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Solvent-induced directional aggregation of human carbonic anhydrase II (hCA) was studied by small angle X-ray scattering and fluorescence and fourth-derivative ultraviolet absorption spectroscopy. We propose that hCA at 5 mg ml(-1) in pure water forms head-to-tail oligomers built up, on average, by four to five monomers. At higher protein concentrations, the oligomers associate pair-wise and side-by-side. Spectroscopic evidence suggests that the subunits forming the aggregates are tightly folded, but with a structure that differs, at least locally, from the native state. A more complex aggregation pattern was observed under solvent conditions that favor the removal of zinc from the enzyme-active site, conditions under which the subunits are significantly less compact than in water. hCA may provide a useful model to investigate the effects of additives and genetic manipulation on protein aggregation.

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BACKGROUND: The macrolides are among the most effective antibiotics against infections due to Chlamydia and Mycoplasma. The drug in such cases must have marked antibacterial activity, good oral bioavailability, and high intracellular diffusion--indispensable for instance with Chlamydia infection. Rokitamycin, a macrolide with a 16-atom lactone ring, has the features for use in the treatment of genital infections caused by Chlamydia or Mycoplasma, penetrating the cell and reaching considerably higher concentrations than other drugs of the same class. The aim of this trial was to gain further knowledge of rokitamycin in genital infections, including cases infected with Mycoplasma hominis, comparing the efficacy and safety of this drug with josamycin, another macrolide widely employed in clinical practice. METHODS: Patients of either sex, over the age of 18 years, with infections due to Chlamydia trachomatis and Mycoplasma hominis, were admitted. The trial was conducted in accordance with the Declaration of Helsinki and amendments. Fifteen patients were given rokitamycin, one 400 mg tablet every 12 h, and another fifteen received josamycin, one 500 mg tablet every 8 h, for 14 days. Before starting treatment, after the 14 days and after 42 days' follow-up the severity of the following symptoms was assessed: pruritus, burning, erythema, pollakiuria, dysuria, using a four-point rating scale (0 = absent, 1 = mild, 2 = moderate, 3 = strong). The presence or absence of leukorrhea was noted. Patients entered the severity of subjective symptoms daily in a diary. At the end of the trial overall assessments were made on the clinical response, microbiological outcome and efficacy. RESULTS: Thirty patients of both sexes were admitted, age 21-43 years, with genital infections due to Chlamydia trachomatis and/or Mycoplasma hominis. Fifteen were given rokitamycin, 800 mg/day, and 15 josamycin, 1500 mg/day, for 14 days. In 13 cases in each group an antibiotic was prescribed for the partner too. At the start of the trial microbiological samples were taken; in 13 cases a urethral swab was taken (six in the josamycin and seven in the rokitamycin group), and 17 cervical swabs were taken (respectively nine and eight). At the end of the trial 93% of patients gave a negative microbiological result. Mycoplasma hominis was isolated from one patient treated with rokitamycin, and Chlamydia trachomatis from one patient given josamycin. Symptoms improved at a similar rate in both groups, with no significant differences between the drugs. Safety was excellent in both groups, with no complaints of adverse reactions. CONCLUSIONS: This trial demonstrates the excellent activity of macrolide antibiotics against genital infections due to Mycoplasma hominis and Chlamydia trachomatis. Rokitamycin and josamycin both gave good or excellent clinical and microbiological outcomes in more than 90% of the cases. Both were extremely well tolerated. These findings confirm and extend the indications for rokitamycin, found in earlier trials to be extremely effective in the treatment of urethritis due to Chlamydia trachomatis and--as a whole--in infections caused by this microrganism.

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The value of the measurement of nuchal translucency thickness for predicting fetal Down's syndrome and other aneuploidies was prospectively evaluated at 8-15 weeks of gestation in 1819 consecutive pregnancies scheduled for karyotyping by chorionic villus sampling. In 43 cases, a chromosomal unbalanced aberration was found. Two teams of ultrasonologists who examined patients attending either National Health Service (Series 1) or private practice clinics (Series 2) were involved in the study. The same type of ultrasound machine and standardized approach were used in both study groups. In those cases in which the maximum subcutaneous thickness of the translucency was 3 mm or greater, the incidence of chromosomal aberration was 18.6% compared to 1.7% in the cases in which this was below 3 mm. The sensitivity, specificity and relative risk for all aneuploidies were 30%, 96% and 10.83, respectively, and no difference was found between trisomy 21 and other types of aneuploidy. The sensitivity and specificity and relative risk were significantly higher at 9-10 weeks than between 11 and 15 weeks. The results were concordant in the two series; however, the overall values for sensitivity (20% vs. 39%), specificity (94% vs. 98%) and relative risk (4.13 vs. 24.20) were clearly higher in the group of private patients. The results obtained confirm the potential application of the measurement of nuchal translucency thickness for fetal aneuploidy screening before the end of the first trimester and suggest that a multiplicity of individual, structural and organizational factors may interact and play a crucial role in determining the actual efficiency of ultrasound screening programs.

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The ethinylestradiol-norgestrel combination (EE-NG) for postcoital contraception, as described by Yuzpe, has been shown to be an effective method but with frequent side effects. To overcome the problem of adverse effects a new approach using danazol was proposed, but the efficacy and acceptability of this treatment have not yet been tested in large studies. In a 5-year period at the AIECS Family Planning Centre in Milan we treated 2448 women requesting postcoital contraception using Yuzpe's regimen and two danazol regimens (800 mg/1200 mg). The patients' acceptability for danazol treatment was higher than for Yuzpe's regimen due to fewer, milder and shorter side effects. Nine pregnancies occurred in the EE-NG group (2.21%), 17 in the 800 mg group (1.71%) and 6 in the 1200 mg group (0.82%). Our study shows a statistically significant efficacy against expected pregnancy rates both with Yuzpe's regimen and with danazol. The 1200 mg danazol treatment seems to be more effective and can be considered a valid alternative to the EE-NG combination for hormonal postcoital contraception.

PIP: The ethinyl estradiol-norgestrel combination (EE-NG) for postcoital contraception as described by Yuzpe has been shown to be an effective method but with frequent side effects. To overcome the problem of adverse effects, a new approach using danazol was proposed, but the efficacy and acceptability of this treatment has not yet been put to the test in larger groups. In a 5-year period at the AIECS Family Planning Center in Milan, the authors treated 2448 women requesting postcoital contraceptives using Yuzpe's regimen and 2 danazol regimens (800 mg/1200 mg). The danazol treatment met with a greater measure of patient acceptability than did Yuzpe's regimen, due mainly to the smaller number of side effects. 9 pregnancies occurred in the EE-NG group (2.21%), 17 in the 800 mg group (1.71%), and 6 in the 1200 mg group (0.82%). This study shows a statistically significant efficacy against expected pregnancy rates, both with Yuzpe's regimen and with danazol. The 1200 mg danazol treatment seems to be more effective and can be considered a valid alternative to the EE-NG combination for hormonal postcoital contraception.

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This retrospective study concerns 537 adolescent pregnant patients followed at the 1st Dep. of Obst. and Gyn. during the time period 1984-87. Preeclampsia, preterm labor and neonatal mortality were more frequent than in the general population.

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During a 9-month period, 84 female patients received post-coital contraception consisting either of an association of ethinyl estradiol/norgestrel or of danazol, in order to compare the safety and any adverse reaction of these 2 treatments. Overall, the patients treated with danazol presented 1/3 as many side effects. Nausea was reduced to 1/3 in frequency and vomiting to 1/9 in this group. 5 pregnancies were confirmed in the ethinyl estradiol/norgesterol group and 2 in the danazol group. Although more cases are needed, it would appear that danazol is characterized by greater efficacy and patient acceptability.

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PIP: During a 3 year period, 1982-85, 851 adolescents approached the Voluntary Abortion Service of the L. Mangiagali clinic in Milan. The observations resulting from the clinical and psychological work as well as current international literature on the subject of attitudes towards birth control methods among adolescents are reported. A study by Zelnick and Kantner in 1979 and a study by Furstenberg in 1978 are discussed. Here percentages of nonmarried adolescents between 15-19 with sexual experience are researched concerning their use of contraceptives and frequency of sexual relations according to race and educational level of mother or of tutor. The research by the clinic itself centers on the psychological experiences relative to the possibility of becoming pregnant. In the majority of the pre-voluntary abortion cases, 78% of the adolescents rely on ineffective methods (e.g., coitus interruptus), 14% used the barrier method, 7.7% oral contraceptives and 0.3% IUDs. It is concluded that the adolescent today initiates sexual relations at a much earlier age and confronts the problems of contraceptives without making a decisive and secure choice. One reason is that there does not seem to be suitable institutions where questions relating to sexuality and contraception can be directed. Another reason consists in the conflict between a subconscious desire for pregnancy versus a rational desire to avoid it. During an adolescent's developing years the counsel and support from parents, instructors and institutions of society are important.^ieng

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The energy trends of the past and their likely evolution in the next 50 years have been analyzed in the light of technological progress. It is concluded that society will tend to become less centralized than in the past and that it is possible to have future per capita values of energy consumption at the world level similar to those at present, with a substantial redistribution to allow for economic growth of the less developed countries. A condition for this is increasing penetration of electricity. The rationale for the suggested scenario is described, and prospects for electricity for both the industrialized and developing countries are discussed.

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