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Biomedical subjects

R W Shaw

Publications and source records attributed to R W Shaw.

At least 127 records · Page 7Linked to original sources

New approaches to the management of fibroids.

It is clear that gonadotropin-releasing hormone agonists have potential as a new therapeutic approach in the treatment of fibroids. They are effective in decreasing the size of most fibroids but, on ceasing treatment, regrowth does occur. Because of their effect on calcium homeostasis, long-term unopposed use of these agonists is not recommended. However, sequential addback therapies could be useful in both counterbalancing the hypoestrogenic side effects and in protecting bone mineral density. Although surgery is likely to remain the primary therapy for fibroids, pretreatment with gonadotropin-releasing hormone agonists for 3 to 4 months before myomectomy or before hysteroscopic resection offer many advantages in facilitating these procedures and reducing peroperative blood loss. Further studies are required to establish the most satisfactory treatment regimens with this exciting group of drugs for a condition whose etiology is still poorly understood.

Bone Density↗

Changes in body composition with danazol therapy.

Whole body lean and fat mass measurements by dual energy x-ray absorptiometry were performed in 14 premenopausal women undergoing danazol treatment for endometriosis. After 6 months, there was a significant increase in lean tissue mass. Body fat decreased but this was significantly less in the android (upper body segment) region than in the gynoid (lower body segment) region. Danazol thus has both anabolic and androgenic effects on body composition. Dual energy x-ray absorptiometry provides a new, noninvasive, and rapid means of studying body composition.

Adipose Tissue↗

Nafarelin in the treatment of pelvic pain caused by endometriosis.

As part of a large, multicenter trial, 82 patients with endometriosis were randomized to 6 months of treatment with either nafarelin or danazol. Among 73 patients who had subjective symptoms (dysmenorrhea, dyspareunia, or pelvic pain) at baseline, 94% of patients treated with nafarelin and 91% of those treated with danazol had improvement. Resolution of physical findings also was observed in similar percentages of patients in each treatment group. Long-term studies are needed to determine whether these two agents are associated with different cure rates or times to recurrence of disease.

Amenorrhea↗

A comparison of nafarelin acetate and danazol in the treatment of endometriosis.

Nafarelin 400 micrograms daily and danazol 600 mg daily were compared in a double-blind randomized study. Eighty-two patients with endometriosis were treated for 6 months after an initial laparoscopy and 74 had a second laparoscopy. Twenty-two (30%) patients had complete disease regression, 42 (57%) patients had a partial regression, and in 10 (13%) patients disease was unchanged or worse. Both treatments led to significant regression of active disease but not of adhesions. At 3 months follow-up, 34 (64%) patients reported their symptoms were improved, 15 (28%) reported no change, and 4 (8%) were worse. Nafarelin was associated with more hot flushes and headaches, and danazol with more weight gain. No significant differences, however, were noted in treatment efficacy between the two groups.

Adult↗

The management of predicted ovarian hyperstimulation involving gonadotropin-releasing hormone analog with elective cryopreservation of all pre-embryos.

Severe ovarian hyperstimulation syndrome complicates up to 6% of IVF treatment cycles. We have utilized our pre-embryo cryopreservation program to manage incipient ovarian hyperstimulation syndrome in an alternative way. Four women, who were at risk of developing ovarian hyperstimulation syndrome, underwent oocyte retrieval, but not embryo replacement. Instead, resulting pre-embryos were cryopreserved for future transfer. The four patients have since become pregnant. Three conceived after thawed embryo replacement cycles, and the fourth conceived spontaneously 1 month after the stimulation cycle. This approach offers maximum flexibility in the management of ovarian hyperstimulation syndrome.

Adult↗

Serum levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), a glycosylated beta-lactoglobulin homologue, in successful and unsuccessful assisted conception.

Pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) is the major secretory protein of the endometrium in the late luteal phase. Serum levels were measured during the implantation period in successful and unsuccessful cycles of assisted conception. The effects of two different treatment regimens were also compared. All patients who underwent ovulation induction therapy showed an endometrial response as measured by a rise in serum levels of alpha 2-PEG. This rise was the same regardless of either implantation or the method of ovulation induction used. Higher levels were seen at oocyte recovery in those cycles treated with clomiphene citrate and may reflect a disordered endometrial response involving a direct effect of the drug on the endometrium. This may explain the difference in success rates in assisted conception when an alternative treatment initially involving down-regulation of endogenous gonadotrophin activity and subsequent administration of gonadotrophins is used. The rise in serum levels seen in pregnancy did not differ statistically according to whether the pregnancy progressed normally or subsequently aborted. Considerably reduced alpha 2-PEG production by the endometrium was identified in one patient who subsequently aborted. The measurement of serum levels of alpha 2-PEG during the implantation phase is unlikely to provide a clinical tool either for early detection of pregnancy or as a prognostic factor of successful implantation.

Abortion, Spontaneous↗

IVF pregnancy after induction of an ovulatory endogenous gonadotrophin surge using an LHRH agonist nasal spray.

A successful human twin IVF pregnancy is reported after using a single 50 micrograms dose of LHRH agonist nasal spray (Buserelin) to induce an ovulatory endogenous gonadotrophin surge 34 h prior to oocyte collection. The couple had 10 years of primary male factor infertility, associated with significant anti-sperm antibodies. The clinical features and endocrine profile are presented.

Administration, Intranasal↗

Hormonal changes in patients with polycystic ovarian disease after ovarian electrocautery or pituitary desensitization.

Eleven patients with polycystic ovarian disease (PCO) were treated by laparoscopic ovarian electrocautery and nine with a long-acting luteinizing hormone releasing agonist (LHRH-A) for 8 weeks. Both groups showed equivalent significant decreases in their 6-h mean values of luteinizing hormone (LH) and testosterone (T) measured in 25 samples collected every 15 min. Patients treated with ovarian electrocautery showed significant increases in their 6-h mean values of follicle stimulating hormone (FSH) and insulin with variable oestradiol (E2) responses. The magnitude of change following treatment was significantly greater for LH than for FSH. Buserelin medication did not cause persistent significant changes in the levels of insulin or FSH but it did cause a significant reduction in the 6-h mean values of E2. We conclude that LH is the gonadotrophin primarily affected after pituitary desensitization and ovarian electrocautery. Furthermore, there is no direct correlation between the levels of circulating insulin and testosterone in patients with PCO.

Buserelin↗

Ovarian electrocautery versus human menopausal gonadotrophins and pure follicle stimulating hormone therapy in the treatment of patients with polycystic ovarian disease.

Eighty-eight clomiphene citrate-resistant infertile patients with oligomenorrhoea or amenorrhoea attributable to polycystic ovarian disease were divided at random into three groups. Twenty-nine patients were treated with ovarian electrocautery, 30 with human menopausal gonadotrophins (hMG) and 29 with pure follicle stimulating hormone (FSH). Successful ovulation was induced in 71.4, 70.6 and 66.7% of the cycles in the groups respectively. Ten patients conceived after electrocautery and pure FSH therapy while 15 conceived after hMG medication (chi-squared = 1.6464, P = 0.439). The six-cycle cumulative pregnancy rate in the three consecutive groups was 52.1, 55.4, and 38.3%. Four further pregnancies were achieved after treating 10 patients in the electrocautery group with clomiphene citrate (100 mg/day for 5 days) for 25 cycles. The rate of pregnancy wastage in the corresponding groups was 21.4, 53.3 and 40% (chi-squared = 3.127, P = 0.2039). Ovarian electrocautery is equally effective as hMG and pure FSH in the treatment of PCO patients resistant to clomiphene citrate therapy.

Adult↗

Assessment of menstrual blood loss using a pictorial chart.

Objective menstrual blood loss measurements (in ml) were compared with the score obtained from a pictorial blood loss assessment chart (PBAC) which took into account the degree to which each item of sanitary protection was soiled with blood as well as the total number of pads or tampons used. Twenty eight women used the chart during 55 menstrual cycles and a single observer assessed 122 cycle collections in a similar manner. A pictorial chart score of 100 or more, when used as a diagnostic test for menorrhagia, was found to have a specificity and sensitivity of greater than 80%. Demonstration of the relation between self assessed pictorial chart scores and the objective measurement of blood loss enables us to provide a simple, cheap and reasonably accurate method of assessing blood loss before embarking upon treatment.

Adult↗

Goserelin--depot preparation of LHRH analogue used in the treatment of endometriosis.

In summary then, Zoladex depot (Goserelin 3.6 mg) administered monthly for a period of six months proved highly efficacious in achieving endocrine parameters of pituitary desensitization and hypo-oestrogenism. Initial studies treating symptomatic patients with endometriosis shows satisfactory relief of symptoms and significant impact on the disease process as shown by resolution or reduction in number and size of disease deposits. The depot can be given as a subcutaneous injection without the need of local anaesthesia and its duration of action is 28 days. Zoladex depot should offer a suitable, acceptable form of treatment for patients with endometriosis.

Buserelin↗

Production, purification and spectral properties of metal-dependent beta-lactamases of Bacillus cereus.

New methods for the production of consistently high levels of metal-dependent beta-lactamases (beta-lactamhydrolase, EC 3.5.2.6) from strains 569/H/9 and 5/B/6 of Bacillus cereus are described which have significant advantages over those reported previously. For example, these techniques do not require a fermentor with pH-stat capabilities. We also describe rapid very-high-yield purification schemes for the metal-dependent beta-lactamases from these strains, employing high-performance ultrafiltration (HPUF) and mass ion exchange techniques. Furthermore, we have developed improved methods for the removal of the active site Zn(II) and reconstitution of the beta-lactamase enzymatic activity with Co(II), which result in higher recovery of the original activity than previously reported. In order to characterize the purified beta-lactamases II of B. cereus 569/H/9 and 5/B/6 we have examined the molecular weights, and steady state kinetic parameters of Zn(II) enzymes, and the electronic and EPR spectra of the Co(II)-reconstituted enzymes. EPR spectra of CO(II)-reconstituted beta-lactamase from B. cereus 5/B/6 have not been previously reported.

Bacillus cereus↗

Prosthetic group content and ligand binding properties of a spinach catalase.

A recently discovered form of spinach catalase that contains both a novel heme and protoheme as prosthetic groups has been characterized using immunological and spectroscopic techniques. The enzyme appears to be a dimer of identical Mr 60,000 monomers. Extraction of the non-covalently bound prosthetic groups, followed by thin-layer chromatography of the extract, suggested that the novel heme contains four carboxylic acid side-chain groups. The resonance Raman spectrum of the resting enzyme indicates that the protoheme prosthetic group is five-coordinate and high-spin. The enzyme was shown to bind formate, azide and cyanide. Cyanide and azide binding to catalase are biphasic, suggesting the existence of two different binding sites for cyanide and azide in the enzyme. Results obtained from EPR and resonance Raman spectroscopies also support the hypothesis that two different ligand-binding sites are present in the enzyme. Western blots suggest that the Mr 60,000 peptide of the novel heme-containing catalase is similar or identical to that of a previously characterized, exclusively protoheme-containing, tetrameric catalase.

Azides↗

The impact of prenatal screening and diagnostic testing upon the cognitions, emotions and behaviour of pregnant women.

The purpose of most screening and diagnostic tests is to initiate treatment when a problem is found and, otherwise, to allay anxiety. The extent to which the second of these objectives is met was studied in a prospective study of 179 pregnant women. Women who had amniocentesis to detect Down's Syndrome or were screened for a fetal neural tube defect had significantly lower anxiety levels in the third trimester of pregnancy than women who did not undergo these tests. Undergoing screening for a neural tube defect was also associated with a more positive attitude towards the pregnancy in the second trimester. These results suggest that the previously reported raised levels of anxiety in women undergoing such tests do not necessarily remain high for the duration of the pregnancy and, indeed, undergoing testing may serve to protect women against high levels of anxiety in the third trimester of pregnancy.

Adult↗