Spontaneous abortion rates after natural and assisted conception.
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Biomedical subjects
Publications and source records attributed to W Collins.
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The authors have undertaken a prospective, randomized clinical trial of six treatments to optimize folliculogenesis in patients prior to oocyte collection, in vitro fertilization, and embryo transfer. All treatments involved the administration of the same daily dose of follicle-stimulating hormone (FSH), but at different times during the antecedent and/or current menstrual cycle. There was a significant difference (P less than 0.01, chi-square test) between treatments in the clinical pregnancy rate/patient (19 clinical pregnancies, 67 patients). No advantages were observed for regimens that involved starting treatment during the antecedent cycle. The study was continued with the three treatments that started during the current cycle (24 clinical pregnancies, 58 patients). The most cost-effective regimen was clomiphene citrate, 100 mg/day for days 2 to 6 inclusive; FSH, 150 units/day for days 1 to 4 inclusive; and human menopausal gonadotropin, 150 units/day from day 5 until the day of human chorionic gonadotropin administration.
The authors describe a nonseparation, time-resolved fluoroimmunoassay involving the use of monoclonal antibodies for the measurement of estrone-3-glucuronide in urine. The method has appropriate sensitivity (12 nmol/l), better specificity than a conventional radioimmunoassay with polyclonal antibodies, and the advantages of speed, simplicity, less imprecision, and improved clinical effectiveness. The labeled antigen is a novel fluorescent europium chelate covalently linked to estrone glucuronide at carbon 6 of the glucuronide moiety. The antibodies were raised against estrone-3-glucuronyl-6-bovine serum albumin. The antibody binding reaction is performed in microtiter wells (or tubes) and involves the addition of labeled antigen in buffer (2 ng/100 microliters), a limited concentration of antibodies in buffer (100 microliters), and standard or urine sample (10 microliters). The mixture is incubated for 15 minutes at room temperature. Time-resolved fluorescence from the unbound label is proportional to the concentration of estrone glucuronide. The method may be used to monitor ovarian function and potential fertility in women.
Urinary amylase activity (UAA) is used for diagnosis of rejection in bladder-drained pancreas grafts. Unfortunately, most rejection episodes occur after the patient has been discharged. In those cases, an early diagnosis is often difficult, and a method for home UAA monitoring is needed. We have developed a method that can be used for this purpose. The method, based on Kodak dry-film technology, is shown to have good response to the wide range of UAA seen in these patients compared with responses to standard laboratory kinetic methods. The analysis (performed by the patient) involves 1) collecting urine for 24 h in a 4-L container, 2) diluting the urine with tap water to a total urine of 4 L, and 3) placing a drop of this dilution onto a slide. The slide is read by a handheld spectrophotometer that displays the UAA in secreted units per hour. The reliability of this system has been tested for wide changes of urine pH, volume of the drop applied to the slide, and tap water from different sources. Temperature coefficients have been determined to correct changes in ambient temperatures. The final handheld prototype is being developed based on these preliminary studies. This device could be of benefit for the early diagnosis of rejection episodes in recipients of bladder-drained pancreas grafts after hospital discharge.
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The diagnostic response toward the administration of a luteinizing hormone-releasing hormone (LH-RH) analogue in the early follicular phase has been used sequentially with conventional human menopausal gonadotropin (hMG) treatment in patients who had previously failed to develop multiple follicles in response to a combination of hMG and clomiphene citrate. Nine of fourteen patients (64%) showed an increase in the number of preovulatory follicles and five subjects reached oocyte recovery for the first time. Two patients (22%) became pregnant after in vitro fertilization and embryo transfer during the treatment cycle and had healthy babies. It is suggested that this treatment regimen may be advantageous in some patients with resistant ovaries.
An enzymatic method for determining red cell glycogen was developed and its recovery and precision ascertained. Initial red cell glycogen values in 24 healthy volunteers ranged from 11-60 micrograms/g haemoglobin which compares with 20-105 micrograms/g haemoglobin previously reported. More thorough removal of leucocytes suggested however that variations in the determined red cell glycogen were due to glycogen derived from leucocytes. In 34 red cell preparations with varying leucocyte numbers, the glycogen concentration correlated positively with leucocyte count (r = +0.81, p less than 0.001), whereas glycogen concentration showed poor correlation with red cell count (r = -0.30, 0.1 greater than p greater than 0.05). The results question the reported presence of glycogen in normal red cells and suggest that contamination by leucocytes has been responsible for the previously reported normal range.
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The levels of immunoreactive follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), cortisol, and estradiol (E2) have been determined in serial samples of peripheral plasma from four subjects during the continuous, subcutaneous administration of Buserelin (Hoechst [UK] Ltd., Hounslow, UK) (250 micrograms/day) and after the intramuscular injection of purified, urinary FSH (Metrodin, Serono Laboratories [UK] Ltd., Welwyn Garden City, UK) (150 IU). During Buserelin administration the geometric mean levels of FSH and LH as measured by immunoradiometric assay were reduced by 87% and 37%, respectively, when compared with the corresponding values for days 1 and 2 of the menstrual cycle. After the intramuscular injection of FSH, peak levels (from 3.4 to 6.2 IU/l) occurred in peripheral plasma between 6 and 18 hours later. The levels were significantly elevated after 72 hours (P less than 0.01, Student's paired t-test). There was no obvious effect of the drugs on the circadian rhythms of plasma PRL or cortisol, and no significant effect on the circulatory levels of LH or E2.
The circulating levels of plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH) and oestradiol (E2) have been determined in three groups of three subjects during the continuous, subcutaneous administration of an LH-RH agonist (250 micrograms/day) and after the intramuscular injection of urinary FSH (group I, 150 IU daily for 8 days, total 1200 IU; group II, 300 IU on alternate days for four injections, total 1200 IU; and group III, 150 IU on alternate days for four injections, total 600 IU). The level of circulating FSH in group I rose steadily from a geometric mean of 1.11 (pre-injection) to 8.76 U/l (at day 8), while the corresponding levels in groups II and III fluctuated according to the time and dose of the injected material. Twenty-four hours after the injection the mean level of FSH in group II was significantly higher (7.31 U/l) than the corresponding value for group I (2.79 U/l) or group III (3.48 U/l). Only those subjects in group II showed a resumption of folliculogenesis (leading, mean maximum follicular diameters of 16, 13 and 14 mm, respectively) and a corresponding increase in the concentration of plasma E2 (from 22, 43 and 103 to 906, 1477 and 2362 pmol/l, respectively).
A simple plasma emission spectroscopic method for the determination of iron in liver and cardiac tissue is described. Using this technique, iron was extracted quantitatively from liver tissue of mass 14.2 to 65.4 mg wet weight, and heart tissue of mass 5.9 to 27.4 mg wet weight. Iron added to liver as aqueous ferric nitrate was recovered in the range 93 to 108%. Reference ranges for liver and myocardial iron on post mortem tissue gave respectively mean values of 0.841 mg/g dry weight (Range 0.310 to 1.600, n = 37) and 0.340 mg/g dry weight (Range 0.290 to 0.470, n = 8). Data on patients with haemochromatosis and transfusion siderosis are also presented.
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Q fever is an important cause of morbidity in Australian meatworkers; recently there have been sharp outbreaks of Q fever in abattoirs in several states. In an attempt to control Q fever by vaccination, 924 nonimmune volunteers at two South Australian abattoirs were inoculated with one dose of a purified, formalin-inactivated, Coxiella burneti, Henzerling strain, phase 1 vaccine. Some 56% of workers in one abattoir, and 64% in the other, seroconverted after vaccination. In the 18 months after vaccination, no Q fever occurred in fully vaccinated subjects, whereas there were 34 cases in 1349 unvaccinated workers. Transient local reactions were noted in most vaccinated subjects; only a few had mild general reactions. No cases of vaccine-enhanced disease were observed. Vaccination of susceptible individuals with a purified C burneti phase 1 vaccine appears to be safe and effective in preventing Q fever in the abattoir.
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71 women were examined daily for the presence of headache in their first post partum week. Post natal headache (PNH) occurred in 27, (39%) of the women and was most frequent on days 4-6 post partum. PNH was significantly associated with a previous or family history of migraine and pre-menstrual migraine. Although 83% of those with PNH had a migraine diathesis, they did not describe their headache as one of their usual migraines as it was considerably milder. Headaches were more frequent among multigravida but as rather more multigravida had a previous migraine diathesis this may reflect a sampling bias. PNH subjects had significantly more tension and depression suggesting that at least some PNH may be tension headache. Around 3 or 4 days post partum, women began to lose weight and the onset of headache often coincided with the start of this weight loss. 12 women with, and 12 without PNH took part in a metabolic study, and collected sequential 24 h urine samples from days 2-7 post partum. Potassium and oestrogen excretion were increased on day 3, and progesterone on days 3, 4 and 5. Differences in the excretion pattern of these hormones might reflect small changes in renal function and further work measuring plasma hormone levels could help to clarify this. PNH, like pre-menstrual headache and pill withdrawal headache may represent a further example of the triggering effect that a fall in sex hormone level has on the migraine diathesis.
Intravenous digital subtraction angiography (iDSA) promises to significantly alter the use of conventional cerebral angiography in the workup of neurological patients. Understanding its diagnostic potential and its limitations are important in incorporating this new examination into the diagnostic thought process of neuroradiologic tests. Different image processing techniques such as integration of mask and contrast images promise to improve image quality for neuroradiologic application. At present, iDSA is suitable for the diagnosis and follow-up of vascular lesions (atherosclerosis, aneurysms, arteriovenous malformations, venous sinus occlusion), and tumor (meningioma). Although limited, the spatial resolution of iDSA studies is capable of demonstrating diffuse vascular disease such as arteritis and vasospasm after subarachnoid hemorrhage. In some patients in conjunction with the CT scan, iDSA may prove sufficient as the primary and only diagnostic angiographic test necessary, supplanting conventional angiography.
The concentrations of various estrogen glucuronides and pregnanediol-3 alpha-glucuronide have been measured in daily samples of early morning urine (EMU) and 24 h pooled collections throughout a total of 70 menstrual cycles (58 subjects). The immediate objective was to identify and assess the potential value of measuring hormone metabolites to locate the fertile period in women, with the ultimate aim of developing a non-invasive immunochemical test. The project was undertaken in five centres and the results showed that: (i) there was good agreement in the patterns and mean concentrations of metabolites between the centres; (ii) estrone-3-glucuronide should be the estrogen glucuronide selected for further study; (iii) the analysis of EMU provided information that was as useful as the corresponding measurements on pooled collections for 24 h; (iv) a rise in the concentration of estrone-3-glucuronide (50% over the mean of three preceding values) could be used to locate the start of the fertile period in greater than 90% of the ovarian cycles (from day LHmax -- 3 to day LHmax -- 7); attempts to locate the end of the fertile period by a threshold value or a defined rise in the level of pregnanediol-3 alpha-glucuronide were disappointing. A 50% rise over the mean of three preceding values in the derived concentration ratio of estrone-3-glucuronide/pregnanediol-3 alpha-glucuronide could be used to indicate the start of the fertile period, and a 50% decrease plus two days the start of the infertile period in greater than 80% of the ovarian cycles. The limitations, implications and future developments are discussed.
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