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Biomedical subjects

I T Cameron

Publications and source records attributed to I T Cameron.

69 records · Page 4Linked to original sources

Prostaglandin-induced pregnancy termination: further studies using gemeprost (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries in the early second trimester.

The use of gemeprost (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries for the termination of pregnancy in the early second trimester has been further investigated. Of 113 women between 12 and 16 weeks gestation, 93 (82%) aborted within 24 hours of the administration of 4.4 +/- 0.1 1 mg gemeprost pessaries. The mean induction-abortion interval was 881 +/- 31 minutes. Successful abortion was achieved in 16 of the remaining 20 women after a second course of gemeprost pessaries without the need for oxytocin supplementation. There were no serious complications. Crampy abdominal pain and vaginal bleeding started after 275 and 756 minutes respectively. Twenty-two (19%) patients did not require pain relief during treatment, but 90 (80%) required parenteral opiates. Vomiting and diarrhoea occurred in 16 (14%) and 23 (20%) cases respectively. The safe induction of therapeutic abortion in 96% of women using vaginal prostaglandin alone offers an acceptable alternative to surgical evacuation in the early second trimester.

Abortifacient Agents↗

Endometrial prostaglandins in women with abnormal menstrual bleeding.

Endogenous prostaglandin (PG) concentrations (6oxo PGF1 alpha, PGE, PGF2 alpha) have been measured by radioimmunoassay in the endometrium of women with objectively assessed menstrual blood loss (MBL). The concentration of PGE and "total" PG (6oxo PGF1 alpha + PGE + PGF2 alpha) was greater in the endometrium of those women with heavy menses (median MBL 152 ml (range 86,432) n = 16) than in those individuals with a normal menstrual loss (MBL 59 ml (18,78) n = 18). The concentrations of PGE and PGF2 alpha were similar in each group, but the concentration of 6oxo PGF1 alpha was significantly less than that of both PGE and PGF2 alpha. In 19 individuals, specimens of endometrium were incubated for 1 and 2 hours in modified 199 medium to assess PG release. There was a direct correlation between endogenous PG content and the production of 6oxo PGF1 alpha, PGE, PGF2 alpha and "total" PG in the first hour, which persisted for the second hour with PGF2 alpha and "total" PG. Endometrial PGs may play a role in the mechanism underlying menstruation; however the observed relationship between the prostanoids and MBL will vary with different experimental methods.

6-Ketoprostaglandin F1 alpha↗

Local prostaglandin administration for mid trimester abortion: a retrospective analysis.

The hospital records of 548 consecutive patients undergoing midtrimester pregnancy termination by the local administration of prostaglandins (PGs) have been reviewed. Most women (352 or 64%) were single and 322 (59%) were pregnant for the 1st time. 2/3 of the patients (361 or 66%) were between 12-16 weeks pregnant, whereas 7 (1%) were considered to be more than 20 weeks pregnant. In 401 cases (92%), abortion was performed under Item 2 of the 1967 Abortion Act, although Item 4 was cited in 34 (81%) of those individuals with a pregnancy of greater than 17 weeks duration. Apart from 10 women (2%) in whom severe hemorrhage was documented, the major complication rate was less than 1%. The use of local PGs provides a safe, effective treatment method for therapeutic abortion in the 2nd trimester.

Abortion, Induced↗

Therapeutic abortion in early pregnancy with antiprogestogen RU486 alone or in combination with prostaglandin analogue (gemeprost).

Abortion was attempted in 39 women in early pregnancy (less than 56 days amenorrhea) with the progesterone antagonist RU486 alone (150 mg per day for 4 days) or in combination with a PG analogue, 16,16-dimethyl-trans-delta 2-PGE1 (Gemeprost) in the form of a 1 mg vaginal pessary. Complete abortion was also attempted in 5 women who received RU486 together with 2 X 1 mg PG pessaries. Vaginal bleeding followed by complete abortion occurred in 18 of 19 women who received RU486 + 1 mg PG pessary as compared to only 12 of 20 women who received RU486 alone (P less than 0.01). All women who received RU486 + 2 mg Gemeprost had a complete abortion. The onset of crampy abdominal pain (median: 3 vs 4 days) and vaginal bleeding (3 vs 3 days) was similar in the RU486 and RU486 + PG groups, respectively. Slightly less than half the patients in both groups had nausea and/or vomiting, but the incidence did not differ from that occurring prior to treatment. The mean duration (range) of vaginal bleeding [RU486 alone: 10 (0,29) days and RU486 + PG: (5,34) days], and the measured blood loss [RU486: 53 (2,227) ml and RU486 + PG: 81 (32,222) ml] did not differ significantly between the two treatments. It is concluded that the combination of RU486 and a single PG vaginal pessary is a highly effective means of inducing therapeutic abortion in early pregnancy and offers an alternative to surgery.

Abortifacient Agents↗

A controlled release form of 16,16-dimethyl-trans-delta 2-PGE, methyl ester for early abortion.

The termination of early pregnancy (less than 56 days amenorrhoea) has been investigated using 16,16-dimethyl-trans-delta 2-PGE, methyl ester in a controlled release preparation. The onset of crampy abdominal pain was seen after 270 +/- 39 minutes and bleeding occurred after 603 +/- 95 minutes. Two (15%) patients required no pain relief during treatment, however 5 (38%) requested oral analgesia, and in 6 (46%) individuals the pain was severe enough to warrant parenteral opiates. The overall success rate for complete abortion was 85%. No serious adverse effects were seen, but vomiting occurred in 2 (15%) women, and diarrhoea in 3 (23%). Although the use of this prostaglandin analogue in slow release form provides an effective treatment method for early abortion using a reduced total dose of prostaglandin, the acceptability of the drug as an agent for menstrual induction continues to be limited by the occurrence of troublesome gastro-intestinal side effects.

Abdomen↗

The stimulation of prostaglandin production by two antiprogesterone steroids in human endometrial cells.

Endometrial stromal cells and isolated endometrial glands obtained from women during days 6-26 of the ovarian cycle were cultured for 24 h in the presence of the progesterone antagonists 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]17 alpha-[1-propynyl] estra-4,9-dien-3-one (RU486) and 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl] 17 alpha-[3-hydroxy-1-propenyl]estra-4,9-dien-3-one (ZK 98734). Both steroids stimulated prostaglandin F2 alpha (PGF2 alpha) production by stromal cells in a dose-dependent manner, in doses ranging from 10-1000 nM. Progesterone (100 nM) inhibited RU486 stimulation, except at the highest dose of antiprogestin. PGE2 was produced in smaller amounts than PGF2 alpha, but, when measurable, it also increased in the presence of RU486. In contrast, RU486 did not increase PG production by endometrial glands. In an experiment to determine the effect of pretreatment, stromal cells were incubated for 24 h with 1000 nM progesterone or RU486 (all with 100 nM 17 beta-estradiol) with either 30 or 6 microM arachidonic acid. These six batches of cells were incubated for a second 24 h with either progesterone or antiprogestin. Cells pretreated with the higher dose of arachidonic acid had a marked increase in PGF2 alpha production during the second 24 h only when also pretreated with progesterone. This finding suggests that progesterone allows an accumulation of PG precursor in a suitable accessible pool. Pretreatment with progesterone also allowed a greater conversion of PG to its 13,14-dihydro-15-keto metabolite. These results suggest that antiprogesterone steroids may act as menstrual regulators by: stimulating endogenous PG production within the endometrial stromal cells and inhibiting PG catabolism.

Dinoprost↗

Menstrual induction: surgery versus prostaglandins.

In most developed countries in which therapeutic abortions are legal, termination of pregnancy is performed at between 8 and 12 weeks of gestation. Because the complication rate after this procedure rises with increasing gestation, there would be many advantages in inducing abortion before the eighth week ('menstrual induction'). With the increasing availability of highly sensitive methods of detecting human chorionic gonadotropin, pregnancy can now be diagnosed as early as 10-14 days after conception. The uterus can be surgically evacuated safely and simply by suction aspiration under local anaesthesia. However, a safe and effective method of inducing abortion by medical means would be a useful and cheaper alternative. Of the potentially useful compounds, only derivatives of prostaglandins E and F administered by vaginal pessary have so far been shown to be effective. Although the rate of haemorrhage and infection is low, 10-30% of women experience moderate side-effects of pelvic pain, diarrhoea and/or vomiting. The possibilities are discussed of reducing the incidence of side-effects by different methods of release or using prostaglandins in combination with other compounds such as antigestogens which might lower the therapeutic threshold.

Abortion, Induced↗

Prostaglandins in the human uterus: an interaction between endometrium and myometrium.

The interaction between the prostaglandin production of the human endometrium and myometrium has been further investigated using intact pieces of endometrium in homogenates of myometrium. There was an increase in the production of 6 oxo PGF, alpha when these tissues were incubated together, whereas there was no change in the production of PGE, PGF2 alpha or 13, 14 dihydro 15 - keto PGF2 alpha. This endometrial - myometrial interaction could have important implications in the pathogenesis of menorrhagia.

6-Ketoprostaglandin F1 alpha↗

X-Y translocation. A case report.

A translocation of genetic material involving the long arm of the X chromosome and the heterochromatic portion of the Y chromosome is reported in a young woman. The phenotypic effect of this translocation and loss of almost half of the long arm of the X chromosome is described.

Adolescent↗

The use of 16,16-dimethyl-trans delta 2 prostaglandin E1 methyl ester (gemeprost) vaginal pessaries for the termination of pregnancy in the early second trimester. A comparison with extra-amniotic prostaglandin E2.

The use of gemeprost pessaries has been compared in an open randomized trial with the extra-amniotic infusion of prostaglandin E2 (PGE2) for the termination of pregnancy between 12 and 16 weeks gestation. The success rates were 77% and 79% for the pessary and infusion group respectively, and these rates were unaffected by parity. There was no significant difference in the cumulative abortion rate between the two groups, nor were there differences in the induction-abortion interval, nor in the time taken to the onset of pain or bleeding. However, women in the pessary group required significantly less analgesia than those in the infusion group. Side-effects, experienced both during treatment and during the 6 weeks after abortion, were similar in both groups. Gemeprost vaginal pessaries are an effective alternative to the extra-amniotic infusion of PGE2 for the termination of pregnancy in the early second trimester.

Abortion, Induced↗

Differential distribution of endothelin receptor subtypes in placentae from normal and growth-restricted pregnancies.

The endothelins (ETs) are potent vasoconstrictor peptides that bind to two distinct receptors, ETA and ETB. This study compares the localization of ETA and ETB receptors in placentae complicated by intrauterine growth retardation (IUGR) and abnormal umbilical Doppler waveform, gestationally matched controls, fetuses that were small for gestational age (SGA), and normal term placentae. Quantitative autoradiography was performed using ETA and ETB subtype-selective ligands. Both ETA and ETB receptors were expressed in the human placenta. Gestational and fetal size effects on the receptor density within stem villi were found, but no effect of abnormal placental blood flow could be demonstrated. A distinct spatial distribution of receptor subtypes within the placenta was observed. Smooth muscle cells expressed both receptors with ETA expression predominant in the proximal regions of the villous tree and ETB abundant in the periphery and decidua. Both receptors were also expressed at lower density on paravascular stromal cells in stem villi. Although these data do not demonstrate aberrant localization of ET receptors in IUGR and SGA placentae, the spatially distinct distribution of ET receptors in the human placenta suggests that ETs play a role in modulation of placental blood flow.

Adult↗

Nitric oxide in the endometrium.

Nitric oxide (NO) is an important mediator of paracrine interactions, especially within the vascular system. It is a powerful inhibitor of platelet aggregation and a potent vasodilator. NO is also a neurotransmitter and it plays a role in cell-mediated cytotoxicity. NO-generating enzymes (nitric oxide synthases, NOS) have been described in the endometrium of a number of species, suggesting that NO might be involved in endometrial function. In human endometrium, endothelial NOS and inducible NOS have been localized to glandular epithelium in the non-pregnant uterus. Weak inducible NOS immunoreactivity has been observed in decidualized stromal cells. NO might participate in the initiation and control of menstrual bleeding. Furthermore, it may play a part in the inhibition of platelet aggregation within the endometrium, where menstrual haemostasis is thought to occur primarily by vasoconstriction rather than clot organization. Endometrially derived NO could also suppress myometrial contractility. Recent attention has focused on the part that NO might play in maintaining myometrial quiescence during pregnancy. NO also appears to relax the non-pregnant myometrium, an action which could be exploited for the medical treatment of primary dysmenorrhoea.

Animals↗