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Biomedical subjects

R W Kelly

Publications and source records attributed to R W Kelly.

At least 145 records · Page 8Linked to original sources
PubMed1983

Metabolism of prostaglandins by the nonpregnant human uterus.

We investigated the ability of the nonpregnant human uterus to metabolize prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) using radiolabeled substrates together with gas chromatography-mass spectrometry for the measurement of specific metabolites. Both the 15-hydroxyprostaglandin dehydrogenase and the delta 13-reductase enzymes are present in endometrium and myometrium. As shown for other tissues, the dehydrogenase is NAD+ dependent, while the delta 13-reductase requires NADPH as cofactor. PGE2 was the preferred substrate in both tissues; however, the metabolizing capacity of follicular phase myometrium was comparable with that of midluteal phase endometrium. The Km values of the dehydrogenase for PGE2 and PGF2 alpha were similar in both endometrium (1.89 X 10(-6) and 18.52 X 10(-6) mol/liter, respectively) and myometrium (2.76 X 10(-6) and 11.64 X 10(-6) mol/liter, respectively), suggesting that the same enzyme is present in both tissues although the regulation of this enzyme may differ in endometrium and myometrium.

15-Oxoprostaglandin 13-Reductase↗
PubMed1983

Levels of circulating and urinary oestrogens during pregnancy in the marmoset monkey (Callithrix jacchus).

The levels of immunoreactive oestrone, oestradiol-17 beta and oestriol in plasma and urine were measured during early, mid- and late pregnancy in the marmoset monkey. In plasma, unconjugated oestrone remained less than 2% of total (conjugated plus unconjugated) oestrone throughout gestation, whereas unconjugated oestradiol-17 beta increased from 3% of the total value in early and mid-pregnancy to 35% in late pregnancy. The reversal in the unconjugated oestrone: oestradiol-17 beta concentration ratio from early (12:1) to late (0 . 15:1) pregnancy occurred despite the continuing predominance of oestrone in terms of total hormone. Total oestriol was measurable but in relatively low concentrations. Oestradiol conjugate was the predominant urinary oestrogen metabolite measured at each stage of pregnancy. The pattern of urinary oestrone and oestradiol-17 beta reflected plasma levels of total hormone, rather than unconjugated hormone, showing no further increase after mid-pregnancy. In contrast, oestriol increased throughout pregnancy and to a proportionately greater extent than oestrone or oestradiol-17 beta, but at lower absolute levels. High-pressure liquid chromatography of urine extract indicated the presence of considerable amounts of oestrogen immunoreactivity not accounted for by oestrone, oestradiol-17 beta and oestriol and with a retention time similar to that of 16 alpha-hydroxyoestrone. Gas chromatography and mass spectroscopy provided further evidence to suggest that 16 alpha-hydroxyoestrone is an abundant urinary oestrogen metabolite during pregnancy in the marmoset monkey.

Animals↗
PubMed1983

CO2 laser laparoscopy. A potential alternative to danazol in the treatment of stage I and II endometriosis.

Most clinicians currently agree that stage I and II pelvic endometriosis, as determined by the American Fertility Society classification, is best treated with danazol when there are no significant peritubal or periovarian adhesions. This therapy offers excellent pregnancy rates and avoids the risk of pelvic adhesions, which can occur after conservative laparotomy. However, the significant disadvantages of danazol include androgenic side effects, breakthrough bleeding, prolonged treatment time and high cost. It is not unheard of for a patient to choose laparotomy over danazol because of these disadvantages. An ideal form of therapy would avoid these disadvantages and be accessible at diagnostic laparoscopy, when the disease is detected. We have worked with such a treatment, the CO2 laser, for one year. With the CO2 laser adapted to the operating laparoscope we have treated stage I and II pelvic endometriosis at the time of the original diagnostic laparoscopy. Due to the precise control the operator has over the laser, implants on the peritoneum over the bladder and bowel or near the ureters can be treated safely. There is little danger of damaging adjacent structures, as one might experience with electrocautery. Ovarian endometriomas of less than 1 cm and mild adhesions can also be removed safely by tissue vaporization.

Adult↗
PubMed1982

The synthesis of prostaglandins from persistent proliferative endometrium.

The pattern of prostaglandins (PGs) synthesized by persistent proliferative endometrium of women with excessive menstrual bleeding (greater than 50 ml) associated with anovulatory cycles was compared to endometrium collected from women with normal menstrual blood loss (less than 50 ml). Levels of PGF2 alpha in normal and persistent proliferative endometrium were lower than the levels of PGF2 alpha found in normal secretory endometrium (P less than 0.005 for both normal and persistent proliferative endometria). When incubated with exogenous [1-14C]arachidonic acid (9.1 nmol), normal secretory endometrium synthesized more PGF2 alpha and PGE2 than did normal proliferative endometrium, but the amounts of PGF2 alpha and PGE2 released by persistent proliferative endometrium were similar to those obtained by normal secretory endometrium. These findings suggest that persistent proliferative and normal secretory endometria have the same PG synthetase activity, and that the low endogenous concentrations of PGF2 alpha in the former arise from a lack of endogenous precursor. PGF2 alpha has predominantly vasoconstricting properties, and a reduced capacity to synthesize this PG by persistent proliferative endometrium may result in excessive menstrual bleeding, as was suggested by the inverse correlation between the ratio of the endogenous concentrations of PGF2 alpha and PGE and the menstrual blood loss (r = -0.7; P less than 0.005; n = 26).

Adult↗
PubMed1982

Morphological selection of human spermatozoa in vivo and in vitro.

Light microscopic assessment of human spermatozoa in post-coital samples of cervical mucus revealed a significant improvement in the general sperm morphology between the semen and the cervix. Further analysis showed that the excluded spermatozoa were more likely to be those with midpiece or tail defects that impaired motility. Significant changes were also found when the morphology of spermatozoa recovered from the uterus and Fallopian tubes following AIH was compared with the semen used for insemination: in the semen, uterus and oviducts there were respectively 53, 77 and 71% spermatozoa with completely normal morphology, and 12, 3 and 0.6% spermatozoa with defects of the midpiece and/or tail (as assessed by surface replica electron microscopy). Selection of spermatozoa in vitro by allowing them to swim upwards through a nickel mesh also reduced the number of spermatozoa with abnormal morphology, particularly of the midpiece and tail. It is concluded that the apparent selection of morphologically normal spermatozoa is not a direct function of the female tract, but that the spermatozoa can effect their own selection because of their differential motility.

Cervix Mucus↗
PubMed1982

Plasma concentrations of LH, prolactin, oestradiol and progesterone in female red deer (Cervus elaphus) during pregnancy.

Peripheral blood samples were collected throughout pregnancy from 11 red deer hinds. During the same period, 6 other hinds which mated but failed to produce calves were also sampled. Pretreatment of some of these hinds included synchronization of oestrus alone (N = 3) or with injection of 1000 i.u. PMSG (N = 9). During early and mid-pregnancy, LH and prolactin were frequently undetectable. Prolactin concentrations in pregnant and non-pregnant hinds were high (greater than 250 ng/ml) in December-January. The results of the hormone analyses suggested that the amount of progesterone in plasma correlates with the number of corpora lutea (CL) present. The concentrations of oestradiol and progesterone were low from mid-winter onwards in the non-pregnant hinds, suggesting a reduction in ovarian activity at this time. In pregnant animals, progesterone concentrations were high for the first 200 days of gestation. Oestradiol rose to peak values concomitant with declining progesterone concentrations just before parturition.

Animals↗
PubMed1982

Androgen conjugates in human breast cyst fluids.

Dehydroepiandrosterone sulfate (DHAS) has been measured by radioimmunoassay in 100 breast cyst fluids obtained from 82 women. Values ranged from 1.5 to 1,155 microM with a median of 140 microM. These concentrations are in excess of those for plasma but are comparable or less than values for breast secretions obtained by nipple aspiration. Levels of DHAS in cyst fluid were not significantly affected by age, menopausal status, or parity of the subject or by the volume of cyst fluid obtained. In patients with multiple cysts, DHAS values from cysts aspirated from the same breast on the same data were relatively comparable, but wide variations were frequently observed between cysts aspirated on different occasions from the same breast and between cysts from different breasts of the same patient, whether sampled simultaneously or sequentially. Such variability must complicate comparative studies among women.

Adult↗
PubMed1981

A role for prostacyclin (PGi2) in excessive menstrual bleeding.

The synthesis of prostanoids from arachidonic acid incubated with endometrium alone or together with myometrium was studied in women with excessive menstrual blood-loss (range 57--186 ml, median 86 ml). Production of prostaglandins F2 alpha, E2, and D2 was similar to that observed for the endometrium of women with normal periods (range 5--50 ml; median 11 ml). However, the endometrium from women with excessive menstrual blood-loss was more effective than endometrium from women with normal menstrual blood-loss at enhancing the production by a control preparation of myometrium of 6-oxo-prostaglandin F1 alpha, the stable metabolite of prostacyclin. The ability of the uterus to generate prostacyclin, a prostaglandin known to inhibit platelet aggregation and stimulate vasodilatation, may influence the degree and duration of menstrual bleeding.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine bleeding.

The endogenous concentrations of prostaglandins F2 alpha (PGF 2 alpha) and E (PGE) were measured during the luteal phase of the menstrual cycle in the endometrium from 14 women with unexplained menorrhagia (measured menstrual blood loss in excess of 50 ml) and 15 women with normal menses (blood loss 50 ml or less). Although there was no significant difference in the PGF 2 alpha/PGE ratio between the two groups, this ratio was significantly lower in the endometrium from eight of the women whose blood loss exceeded 90 ml (p less than 0.05). There was a significant inverse correlation between the PGF 2 alpha/PGE ratio and blood loss (r = 0.36, p less than 0.025). The synthetic capacity of the endometrium was assessed by incubation of the tissue with 14C arachidonic acid. Endometria from nine women with unexplained menorrhagia synthesized more PGE2 than PGF 2 alpha, whereas the converse was true with 11 control endometria. Consequently the PGF2 alpha/PGE2 ratio was significantly reduced in the former group (p less than 0.025). Oestradiol-17 beta (200 microM) and to a greater extent 2 hydroxy oestradiol (200 microM) increased the total prostaglandin synthesis by the endometria, but did not significantly alter the PGF2 alpha/PGE2 ratio. These results suggest that excessive blood loss may be associated with a shift in the endometrial conversion of prostaglandin endoperoxide from PGF2 alpha to PGE2.

Adolescent↗
PubMed1981

Neonatal spongioform myelinopathy after restricted application of hexachlorophane skin disinfectant.

At least four out of 97 low birth weight (less than 1750 g) newborn infants who had received only limited skin disinfection with 3% hexachlorophane (HCP) emulsion developed spongioform myelinopathy in association with detectable amounts of HCP in their brains. These four cases were found in a post-mortem survey of 20 out of the 27 infants who died. Another nine of these infants had detectable amounts of HCP in the brain but no myelinopathy. It is at present not possible to define a 'safe" level of exposure to 3% HCP emulsion for small preterm infants in the first 2 weeks of life.

Brain↗
PubMed1980

Catechol oestrogens stimulate and direct prostaglandin synthesis.

We have tested the action of a catechol oestrogen -2,3,17 beta-trihydroxy oestra-1,3,5 (10)-triene (2-OH oestradiol) in stimulating prostaglandin (PG) production by an homogenate of rat uterus. Marked and dose dependent stimulation was observed in PGF2 alpha and PGE2 production using 20-250 microM concentrations of catechol oestrogen; a concentration of 250 microM 2-OH oestradiol resulted in a 23 fold increase in PGF2 alpha production with a 50% reduction in the synthesis of 6-keto PGF1 alpha. Tryptophan, catechol and glutathione were without effect on PGF2 alpha and PGE2 production whereas adrenalin stimulated the production of all PGs, although the increase was less than that seen with 2-OH oestradiol. Oestradiol had a slight stimulatory action on PGF2 alpha production which reached a maximum at around 40 microM but had a more marked stimulation of 6-keto PGF1 alpha formation. Stimulation of prostaglandin production by oestradiol and 2-OH oestradiol showed no variation at different stages of the rat oestrous cycle. The use of 5 to 100 mg of tissue/ml gave similar product distribution although the effect of catechol oestrogen both in terms of stimulation of E and F formation (expressed per mg of tissue) and in its action on product distribution was more marked at lower concentrations of tissue.

Animals↗
PubMed1979

Differential production of prostaglandins within the human uterus.

The ability of broken cell preparations of human endometrium, myometrium and a mixture of endometrium and myometrium to convert 14C arachidonic acid to prostaglandins (PG's) was compared. Endometrium metabolished arachidonic acid predominantly to a mixture of PGF2 alpha and PGE2. A similar weight of myometrium showed relatively little activity, the major product identified was 6 oxo PGF1 alpha. However, a combination of endometrium and myometrium showed an enhanced conversion of arachidonic acid to 6 oxo PGF1 alpha associated with a decreased production of PGF2 alpha and PGE2. This suggests that human endometrium and myometrium differ in their ability to metabolize arachidonic acid and in their ability to convert the endoperoxides formed, to PG's.

Arachidonic Acids↗