Search PubMed⌕ Search

Biomedical subjects

T Leonard

Publications and source records attributed to T Leonard.

At least 37 records · Page 2Linked to original sources
PubMed1995

Pharmacological characterization of MCCG and MAP4 at the mGluR1b, mGluR2 and mGluR4a human metabotropic glutamate receptor subtypes.

The two reported metabotropic glutamate receptor (mGluR) antagonists, alpha-methyl-cyclopropyl glycine (MCCG) and alpha-methyl-aminophosphonobutyrate (MAP4) were tested on the mGluR1b, mGluR2 and mGluR4a subtypes of human mGluRs. Neither MCCG (500 microM) nor MAP4 (500 microM) antagonized the activation of mGluR1b by 10 microM quisqualate. MCCG was found to potently antagonize the action of 30 microM (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] at mGluR2 (IC50 = 87.5 microM; apparent Kd = 25 microM) but did not block the action of 1 microM S-2-amino-4-phosphonobutyric acid at mGluR4a (IC50 >> 1 mM). MAP4 was found to be a weak antagonist or partial agonist at mGluR4a (IC50 > 500 microM) and, less potently, also antagonized the action of 30 microM (1S,3R)-ACPD) at mGluR2 (IC50 approximately 2 mM).

Amino Acids, Dicarboxylic↗
PubMed1995

Comparison of SUZI and ICSI for severe male factor.

We compare the results of subzonal insemination (SUZI) and intracytoplasmic sperm injection (ICSI) carried out between February 1993 and end of August 1994. A total of 232 couples underwent 302 cycles of micro-assisted fertilization (79 patients had SUZI for a total of 93 cycles, 153 patients ICSI for a total of 209 cycles). The indications for treatment were obstructive azoospermia in 35 cycles, ejaculatory failure with severely low sperm count in 7 cycles, and failure of fertilization in a previous IVF cycle or less than 10% of oocytes fertilized in 87 cycles. In 173 cycles the indication for treatment was a poor semen parameter. Patients undergoing ICSI had significantly higher fertilization rates [43 (728/1692) versus 22.3% (151/ 676), chi 2 = 86.308, P < 0.0001], better chances of embryo transfer [95 (199/209) versus 73% (68/93), chi 2 = 30.671, P < 0.001], and greater numbers of embryos transferred (2.4 +/- 0.9 versus 1.6 +/- 1.2 F = 42, P < 0.0001) than patients who had SUZI. Eighteen patients became pregnant following the SUZI procedure, a pregnancy rate of 19% per egg collection, compared with 28% for those who underwent the ICSI procedure, where 58 out of 209 became pregnant. The pregnancy rate was similar in those who underwent embryo transfer, whether they had ICSI or SUZI (29.2 and 28.6% respectively). Overall, the pregnancy rate doubled with each number of embryos transferred, so it was 8.9% when one embryo was transferred, which increased to 18.3% when two embryos were transferred, and this rose to 37.7% when three embryos were transferred. There was no significant difference in the pregnancy wastage rate between SUZI and ICSI. None of the offspring from either SUZI or ICSI showed any evidence of fetal abnormalities. Pregnancy rate was negatively correlated, with sperm progression being 36% (36/100) if progression was < 2 and 19.8% (40/202) if it was > or = 2 (chi 2 = 8.99, P < .002). ICSI therefore provides a higher number of embryos available for transfer and should be the primary treatment for severe male factor infertility.

Adult↗
PubMed1993

Age, pregnancy and miscarriage: uterine versus ovarian factors.

This study was performed to evaluate the relative contribution of oocyte and uterine factors to the age-related reduction in fecundity. The pregnancy and miscarriage rates in women receiving donated oocytes were compared to those in women using their own oocytes in in-vitro fertilization (IVF) and gamete intra-Fallopian transfer (GIFT) procedures. Oocyte donation with embryo transfer was performed on 241 women in 371 cycles; 116 of these women became pregnant (48% per patient and 31.5% per cycle) of whom 40 (35%) miscarried, giving a live birth rate of 20.5%. Assisted conception, in the form of IVF/GIFT procedures, was performed on 1331 women using their own oocytes in 2194 cycles; 627 of these women became pregnant (47% per patient and 28.7% per cycle), of whom 228 (36%) miscarried, giving a live birth rate of 18.2%. Neither the age of the donor nor the age of the recipient was related to pregnancy rate. The age of the donor, however, was directly related to the miscarriage rate. On the other hand, the age of patients undergoing IVF/GIFT was inversely related to the pregnancy rate and directly related to the miscarriage rate. In women of 40 years or over, the overall pregnancy and live birth rates were significantly higher and the miscarriage rate was significantly lower in the group receiving donated oocytes compared to the group using their own oocytes. In summary, we suggest that the age-related decline in fecundity is associated with the age of the oocytes rather than the age of the uterus.

Abortion, Spontaneous↗
PubMed1990

In vivo biliary excretion and in vitro cellular accumulation of thyroxine by rats or cultured rat hepatocytes treated with a novel histamine H1-receptor antagonist.

Rats treated with temelastine (SK&F 93,944), a novel histamine H1-receptor antagonist, develop thyroid lesions characterized by hypertrophy and colloid depletion. To investigate the mechanism underlying the lesion the biliary clearance and hepatocellular accumulation of radio-labelled iodothyronines was measured in rats or cultured rat hepatocytes. Treatment with temelastine increased both the biliary clearance (approximately 300% of control) and hepatocellular accumulation (approximately 200%) of thyroxine (T4) but had little or no effect on tri-iodothyronine (T3). Chromatographic analysis of bile samples from temelastine-treated rats showed that the majority (approximately 78%) of T4 was present in the unconjugated form. This contrasted with data from phenobarbitone-treated rats which showed that approximately 80% of T4 in the bile was present as the glucuronide conjugate. Studies with cultured hepatocytes showed that the hepatocellular accumulation of T4 was energy dependent. At 4 degrees C the treatment-related increases in accumulation of T4 were abolished, suggesting that temelastine is specifically affecting the high affinity, energy dependent system which preferentially transports thyroxine into hepatocytes. Because temelastine is metabolized extensively, investigations were undertaken to discover if the hepatic effects were caused by the parent compound or an oxidative metabolite. The results showed that the hepatocellular accumulation of T4 remained increased in hepatocytes co-incubated with temelastine and 1-aminobenzotriazole (a suicide inhibitor of cytochrome P450), even though no measurable P450 could be found in the cells. Also, in studies with two major "rat" metabolites of temelastine, i.e. 93,944-Met I or 93,944-Met VIII, treatments failed to reproduce the responses seen with the parent compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Comparative trial of luteinizing hormone-releasing hormone analog/human menopausal gonadotropin and clomiphene citrate/human menopausal gonadotropin in an assisted conception program.

To establish the usefulness of a new drug regimen in an assisted conception program, a trial was performed comparing clomiphene citrate (CC) plus human menopausal gonadotropins (hMG) with a new regimen of intranasal luteinizing hormone-releasing hormone (LH-RH) analog plus hMG. One hundred two patient cycles received treatment with CC and hMG and 118 patient cycles received treatment with LH-RH analog and hMG. Fifteen percent of cycles were canceled in the CC group and 8% in the analog group. Four percent of cycles in the CC group were canceled due to premature ovulation. The number of oocytes collected in the analog group was significantly higher than in the CC group (8.5 versus 5.5), as was the number of mature oocytes (3.5 versus 2.7). However, the percentage of mature oocytes was higher in the CC group (54.2% versus 42.3%). The number of embryos resulting from in vitro fertilization as well as the number of cleaving embryos were significantly higher in the analog group (5.2 versus 2.8 and 4.6 versus 2.3, respectively). The pregnancy rate in the analog group was significantly higher than in the CC group (30.6% versus 16.1%), as was the live birth rate (21% versus 8%). Early pregnancy loss was significantly higher in the CC group than in the analog group (35% versus 9%); and the serum level of LH on the day of human chorionic gonadotropin (hCG) administration was also significantly elevated in the CC group when compared with the analog group (8.1 versus 4.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1990

A comparison of the attitudes of volunteer donors and infertile patient donors on an ovum donation programme.

The attitudes of anonymous volunteer donors (n = 20) and infertile patients who were undergoing treatment in an IVF programme and who donated oocytes (n = 15) towards the donation, the recipient, the potential children conceived, the recording of information and their experience of the procedures were sought by posted questionnaires. All donations were made for altruistic reasons and no payments other than expenses were made. Both groups agree that donors should not be paid and they both deny any connection with the child resulting from their donation. The majority in both groups also did not object if their eggs were donated to unmarried single women and they did not wish to meet with the recipient. The majority of both groups would however agree to donate to known recipients. Over 80% had told others of their donation and a similar number in the volunteer group held no objection to the recipients knowing their name whilst only 40% held the same view in the patient donor group (17/20 versus 6/15 P less than 0.02). The feelings of the groups was also different in relation to their desire to know if a child was born from their eggs. Eighty five per cent in the volunteer group (17/20) would like to know the outcome and only 40% (6/15) of the patient donor would want to know the outcome, P less than 0.02. Although greater than 50% in both groups experienced side effects, 60% of volunteers and 90% of patient donors expressed a willingness to donate eggs again.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

A report on 100 cycles of oocyte donation; factors affecting the outcome.

Eighty-two patients had 100 cycles of oocyte donation from 68 donors resulting in 27 clinical pregnancies. The source of donated oocytes was 42 fertile volunteers and 26 patients from the assisted conception programme. The pregnancy rate was significantly higher when intra-Fallopian transfer was performed (36%; 21/59), compared with intrauterine transfer (15%; 6/41). The pregnancy rate following fresh gamete/embryo transfer (39%; 15/39) was slightly higher than for frozen embryo transfer (20%; 12/61). The age of the recipient significantly affected the pregnancy rate. The pregnancy rate was 50% in the 25-29 years age group and steadily dropped to 9.7% in the 45-49 age group. The pregnancy rate in patients with primary ovarian failure (50%; 8/16) was significantly higher than in patients with secondary ovarian failure (18%; 9/50). The pregnancy rate was significantly greater when parous donors (33%; 23/69) were used compared with non-parous donors (13%; 4/31). The number of gametes/embryos transferred significantly affected the pregnancy rate regardless of the treatment used. If one or two gametes/embryos were transferred, the pregnancy rate was 11% compared with 33% if three to four embryos were transferred. The age of the donors did not affect the pregnancy rate. The majority of the donors were under the age of 35 years. The best results (50% per cycle) were therefore achieved using gametes from parous donors and transferring three to four oocytes fresh to the Fallopian tubes of a young recipient.

Adult↗
PubMed1989

In vitro accumulation of thyroid hormones by cultured rat hepatocytes and the biliary excretion of iodothyronines in rats treated with a novel histamine H2-receptor antagonist.

The administration of SK&F 93479, a novel histamine H2 antagonist, to Wistar rats has been shown to produce thyroid lesions associated with an increased clearance of plasma thyroxine (T4) and elevated plasma TSH concentrations. To determine if these changes were mediated via an increase in the hepatic clearance of thyroid hormones, the biliary clearance and hepatic accumulation of iodothyronines were measured in rats and cultured hepatocytes treated with SK&F 93479. Both the in vitro and in vivo results showed that treatment with SK&F 93479 caused an increased hepatic accumulation (approx. 200% of control) and biliary excretion (2-3-fold control values) of T4 but had little or no effect on T3 uptake. The in vitro studies showed that the treatment related increase in hepatic thyroxine accumulation was temperature and therefore probably energy dependent, while inhibition of cytochrome P-450 dependent enzyme activity did not alter the accumulation of T4 suggesting that the parent compound and not some oxidative metabolite was responsible for the hepatic effects. Chromatographic analysis of bile from SK&F 93479 and phenobarbitone-treated rats showed that in the latter animals 81% of the T4 was present as the glucuronide conjugate (consistent with enzyme induction) whereas in the SK&F 93479-treated rats only 25% was present as the conjugate with 75% being in the unconjugated form. These studies show that SK&F 93479 increases the hepatic accumulation and biliary clearance of T4 by a novel mechanism not associated with liver microsomal enzyme induction.

Animals↗
PubMed1989

The value of sperm swimming speed measurements in assessing the fertility of human frozen semen.

The purpose of this study was to evaluate relationships between measured sperm velocity and in-vivo fertility, using donor semen samples from an artificial insemination (AID) programme. Seventy-one frozen semen samples were examined; measurements of sperm velocity were made immediately after thawing, upon a motile 'swim-up' fraction, and finally after 3.5 h incubation at 37 degrees C in the freezing mixture. Zona-free hamster egg penetration assays were performed upon all samples. Two groups of samples were identified; seven donors (11 samples) had failed to produce any pregnancies through AID from a range of 3 to 14 cycles tested, whilst the remaining samples (from 25 donors) had achieved at least one pregnancy each. The mean sperm velocity (+/- SEM) for the latter 'fertile' group was significantly higher than the corresponding value for the 'infertile' group; (i) after thawing, 65.9 +/- 1.8 versus 50.4 +/- 3.2 microns/s (P less than 0.001) and (ii) after 3.5 h incubation, 42.1 +/- 2.1 versus 24.7 +/- 5.7 microns/s (P less than 0.002). Using the maintenance of sperm velocity during incubation as an indicator of survival, life-table analyses were used to calculate monthly conception rates on various sub-groups of the semen samples. Poor survival (greater than 40% decline in velocity over 3.5 h) was associated with a monthly pregnancy rate of only 11.58% (362 cycles), whilst better survival (less than 40% decline) was associated with the significantly higher (P = 0.024) pregnancy rate of 16.87% (480 cycles).

Evaluation Studies as Topic↗
PubMed1989

Timed oocyte collection in an assisted conception programme using GnRH analogue.

Three-hundred-and-twenty-five patients on an assisted conception programme underwent 378 cycles of oocyte retrieval (OPU) following ovarian stimulation using a GnRH analogue and human menopausal gonadotrophins (HMG), a regimen which allows programmed cycles and delayed oocyte retrieval. Eighteen cycles were excluded (failed OPU in three and failure of fertilization in 15). In 360 cycles, patients completed their treatment with either in-vitro fertilization/embryo transfer (IVF/ET) (116) or gamete intra-Fallopian transfer (GIFT) (244), of which 241 took place at the normal time and 119 were delayed for 24 h or more to avoid weekend operating. The overall pregnancy rate per OPU was 29.5%, with the IVF group being 24.1% and the GIFT group being 32.8%. In the group of patients in whom OPU was delayed, the pregnancy rate was significantly higher in each sub-group than in the corresponding non-delayed sub-group (overall, 37.0 versus 25.7%; IVF/ET, 38.5 versus 16.9%; GIFT, 36.3 versus 31.1%). There was a significantly higher number of oocytes collected, gametes/embryos transferred in the group whose OPU had been delayed. In patients receiving GnRH analogue and HMG for ovarian stimulation, delaying oocyte retrieval is not harmful, may result in an improved outcome and allows OPU to be performed on routine operating lists. This facility, together with the improved pregnancy rates associated with this protocol of ovarian stimulation should improve the cost-effectiveness of assisted conception programmes.

Adult↗
PubMed1989

Pregnancy in women with premature ovarian failure using tubal and intrauterine transfer of cryopreserved zygotes.

Twenty-nine women, mean age 36.3 (SD 5.5) years, with premature ovarian failure received donated ova on an ovum donation programme. Three had Turner's syndrome, four a surgical menopause, one a chemotherapy-induced menopause and 21 had idiopathic premature ovarian failure. All donated oocytes were fertilized with frozen-thawed spermatozoa from the recipient's partner, and the resulting zygotes were frozen until transfer had been arranged. Overall, 19 women had intrauterine embryo transfer (ET) and a mean of 2.7 (SD 0.9) embryos were transferred on 20 occasions; 10 women underwent zygote intrafallopian transfer (ZIFT) and a mean of 3.5 (SD 0.5) zygotes were transferred on 10 occasions. Both groups were matched for age. The pregnancy rate per transfer was 20% in the ET group and 40% in the ZIFT group. After excluding the 10 women in the ET group who had fewer than three embryos transferred, the pregnancy rates were similar in the two groups, 30% in the ET group and 40% in the ZIFT group. Cryopreserved embryos may be used for ovum donation to preserve anonymity and still show a high pregnancy rate of at least 30% per transfer.

Adult↗
PubMed1988

The value of IVF-ET in patients undergoing treatment by the GIFT procedure.

In patients undergoing the gamete intra-Fallopian transfer (GIFT) procedure, a prospective study was performed to establish the predictive value of attempting in-vitro fertilization (IVF) using extra oocytes obtained at laparoscopy and also the value of transferring the resulting embryo(s), in conjunction with GIFT, in the same treatment cycle. The GIFT procedure was performed in 50 treatment cycles involving 43 patients, of whom 20 have achieved clinical pregnancy with an overall success rate of 40% per treatment cycle. In 38 of these patients, one or more extra oocytes were available and an attempt was made in each case to fertilize them in vitro. When fertilization failed to occur in vitro, the chances of pregnancy were significantly reduced (9.1%). In patients for whom IVF of extra oocyte(s) was successful, there was no significant difference in the pregnancy rate whether embryo transfer was performed or not (54 and 57.1%, respectively). The success rate was also influenced by the number of oocytes collected rather than the number of oocytes/embryos transferred. Therefore these results suggest that IVF of extra oocytes is a good indicator of in-vivo fertilization and that if extra embryos are obtained they should be cryopreserved.

Adult↗
PubMed1985

Metabolism of leukotriene B4 in hepatic microsomes.

Leukotriene B4 was metabolized in rat hepatic microsomes to two products. Mass spectral analysis of these two metabolites indicated that the major metabolite was the 20-hydroxy metabolite while the minor metabolite was the 19-hydroxy metabolite. The formation of these metabolites required NADPH and was linear with time (20 min) and protein (1.6 mg/ml). The Km apparent and Vmax for omega hydroxylation of LTB4 was 14 uM and 0.138 nmol/min/mg protein. In contrast, the km and Vmax for omega minus one hydroxylation was 54 uM and 0.093 nmol/min/mg protein. These results suggest that omega and omega minus one hydroxylations of LTB4 may be mediated by different isozymes of hepatic P-450.

Animals↗
PubMed1985

Assessment of bleeding in eye surgery.

A new method for assessing microhaemorrhage in eye surgery was used in 16 patients for cataract extraction. It was shown that bleeding was greatest in the first five minutes and that it correlated with the surgeon's clinical estimate of blood loss. The method was used to assess the effect of two different general anaesthetic induction regimens on intraoperative bleeding.

Aged↗