Immunotherapy of genital warts with inosine pranobex and conventional treatment: double blind placebo controlled study.

In a multicentre, prospective, randomised, placebo controlled study of 55 patients with histories of genital warts for at least one year, a four week course of inosine pranobex 3 g a day improved the clinical response to conventional treatment (primarily podophyllin or trichloroacetic (now called trichlorethanoic) acid). Although more patients given inosine pranobex improved than those given placebo, the difference in general response between the two groups was not significant. When other variables (numbers of warts and extent of lesions) were considered, however, the patients given inosine pranobex fared significantly better. These results suggest that inosine pranobex may be worth considering as adjunct to treatment of patients with refractory genital warts.

Developmental toxicity of alprostadil in rats after subcutaneous administration or intravenous infusion.

Timed-pregnant Upj:TUC(SD)spf (Sprague-Dawley) rats were dosed with alprostadil (prostaglandin E1), either subcutaneously on Days 6-15 of gestation at 0.0, 0.5, 1.0, or 2.0 mg/kg/day or by iv infusion into the jugular vein (24 hr/day) on Days 7-15 at 0.0, 0.5, 1.0, 2.0, 4.0, or 6.0 mg/kg/day. Maternal toxicity was observed in all dams receiving alprostadil subcutaneously, the severity of which increased in a dose-related manner. Toxicity also was evident in the offspring in the 2.0 mg/kg/day group as evidenced by a significant increase in the percentage of resorptions and a significant decrease in the percentage of live fetuses. Mean fetal weight was significantly depressed in all three alprostadil-treated groups and several skeletal and visceral variations were significantly higher in the 1.0 and 2.0 mg/kg/day groups than in the vehicle control group; in addition, there were two instances of significantly increased frequencies of skeletal variations in the 0.5 mg/kg/day group. Gross, visceral, and skeletal malformations were significantly increased in the high-dose group. During iv infusion of alprostadil more than 50% of the dams in the 6.0 mg/kg/day group died and there was one death in the 4.0 mg/kg/day group. Significant decreases in maternal weight gain between Days 7 and 11 of gestation were observed at doses of 1.0 mg/kg/day and above. However, continuous iv infusion of this prostaglandin, at dosages which were not severely toxic to the dams, was judged not to be teratogenic or otherwise embryotoxic in rats. The increase in uterine contractions, observed at 1.0 and 2.0 mg/kg after sc administration to rats implanted with chronic uterine microballoons, was consistent with the hypothesis that the developmental toxicity observed after bolus sc administration was the consequence of decreased blood flow in the uterus and/or placenta and/or embryos.

Effects of losulazine on rat reproduction and development.

Losulazine, a hypotensive agent, was given orally by gastric intubation to Sprague-Dawley rats in doses of 0, 2, 4, or 8 mg/kg/day in a study of fertility and general reproductive performance. Eighteen males per group were treated for 67 days before cohabitation, then daily until killed. Thirty-six females per group were treated for only 14 days because estrous cycles had been disrupted. Females remained untreated for 7 days before cohabitation; treatment was resumed after insemination was confirmed or when the cohabitation period ended. Males were cohabited on a 1:2 basis with females from the same treatment group for up to 14 days, then for 14 days with untreated females. The conception rate of both treated and untreated females was statistically significantly decreased as the dose increased. Mean body weights were statistically significantly greater and mean gestation periods were statistically significantly longer in losulazine-treated females than in females of the vehicle control group. Throughout the preweaning period mean body weights were significantly less in offspring from treated dams than in offspring of dams in the vehicle control group. This adverse effect on weight gain continued in male offspring until at least postpartum day 79. Functional development was significantly delayed in the offspring of losulazine-treated dams tested for pinna detachment, auditory startle, negative geotaxis, eye opening, and learning (swimming M-maze). Delays in development were generally greater in offspring of dams and sires treated with higher doses of losulazine. Fertility of male offspring from dams and sires treated with losulazine at 4 and 8 mg/kg/day was also affected adversely.

Reproductive and developmental effects on rats after prenatal, postnatal, or pre- and postnatal exposure to the hypotensive agent losulazine.

Losulazine was administered orally to 21 bred Sprague-Dawley rats per group at 0, 4, and 8 mg/kg/day by three dosing schedules: gestation day 15 until term (prenatal section); postnatal days 1 to 21 (postnatal section); and gestation day 15 until postnatal day 21 (pre- and postnatal section). Dams were allowed to deliver and the number of live and dead pups recorded. Each pup was sexed and weighed on days 0, 4, and 21. Also, pinna detachment and eye opening were monitored. Randomly selected offspring were allowed to mature and then cohabited for assessment of reproductive performance. Dam body weight gain during dosing was reduced in the high dose group of the pre- and postnatal section. Treated dams in the postnatal and pre- and postnatal sections had litters with reduced body weight, delayed development, and decreased survival. In the F1 mating portion of the postnatal and pre- and postnatal sections, F1 offspring from losulazine-treated dams had reduced body weights over the entire study. A dose-related decrease was found for both the percentage of F1 males that bred and the conception rate of bred F1 females. All F1 females entered estrus at least once, and those that conceived delivered normal litters. Neither microscopic examination of F1 male reproductive organs nor analyses of serum prolactin, luteinizing hormone (LH), and testosterone levels indicated the cause of impaired fertility. Thus, although prenatal exposure only did not result in adverse effects, postnatal exposure to losulazine via lactation affected offspring growth, development, and reproductive capacity.

Mechanism of anestrus in rats treated with an antihypertensive agent, losulazine hydrochloride.

The mechanism of anestrus in rats treated with losulazine, a peripheral sympatholytic antihypertensive agent, was investigated by determining its effect on hypothalamic catecholamines and serum sex hormones and by evaluating the influence of bromocriptine on the reproductive functions of rats treated with losulazine. Groups of six female Upjohn Sprague-Dawley rats were treated orally with 10 mg/kg/day of losulazine and/or 18.75 mg/kg/day of bromocriptine for 15 or 27 days. Six rats were treated with losulazine plus 6.25 mg/kg/day of bromocriptine for 16 days followed by losulazine alone for 11 days. Rats treated with losulazine only were depleted of hypothalamic catecholamines, were hyperprolactinemic, and had interrupted estrous cycles and attenuated vaginal mucosa. Treatment with bromocriptine, a dopamine receptor agonist, resulted in suppression of serum prolactin and normal estrous cycles. Rats reverted back to hyperprolactinemia and anestrus shortly after bromocriptine withdrawal. These results suggest that hyperprolactinemia mediated through hypothalamic dopamine depletion is the mechanism of anestrus in rats treated with losulazine.

Determination of rhenium in geological materials by radiochemical neutron-activation analysis.

A neutron-activation method for the determination of rhenium in geological materials is described. Radiochemical separation, using Re-carrier and liquid-liquid extractions, yields (186)Re in a state of radiochemical purity. The gamma-ray activity of the radionuclide is counted with an NaI(Tl) crystal scintillation detector, and the chemical yield is determined spectrophotometrically. Results for the contents of rhenium in the standard rock W-1 and in nickeliferous lateritic profiles are reported. Particular problems arising in neutron-activation analysis for rhenium in lunar surface materials are discussed.

Miconazole nitrate compared with chlordantoin in the treatment of vaginal candidiasis.

In a double-blind study of the treatment of vaginal candidiasis, miconazole nitrate gave a cure-rate of 88 per cent. (29 out of 33) compared with 58 per cent. (21 out of 36) using chlordantoin. Although approximately two-thirds of the patients who responded did so to a 10-day course of treatment, the different rates of cure with these preparations at this stage were not statistically significant. However, when a second course of treatment was given to those women who still had proven candidiasis, the overall cure-rate with miconazole was significantly greater than that with chlordantoin.

Antibodies to Candida albicans in hospital patients with and without spinal injury and in normal men and women.

The presence of serum agglutinins and precipitins to Candida albicans in men and women who had impaired bladder function following spinal injury is compared with that in other patients in hospital and in apparently fit men and women. Antibody levels which have commonly been regarded as significant were found in 35 of 76 patients who had urinary candidiasis; in 10 of 52 patients who had spinal injury without urinary candidiasis; in eight of 57 patients who had neither of these conditions, and in nine of 191 normal men and women. Observations are made on the antigens involved in these reactions and on the need for standardization of both reagents and techniques.

Letter: Eugynon 30 and dermatitis.

PIP: In 1967; 1972 and 1974, Lyndiol-2.5; Norinyl-1; and Microgynon 30 were respectively prescribed to a woman who, after taking a few tablets on each occasion, developed a mild diffuse urticarial rash, mostly on the limbs and chest. She took the 1st 2 drugs for only 2 weeks but completed the course of Microgynon 30. The rash disappeared during the pill-free week. Piriton 4 mg was prescribed with the 2nd pill cycle to determine if it would modify the effect; it did not and the woman discontinued the pill on the 5th day. She 1st conceived in 1957 and was found to be allergic to nickel; she had uneventful pregnancies in 1961 and 1967. These oral contraceptives do not have any common hormone; dye; nor manufacturer, and the problem has yet to be resolved.^ieng

Application of solvent extraction to the refining of precious metals-III Purification of gold.

A procedure for the separation of gold from precious metal concentrates, based on its extraction by "dibutyl carbitol", is described. Spectrographic analyses indicate that the resultant metal is of high purity and tests have shown that recovery of the element is essentially quantitative. It appears that advantages could ensue from the incorporation of a scaled-up version of the procedure in an industrial process for the refining of precious metals.

Stability constants of manganese(II) bromide complexes.

Manganese-54 has been used as a tracer in an investigation of solutions containing manganese(II) bromide complexes. By a cation-exchange method values have been obtained for the stability constants beta(j) = [MnBr((2-j)+)(j)]/[Mn(2+)][Br(-)](j), valid for 20 degrees and ionic strength 0.691M maintained with perchloric acid.

Normal vaginal microbiology of women of childbearing age in relation to the use of oral contraceptives and vaginal tampons.

The vaginal microbiology of women attending a family planning clinic was found to be unrelated to the use of oral contraceptives and vaginal tampons. Beta haemolytic streptococci isolated from this ;normal' population were compared with those from 1,104 women attending general practitioners complaining of vaginal discharge. There is a caution regarding the indications for antibiotic therapy. Observations were made on the effects of contamination of vaginal swabs with yeasts and beta-haemolytic streptococci from the vulva. The persistent character of the vaginal flora over a six-month period is described.