Comparative evaluation of oral prostaglandin E2 & intravenous oxytocin for induction of labour.

Oral prostaglandin E2 tablets (group I) and iv Oxytocin (group II) were evaluated in 120 randomly selected women subjected to induction of labour. In group I, 60 women received oral prostaglandin E2 tablets in incremental doses from 0.5-1.5 mg hourly, depending upon the parity and Bishop score of the patient. Group II women received oxytocin iv in 5 per cent dextrose, starting at a rate of 2 mU/min and gradually increasing to a maximum of 64 mU/min. Overall success rate in group I (prostaglandin E2) and group II (intravenous oxytocin) was 85 and 93.3 per cent respectively (P greater than 0.05). In the favourable group (Bishop score 6-13) the induction delivery interval (IDI) for group I and group II was 8.86 h and 7.95 h respectively (P greater than 0.05), while in the unfavourable group (Bishop score less than or equal to 5), the IDI for the respective groups were 13.42 h and 10.11 h (P less than 0.05). Side effects with prostaglandin E2 were mostly mild gastrointestinal ones. A significantly higher incidence of foetal distress was observed with intravenous oxytocin (15%) as compared to prostaglandin E2 (3.33%). Oral prostaglandin E2 was thus found to be a better alternative to intravenous oxytocin in multiparous women with favourable Bishop score (greater than 6) and in those in whom fluid retention is to be avoided (e.g., conditions like toxemias, renal disease).

Randomized clinical trial with intrauterine devices (levonorgestrel intrauterine device (LNG), CuT 380Ag, CuT 220C and CuT 200B). A 36-month study. Indian Council of Medical Research Task Force on IUD.

A total of 1905 subjects were randomly allocated to four types of intrauterine devices (IUDs) and were observed for 45,683 woman-months of use. While no method failure was observed with levonorgestrel (LNG) IUD, 11 women became pregnant with other devices; 4 with Copper T 380Ag, 1 with Copper T 220C, and 6 while using Copper T 200B, indicating method failure rates of 1.0, 0.3 and 1.6, respectively, at 36 months of use. These rates were within acceptable range. Continuation rates were significantly lower with LNG IUD (74.5, 58.7, 38.8 at 1 year, 2 years and 3 years, respectively) as compared to other copper devices, which ranged between 82.4 to 84.4 at 1 year, 66.6 to 69.9 at 2 years and 45.4 to 50.4 at 3 years. The difference in continuation rates was mainly due to menstrual disturbances (e.g. amenorrhoea, irregular bleeding) which were higher with LNG IUD (27.9 per 100 users) as compared to the copper devices (13.4-15.4 per 100 users) at 36 months of use. The risk of expulsion ranged between 8.3 to 10.6 per 100 users and was comparable for all the devices. The observations from the present study based on 36 months of experience with different intrauterine devices do not indicate the need to replace CuT 200, the device currently in use in the National Programme.

Phase III-clinical trial with Norplant-2 (covered rods). Report of a 24-month study. National Programme of Research in Human Reproduction. Division of Human Resource Development Research Indian Council of Medical Research Ansari Nagar, New Delhi, India.

In a phase III multicentre clinical trial, the subdermal implant NorplantR-2 was studied for its clinical use effectiveness, safety and bleeding pattern. A total of 1466 healthy volunteers, with no contraindication to steroid use, were observed for 29,669 woman-months of use. One method failure was reported at 18 months of NorplantR-2 use. The method was associated with altered menstrual pattern with a trend towards reduced blood loss. The continuation rates were 88.1 and 73.5 per 100 users at 12 and 24 months of use, respectively. Menstrual disturbance, mainly prolonged bleeding, accounted for the majority of the discontinuations. Removal of NorplantR-2 due to local infection was rare (0.4 per 100 users at 24 months). In similar clinical trial conditions, the continuation rate with NorplantR-2 is significantly higher than those observed with LNG IUD and injectable contraceptives, norethisterone oenanthate 200 mg given every 60 +/- 5 days, and is comparable to that of CuT 200 IUD.

INDUCTION OF SECOND TRIMESTER ABORTION BY INTRAAMNIOTIC ADMINISTRATION OF 15(S)15 METHYL PGF2α.

In a multicentre trial 139 women between 15 and 20 weeks of gestation were treated with 2.5 mg intraamniotic administration of 15(S)15 methyl PGF2α (Prostin 15M, Upjohn) for termination of pregnancy. Following treatment 97% of the primigravida and 94.5% of multigravida aborted. The induction abortion interval (Mean ± S.E.M.) in the primigravida was 22.8 ± 1.1 hours, while in the multigravida it was 18.3 ± 1.0 hours. The mean number of episodes of vomiting was 1.4 and 0.9 in primigravidae and multigravidae, respectively. The mean number of episodes of diarrhoea was 0.7 in both groups. Of the primigravidae 10.9% and of the multigravidae 21.7% had incomplete abortions. No injuries to the genital tract were reported.

Teratologic effects of d,1-2-(o-chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride (ketamine hydrochloride) in rats.

Studies were conducted of the teratologic effects of ketamine hydrochloride in rats. Ketamine treatment had no significant effect on the number of animals per litter. The histological examination of heart, liver, and kidney showed focal nuclear hypochromatosis and interfibrillary edema; diffuse hemopoietic cell infiltration, and parenchymal cell degeneration; proximal convoluted tubule degeneration. The degenerative effect is also dependent upon the dose and the duration of treatment.

Phase II randomized comparative clinical trial of Norplant (six capsules) with Norplant-2 (two covered rods) subdermal implants for long-term contraception: report of a 24-month study. National Programme of Research in Human Reproduction.

In a randomized clinical study, contraceptive efficacy and bleeding patterns were studied in a group of healthy, regularly menstruating, non-lactating women (n = 84) using two 4.4 cm covered silastic rods containing levonorgestrel, Norplant(R)-2, and compared with another group of women (n = 88) using six 3.4 cm capsules also containing levonorgestrel, Norplant(R). The silastic rods or capsules were placed subdermally in the medial aspect of the upper arm. No method failure was reported up to 24 months of use in this study with either of the device. The bleeding pattern was also similar for both devices as indicated by average episode length, number of bleeding runs and number of spotting days. The continuation rates with both devices were over 80 per 100 users at the end of 12 months and over 65 per 100 users at the end of 24 months. Discontinuations due to expulsion of the device, bleeding problems or personal reasons were few and similar for both devices. The results suggest that silastic-covered rods, Norplant(R)-2, which are comparatively easier to insert and remove and have similar clinical effect, could replace capsules, Norplant(R), as a long-term reversible subdermal contraceptive.

Effects of ketamine on brain monoamine levels in rats.

The effects of ketamine (50 mg/kg i.p.) on brain monoamines, including epinephrine, norepinephrine, dopamine, serotonin and its metabolite 5-hydroxy indoleacetic acid, were studied in three groups of male Sprague-Dawley rats. A rapid, simple, accurate, and sensitive spectrophotoflurometric method was developed to determine monoamines extracted from rat brain. Ketamine significantly increased brain epinephrine (25%), serotonin (28%) and 5-hydroxy indoleacetic acid (32%) in rats. In contrast, norepinephrine (43%) and dopamine (58%) levels were significantly reduced at 30 minutes. The increase in epinephrine (13%) and decrease in norepinephrine (31%) and dopamine (38%) levels remained significant 12 hours after ketamine injection. Serotonin and 5-hydroxy indoleacetic acid levels returned to almost normal in ketamine pretreated animals after 12 hours. Thus, the ability of ketamine to interfere with monoamine metabolism was revealed.

The identification of ketamine and its metabolites in biologic fluids by gas-chromatography-mass spectrometry.

A simple gas chromatography-mass spectrometric method for the identification of ketamine and its metabolites in urine, blood, serum, and plasma has been developed in order to investigate a coma due to overdose of the drug.

Metabolism and probable active metabolite of alpha-l-acetylmethadol in rat.

alpha-l-Acetylmethadol is being currently evaluated as a substitute for methadone in the treatment of heroin addicts. The metabolites, isolated from urine, liver, and serum, were identified by gas-liquid chromatography. Methadone and its metabolites were found to be present in urine, liver and serum of rats treated with alpha-l-acetylmethadol. The presence of methadone was confirmed by gas-chromatography-mass spectometry. The purpose of this study was to determine whether alpha-l-acetylmethadol is metabolized to methadone, which might explain in part the longer duration of action of alpha-l-acetylmethadol.

Thin-layer and gas chromatographic determination of ketamine and its biotransformed products in biological fluids.

Ketamine, (2-(o-chlorophenyl)-2-methylamine cyclohexanone) and its in vivo metabolite I (2-(o-chlorophenyl)-2-aminocyclohexanone) and metabolite II (2-(o-chlorophenyl)-2-amino-5-cyclohexene-1-one) were determined by thin-layer (TLC) and gas chromatography (GC). In vivo studies include intraperitoneal injection of ketamine in rats. Urine and blood samples were collected at regular intervals. The unreacted ketamine and its biotransformed products were extracted from urine and blood and subjected to TLC and GC analysis. 1% Carbowax-20M on Gas Chrom G-AW-DMCS and precoated LQ6D TLC plates were used in this study. In conclusion a rapid, simple, accurate, and sensitive thin-layer and gas chromatographic method for the identification of ketamine and its metabolites from biological fluids have been developed.

Rapid TLC determination of methadyl acetate and some in vitro metabolites.

Methadyl acetate was metabolized by microsomal preparations of rat liver to yield nor-methadyl acetate and 6-(dimethylamino)-4,4-diphenyl-3-heptanol. The identification and separation of these three compounds was established by TLC, using iodoplatinate spray as a visualizing agent.

A training program in bioanalytical toxicology.

Students of diversified backgrounds are taught methods used in bioanalytical toxicology such as TLC, GLC, RIA, EMIT, UV, and spectrofluorometry. Major emphasis is placed on the detection of abused drugs in biologic specimens. It was found that the students with more advanced formal education have learned the lecture theory and instrumentation quicker and in greater detail. However, as far as the ability to work rapidly and accurately, many of the trainees who have had less formal education have shown better ability. Perhaps it could be said that the theory is a science, whereas the work is an art. This art through practice can be better developed by some people regardless of education. On completion of this training, they will be able to help fill the great need for toxicologic technicians.