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Biomedical subjects

S M Karim

Publications and source records attributed to S M Karim.

At least 37 records · Page 2Linked to original sources
PubMed1983

Control of gonadotrophin secretion by steroid hormones in male castrates: site of oestradiol action.

Four normal healthy castrated male transsexuals who were not on hormone therapy for at least 4 months volunteered for this study. Each subject received 3 infusions at weekly intervals--the first consisting of LHRH alone, the second of LHRH and oestradiol and the third of oestradiol alone. Venous blood samples were collected at 20-minute intervals 1 hour before the start and during the whole period of infusion. Plasma concentrations of FSH, LH and oestradiol were measured by radio-immunoassay. On an average, 100 micrograms of LHRH enhanced the area under the LH secretion curve by 177% and under the FSH curve by 68%. Oestradiol had a differential effect on the endogenous secretion of LH and FSH, suppressing them by 53% and 18%, respectively. Similarly, the LHRH-stimulated release of LH was significantly inhibited to a greater extent (42%) than that of FSH (23%, P less than 0.05; paired t test). Such an observation and in the light of our acceptance of the single releasing hormone theory, suggests that the differential actions of oestradiol on the secretions of FSH and LH are due to mechanisms residing in the pituitary.

Castration↗
PubMed1983

Evidence for cleavage of [26-14C]cholesterol side-chain by human foetal membranes in vitro.

With a view to establish the hitherto undescribed role of cholesterol in foetal-membranous steroidogenesis, homogenates of term chorion pars reflexa and amnion pars reflexa and pars placentaris collected from 6 women after spontaneous labour at term (38 to 41 weeks gestation) were incubated with [26-14C]cholesterol. Using reverse-isotope dilution analysis, [14C]isocaproic acid was isolated and characterized. This conversion constitutes strong evidence that C-20, 22-desmolase activity, normally present in the adrenal, gonadal and placental tissues, is present in the homogenates of both membranes. The efficiency of the enzymic conversion suggests that the chorion possesses a more active desmolase system compared to that of the amnion.

Adult↗
PubMed1982

Termination of second trimester pregnancy with laminaria and intramuscular 16 phenoxy-omega-17, 18, 19, 20 tetranor PGE2 methylsulfonylamide (sulprostone)-A randomised study.

16 phenoxy-omega-17, 18, 19, 20 tetranor PGE2 methylsulfonylamide (Sulprostone) was used for termination of second trimester pregnancy in four groups of 30 patients. The drug was administered in intramuscular doses of either 0.5 mg four hourly or 1.0 mg 8 hourly. In two groups of 30 patients a medium size sterile laminaria was inserted into the cervical canal eight hours before the start of prostaglandin treatment. In the group treated with 1.0 mg sulprostone eight hourly, 96.7% of those with laminaria and 86.7% without laminaria aborted in respective mean times of 11.2 hrs and 17.5 hrs. All 30 patients (100%) in the laminaria group treated with 0.5 mg sulprostone four hourly aborted within 30 hours in a mean time of 10.4 hours compared with 26 patients (86.7%) in a mean time of 16.7 hours in the group without laminaria. One patient receiving 0.5 mg sulprostone four hourly (no laminaria) sustained a cervical tear requiring repair. The incidence of nausea, vomiting, diarrhoea, cold and shivering was low an similar in the four groups.

Abortifacient Agents↗
PubMed1982

Reversal of vasopressin-induced coronary vasoconstriction by a PGE1 analogue (ONO 1206) in primates.

17 (S)methyl-omega-homo trans delta 2 PGE1 (ONO 1206) an analogue of PGE1 was studied on vasopressin-induced ECG changes in four male monkeys and three female baboons. Bolus intravenous doses of vasopressin (0.8 I.U. to 1.0 I.U./kg) produced flattening of the T wave (2 monkeys) elevation of ST segment (1 baboon and 1 monkey) and inversion of T wave (1 baboon). Inverted T waves were also present in one baboon and one monkey prior to any drug administration. In four out of seven animals, boLus intravenous doses (5 to 15 micrograms/kg) of ONO 1206 reversed the ECG changes produced by vasopressin and in one animal ONO 1206 reversed the existing inverted T wave. These findings indicate that vasopressin is a suitable agent for the induction of coronary vasoconstriction in primates and that ONO 1206 is able to reverse this effect.

Alprostadil↗
PubMed1982

pH dependent inhibition of serum oxytocinase activity by prostaglandins and cyclic GMP.

The effect of pH in the range 6.2 to 7.7 on the inhibition of serum oxytocinase (EC 3.4.11.3) activity by various compounds was studied using S-benzyl-L-cysteine-p-nitroanilide (BCN) as substrate. Prostaglandins E1, E2, F2 alpha, 8-bromo-cGMP, cGMP, indomethacin and polyphloretin phosphate (PPP) produced a dose related pH dependent inhibition of serum oxytocinase. Their effect was maximum at pH 6.2 and minimum at pH 7.7. Hypertonic urea and saline also caused pH dependent inhibition; saline being most active at pH 6.2, and urea at pH 7.7. A similar pH dependent inhibition was found when these compounds were examined for their effect on the hydrolysis of L-leucine-p-nitroanilide (LN) by serum aminopeptidases at pH between 6.2 and 7.7. Although the inhibitors were more effective against the hydrolysis of LN than BCN substrate, cGMP and its 8-bromo derivative were more active against the BCN hydrolysis. cAMP, 8-bromo-cAMP, dibutyryl (db)-cAMP, db-cGMP, AMP, ADP, ATP, GDP, GTP, aspirin, sodium salicylate, paracetamol, theophylline and isobutylmethylxanthine (IBMX) at comparable concentrations and within the same pH range had no effect on the hydrolysis of either substrate. It is concluded that in serum obtained during pregnancy, the hydrolysis of LN may largely be attributed to oxytocinase activity. Thus, inhibition of LN hydrolysis by prostaglandins and other substances may be regarded as inhibition of oxytocinase activity.

Aminopeptidases↗
PubMed1982

Inhibition of platelet aggregation and reversal of vasopressin-induced ECG changes by a carboprostacyclin analogue, ONO 41483, in primates.

15-cyclopentyl-omega-pentanor-5(E)-carbacyclin (ONO 41483), a chemically stable carboprostacyclin analogue, was 3.3 times less active than prostacyclin but was 2.6 times more active than carboprostacyclin in inhibiting aggregation of ADP-induced baboon platelet in vitro. On human platelets in vitro, ONO 41483 was 9.4 times less active than prostacyclin and 12.7 times more active than carboprostacyclin. ONO 41483 was 3.7 times less active than prostacyclin but was 2.2 times more active than carboprostacyclin in producing a fall in arterial blood pressure in anaesthetised baboons. Intravenous and oral administration of ONO 41483 in baboons produced ex vivo inhibition of ADP-induced platelet aggregation at doses that did not affect blood pressure or heart rate. In addition, bolus intravenous doses (3 to 10 micrograms/kg) of ONO 41483 reversed vasopressin-induced ECG changes in the monkey, suggesting an ability of the compound to relieve coronary spasm.

Adenosine Diphosphate↗
PubMed1982

Elevated intravesicular fluid luteinizing hormone concentration in hydatidiform mole.

Concentrations of human chorionic gonadotrophin (beta-hCG), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) were measured by radioimmunoassay in the serious fluid of hydatid vesicles obtained from 27 patients with hydatidiform mole. High amounts of all four hormones were found in every case. The mean concentrations +/- SEM were 710.8 +/- 100.8 i.u./1 X 10(-3) for beta-hCG, 13.8 +/- 0.3 i.u./1 for FSH, 302.2 +/- 34.5 i.u./1 X 10(-3) for LH and 2610.8 +/- 562.1 m-i.u./1 for PRL. It is suggested that aberrations in the mechanisms controlling the synthesis and release of luteinizing hormone-releasing factor (LH-RF) could result in chronically elevated LH levels leading to changes characteristic of the disease.

Adolescent↗
PubMed1982

Clinical applications of prostaglandins in Obstetrics and Gynaecology.

Although a number of potential practical uses of prostaglandins have been identified, these compounds have so far found clinical applications mainly in Obstetrics and Gynaecology. It is almost 15 years since a prostaglandin was first used for the induction of term labour and prostaglandin E2 is now commercially available for this purpose in many countries. For the termination of second trimester pregnancy, prostaglandins have almost completely replaced other methods previously in use. Other areas where prostaglandins are routinely used or where their uses are being developed, include menstrual induction, preevacuation dilatation of the cervix in the first trimester, termination of pregnancy in cases of missed abortion, intrauterine fetal death and other types of abnormal pregnancies, control of post-partum haemorrhage, treatment of post-partum or post surgical urine retention and ripening of the cervix prior to induction of labour at term. In early studies, prostaglandins E2 and F2 alpha were used for all the applications listed above. In order to increase efficacy and reduce side effects, a number of synthetic analogues were later evaluated for application in selected areas. Those with modification in the 15 and 16 positions of PGE2 and PGF2 alpha molecules have undergone extensive clinical trials and some of these analogues are now in routine use. The current status of the practical applications of prostaglandins in Obstetrics and Gynaecology is reviewed.

Abortifacient Agents↗
PubMed1982

Cigarette smoke-induced cholesterol C-20, 22-desmolase inhibition in pregnancy.

In an attempt to demonstrate the physiological importance of cholesterol C-20, 22-desmolase regulation of pregnenolone formation in maternal cigarette smoking during pregnancy, the in vitro effect of cigarette smoke extract on corpus luteal and placental desmolase ability to cleave (26-14C) cholesterol to (14C) isocaproic acid, was studied. Using the reverse-isotope dilution technique, (14C) isocaproic acid was isolated and characterized. With the homogenates of corpora lutea of pregnancy (4 to 9 weeks gestation) the maximal inhibitory effect (98.3%) on desmolase efficiency became evident at equivalent of 4 cigarettes. In response to concentrations of the extract at 1/2, 1, 2 and 4 cigarette equivalents on the preparations of placentae (18 to 20 weeks gestation), a dose-dependent pattern of inhibitory effect was observed (29.1 to greater than 95.1%). These results are consistent with the interpretation that decreased supply of pregnenolone for the biosynthesis of progestational and oestrogenic hormones may be causally related to changes characteristic of cigarette-smoke induced pathologic state. It is suggested that similar studies directed towards alteration in biosynthetic capacity of steroidogenic enzymes may provide the basis for our understanding of molecular events initiated in response to the common insult.

Adult↗
PubMed1982

Research and development in obstetrics & gynaecology in the Department of Obstetrics & Gynaecology at the National University of Singapore.

This is a review of the research and achievements of the Department of Obstetrics and Gynaecology, National University of Singapore since 1949. The research activities reviewed are Fertility Control, Subfertility, Reproductive Endocrinology, In-Vitro Fertilization, Trophoblastic Disease, Prostaglandins and Perinatal Medicine. The University Department has kept abreast with the Singapore norm of two-child families by providing the most sophisticated technology and expertise. The perinatal mortality and stillbirth rates have been reduced to 11 and 6 per thousand births. Prostaglandin research in the Department includes an investigation of the involvement of these substances in various physiological processes, pharmacological studies with different prostaglandins and development of clinical applications. Between 1974 and 1981 we had studied 12 intrauterine contraceptive devices, both on a departmental basis and in conjunction with international agencies. The newer medicated devices have proved to offer significant advantages over the original inert plastic configuration. Metabolic changes in Singapore women on the oral pill and injection Depoprovera were studied. Impaired glucose tolerance and raised fasting total lipids were found in women on the pill. Marginal changes in carbohydrate metabolism only were found in women on injection Depoprovera. Hypercoagulation changes in the blood occurring in Singapore women varied with the dose of the synthetic or natural oestrogen medication. Initially, the fibrinolytic activity was enough to compensate for these changes; however after two years there were signs of decompensation. Progestogens affect coagulation via their influence on the liver functions. Hypercoagulation changes also occurred in pregnancy and was of a greater magnitude than oestrogen or progestogen medication. In many obstetric disorders, including hydatidiform mole, there was evidence of intravascular coagulation. The introduction of endocrine function tests has greatly improved patient care in our Department, in particular those related to endocrine disorders. Application of the immunoassays to basic research has shown that physiological levels of oestradiol exert a negative feedback effect on both FSH and LH secretions in men. The greater suppression of LH than of FSH secretion by pharmacological doses of estradiol is possibly due to different control mechanisms in the pituitary for the synthesis and release of both gonadotrophins. Physiological level of testosterone per se has a definite negative feedback effect on the secretion of LH but not on FSH. Pharmacological doses of the 5-alpha-reduced metabolites of testosterone have been shown to suppress both LH and FSH indicating that some of the actions of testosterone could be medicated by these metabolites of which the 3 alpha-androstanediol and 3 beta-androstanediol are the more likely candidates.

Academic Medical Centers↗
PubMed1982

Induction of labour with prostaglandin E2 and amniotomy--a multicentre, three dose schedule study in 1533 patients.

Prostaglandin E2 administered orally and combined with amniotomy was used for induction of labour at or near term in 1533 patients. The study was carried out as a collaborative project between the University Departments of Obstetrics and Gynaecology in Singapore, Medan (Indonesia) and Kuala Lumpur (Malaysia). The overall success rates for Medan, Kuala Lumpur and Singapore were 95.6%, 88.1% and 84.7% respectively.

Drug Administration Schedule↗
PubMed1982

Termination of pregnancy in cases of intrauterine fetal death, missed abortion, molar and anencephalic pregnancy with intramuscular administration of 2a 2b dihomo 15(S) 15 methyl PGF2 alpha methyl ester--a multicentre study.

2a 2b dihomo 15(S) 15 methyl PGF2 alpha methyl ester (dihomo 15 me PGF2 alpha) in intramuscular doses of 0.5 mg 8 hourly was used in 631 patients with abnormal intrauterine pregnancy comprising 282 cases of intrauterine fetal death, 233 cases of missed abortion, 34 and 82 cases respectively anencephalic and molar pregnancies. The study was carried out as a collaborative project between the University Departments of Obstetrics and Gynaecology in Singapore (Singapore), Medan (Indonesia) and Kuala Lumpur (Malaysia) during the period June 1974 and November 1979. Six hundred patients (95.1%) aborted or delivered in a mean time of 11.3 hours (S.D. +/- 7.0) with an average of 1.8 injections of the prostaglandin analogue per patient. Side effects included vomiting (23.6%; mean 0.45 episodes per patient), diarrhoea (44.4%; mean 1.00 episode per patient), cold and shivering (11.9%) and pyrexia (12.4%). One patient sustained a cervical laceration which did not require repair. There were no complications.

Abortion, Missed↗
PubMed1982

Hydatidiform mole in Singapore.

A five year retrospective analysis of 198 cases of hydatidiform mole recorded in three maternity hospitals in Singapore is presented. The incidence was 1 in 868 deliveries. The number of molar pregnancies in the first half of the year was higher than in the subsequent six months. The incidence of hydatidiform mole and its correlation with possible environmental factors is discussed.

Communicable Diseases↗
PubMed1981

Some pharmacological effects of 17(S) methyl-omega-homo-trans-delta2-PGE1 (ONO 1206).

17(s) methyl-omega-homo-trans-delta2-PGE1 (ONO 1206) produced qualitatively similar effects to PGE1 in several systems. It was 18.4 and 25.6 times respectively more potent than PGE1 in inhibiting ADP-induced baboon and human platelet aggregation in vitro. Intravenous infusion of ONO 1206 in baboon also produced ex-vivo inhibition of ADP-induced platelet aggregation. However, this was accompanied by a significant fall in blood pressure and an increase in heart rate. The potent relaxant effect of ONO 1206 on human respiratory tract smooth muscle in vitro suggests that this compound may be a bronchodilator in man.

Alprostadil↗
PubMed1981

Inhibition of platelet aggregation with intravenous and oral administration of carboprostacyclin in man.

Intravenous infusion of carboprostacyclin, a chemically stable analogue of prostacyclin (PGI2) resulted in ex-vivo inhibition of ADP-induced platelet aggregation at doses that did not produce significant changes in blood pressure or heart rate. Oral administration of relatively large doses of this compound also inhibited ex-vivo ADP-induced platelet aggregation but this was accompanied by headache, facial flush, tachycardia and changes in blood pressure.

Adenosine Diphosphate↗