S.M.M. Karim

EFFECT OF 15(R)15 METHYLPROSTAGLANDIN E2 METHYL ESTER ON HEALING OF GASTRIC ULCERS: Controlled Endoscopic Study

Abstract 15(R)15 Methylprostaglandin E 2 methyl ester has been given orally in doses of 150 μg. 6-hourly to 10 Chinese subjects with proven gastric ulcer for 2 weeks. The control group consisted of 9 Chinese subjects with proven gastric ulcer without prostaglandin treatment. All were inpatients and were prescribed bed rest. Gastric-ulcer healing was assessed endoscopically with a duodenofiberscope. Endoscopic visualisation of the ulcer and colour photography of the ulcer crater were undertaken just before and 2 weeks after treatment. In the prostaglandin group complete healing was seen in 3 cases, considerable healing in 6 cases, and slight healing in 1 case. In the control group complete healing was seen in none, considerable healing in 2 cases, slight healing in 4 cases, and no healing in 3 cases. This difference was highly significant. There was no significant difference between the two groups in the severity of ulcer or in age and sex distribution. 15(R)15 Methyl P.G.E 2 methyl ester is highly effective in promoting the healing of gastric ulcers in Chinese subjects.

The effect of loperamide on prostaglandin induced diarrhoea in rat and man.

Loperamide, a new antidiarrhoeal compound, effectively antagonised prostaglandin induced diarrhoea in adult healthy male volunteers and in patients undergoing pregnancy termination with prostaglandins. This compound is effective in inhibiting prostaglandin induced fluid accumulation in the small intestine in rats. Loperamide also blocked smooth muscle stimulating action of prostaglandins, acetylcholine and histamine on gastrointestinal smooth muscle preparations from several laboratory animals.

Effect of prostaglandin 15 (R) 15 methyl-E2-methyl ester on the gastric mucosa in patients with peptic ulceration — An endoscopic and histological study

Abstract Endoscopic and Histological study of the locally administered prostaglandin 15 (R) 15 methyl-E 2 -methyl ester on the gastric mucosa in patients with peptic ulceration was carried out. The results show that the Prostaglandin analogue in a single oral dose of 150 μg possesses a powerful stimulant effect on the mucus-secreting cells of the gastric mucosa. The implications of these finding in the healing of gastric ulceration is discussed.

Termination of second trimester pregnancy with intramuscular administration of 16 phenoxy-ω-17,18,19,20 tetranor PGE2 methylsulfonylamide

A new prostaglandin analogue, 16 phenoxy-omega-17,18,19,20 tetranor PGE2 methylsulfonylamide was used for the termination of second trimester pregnancy in 60 patients. The drug was injected intramuscularly in doses of 0.5 mg 4 hourly, 1 mg 8 hourly or 1 mg 6 hourly for a maximum of 36 hours. Fifty five patients aborted. The incidence of gastrointestinal side effects was low and there were no complications.

F prostaglandin levels in amniotic fluid in premature labour

The concentration of prostaglandin F (PGF) in amniotic fluid was measured by radioimmunoassay in 27 patients admitted in premature labour. There was a strong correlation between PGF levels in amniotic fluid and both cervical dilatation (r = 0.81; P less than 0.001) and duration of labour (r = 0.79; P less than 0.001). Cervical dilatation greater than 7 cm was associated with levels exceeding 2000 pg/ml. When contractions were present for less than one hour, levels of PGF were below 50 pg/ml. Low levels of PGF were found in amniotic fluid from a separate group of three patients, of whom two had cervical incompetence. It is concluded that the onset of premature labour is not associated with elevated levels of PGF in amniotic fluid. During premature labour, concentrations rise to an extent comparable to that observed in labour at term.

Termination of second trimester pregnancy with laminaria and intramuscular 16 phenoxy-ω-17,18,19,20 tetranor PGE2 methylsuldonylamide (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 action of orally administered 16,16 dimethyl prostaglandin E2 and its methyl ester.

16, 16 dimethyl Prostaglandin E2 (Free acid and methyl ester) administered orally have a stimulant effect on the pregnant human uterus. Pregnancy was terminated in twelve out of twenty women by two hourly oral doses of 100μg of these analogues The relatively high incidence of gastrointestinal side effects — nausea, vomitting and diarrhoea — would tend to limit the usefulness of orally administered 16, 16 dimethyl PGE2 and its methyl ester as abortifacients.

Platelet and other effects of carboprostacyclin - A stable prostacyclin analogue

Carboprostacyclin, a chemically stable analogue of prostacyclin (PGI2) is 12.5 and 25.0 times respectively weaker than PGI2 in inhibiting ADP-induced aggregation of baboon and human platelets in vitro. Carboprostacyclin was also 28.5 times weaker as a vasodepressor than PGI2 in anaesthetised baboons. Intravenous and oral administration of carboprostacyclin in baboons resulted in ex-vivo inhibition of ADP-induced platelet aggregation at doses that did not produce changes in blood pressure or heart rate. Like PGI2, carboprostacyclin contracted guinea pig tracheal chain preparation in vitro but decreased histamine induced lung resistance in anaesthetised guinea pigs. Both PGI2 and carboprostacyclin relaxed the human respiratory tract smooth muscle in vitro.

Inhibition of platelet aggegation 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.

Intramuscular administration of 16 phenoxy ω 17,18,19, 20 tetranor PGE2 methyl sulfonylamide for pre-operative cervical dilatation in first trimester nulliparae

A single intramuscular dose of 500 microgram 16 phenoxy omega 17,18,19,20 tetranor PGE2 methyl sulfonylamide was used for cervical dilatation prior to vacuum aspiration in 80 first trimester nulliparae. Three hours after prostaglandin administration the cervix had dilated to 8 mm or more in 60 patients (75%). The uterus was evacuated in these patients without mechanical dilatation of the cervix. In the remaining 20 patients the cervix had dilated 4 to 7 mm. Further mechanical dilatation to 8 mm was carried out easily in most of these patients. Side effects included pain requiring analgesic (3 patients), vomiting (4 patients) and transient pyrexia (greater than 1 degrees C, 2 patients). There were no complications or damage to the uterus or the cervix during evacuation of the uterus.