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Biomedical subjects

R W Shaw

Publications and source records attributed to R W Shaw.

At least 163 records · Page 9Linked to original sources

Endocrinologic and clinical evaluation following a single administration of a gonadotrophin-releasing hormone agonist (Zoladex), in a depot formulation, to premenopausal women.

A single 3.6-mg Zoladex subcutaneous depot injection was effective in suppressing the pituitary-ovarian function for about 5 weeks in nine regularly menstruating, premenopausal volunteers. Menses returned approximately 9 weeks after the injection. Zoladex depot is a novel approach in the administration of GnRH agonists and offers great therapeutic potential.

Adult↗

Doppler assessment of uterine blood flow changes in patients with fibroids receiving the gonadotropin-releasing hormone agonist Buserelin.

Uterine arterial blood FVWs were studied by doppler ultrasound in eight patients with large uterine fibroids who were treated with the GnRH agonist Buserelin intranasally for 4 months. At the end of treatment, reductions in the uterine and discrete fibroid volumes were associated with significant increases in the mean RI values for the uterine (P less than 0.01) and fibroid (P less than 0.001) vasculature, thus indicating reduction in blood flow.

Adult↗

A randomized comparative study of purified follicle stimulating hormone and human menopausal gonadotropin after pituitary desensitization with Buserelin for superovulation and in vitro fertilization.

Twenty patients entered a randomized, crossover study of purified follicle-stimulating hormone (pure-FSH) or human menopausal gonadotropin (hMG) superovulation, 2 ampules per day after pituitary desensitization with the luteinizing hormone-releasing hormone (LH-RH) analogue Buserelin (D-Ser tBu6 LH-RH 1-9 ethylamide) nasal spray. There were no cycles cancelled. Six patients conceived (five on pure-FSH, one on hMG). There were 24.2 +/- 2.5 (mean +/- standard error of the mean [SEM]) ampules of pure-FSH and 24.3 +/- 3.6 ampules of hMG stimulation required. There were similar numbers of preoperation follicles: 6.9 +/- 1.0 on hMG and 6.6 +/- 1.1 on pure-FSH, of oocytes collected; 8.5 +/- 1.4 on hMG and 5.8 +/- 1.4 on pure-FSH, and of pre-embryos achieved; 5.1 +/- 0.9 on hMG and 3.4 +/- 1.0 on pure-FSH; on either treatment. The fertilization rate on hMG was 60% and on pure-FSH was 55%. Pre-embryo transfer rates were 3.2 +/- 0.3 in the hMG group and 2.7 +/- 0.4 in the pure-FSH group. There were no differences in serum FSH, LH, estradiol, or progesterone levels between the hMG and pure-FSH groups. Mean +/- SEM luteal phase length was 10.6 +/- 0.4 days in the nonpregnant cycles.

Adult↗

LHRH analogues in the treatment of endometriosis--comparative results with other treatments.

The induction of a state of hypo-oestrogenism has been found to be effective in the treatment of endometriosis. Continued administration of agonistic analogues of luteinizing hormone-releasing hormone (LHRH) results in the normal menstruating female developing normogonadotrophic-amenorrhoea with reduced circulating levels of oestradiol-17B, often within the menopausal range. Uncontrolled studies reported the efficacy of LHRH analogues in patients with mild, moderate and even severe endometriosis (American Fertility Society classification) following 6 months therapy. A number of large multi-centre randomized open or double blind trials comparing various LHRH analogues against danazol are currently underway. Published results available to date indicate that LHRH analogues and danazol are equally effective at reducing the symptoms of endometriosis and inducing complete or partial resolution of endometriotic deposits. Side-effects are, however, more severe with danazol therapy. The side-effects experienced with LHRH analogues are those expected from an induced state of hypo-oestrogenism--hot flushes, dry vagina, headaches, superficial dyspareunia--but are well tolerated by patients. The alterations observed in bone and calcium metabolism are comparable to those in the menopause--increased Ca++ loss and reversible loss of trabecular bone density have been reported. These effects may limit the duration and/or frequency of LHRH analogue treatment regimens. The valuable role of LHRH analogues in the treatment of endometriosis has been established and, as newer formulations become available, they are likely to play an increasingly important part in patient management.

Endometriosis↗

Reversible trabecular bone density loss following induced hypo-oestrogenism with the GnRH analogue buserelin in premenopausal women.

Thirteen premenopausal women who each received 400 micrograms three times daily of intranasal buserelin for 6 months as treatment for endometriosis participated in this study. Cortical bone mineral content (BMC) in the mid-shaft of the right femur measured by dual photon densitometry, and trabecular bone density (TBD) in the lumbar vertebrae (L2-4) measured by quantitative computed tomography, were evaluated prior to, at the end of 6 months' buserelin treatment and after 6 months off treatment. Significant hypo-oestrogenism (P less than 0.001) was sustained during the period on treatment. The significant reduction in the mean lumbar vertebral TBD of 5.9% (P less than 0.02) observed at the end of treatment with buserelin was regained within 6 months following resumption of ovarian activity. There was a marginally significant (P = 0.07) reduction of only 0.9% in the mean femoral cortical BMC at the end of treatment. Six months after the end of treatment cortical BMC values were not significantly different from the pretreatment values. There was no significant correlation between the degree of hypo-oestrogenism and the corresponding change in vertebral TBD, (r = 0.20; P less than 0.10).

Adult↗

Cloning, nucleotide sequence, and expression of the Bacillus cereus 5/B/6 beta-lactamase II structural gene.

Two forms of heat-stable, zinc-containing beta-lactamase II have been described for strains of Bacillus cereus and have been shown to differ in substrate specificity (R. B. Davies, E. P. Abraham, J. Fleming, and M. R. Pollock, Biochem. J. 145: 409-411, 1975). We report here the nucleotide sequence, inferred amino acid sequence, and expression of beta-lactamase II from B. cereus 5/B/6 and compare our results with those for its homolog characterized in B. cereus 569/H (M. Hussain, C. Anthony, M. J. Madonna, and J. O. Lampen, J. Bacteriol. 164: 223-229, 1985) to document amino acid differences contributing to the specific properties of these enzymes.

Amino Acid Sequence↗

Prosthetic group content and ligand-binding properties of spinach nitrite reductase.

Chemical analysis of the ferredoxin-dependent native form (Mr = 85,000) of spinach nitrite reductase has demonstrated a siroheme content that approaches 2 mol of siroheme/mol of enzyme. A widely studied modified (Mr = 61,000) form of nitrite reductase, that has lost much of the native enzyme's ability to use ferredoxin as an electron donor, contains approximately 1 mol of siroheme/mol of enzyme. Quantitation of the high spin ferri-siroheme EPR signals and of nitrite-binding sites of the two preparations confirmed that the native enzyme's siroheme content is approximately twice that of the modified enzyme. Plots of nitrite and cyanide binding to the native enzyme versus ligand concentration are sigmoidal, with Hill coefficients of 1.6-1.8 and 2.3-2.8, respectively. Plots of enzyme activity versus nitrite concentration for the native enzyme are sigmoidal with a Hill coefficient of 2.4. Cyanide inhibition of enzymatic activity was shown to be not competitive. Addition of cyanide to the native enzyme resulted in a diminution of the high spin ferri-siroheme EPR signal and produced EPR signals with g values of 2.71, 2.33, and 1.49 due to low spin ferri-siroheme.

Binding Sites↗

Ultrasound measurement of endometrial thickness on different ovarian stimulation regimens during in-vitro fertilization.

Endometrial thickness was measured ultrasonographically in three groups of patients undergoing in-vitro fertilization (IVF) on three different ovulation induction regimens. The endometrial thickness was comparable on all three regimens and similar to that observed in a group of spontaneously ovulating, normal, fertile controls. These patterns of endometrial thickness were observed despite significantly higher levels of serum oestradiol-17 beta in all of the hyperstimulated cycles, suggesting that in the normal cycle a maximum response in terms of endometrial development may be achieved. In the three conception cycles endometrial thickness continued to increase throughout the luteal phase, whilst in non-conception cycles plateauing of thickness increase occurred in the mid-luteal phase and reduction in late luteal phase. Whether ultrasonographic evaluation of endometrium during IVF stimulation cycles has any prognostic value regarding prediction of conception has yet to be determined.

Clomiphene↗

Endocrine changes following pituitary desensitization with LHRH agonist and administration of purified FSH to induce follicular maturation.

Pituitary desensitization was induced in 13 normally menstruating women by administration of an LHRH agonist, Buserelin, intranasally, 100 micrograms at intervals of 4 h, for a period of 14 days starting on day 22 of the menstrual cycle. Whilst continuing with Buserelin, multiple follicular development was induced by administration of purified FSH (Metrodin) for between 8 and 15 days at a dose of 150 i.u. daily. In one patient no follicular growth was induced after 14 days treatment. In the remaining subjects between 3 and 11 follicles with mean diameter greater than 16 mm were stimulated and between 2 and 10 mature oocytes were recovered laparoscopically for IVF, 34 h after hCG administration. Eight patients underwent embryo transfer and four conceived.

Adult↗

Outcome of in-vitro fertilization and embryo transfer after different regimens of ovarian stimulation.

Sixty-eight women with bilateral tubal disease and fertile male partners underwent ovarian stimulation in 187 cycles for IVF after randomization to different ovulation induction regimens. All patients initially received 150 mg clomiphene citrate on days 5-9, this regimen induced sufficient stimulation in a smaller proportion of patients than the two other regimens used subsequently which included clomiphene in combination with human menopausal gonadotrophins (hMG). The fertilization rate was significantly reduced (52.4%) in oocytes collected from cycles stimulated with hMG alone (in a small sub-group of poor responders) compared with a rate of 64.1-66.4% in cycles stimulated with clomiphene alone or in combination with hMG. Embryonic development 44-48 h after insemination was significantly retarded when clomiphene alone was utilized but a higher proportion of fragmented or abnormal embryos was observed after stimulation with hMG alone. In 118 cycles embryo transfer was performed and 20 pregnancies were established, a pregnancy rate of 16.9%. All but two pregnancies were established when two or more embryos were transferred and when the embryos were at the 4-cell or later stage of development. The regimen of clomiphene in combination with 150 i.u. hMG resulted in significantly greater numbers of oocytes recovered and embryos available per patient for transfer than the other two regimens studied.

Chorionic Gonadotropin↗

Attempts to stimulate multiple follicular growth for IVF by administration of pulsatile LHRH.

Administration of pulsatile LHRH (14.4 microgram/pulse per 90 min) from day 5 to 9, or day 7 to 11 of the cycle following clomiphene pretreatment on days 2-6 induced multiple follicular growth for oocyte recovery for in vitro fertilisation. Administration of LHRH without clomiphene pretreatment failed to induce multiple follicular development. The same group of patients treated with clomiphene alone had fewer numbers of mature follicles, fewer oocytes recovered and less pre-embryos for transfer than when treated with clomiphene and LHRH in combination. Peak gonadotrophin release following commencement of LHRH was seen within the first 24 h of administration with a gradual fall in both LH and FSH toward baseline pretreatment values by the fourth day of administration. A discernible LH increment to LHRH was still present on the fourth day of LHRH treatment, but in many individuals no FSH increment was observed. The preovulatory oocytes recovered were predominantly mature with fertilisation rates of 70% and 85.7% for the two regimens. No pregnancy occurred in the six patients who underwent pre-embryo transfer.

Adult↗

Stimulation of multiple follicular growth for in vitro fertilization by administration of pulsatile luteinizing hormone-releasing hormone during the midfollicular phase.

Pulsatile subcutaneous administration of LH-RH (14.4 micrograms/pulse/90 minutes) during the midfollicular phase (days 7 to 11) of the cycle induced significant increases in circulating LH, FSH, and E2 in all eight women treated. When CC (150 mg/day on days 2 to 6) was administered prior to the LH-RH, multiple follicular development occurred, five to seven mature follicles (greater than 16 mm) being found on day 12 of the cycle. The administration of pulsatile LH-RH in this manner may prove to be an additional regimen for use in IVF programs.

Adult↗

Follicular fluid alpha 1-antitrypsin--correlation with fertilizing capacity of oocytes.

Follicular fluid and serum concentrations of alpha-antitrypsin (alpha 1-AT) were determined by radial immunodiffusion in 72 samples obtained from 33 infertile women undergoing in-vitro fertilization and embryo transfer. A statistically significantly lower concentration of alpha 1-AT was found in follicular fluids from which mature oocytes were recovered (mean 1.52, SE 0.06 g/l) than in those yielding immature oocytes (mean 2.96, SE 0.22 g/l). There was also a significantly higher rate of fertilization (85%) for oocytes from follicular fluids with alpha 1-AT concentrations of less than or equal to 2.0 g/l than for those obtained when the alpha 1-AT concentration was greater than 2.0 g/l (only 25%). The mean follicular fluid alpha 1-AT concentration (1.52, SE 0.06 g/l) of follicles yielding mature oocytes was significantly lower than the relevant mean serum concentration (3.17, SE 0.10 g/l). There was, however, no significant difference between follicular and serum concentration of alpha 1-AT in the group yielding immature oocytes or in the serum concentrations between the different oocyte maturity groups. The measurement of follicular alpha 1-AT may be a useful adjunct in predicting which oocytes are mature and likely to be fertilized.

Adult↗