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Biomedical subjects

P D Griffin

Publications and source records attributed to P D Griffin.

14 recordsLinked to original sources
PubMed2000

Evaluation of the ability of levonorgestrel butanoate alone, or in combination with testosterone buciclate, to suppress spermatogenesis in the bonnet monkey (Macaca radiata).

Levonorgestrel butanoate, 0.25, 1.0 and 2.5 mg/kg, administered as two injections 60 days apart (groups II, III, IV), failed to suppress spermatogenesis consistently and uniformly in adult bonnet monkeys (group size, n=6) compared to controls (group I). Levonorgestrel butanoate at the same doses combined with two simultaneous injections of 40 mg testosterone buciclate (groups V, VI, VII), consistently suppressed spermatogenesis in the period 60-240 days and in most animals to azoospermia or severe oligozoospermia (<5 x 106/mL) during days 90-210. The degree and duration of suppression were greatest in group VI. Sperm motility declined in all treated animals and spermatozoa in the semen of animals from groups V and VI lost all progressive motility in the period 60-150 and 60-210 days, respectively. The changes in testosterone levels were similar in groups V and VI, increasing within 24 h after the combined injection to reach a peak by day 28 followed by a sharp decrease until day 67. The second injection increased testosterone levels by a lesser degree to peak levels on day 81. In group VII, testosterone levels decreased until day 59 after the first injection but increased to a maximum on day 81 after the second injection followed by a gradual decrease until day 150 to below baseline values. Peak levels of serum levonorgestrel were observed 1-7 days after injection of levonorgestrel butanoate alone. Clearance of the drug was slow, being detectable in the circulation until day 330 of the 360 day study period in the high dose group. Dose-response increases to peak levels of levonorgestrel were attained on day 7 in groups V, VI and VII, after the first injection. After the second injection, peak levels were seen on day 61 in groups V and VI and on day 81 in group VII. Levonorgestrel was no longer detectable in blood in groups V and VI by days 210 and 300, respectively, but small circulating amounts remained in group VII at the conclusion of the study on day 360. This study indicates that when levonorgestrel butanoate is combined with a long-acting androgen and injected at two-monthly intervals, effective and reversible suppression of spermatogenesis is achieved.

Animals↗
PubMed1999

Pushing the frontiers of science--the WHO/Rockefeller Foundation Initiative on implantation.

One approach to fertility regulation for which there is still a large unmet need is a once-a-month method that can be taken at the end of the luteal phase as a menses-inducer. Such a method would have a number of logistical and economic advantages for many women over other currently available methods. However, to be acceptable, menses-inducers of this type must not produce disturbances in subsequent menstrual cycles that would lead to unpredictable menstrual patterns or advance or delay subsequent ovulations. A number of structural and functional factors associated with the cyclical development and demise of the endometrium and corpus luteum in fertile and infertile women have been identified and the opportunity is now presented for interfering with implantation by disrupting the function of these factors at the local level in these tissues without systemic involvement or prolonged activity. The Rockefeller Foundation and WHO are supporting six centers and investigators around the world, as an international collaborative research initiative, to investigate the molecular biology of these factors and the effect on fertility of their manipulation. It is intended that promising leads identified and selected in this way will be developed into new products with industry.

Cooperative Behavior↗
PubMed1998

Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug.

Following clinical trials conducted in China in the 1970s, gossypol was proposed as a drug for male contraceptive use. This review summarizes the extensive investigations on formal animal toxicology and on the recovery of fertility in men after stopping gossypol treatment which led to the decision by the Special Programme of Research, Development and Research Training in Human Reproduction (HRP) at the World Health Organization (WHO), that gossypol would not be acceptable as an antifertility drug. It is concluded that the assessment of gossypol reinforces the mandatory requirement that future contraceptive drugs must be developed by the established routes of appropriate animal toxicology and phased clinical studies.

Acetates↗
PubMed1994

Immunization against HCG.

The possibility of using the immune system to provide protection against an unwanted pregnancy has been postulated since the very early days of modern immunology. During the past two decades or more, a major goal-directed research effort, involving several independent groups of investigators, has been underway with the objective of developing birth control vaccines suitable for use by men and women at all stages of their reproductive lives. The most advanced work in this area is concerned with the development of a vaccine directed against human chorionic gonadotrophin (HCG), a hormone that is produced by the peri-implantation embryo and that is essential for successful implantation and the establishment of early pregnancy. These studies have reached the stage of clinical testing of a number of prototype vaccines based on different parts of the HCG molecule. No adverse side effects have been observed or reported in these clinical trials and larger scale clinical studies are being planned to assess further the safety, efficacy and acceptability of these preparations. Research is also underway to develop improved versions of these HCG vaccines that will offer 12-18 months protection following a single injection. The stage is set for the introduction, by the turn of this century, of the first totally new method of family planning in four decades.

Amino Acid Sequence↗
PubMed1992

Options for immunocontraception and issues to be addressed in the development of birth control vaccines.

Although the number of family planning methods currently available to couples has never been greater, the range and type of options are still not adequate to meet the widely varying personal needs and demands of individuals worldwide. Birth control vaccines offer a number of theoretical attractions although the development, preclinical and clinical testing of such vaccines pose a number of unique problems requiring novel solutions. If the on-going studies in this area are successful, a valuable new family planning method may be available by the end of the current decade.

Animals↗
PubMed1991

The preliminary clinical evaluation of the safety and efficacy of a fertility regulating vaccine.

Since the mid 1970s, the World Health Organization's Special Programme of Research, Development and Research Training in Human Reproduction, through its Task Force on Vaccines for Fertility Regulation, has been supporting and coordinating the development of a birth control vaccine based on a synthetic peptide representing part of the beta subunit of human chorionic gonadotrophin (beta-hCG). The majority of this work has been carried out in the laboratories of Dr V.C. Stevens at Ohio State University. This hCG vaccine has recently been tested for tolerability and immunogenicity in a phase I clinical trial, and a preliminary evaluation of the vaccine's efficacy in fertile women volunteers is currently being planned. This paper describes the preclinical and clinical testing of this vaccine and the problems and challenges presented by this novel preparation. These have included the need to carry out safety and efficacy studies in the baboon, and the difficulties of designing appropriate preclinical toxicity and immunosafety studies and clinical trial protocols in the absence of previous experience with vaccines of this type.

Animals↗
PubMed1991

The WHO Task Force on Vaccines for Fertility Regulation. Its formation, objectives and research activities.

Over the past 18 years, the WHO Task Force on Vaccines for Fertility Regulation has been supporting basic and clinical research on the development of birth control vaccines directed against the gametes or the preimplantation embryo. These studies have involved the use of advanced procedures in peptide chemistry, hybridoma technology and molecular genetics as well as the evaluation of a number of novel approaches in general vaccinology. As a result of this international, collaborative effort, a prototype anti-HCG vaccine is now undergoing clinical testing, raising the prospect that a totally new family planning method may be available before the end of the current decade.

Animals↗
PubMed1988

Phase I clinical trial of a World Health Organisation birth control vaccine.

A birth control vaccine incorporating a synthetic peptide antigen representing the aminoacid sequence 109-145 of the C-terminal region of the beta subunit of human chorionic gonadotropin (hCG-beta) was submitted to a phase 1 clinical trial. Thirty surgically sterilised female volunteers, divided into five equal groups for different vaccine doses, received two intramuscular injections six weeks apart. Over a six-month follow-up there were no important adverse reactions, and potentially contraceptive levels of antibodies to hCG developed in all subjects. In the highest vaccine dose group, the results gave promise of a contraceptive effect of six months' duration.

Adult↗
PubMed1987

Monoclonal antibodies to human trophoblast and sperm antigens: report of two WHO-sponsored workshops, June 30, 1986--Toronto, Canada.

Two WHO-sponsored workshops were recently held to obtain a consensus view from researchers active in the field of reproductive immunology on the current status of the application of monoclonal antibodies to studies of molecular events underlying reproduction and to determine the feasibility of using this approach to identify trophoblast- or sperm-specific antigens that might represent suitable candidates for the development of antifertility vaccines. A total of 66 mouse monoclonal antibodies reacting with human sperm and 45 monoclonal antibodies reacting with human trophoblast membrane components were submitted by 29 laboratories. These were evaluated in coded form by 42 laboratories with the appropriate expertise in biochemistry, immunohistology and tests of reproductive cell function. The majority of both anti-sperm and anti-trophoblast monoclonal antibodies cross-reacted with cellular elements in non-reproductive tissues. However, at least five monoclonal antibodies (two anti-trophoblast and three anti-sperm) appeared to demonstrate sufficient specificity to warrant further investigation as reagents for the identification of antifertility vaccine candidates.

Antibodies, Monoclonal↗
PubMed1985

The identification of candidate antigens for the development of birth control vaccines. An international multi-centre study on antibodies to reproductive tract antigens, using clinically defined sera.

In an attempt to identify appropriate antigens for birth control vaccines, the Task Force on Immunological Methods for Fertility Regulation under WHO's Special Programme of Research, Development and Research Training in Human Reproduction carried out an investigation of naturally occurring immune responses to reproductive tract antigens which were consistently associated with infertility. Large volumes of sera from subjects satisfying the criteria for one of 16 different clinical categories (listed in Table 1) were collected and samples were subsequently assessed, under code, by investigators with experience in the detection of antibodies to antigens involved in the reproductive process. Sera from 329 persons were included in the study and 20 laboratories examined the sera for antibodies to sperm, zona pellucida, and trophoblast or trophoblast products. In addition, antibodies to certain microbial antigens and to various leucocyte and organ antigens were investigated. The results of these studies are presented in the following papers.

Antibodies↗