally predisposed to take risks and experiment with sex, teenagers engage in serial monogamy, moving into and out of a series of monogamous sexual relationships early in life. One study found that high school-aged boys had had an average of 5 sex partners. Studies also indicate that teens who plan to go to college more effectively delay their first sexual intercourse than do teens who do not plan to pursue higher education. While abstinence from risky sexual behaviors is the best way to avoid any adverse consequences from such behavior, many adolescents nonetheless have sexual relations. Physicians who treat adolescents must therefore be prepared to accommodate the reproductive health needs of sexually active teens. Providing contraception when needed is one way in which clinicians can help. Injectable contraception, contraceptive implants, the new oral contraceptives, emergency contraception, and beginning hormonal contraception are discussed.

Update on adolescent contraception.

Recent advances in OCPs include less androgenic progestins and lower doses of ethinyl estradiol. All low-dose OCPs are safe in terms of venous thrombosis risk in appropriately chosen patients. DMPA is a safe and effective long-acting contraceptive agent; clinical attention should be directed to its most common side effect, irregular bleeding. DMPA does not seem to affect mood, and it is uncertain what impact it has on weight changes. More research needs to be conducted on its impact on adolescent bone metabolism. Norplant continues to be the only subdermal contraceptive implant marketed in the United States. It provides safe and effective contraception and has the best continuation rate of all types of hormonal contraception. Its most common side effect is irregular bleeding. Norplant may be especially well suited for adolescents who have recently been pregnant or who are not tolerating other types of contraception. Emergency postcoital contraception continues to be underused in the United States, with a lack of awareness among patients and clinicians. Mechanisms of action include a delay in ovulation and interference with implantation. Research and public health groups are striving to increase patient and provider awareness and use of emergency contraception.

Adolescent sexuality and issues in contraception.

The influence of physiologic, psychologic, and cultural influences on human sexuality is reviewed. These factors are considered in the exploration of how adolescents express their sexuality and the consequences of that expression.

Increasing appointment compliance through telephone reminders: does it ring true?

This study evaluated the effectiveness of telephone reminders on appointment-keeping in young people treated for gonorrhea. Compliance with scheduled follow-up was recorded for a total of 339 patients during three two-week periods, namely, initial baseline phase, intervention phase during which attempts were made to remind the patients by telephone, and repeat baseline phase. There was no overall improvement in compliance with follow-up during intervention (31%), compared to baseline (32%). However, data from the intervention phase revealed a significantly higher rate of appointment-keeping for those patients who were contacted (44%) than for patients who were not reachable (20%). Furthermore, when we reanalyzed the data as a function of telephone ownership for all patients who did not receive a reminder, return rates were significantly higher for patients owning telephones (32%) than for those denying phone ownership (18%). Thus, we conclude that the likelihood for appointment compliance was related more to sociobehavioral factors reflected in telephone ownership than to the telephone reminders.

The school breakfast program and cognition in adolescents.

We studied cognitive function and metabolic status in a group of healthy adolescents fed the government supplied breakfast (n = 18) versus a control group (n = 16) fed a very low calorie meal. Serum glucose and beta-hydroxybutyrate levels were repeatedly measured at predetermined intervals throughout the testing period. Acute cognitive and mood effect were evaluated in all subjects on a pre-post basis. No significant group differences emerged on a battery of psychological measures that assessed short-term auditory memory, vigilance, impulsivity, and mood. Neither serum glucose or beta-hydroxybutyrate levels correlated significantly with any behavioral measure. Results are discussed in the context of previous studies of nutrition and cognition.

An inventory to measure medical staff knowledge of behavioral methods with pediatric pain patients.

An inventory is described for assessing medical staffs' knowledge of behavioral methods with pediatric pain patients. It was adapted from a measure designed by Sanders and Webster (1982) for use with nurses treating adult chronic pain patients. The modified inventory was administered to three groups of medical staff: (a) pediatric residents, (b) pediatric nurses and (c) medical students. A series of analyses provided data supporting the psychometric integrity of the inventory. The measure successfully discriminated trained from untrained staff. The utility of the instrument for staff assessment and development is discussed.

Management of clinical side effects of DMPA.

This edition of Tips for Clinicans tackles a common patient complaint: side effects of depot medroxyprogesterone acetate (DMPA). If perception is reality, patient compliance can be greatly enhanced by addressing perception of DMPA side effects proactively. As clinicians, we can educate teens on actual as well as perceived side effects, anticipating problems and providing solutions when problems arise. Doctors Stager and Cromer provide a nice review of what to expect from DMPA and how to help.

Sexual activity and other high-risk behaviors in adolescents with chronic illness: a review.

This article is a literature review of high-risk behaviors, including sexual activity, in adolescents with chronic illness. Three different models describing biopsychosocial constructs for risky behaviors are discussed. Regarding specific behaviors, findings from the literature include a substantial prevalence of sexual activity, but low level of knowledge and low prevalence of contraceptive use, in youth with chronic illness. Regarding substance use, alcohol was the most commonly used substance regardless of medical condition. Overall, substance use, as well as delinquent behavior, was lower among youth with chronic illness when compared to that in comparison groups. Results were mixed regarding the prevalence and determinants of unhealthy eating habits in these populations. Although high-risk behaviors in teenagers with chronic illness may be a normal part of development, awareness of their prevalence, along with early identification and counseling are important in order to anticipate adverse effects on their medical conditions.

Comparison of continuation rates for hormonal contraception among adolescents.

BACKGROUND: Inadequate contraception is common among sexually active female adolescents, resulting in a high incidence of unwanted pregnancy. The authors were interested in comparing continuation rates for the different forms of hormonal contraception in this age group. METHODS: A retrospective chart review. The setting was an urban clinic in a large Midwestern city. Participants were 64% black, 34% white, and the average age was 15.5 years (+/- 1.6 SD), with implant users significantly older than oral contraceptive pill (OCP) users (P < .05). Interventions were self-selection to depo-medroxyprogesterone acetate (Depo-Provera; DMPA), levonorgestrel implants (Norplant), or oral contraceptive pills (OCPs). Previous pregnancy was significantly more prevalent in implant and DMPA users than in OCP users (P < .001). Over 4 years of follow-up, continuation rates were significantly higher for implant users than for the other hormonal groups (P < .001). At 1 year, continuation rates were as follows: 82% implants, 45% DMPA, and 12% OCPs. Combining these rates with those of the subsample who switched without interruption to another hormonal method, "continued protection" rates were much higher after 1 year: 96% implants, 83% DMPA, and 49% OCPs. Calculations of contraceptive "restarts," i.e., hormonal method use in those who discontinued and then restarted after a gap of time, also increased to the prevalence of contraceptive protection. CONCLUSION: Continuation rates for levonorgestrel implants were significantly higher than those for DMPA and OCPs, the latter group having the lowest continuation rates. Factoring in switches and restarts to other hormonal methods further boosted the prevalence rates of contraceptive use in the adolescent population.