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Biomedical subjects

G Bahadur

Publications and source records attributed to G Bahadur.

35 records · Page 2Linked to original sources

Testicular tissue cryopreservation in boys. Ethical and legal issues: case report.

Sperm preservation prior to chemotherapy and radiotherapy is common practice in adult males. Spermatozoa are usually retrieved from an ejaculated sample although there are occasions when testicular tissue is used as the source. These techniques of sperm preservation present minimal ethical objections as the patients give their informed consent. Sperm preservation in children presents practical and ethical dilemmas in that the children cannot always give their informed consent, there are no regulatory guidelines and there is no guarantee that spermatogenesis is occurring. With the rapid advances in reproductive technology and the possible future use of immature germ cells by in-vitro maturation or transplantation, the demand for immature testicular tissue preservation is likely to increase. More information for the parents and oncologists with regard to this subject is needed to allow informed decisions to be made on behalf of the children. These issues are discussed using two cases of children having testicular tissue preservation.

Adolescent↗

Gonadal tissue cryopreservation in boys with paediatric cancers.

In considering gonadal tissue cryopreservation in children about to undergo chemotherapy or radiotherapy for cancer, numerous issues need to be confronted. This relates firstly to a dearth of information available on the subject of children's gonads coupled to ill-defined fertility preservation procedures, technologies and perhaps less well-publicized regulatory, ethical and legal controls. There may be benefits in considering gonadal tissue preservation for children prior to chemotherapy or radiotherapy, in the hope that future technologies can utilize their immature gametes. Whether or not freezing of gonadal tissue is encouraged prior to cancer therapy, there is a growing demand from parents and clinicians for more information to be made available. This paper reviews our current knowledge of children's gonads in terms of physiology and of fertility experience gained after childhood cancer treatment. It further examines the various issues and concerns regarding children's gonadal tissue storage, its potential use, the present law and the demands and pressures under which clinicians find themselves with patients and parents. This information is important for both the counselling process and decision-making when presented with potential fertility issues in paediatric oncology patients.

Child↗

Kaposi's sarcoma-associated herpes virus--a new concern for human reproduction?

The detection of the recently discovered Kaposi's sarcoma-associated herpes virus (KSHV) in human immunodeficiency virus-uninfected donor semen and in blood from a normal blood donor has led us to review this new area of health concern, with emphasis on a number of studies conducted into the presence of the virus in semen and the possibility of transmission during assisted conception procedures.

Female↗

Detection of human herpesvirus 8 DNA in semen from HIV-infected individuals but not healthy semen donors.

OBJECTIVE: To ascertain the prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, and cytomegalovirus (CMV) DNA in semen was investigated. METHODS: Amplification by nested polymerase chain reaction was used to detect viral DNA sequences in samples from 24 HIV-infected gay men, 15 of them with Kaposi's sarcoma (KS), and 115 healthy donors. RESULTS: Six of the 24 HIV-infected patients had detectable HHV-8 DNA in their semen: three of the 15 patients with KS and three of the nine patients without KS. CMV DNA was detected in 20 semen samples from HIV-infected patients. None of the semen samples from healthy donors had detectable HHV-8 DNA and rates of CMV DNA detection were low (3%). CONCLUSIONS: The study demonstrates the presence of HHV-8 in semen from HIV-infected individuals with, or at risk, of developing KS and the potential for sexual transmission of the virus. We found no evidence of HHV-8 in the semen of HIV-uninfected donors.

Cytomegalovirus↗

Ovarian tissue cryopreservation for patients.

For patients about to receive chemotherapy, radiotherapy or to undergo a surgical procedure, loss or impairment of fertility is a major issue. For males, sperm banking is a standard accepted procedure to circumvent loss or damage to spermatozoa and this has been undertaken in this unit since 1975 (Steele et al., 1995). For women there is no established procedure for gamete storage. Embryo preservation is not an option for single women or even for those in a stable relationship, as treatment would have to be delayed while ovarian stimulation and oocyte retrieval took place. With the general shortage of donor oocytes, the possibility of maturing primordial follicles from fetal ovaries has become a subject for debate (HFEA 1995: Recent deliberations). In animals, the use of frozen ovarian tissue has been encouraging with a report of a live birth in lamb after orthotopic transplantation (Gosden et al., 1995). Media attention to the future prospect for freezing ovarian tissue has meant that pressure from patients is likely to increase either for information or as requests to freeze the ovarian tissue which could irretrievably be lost as a result of surgery and/or treatment. In the absence of well defined procedures and technologies, should women be given the chance to preserve ovarian tissue prior to receiving intensive chemotherapy or radiotherapy?

Adult↗

Statistical modelling reveals demography and time are the main contributing factors in global sperm count changes between 1938 and 1996.

Declining sperm count reports have caused enormous concern to both the scientific community and to society. We reproduced the linear regression analysis and the quadratic model analysis using the 50 year sperm count data published in Carlsen's report and found that neither model adequately described the data. The reported decline in sperm count could be due to observational bias and overinterpretation of linear regression. In fact only 36% of the total variability in sperm count was explained by the linear model and 42% by the quadratic model. The linear model was no longer valid when three new European reports on sperm counts were included in the analysis. The quadratic model, however, suggested an upward trend of sperm count after 1975 (R2 = 0.48, P < 0.0001). Factors other than the 'passage of time' may have contributed to the initial decline of sperm count. An immediate candidate was demography. Our analysis showed that sperm counts in USA were significantly higher in 1938-1956 compared with those in 1957-1974 and 1975-1988, but not in the European or Asian/African/South American countries. The variability of the USA sperm count (1938-1988) explained by the linear and quadratic models was found to be 71 and 70% respectively. The quadratic model importantly indicated that the sperm count in USA decreases asymptotically towards a limiting value and global sperm counts could be increasing since 1970. The non-uniform nature of the global sperm count change suggested that local variations in pollution, diet but not global warming were important determinants of reproductive health.

Demography↗

In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests.

The results of in-vitro cervical mucus-sperm penetration tests and cross-hostility tests in 178 couples with repeatedly negative post-coital tests were recorded. Using a protocol of three cycles with intra-uterine inseminations (IUI) followed by three cycles with ovulation induction + IUI, the association between the cause of infertility, results of the in-vitro tests and the outcome of infertility treatment was investigated. We found that repeatedly negative post-coital tests are a good indicator of a cervical mucus-sperm penetration problem. The cross-hostility test clearly differentiates the abnormal factor in this interaction, and a good performance of the donors' spermatozoa in the cervical mucus correlates with increased pregnancy rate. In male factor infertility, failure of the husbands' spermatozoa to penetrate cervical mucus was not indicative of a deficient fertilization potential in vivo. In these patients a serious attempt should therefore be made to reverse the infertility by treatment with IUI or ovulation induction + IUI before attempting assisted reproduction. Women with polycystic ovaries and repeatedly negative post-coital tests should be investigated for sperm receptivity of the cervical mucus. Low receptivity of the cervical mucus may imply that endometrial receptivity and oocyte quality are also low. Ovulation induction and not IUI alone should therefore be used as the preferred mode of treatment to improve pregnancy rate.

Cervix Mucus↗

Specific structural alteration of the influenza haemagglutinin by amantadine.

Amantadine hydrochloride specifically blocks the release of virus particles from H7 influenza virus infected cells. This appears to be the direct consequence of an amantadine induced change in the haemagglutinin (HA) to its low pH conformation. The effect is indirect and mediated via interaction of the drug with the M2 protein since mutants altered in this component alone are insensitive to amantadine. The timing of drug action, some 15-20 min after synthesis, and its coincidence with proteolytic cleavage indicates that the modifications to HA occur late during transport but prior to insertion into the plasma membrane. Reversal by mM concentrations of amines and 0.1 microM monensin indicates that amantadine action causes a reduction in intravesicular pH which triggers the conformational change in HA. We conclude, therefore, that the function of M2 inhibited by amantadine is involved in counteracting the acidity of vesicular compartments of the exocytic pathway in infected cells and is important in protecting the structural integrity of the acid-sensitive glycoprotein.

Amantadine↗

Sexual function and fertility in patients treated for posterior urethral valves.

We interviewed 21 men treated in infancy for posterior urethral valves about their sexual function. Of the men 10 provided semen samples (1 of which was incompletely analyzed) and 7 provided urine voided after masturbation. Erections and orgasm were normal in 20 men and 1 had lifelong impotence. Nine men had slow or dry ejaculation. There was no evidence on urinalysis of retrograde ejaculation except in 1 patient. Semen counts were within the fertile range. Of 9 patients 5 had viscous semen with a pH of more than 8.0. Three patients had initiated pregnancies.

Adult↗

The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides.

A proportion of cytotoxic T lymphocytes (CTL) responding to infection by influenza recognize target cells that express the viral nucleoprotein. Recent work showed that CTL can recognize short overlapping regions of large nucleoprotein fragments expressed in transfected L cells. This led to the suggestion that CTL recognize segmental epitopes of denatured or degraded proteins in a similar way to helper T cells. One corollary of this idea is that CTL should recognize appropriate short peptides on the target cell surface. We demonstrate that the epitopes of nucleoprotein recognized by CTL in association with class I molecules of the major histocompatibility complex in both mouse and man can be defined with short synthetic peptides derived from the nucleoprotein sequence.

Alleles↗

The moral status of the embryo: the human embryo in the UK Human Fertilisation and Embryology (Research Purposes) Regulation 2001 debate.

The use of the embryo in research into birth defects, infertility and the possible therapeutic value of embryonic stem cells, has given rise to vigorous discussion of the ethical, moral and legal status of the embryo. This paper considers the parliamentary debate that surrounded the passing of legislation in the UK in 2000 governing the use of the embryo in research. Underlying disagreement by members of Parliament as to whether embryo research was permissible, were considerable differences regarding when life was thought to begin--whether at the moment of fertilization of the egg, or whether after 14 days, at the time of the beginnings of cell differentiation, and the point after which the embryo can no longer split to form twins. Those who favoured the latter view argued that, while the conceptus might possess a unique genetic formula, it had only the potential for life before 14 days, the development of human life being a gradual and continuous process. They considered it mistaken to accord the embryo full human rights. Those who adopted an opposed standpoint insisted that life was present and actual from the moment of conception and therefore sacrosanct and inviolable. The notion of the pre-embryo, they maintained, merely serves to disguise the embryo's humanity.

Bioethics↗

Novel PDE5 inhibitors for the treatment of male erectile dysfunction.

Erectile dysfunction (ED) affects the lives of approximately 150 million men worldwide. ED may be a cause of male sub-fertility in a significant proportion of patients. There is now an expanding armamentarium for the management of ED, including oral agents such as phosphodiesterase type 5 (PDE5) inhibitors. PDE5 inhibitors may also be useful in situations of temporary ED in couples undergoing IVF. Two novel PDE5 inhibitors have been commercially launched in the European Union in the first quarter of 2003. This article reviews the pharmacology and clinical efficacy of these new agents and their potential role in treating patients with male sub-fertility.

3',5'-Cyclic-GMP Phosphodiesterases↗