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Biomedical subjects

S L Tan

Publications and source records attributed to S L Tan.

At least 19 recordsLinked to original sources

Tyrosine kinase B receptor and its activated neurotrophins in ovaries from human fetuses and adults.

The signals initiating the growth of primordial follicles are unknown. Growth factors such as neurotrophin 4/5 (NT-4/5) and brain-derived neurotrophic factor (BDNF) may play a role in this process. To investigate the expression of NT-4/5 and BDNF and their receptor tyrosine kinase B (TrkB) in the early developing follicles, we fixed and froze 12 ovarian samples from adolescents/adults and 31 ovaries from human fetuses. The fixed samples were prepared for immunohistochemical staining for NT-4/5, BDNF and the TrkB receptor. Total RNA was extracted from the frozen ovarian samples, and the expression of NT-4/5, BDNF and the TrkB receptor (full length and two truncated isoforms) was investigated by RT-PCR. Products were resolved by 1% agarose gel electrophoresis and image analysis. Immunohistochemical staining revealed the expression of NT-4/5 and BDNF mainly in oocytes and, in a minority of samples, also in the granulosa cells (GCs); TrkB receptor was identified in oocytes and GCs. Transcripts of NT-4/5, BDNF and all forms of TrkB receptor were identified in the samples. To elucidate whether indeed NT-4/5 and BDNF are involved in growth initiation of human primordial follicles, they should be added to the culture medium.

Adolescent↗

Prevalence, incidence and predictors of pressure ulcers in a tertiary hospital in Singapore.

OBJECTIVE: In 2002 the hospital under study implemented a pressure ulcer standard care plan. This follow-up study aimed to determine the prevalence and incidence of pressure ulcers, whether demographic characteristics and medical diagnosis differed between those individuals who did and those who did not develop ulcers and the predictors of pressure-ulcer formation. METHOD: The prevalence study used a cross-sectional design, while the incidence study was a prospective cohort study. Participants were scored using the Braden scale and were examined for the presence of pressure ulcers. Those who were ulcer free were monitored twice weekly until they were discharged or for 28 days. RESULTS: The prevalence of pressure ulcers was 18.1% (95% CI: 15.5-20.9%), while the incidence was 8.1% (95% CI: 6.1-10.4%). Participants with ulcers were older, had a longer mean length of hospital stay, lower Braden scores and were diagnosed with or had a history of cardiovascular diseases or sepsis. Logistic regression found that the total Braden score was the only significant predictor of pressure ulcers. Compared with scores 16-23, the odds ratios were 7.7 (95% CI: 3.5-17.1, p < 0.001) and 12.5 (95% CI: 4.5-34.6, p < 0.001) for scores 12-15 and 6-11 respectively. Demographic characteristics, diagnosis and length of hospital stay were not significant predictors. CONCLUSION: The study identified a modest decrease in incidence and improvements in nursing care following the implementation of the care plan. It suggests that Braden scores are predictive of those at-risk of developing pressure ulcers.

Aged↗

What is true community-acquired urinary tract infection? Comparison of pathogens identified in urine from routine outpatient specimens and from community clinics in a prospective study.

In order to identify the true nature of community-acquired urinary tract infections, the uropathogens isolated from 100 patients with urinary tract infection included in a prospective study conducted in community clinics were compared to 244 isolates from outpatient urine specimens routinely submitted to the laboratory. Significant differences in both the spectrum of bacteria and their antibiograms were found between the two groups. Laboratory data analysis of uropathogens from outpatient urine specimens may not reflect the true bacteriology of urinary tract infections acquired in the community. Hence, surveys based on laboratory data alone may overestimate resistance rates, leading to misinformed choices being made when treatment is empirical.

Anti-Bacterial Agents↗

Reversible changes in protein phosphorylation during germinal vesicle breakdown and pronuclear formation in bovine oocytes in vitro.

This study examined the event of protein phosphorylation in bovine oocytes during germinal vesicle breakdown (GVBD) and formation of pronuclei following fertilisation in vitro. Immature oocytes were obtained from abattoir materials and cultured in vitro. The oocytes were labelled with [32P]orthophosphate at 3 h intervals from 0 to 12 h following maturation in culture or from 3 to 18 h following insemination. One-dimensional gel electrophoresis indicated that levels of protein phosphorylation are low prior to GVBD. However, the levels of protein phosphorylation at approximately 40 kDa, 27 kDa, 23 kDa and 18 kDa increased substantially following GVBD and then decreased gradually as maturation in culture progressed. In contrast, the levels of protein phosphorylation increased gradually in the oocytes following pronucleus formation. Further, two-dimensional gel electrophoresis indicated that the protein at approximately 18 kDa reversibly changed in the oocytes during maturation and fertilisation. These results indicate that the reversible changes of this phosphoprotein may be related to either cell cycle transition or pronucleus formation during maturation and fertilisation in bovine oocytes.

Animals↗

The cryobiology of assisted reproduction.

Cryopreservation of human gametes and embryos has become an integral part of assisted reproduction. The major developments in cryopreservation technology have mirrored the rapid expansion of reproductive technology over the past 2 decades. It is now possible to cryopreserve sperm, oocytes and embryos at their various stages of development. The introduction of vitrification and rapid freezing techniques is gaining widespread recognition and may become the method of choice over traditional slow freezing methods. Ovarian tissue cryopreservation offers the hope of fertility preservation for women who are faced with potentially sterilizing medical or surgical treatments. Paralleling the introduction of cryobiology to assisted reproduction has been the realization of a number of moral and ethical issues related to gamete and/or embryo storage.

Cryopreservation↗

Cancer incidence following treatment for infertility at a clinic in the UK.

BACKGROUND: There is concern about the long-term health impact of ovarian stimulation treatment for infertility, in particular the effect on cancer risk. The aim of this study was to investigate the incidence of cancer in a cohort of women attending a large infertility clinic in the UK. METHODS: Women who were UK residents attending the clinic between January 1, 1975 and December 31, 1989 were identified for the study. The cohort was followed-up and cancer incidence rates calculated. RESULTS: The study cohort was made up of 5556 women of whom 75% had received ovarian stimulation drug treatment at the clinic. A total of 118 cancers (including 55 breast, four corpus uteri and six ovarian) were incident in the cohort from the beginning of 1990 to the end of 1997. The incidence rates of cancer of the breast, corpus uteri and ovary were not significantly different from expectation based on national cancer rates, and were similar for women who had received hormonal treatment to stimulate their ovaries and those who had not. CONCLUSIONS: These data do not support a hypothesis linking infertility treatment involving ovarian stimulation with increased breast, uterine and ovarian cancer over the follow-up period studied.

Adult↗

How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A.

Interferons (IFNs) induce an antiviral state in the cell through complex and indirect mechanisms, which culminate in a direct inhibition of viral replication and stimulation of the host adaptive responses. Viruses often counteract with elaborate strategies to interfere with the induction as well as action of IFN effector molecules. This evolutionary battle between viruses and IFN components is a subject of intense research aimed at understanding the immunopathogenesis of viruses and the molecular basis of IFN signaling and action. In the case with hepatitis C virus (HCV), this may have profound implications for the therapeutic use of recombinant IFN in treating chronic hepatitis C. Depending on the subtype of HCV, current IFN-based treatment regimens are effective for only a small subset of chronic hepatitis C patients. Thus, one of the Holy Grails in HCV research is to understand the mechanisms by which the virus may evade IFN antiviral surveillance and establish persistent infection, which may eventually provide insights into new avenues for better antiviral therapy. Despite the lack of an efficient tissue culture system and an appropriate animal model for HCV infection, several mechanisms have been proposed based on clinical studies and in vitro experiments. This minireview focuses on the HCV NS5A nonstructural protein, which is implicated in playing a role in HCV tolerance to IFN treatment, possibly in part through its ability to inhibit the cellular IFN-induced PKR protein kinase.

Animals↗

Effects of laparoscopic ovarian drilling on adrenal steroids in polycystic ovary syndrome patients with and without hyperinsulinemia.

OBJECTIVE: To evaluate adrenal steroid responses to ACTH stimulation and insulin responses to oral glucose tolerance test (OGTT) in clomiphene-citrate-resistant anovulatory women with polycystic ovary syndrome (PCOS) before and after laparoscopic ovarian drilling. DESIGN: Prospective study. SETTING: Healthy participants in a university teaching hospital. PATIENT(S): Twenty clomiphene-citrate-resistant anovulatory women with PCOS. INTERVENTION(S): Laparoscopic ovarian drilling. MAIN OUTCOME MEASURE(S): Adrenal steroid responses to ACTH stimulation and insulin responses to OGTT before and after ovarian drilling. RESULT(S): Fourteen of 20 women completed the study. There was a correlation between body mass index and basal insulin levels before ovarian drilling. This correlation was lost after surgery. Area-under-the-curve glucose and insulin values before surgery in women with hyperinsulinemia (1,033.3 +/- 112.7 mmol/L and 141,919 +/- 26,177 pmol/L, respectively) were significantly higher than in those with normoinsulinemia (777.1 +/- 77.2 mmol/L and 69,867 +/- 19,390 pmol/L respectively, P<.05). There was a significant difference in insulin and glucose responses before and after ovarian drilling in women with hyperinsulinemia. No difference was found in women with normoinsulinemia. There was no significant difference in adrenal steroid responses to ACTH stimulation before and after ovarian drilling. CONCLUSION(S): PCOS women with hyperinsulinemia respond differently to laparoscopic ovarian drilling than do those with normoinsulinemia. Among women with hyperinsulinemia, surgery decreases glucose and insulin responses to OGTT. Regardless of the insulin level, laparoscopic ovarian drilling does not influence adrenal steroid dynamics.

Adrenocorticotropic Hormone↗

In vitro maturation and fertilization of oocytes from unstimulated normal ovaries, polycystic ovaries, and women with polycystic ovary syndrome.

OBJECTIVE: To investigate differences in immature oocyte maturation, fertilization, and pregnancy rates among women with unstimulated normal ovaries, polycystic ovaries (PCOs), or PCOS. DESIGN: Prospective observational study. SETTING: University fertility clinic. PATIENT(S): One hundred forty-four women undergoing 180 in vitro oocyte maturation treatment cycles. INTERVENTION(S): Transvaginal immature oocyte recovery from unstimulated ovaries 36 hours after hCG priming. In vitro oocyte maturation and fertilization. Fresh embryo transfer. MAIN OUTCOME MEASURE(S): Immature oocytes collected, metaphase II oocytes, and embryos produced. Implantation and pregnancy rates. RESULT(S): The overall oocyte maturation and fertilization rates attained were 80.3% (1,222 of 1,522) and 76.5% (935 of 1,222), respectively. Significantly fewer immature oocytes were retrieved from normal ovaries (5.1 +/- 3.7) compared with the PCO (10.0 +/- 5.1) or PCOS (11.3 +/- 9.0) groups. Fertilization and cleavage rates were comparable among the three groups. The implantation, pregnancy, and live birth rates per transfer for normal ovaries were 1.5%, 4.0%, and 2.0%, respectively; for PCOs 8.9%, 23.1%, 17.3%, respectively; and for women with PCOS 9.6%, 29.9%, and 14.9%, respectively. CONCLUSION(S): Immature oocytes retrieved from normal ovaries, PCOs, or women with PCOS, when using hCG priming before oocyte retrieval, have a similarly high maturation, fertilization, and cleavage potential. In vitro maturation is a useful treatment option, particularly for women with PCOs.

Cells, Cultured↗

Industry-sponsored research in minimally invasive surgery.

In many disciplines, including minimally invasive surgery, pharmaceutical and instrument companies are major sources of industry-sponsored research. There are two types of such research, industry-initiated and investigator-initiated. Distinction between them is sometimes blurred. In industry-sponsored research a conflict may occur between clinicians and sponsor. In all cases, a clinical trial should be done properly and ethically, and results, whether negative or positive, should be published. Disposition of intellectual property and authorship should be established before starting the trial.

Humans↗

Direct comparison of detection systems used for the development of single-cell genetic tests in preimplantation genetic diagnosis.

PURPOSE: Single-cell polymerase chain reaction (PCR) requires efficient amplification and accurate detection. We compare the accuracy of heteroduplex, fluorescent-fragment, and fluorescent single-strand conformation polymorphism (F-SSCP) analysis as detection systems for analysis of a PCR assay developed for preimplantation genetic diagnosis. METHODS: A single-cell, fluorescent multiplex PCR assay was developed for the cystic fibrosis delta F508 mutation and the short tandem repeat, D21S11. Detection systems were compared by analyzing blinded PCR products. RESULTS: Amplification rates for cystic fibrosis were 89% by heteroduplex and 91% by fragment analysis, while it was 72% for D21S11 by fragment analysis. No difference in allele dropout was detected for cystic fibrosis by any method (2%). Overall accuracy was high, > 97%, although SSCP was the least accurate. CONCLUSIONS: Heteroduplex and fragment analysis proved equal in the diagnosis of a single amplified locus. We determined that fragment analysis allows maximal accuracy of detection and permits analysis of a second loci, controlling for DNA contamination and allelic dropout.

Cystic Fibrosis↗

Trends in the incidence of births and multiple births and the factors that determine the probability of multiple birth after IVF treatment.

BACKGROUND: We aimed to review trends in the probability of birth and multiple birth before and after the legal restriction limiting the maximum allowable number of embryos transferred, and to examine factors that determine the probability of multiple birth following IVF treatment. METHODS: We analysed data relating to 7170 IVF and 530 intracytoplasmic sperm injection cycles reaching embryo transfer undertaken by 4417 women at a single tertiary referral assisted conception centre in the UK between 1984 and 1997. Probability of birth, and of proportion of multiple births among those who gave birth, was explored using logistic regression analysis. RESULTS: Between 1984 and 1997 there was a significant increase in probability of birth but no change in the probability of multiple birth. The trend in probability of birth was almost wholly explained by the significant increase in number of embryos created per cycle. Pooling all the data, risk factors for increased chance of birth and multiple birth were: younger age (<35 years), diagnoses other than tubal infertility, fewer than three previous unsuccessful cycles, previous IVF live birth and a large number of embryos created. Given these factors, increasing the number of embryos transferred did not increase the chance of a birth, but did increase the chance of a multiple birth. CONCLUSIONS: The probability of birth has increased and the probability of multiple birth has remained unchanged, despite legislation limiting the number of embryos transferred in the UK. Efforts should be made to reduce the incidence of multiple births by transferring fewer embryos, especially in the presence of good prognostic factors for birth.

Adult↗

A documented clomiphene-induced follicular development in pregnancy.

A case of clomiphene-induced follicular growth in pregnancy is presented in a 34-year-old woman with ectopic pregnancy treated at a university teaching hospital. Following administration of clomiphene citrate in pregnancy, follicular growth to 18 mm mean diameter was noted. It is concluded that clomiphene citrate can induce follicular growth and maturation in pregnancy, possibly by reversing pregnancy-induced pituitary suppression.

Adult↗

Ongoing twin pregnancy after ICSI of PESA-retrieved spermatozoa into in-vitro matured oocytes: case report.

The recovery of immature oocytes from unstimulated ovaries followed by in-vitro maturation (IVM) is an attractive alternative to conventional IVF in the treatment of female infertility. Similarly, surgical recovery of spermatozoa from the epididymis by percutaneous sperm aspiration (PESA) has simplified the retrieval of the male gamete in treatment of men with obstructive azoospermia. We report the first ongoing clinical twin pregnancy resulting from intracytoplasmic sperm injection (ICSI) of spermatozoa retrieved by PESA into IVM oocytes. In the treatment of a 24-year old woman, 12 immature oocytes were retrieved. Six oocytes matured (maturation rate 50%) after 24-hour incubation and were inseminated by ICSI. Four oocytes had two pronuclei (fertilization rate 67%) and 3 good quality embryos were transferred. A viable twin pregnancy was confirmed by ultrasound scan. This report illustrates the use of a combination of less invasive assisted reproductive techniques in overcoming barriers to infertility.

Adult↗