Delwyn G Cooke

Massey University, Palmerston North, Manawatu-Wanganui, New Zealand

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Publications (5)13.6 Total impact

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    ABSTRACT: What are the characteristics of, and how variable are, individual normal menstrual cycle profiles of excretion rates for the urinary metabolites oestrone glucuronide (E1G) and pregnanediol glucuronide (PdG)? There is a continuum of menstrual cycle profiles that differ from standard textbook profiles but which can be understood simply in terms of growth, atresia and ovulation of ovarian follicles. Point-of-care assays with the Ovarian Monitor pre-coated assay tubes, using urine samples diluted to a constant volume per unit time, give laboratory accurate clinical data for individual menstrual cycles. Lay operators can perform the point-of-care assay system at home to achieve reliable and reproducible results, which can be used for natural family planning. This prospective study involved 62 women, with normal menstrual cycles, recruited from three centres: Palmerston North, New Zealand, Sydney, Australia and Santiago, Chile. The study lasted 3 years. Women collected daily urine samples and determined their E1G and PdG rates with a pre-coated enzyme assay system known as the Ovarian Monitor. For two cycles, the assays were repeated in a study centre and the results were averaged to give 113 individual menstrual cycles for analysis. The cycles were displayed individually in a proprietary database program. The individual normal hormonal profiles were more complex than the classic composite curves for 40% of the cycles. Of 113 ostensibly normal cycles, only 91 were potentially fertile and 22 had some luteal phase defect. The oestrone glucuronide and PdG excretion rates were reliable and informative in the non-invasive elucidation of ovulation and ovarian function for both simple and complex profiles. Daily monitoring revealed the variability of normal menstrual cycle profiles. The LH peaks were variable and ambiguous markers for ovulation. The study consisted of cycles only from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study thus the limits of the fertile window were not tested. The principles established in this study should apply to cycles of any length. All peaks in oestrone glucuronide excretion should be tested by concurrent measurements of PdG, which gives a positive indication of the fate of the follicle it represents. The Ovarian Monitor provides a useful addition for practitioners of natural family planning. Financial support for this study was obtained from the UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. is currently employed by and holds stock in Manawatu Diagnostics Ltd, a company in the development phase of a potentially competing product. The remaining authors have nothing to declare.
    Human Reproduction 10/2013; · 4.67 Impact Factor
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    ABSTRACT: The UNDP/WHO/World Bank/Special Programme of Research, Development and Research Training in Human Reproduction (Geneva) set up a study to determine whether it is feasible for women to monitor their ovarian activity reliably by home testing. Daily self-monitoring of urinary hormone metabolites for menstrual cycle assessment was evaluated by comparison of results obtained with the Home Ovarian Monitor by untrained users both at home and in study centres. Women collected daily data for urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) for two cycles, then the procedure was repeated in the women's local centre (in Chile, Australia or New Zealand) giving a total of 113 duplicate cycles. The tests were performed without the benefit of replicates or quality controls. The home and centre cycles were normalized and compared to identify assay errors, and the resulting home and centre menstrual cycle profiles were averaged. Reliable mean cycle profiles were obtained with the home and centre excretion rates agreeing to within 36 ± 21 nmol/24 h for E1G and 0.77 ± 0.28 µmol/24 h for baseline PdG values (1-5 µmol/24 h). The cycles had a mean length of 28.1 ± 3.1 days (n = 112; 5th and 95th percentiles: 24 and 35 days, respectively), a mean follicular phase of 14.8 ± 3.1 days (n = 107; 5th and 95th percentiles: 11 and 21 days) and a mean luteal phase length of 13.3 ± 1.5 days (n = 106; 5th and 95th percentiles: 11 and 17 days), calculated from the day of the LH peak. The study confirmed that the Ovarian Monitor pre-coated assay tubes worked well even in the hands of lay users, without standard curves, quality controls or replicates. Point-of-care monitoring to give reliable fertility data is feasible.
    Human Reproduction 11/2011; 27(2):550-7. · 4.67 Impact Factor
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    ABSTRACT: A direct enzyme linked immunosorbent assay (ELISA) system has been optimized as a reference method for the measurement of first statistically significant rises in estrone glucuronide excretion rates in human urine by analysing samples pre-diluted at the time of the collection by the women subjects to a constant urine production rate of 150 mL/h. Validation was achieved by correlation of the individual menstrual cycle profiles with the corresponding estrone glucuronide excretion rates determined by radioimmunoassay (RIA) on the same urine samples for a total of 221 samples from nine cycles. The pre-dilution procedure removed random variations due to fluctuations in the daily rate of urine excretion and minimized between sample matrix effects. When the ELISA data were correlated with the RIA data, Deming regression gave a slope of 1.20+/-0.03 and an intercept of 4.6+/-1.8 nmol/24h (r=0.944) and a random experimental error of 14.2 nmol/24h. The major difference in the measurements was a proportional error of 20%, which was present in either the ELISA or RIA methods or in both. Comparison of the standard normal variate transformation of the ELISA and RIA data gave hormonal profiles of the individual menstrual cycles (N=9) that overlapped almost perfectly. Statistically significant rises or falls in the magnitude of the excretion rate in one profile were mirrored faithfully in the other.
    Steroids 07/2007; 72(6-7):580-91. · 2.80 Impact Factor
  • Delwyn G Cooke, Leonard F Blackwell
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    ABSTRACT: Lysozymes (3.2.1.17) from goose (Anser anser) egg white, turkey (Melagris gallopavo) egg white, phage T4 and human milk were compared with hen egg white lysozyme in their ability to clear a suspension of Micrococcus lysodeikticus. All of the lysozymes, except hen egg white lysozyme, catalysed the clearing of the Micrococcus lysodeikticus suspension in a biphasic fashion. Compared to hen egg white lysozyme, the total absorbance or transmission change over 5 and 20 minutes was less in all cases, except for human lysozyme. Human lysozyme was, therefore, a potential alternative, more rapid signal generator for the measurement of urinary estrone glucuronide excretion rates because of its structural similarity to hen egg white lysozyme. The apparent K(M) values for hen egg white lysozyme increased with the enzyme concentration.
    Journal of Immunoassay and Immunochemistry 01/2007; 28(2):67-90. · 0.73 Impact Factor
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    ABSTRACT: Three structurally characterized estrone glucuronide-lysozyme conjugates, E1 (a 60:40 mixture acylated at K3 and K97), E3 (acylated at K33), and E5 (acylated at both K33 and K97) were isolated and purified using a combination of cation-exchange chromatography on S-sepaharose in 7M urea and hydrophobic interaction chromatography on butyl sepharose. Urea was essential to separate the conjugates into six chromatographically homogeneous fractions. In the absence of urea, complex mixtures of lysozyme and the six conjugate fractions were always encountered. The E1, E3, and E5 conjugates were highly inhibited by a sheep polyclonal anti-estrone glucuronide antibody only after the hydrophobic interaction chromatography step. The high level of inhibition enabled all three conjugates to be utilized as signal generators in homogenous enzyme immunoassays for urinary estrone glucuronide. Despite the apparently higher affinity of E3 for the antibody, both E1 and E3 gave standard curves that were indistinguishable provided that 1.7-fold more antiserum was used for E1. Both E1 and E3 yielded menstrual cycle urinary data that agreed with that provided by the Ovarian Monitor pre-coated assay tubes. Although, the menstrual cycle pattern was similar for the three signal generators, the E1G excretion rates yielded by E5 as the signal generator were only 60% of the reference values. Despite structural differences, there was no advantage gained in separating E1 and E3, but higher substituted conjugates such as E5 need removal for best assay performance.
    Journal of Immunoassay and Immunochemistry 02/2003; 24(2):147-72. · 0.73 Impact Factor

Publication Stats

11 Citations
13.60 Total Impact Points

Institutions

  • 2003–2007
    • Massey University
      • • Institute of Molecular BioSciences
      • • Institute of Fundamental Sciences
      Palmerston North, Manawatu-Wanganui, New Zealand