Biomedical subjects
J Timson
Publications and source records attributed to J Timson.
Evaluation of 225 patients undergoing subzonal insemination for the procurement of fertilization in vitro.
OBJECTIVE: To evaluate subzonal insemination for the procurement of fertilization in infertile males. DESIGN: The spermatozoa of infertile males was used, where possible, for in vitro fertilization (IVF) and subzonal insemination with the same cohort of oocytes obtained from their partner. SETTING: An individual unit in a general hospital, Clinical Nomentana, Rome, Italy. PATIENTS: Males who had repeatedly failed to achieve conception in vitro by IVF or in whom seminal parameters were unacceptable for IVF were treated. INTERVENTIONS: Two hundred twenty-five transvaginal oocyte retrievals were performed. MAIN OUTCOME MEASURES: The incidence of fertilization, cleavage, and pregnancy was evaluated in relation to the numbers of spermatozoa injected and the individual spermatozoa parameters. RESULTS: Fertilization occurred in 39% of patients and 16% of eggs, and 12 clinical pregnancies were established. Fertilization increased with increasing numbers of spermatozoa injected. Fertilization with subzonal insemination was significantly greater (39%) than after in vitro insemination (6%) (P less than 0.0001). CONCLUSIONS: Subzonal insemination improved the incidence of fertilization in this series of patients, and a new classification of spermatozoa based on total motile count aided prognosis for fertilization.
Caffeine.
Most of the population of the world is exposed to caffeine to a greater or lesser extent since it occurs in a number of plants used in the preparation of widely consumed drinks, and has in addition a limited therapeutic use. Chromosomal abnormalities are induced by caffeine in both plant cells and in mammalian cells in culture and it also has some anti-mitotic activity. DNA-repair processes sensitive to caffeine have been demonstrated in a number of cell systems and it has been shown to affect a wide range of other cellular processes. Caffeine has potent mutagenic effects in Escherichia coli and other micro-organisms both when acting alone and in combination with other mutagens. However its mutagenic activity in Drosophila has been disputed and the available evidence suggests that it is neither mutagenic in mammals nor synergistic with other mutagens although at very high doses it appears to have some teratogenic activity in mammals.
Hydroxyurea.
Hydroxyurea (HU) is an anti-leukaemia and anti-tumour drug which has also found limited application in the treatment of dermatological disorders. It is a potent inhibitor of DNA synthesis in many organisms from viruses to man and in cell culture systems. To a lesser degree it can also inhibit RNA and protein synthesis. It is anti-mitotic and cytotoxic depending on the concentration used, the duration of exposure, and the sensitivity of the organism. In most cells HU is active mainly in the S-phase of the cycle and because of the easy reversibility of its action it has been used as a synchronising agent in cell cultures with some success. There is conflicting evidence about the ability of HU to act as an inhibitor of the natural DNA repair mechanisms in cells exposed to radiation or alkylating agents. HU has, however, been shown to induce chromosome damage in a number of organisms including man. It is clearly teratogenic in mammals and can cross the placental barrier at least in rats and the golden hamster, but it is believed to have only a limited mutagenic activity. Studies involving a direct comparison of the action of HU with other compounds suggest that the = C--NHOH moiety is responsible for its biological activity.
Theobromine and theophylline.
Theobromine and theophylline have a limited therapeutic use and in addition they occur in plants used in the preparation of a number of widely consumed drinks. Thus most of the population must be exposed to both compounds. Chromosome abnormalities are caused by both theobromine and theophylline in plant cells and in mammalian cells in culture, and both have anti-mitotic activity. While they are fairly potent mutagens in Escherichia coli and other lower organisms the rather scanty available evidence suggests that they are not mutagenic in mammals. The difference in mutagenic activity may be due to the reported inability of E. coli to demethylate these compounds, a process which occurs readily in mammals including man. The structure-activity relationships of these compounds are complex but the available evidence suggests that methylation at position 1 is the most important for both mutagenic activity and the anti-mitotic effect while methylation at position 3 is of most importance in the action on chromosomes.