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Biomedical subjects

M D Mitchell

Publications and source records attributed to M D Mitchell.

At least 325 records · Page 18Linked to original sources

Melatonin in the maternal and umbilical circulations during human parturition.

The concentration of melatonin in maternal peripheral plasma was measured during late pregnancy, term and pre-term labour. There was a small increase in the mean concentration of melatonin during labour which was significant in term labour. Umbilical arterial and venous plasma, whether obtained at term, after spontaneous vaginal delivery or at Caesarean section, contained significantly greater concentrations of melatonin than maternal plasma. A significant arterio-venous difference was demonstrated for both groups of umbilical samples with raised venous levels after spontaneous vaginal delivery but higher arterial levels at Caesarean section.

Cesarean Section↗

Prostaglandins in umbilical plasma at elective caesarean section.

Prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-ketoprostaglandin F (PGFM) have been measured in umbilical cord plasma obtained immediately after delivery by elective Caesarean section. Umbilical venous plasma levels of PGE were significantly greater than the corresponding arterial levels (p less than 0.02); there were no significant arterio-venous differences for PGF or PGFM. In general, concentrations of PGFM exceeded those of PGE which in turn were greater than concentrations of PGF. Umbilical venous levels of PGE and both arterial and venous levels of PGF and PGFM were significantly greater after spontaneous labour with vaginal delivery than after elective Caesarean section.

Cesarean Section↗

Persistent pulmonary hypertension and abnormal prostaglandin E levels in preterm infants after maternal treatment with naproxen.

Twins and a singleton were born at 30 weeks' gestation although naproxen (d-2 (6'methoxy-2-naphthyl) propionic acid) had been given to the mothers in an attempt to delay parturition. Inhibition of prostaglandin synthesis was shown by very low plasma concentrations of prostaglandin E and the ductus arteriosus remained closed despite signs of pulmonary hypertension with severe hypoxaemia. Abnormalities in blood clotting, renal function, and bilirubin metabolism were also found and one infant died. Further studies of the benefits and risks of the inhibition of prostaglandin synthesis are required before this treatment of preterm labour is accepted.

Adult↗

Orogranulocyte peroxidase activity as a measure of inflammatory periodontal disease.

Benzidine dihydrochloride in the presence of dimethylsulfoxide reacts with myeloperoxidase contained within the granules of polymorphonuclear leukocytes obtained from the oral cavity. A blue meriquinoid oxidation product is formed in the presence of hydrogen peroxide, which can be extracted from the granules with a combination of methyl alcohol and dimethylsulfoxide. A stable yellow-brown pigment is formed which can be measured spectrophotometrically. The values are expressed in optical density units and correlate with the Orogranulocytic Migratory Rate units obtained by other means. Consequently, the spectrophotometric method is an additional non-subjective technique available for the evaluation, monitoring, and indexing the inflammatory periodontal disease.

Adolescent↗

Thromboxane B-2 in the plasma and amniotic fluid of late pregnant and periparturient sheep.

The concentration of thromboxane (TX) B-2 was similar in plasma from all sources but was significantly greater (P less than 0.01) in amniotic fluid. Fetal hypophysectomy was without effect on maternal or fetal levels of TXB-2 (P greater than 0.1). Neither normal parturition at term nor prematurely induced delivery was associated with any significant trend in TXB-2 levels. During late pregnancy (105--145 days of gestation) the concentrations of TXB-2 and 13, 14-dihydro-15-keto-prostaglandin F (PGFM) in maternal and fetal plasma were significantly correlated (P less than 0.001). There was, however, no correlation between TXB-2 and PGFM levels in samples taken during the 36 h before delivery. These data suggest that thromboxanes play little part in the mechanism of parturition in sheep.

Amniotic Fluid↗

Intra-uterine tissues from late-pregnant rhesus monkeys (Macaca mulatta) produce 6-oxo-prostaglandin F1 alpha in vitro.

The rates of production of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) in vitro by intra-uterine tissues taken from late-pregnant monkeys at Caesarean section have been determined. For tissues obtained between days 140 and 149 of pregnancy (late pregnancy) the general quantitative order of rates of production (per unit weight) was decidua basalis greater than placenta greater than decidua parietalis greater than amnion greater than chorion = myometrium. When tissues were taken between days 160 and 168 of pregnancy (near term) this order was placenta greater than decidua parietalis = amnion greater than myometrium = decidua basalis greater than chorion. There was a significant reduction near term in the rate of production of 6-oxo-PGF1 alpha by decidua basalis; all other tissues exhibited similar rates of production at the two gestational periods investigated.

Amnion↗

Prostaglandin E, thromboxane B2 and 6-oxo-prostaglandin F1 alpha in amniotic fluid and maternal plasma of rhesus monkeys (Macaca mulatta) during the latter third of gestation.

The concentrations of prostaglandin E (PGE), thromboxane B2 (TXB2) and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) were measured by radioimmunoassay in serial samples of amniotic fluid and maternal peripheral plasma in the latter third of pregnancy in rhesus monkeys (Macaca mulatta). The samples were collected under ketamine-induced anaesthesia. The concentration of PGE was undetectable in amniotic fluid until a few days before delivery when a large increase was observed in three of the five animals. There were small increases of TXB2 and 6-oxo-PGF1 alpha in amniotic fluid before delivery. In maternal plasma the concentrations of PGE, TXB2 and 6-oxo-PGF1 alpha were generally higher and more variable than in amniotic fluid and did not increase with advancing gestation. It is suggested that increased production of primary prostaglandins occurs before, and is involved in, the onset of parturition in the rhesus monkey.

Amniotic Fluid↗

Concentrations of 6-oxo-prostaglandin F 1 alpha in the maternal and foetal plasma of sheep during spontaneous and induced parturition.

The concentrations of 6-oxo-prostaglandin F 1 alpha (6-oxo-PGF 1 alpha) have been determined in maternal and foetal plasma from nine chronically catheterized sheep during late pregnancy and parturition. Labour occurred either spontaneously (three sheep) or was induced by continous intrafoetal infusion of Synacthen (ACTH 1-24; 0.24 mg/24 h; three sheep) or dexamethasone (1 mg/24 h; three sheep). During spontaneous and Synacthen-induced parturition, concentrations of 6-oxo-PGF 1 alpha in maternal and foetal plasma remained at basal levels until 24 h before delivery. At varying times during the 24 h before delivery, levels of 6-oxo-PGF 1 alpha in maternal and foetal plasma were generally increased. When parturition was induced with dexamethasone, however, no increase was observed in the foetal plasma although the concentration of 6-oxo-PGF 1 alpha in maternal plasma was raised close to delivery.

Animals↗

Bartter's syndrome: 10 cases in childhood. Results of long-term indomethacin therapy.

Ten children with Bartter's syndrome are described. Their ages at diagnosis ranged from three months to 15 years and there was an equal sex distribution. A wide spectrum of severity of clinical and biochemical features was found. Hypercalcaemia, hypophosphataemia, hypercalcuria, nephrocalcinosis, rickets and urine acidification defects were seen in some patients. Two affected children were siblings. Six children were treated over periods of six to 24 months with indomethacin with remarkable clinical and biochemical improvement. Catch-up growth was demonstrated in all treated cases. Tolerance to indomethacin appeared to develop in some children. Only one serious complication was seen with this therapy, a duodenal ulcer in a child on high dosage. Of those children not treated with indomethacin, one died, one is now on indomethacin elsewhere and two are well without therapy.

Adolescent↗

Prostaglandins in maternal and fetal plasma and in allantoic fluid during the second half of gestation in the mare.

The concentrations of the primary prostaglandins (PG) F-2alpha and E-2 and the metabolite 13,14-dihydro-15-oxo-prostaglandin (PGFM) in maternal and fetal plasma and in allantoic fluid were measured in chronically catheterized mares and fetuses. A gradual rise in all 3 PGs occurred with increasing gestational age. PGE-2 and PGF-2 alpha levels were highest in the allantoic fluid and lowest in the maternal plasma, whereas PGFM concentrations were greatest in maternal plasma. Significant venous-arterial plasma differences in PGFM concentration were detected across the uterine circulation between 180 and 280 days gestation. The 3--5-fold rise in maternal PGFM associated with fasting or intrauterine surgery was virtually abolished by meclofenamic acid, a prostaglandin synthetase inhibitor. Increases in PGE-2 and PGF-2 alpha in the fetal fluids preceded premature delivery of the foal, while PG changes in maternal plasma were minimal even 10--20 h before delivery.

Allantois↗

Plasma-prostaglandins in pre-term neonates before and after treatment for patient ductus arteriosus.

9 pre-term babies with patent ductus arteriosus (P.D.A.) and cardiac failure were found to have significantly higher plasma-levels of three prostaglandins (P.G.E, P.G.F, and P.G.FM) than a group of normal pre-term infants of the same age. There was no difference in the plasma-prostaglandin levels before and after surgery in the 5 infants who underwent ligation of the ductus, suggesting that the high P.G. levels are not the result of a patent ductus, but that P.G.S may have a role in the pathogenesis of P.D.A. 3 infants who were treated by indomethacin (a P.G. synthetase inhibitor) showed a sharp initial drop in plasma-levels of the three P.G.S, but levels of P.G.F and P.G.FM had risen either during or within 48 h of completion of the course of indomethacin. These results may explain why high failure-rates have been reported for treatment of P.D.A. by indomethacin.

Ductus Arteriosus, Patent↗

Comparison of intrauterine prostaglandin metabolism during pregnancy in man, sheep and guinea pig.

Metabolism of prostaglandin F2 alpha (PGF2 alpha) was studied in uterine tissues from pregnant women (n = 10), sheep (n = 6) and guinea pigs (n = 6). Two maternal tissues, myometrium and decidua or maternal placenta, and two fetal tissues, fetal placenta and membranes, were studied in each species. PGF2 alpha was metabolized via the well-known pathway into 15-keto-PGF2 alpha and 13,14-dihydro-15-keto-PGF2 alpha, while 13,14-dihydro-PGF2 alpha was tentatively identified in some tissues. The presence of 15-hydroxyprostaglandin dehydrogenase (PGDH) and 13,14-prostaglandin reductase was demonstrated in all tissues from each of the three species studied, but the quantitative intrauterine distribution of these enzymes differed from one species to another. In man, PGDH activities were highest in fetal membranes followed by fetal placenta and then by decidua and myometrium. In sheep, PGDH activities were highest in the maternal placenta followed in decreasing order by myometrium, fetal placenta and membranes. In the guinea pig, PGDH activity was highest in the fetal membranes followed in decreasing order by maternal placenta, fetal placenta and myometrium. Quantitative assay of PGDH showed that PGDH activity in the pregnant uterus is higher in women than in sheep and guinea pig. The results are discussed in relation to the involvement of prostaglandins in parturition.

Animals↗

Plasma prostaglandin levels during early neonatal life following term and pre-term delivery.

The concentrations of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-oxo-PGF (PGFM) have been measured by sensitive and specific radioimmunoassays in neonatal plasma after term and pre-term delivery. Blood samples were taken in the term delivery group from the umbilical artery at birth and on the sixth post-natal day and after pre-term delivery at 2-4 days, on the sixth day, at 2-4 weeks and at 5-8 weeks after birth. The levels of prostaglandins circulating during the first month of life were far greater than those found in normal adults. In neonates delivered at term the plasma concentration of PGE was significantly lower six days after delivery compared with the concentration at delivery whereas the concentrations of PGF and PGFM were essentially unchanged. Following pre-term delivery prostaglandin concentrations declined with increasing neonatal age although only levels of PGE at 5-8 weeks of age were within the normal range of adult values. Comparison of prostaglandin levels six days after delivery between neonates born at term and pre-term showed no significant differences. These results suggest that prematurity per se is not associated with marked abnormalities in the ability of the neonate to synthesize or metabolize prostaglandins.

Age Factors↗

Possible role for prostacyclin in human parturition.

Human amnion, chorion, decidua and placenta produced 6-oxo-PGF1alpha when superfused in vitro. Furthermore amnion, an avascular tissue, produced more 6-oxo-PGF1alpha after labour than all other tissues investigated and its production of 6-oxo-PGF1alpha was significantly greater after labour than before the onset of labour. These findings suggest that prostacyclin production by foetal membranes may have a role in the mechanisms controlling human parturition. Moreover, this is the first evidence for the production of prostacyclin by an avascular tissue.

Epoprostenol↗