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Biomedical subjects

S C Ng

Publications and source records attributed to S C Ng.

At least 109 records · Page 6Linked to original sources

Blastocyst transfer after enzymatic treatment of the zona pellucida: improving in-vitro fertilization and understanding implantation.

It has been shown recently that delayed transfers improve implantation rates in assisted reproductive technology programmes. In a prospective study, the pregnancy rates and safety of outcome were evaluated in a group of patients after the transfer of day 5 blastocysts with enzymatic treatment of the zona pellucida. Nineteen women with a mean age of 32.6+/-5.2 years and mean 2.1+/-2.2 repeated attempts had blastocyst transfers with a mean number of 2.5+/-0.7 embryos replaced per patient. The clinical pregnancy rates per cycle/transfer and implantation rate were 53% and 33%, respectively. The multiple pregnancy rate was 40% (two pregnancies were triplets). The pregnancy and implantation rates were very much higher than observed for most assisted reproduction technology centres. The 'in-vitro implantation' rates of zona-free blastocysts on a variety of feeder monolayers was 92%, offering some thoughts as to the role of the zona and interaction of the inner cell mass and trophoectoderm with the endometrium in implantation. Based on the in-vitro studies and the high multiple pregnancy rates, it appears that zona-manipulated blastocysts implant relatively well and there would be a need to reduce the number of transferred embryos to one or two, thus reducing multiple pregnancies and having spare blastocysts available for cryopreservation. The results also suggest that using the embryo culture protocol and method of transfer in the present study offers encouraging improvements to assisted reproduction technology, and enzymatic treatment of the zona may allow better anchorage and dialogue of the embryo with the endometrium, helping us to improve and understand implantation.

Adult↗

Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion.

Submicroscopic deletions of the Y chromosome and polymorphisms of the androgen receptor (AR) gene in the X chromosome have been observed in men with defective spermatogenesis. To further define the subregions/genes in the Y chromosome causing male infertility and its relationship to polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of 202 subfertile males and 101 healthy fertile controls of predominantly Chinese ethnic origin. Y microdeletions were examined with 16 sequence-tagged site (STS) probes, including the RBM and DAZ genes, spanning the AZFb and AZFc subregions of Yq11, and related to the size of trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions were detected and confirmed in three out of 44 (6.8%) of azoospermic and three out of 86 (3.5%) severely oligozoospermic patients. No deletions were detected in any of the patients with sperm counts of >0.5 x 10(6)/ml, nor in any of the 101 fertile controls. All six affected patients had almost contiguous Y microdeletions spanning the entire AZFc region including the DAZ gene. The AZFb region, containing the RBM1 gene, was intact in five of the six subjects. Y deletions were not found in those with long AR polyglutamine tracts. Our study, the first in a Chinese population, suggest a cause and effect relationship between Y microdeletions in the AZFc region (possibly DAZ), and azoospermia or near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear to be independent contributors to male infertility.

Adult↗

Gastroesophageal reflux in preterm infants: norms for extended distal esophageal pH monitoring.

BACKGROUND: Preterm infants are predisposed to gastroesophageal reflux, which may manifest itself in many ways ranging from failure to thrive to vomiting. Extended distal esophageal pH monitoring is the gold standard for diagnosing reflux in the preterm infants and it is our objective to establish extended distal esophageal pH norms (reference values) for well, asymptomatic preterm infants and to compare with norms already established for term infants, children, adolescents, and adults. METHODS: Twenty-one well, asymptomatic preterm infants consuming at least 70% of required maintenance oral feedings were recruited. The mean +/- standard deviation birth weight was 1549 +/- 439 g (range, 670-2470 g); the mean postconceptional age was 30.7 +/- 2.6 weeks (range, 25-35 weeks) and the mean postnatal age was 14 +/- 9 days (range, 2-40 days). Extended distal esophageal pH monitoring was performed on each of the infants, and the following parameters were calculated: reflux index, number of reflux episodes per day, number of reflux episodes lasting more than 5 minutes per day, and the longest recorded reflux episode. RESULTS: The mean reflux index was 0.7 +/- 1.1%, the mean number of reflux episodes per day was 7.6 +/- 11.2, the mean number of reflux episodes lasting more than 5 minutes per day was 0.5 +/- 1.1 and the mean longest recorded reflux episode was 4.2 +/- 6.1 minutes. These results were comparable to those seen in term infants, children, adolescents, and adults. The trends for pH norms according to postconceptional age and postnatal age seemed to suggest that lower esophageal sphincter maturation might be related to postconceptional age, but the differences observed were not statistically significant (p > 0.05). CONCLUSION: The norms (reference values) for well, asymptomatic preterm infants were comparable to those seen in term infants, children, adolescents, and adults. With the establishment of these norms, the search for a causal link between many of the respiratory problems encountered in prematurity and gastroesophageal reflux may be aided and the complications associated with gastroesophageal reflux may consequently be reduced.

Aging↗

The first 2 case reports of frozen embryo donation twin pregnancies in Singapore: hormonal profiles and obstetrical outcome.

A 35 year old women with premature ovarian failure and another 30 year old women with gonadal dysgenesis were the recipients of donated supernumerous frozen embryos after successfully prepared with cyclic steroid replacement therapy as described previously. One patient received 4 and the second 2 frozen embryos, transferred transcervically on the 3rd day of progesterone administration. Both patients had viable twin pregnancies. The plasma beta hCG levels for both patients at 2 weeks post replacement (4 weeks gestation) were lower than the median values in our normal, uncomplicated singleton pregnancy for the same gestation. The level after 4 weeks post-replacement (6 weeks gestation) became comparable. Plasma progesterone profiles suggested a level of above 70 ng/ml would be enough to support the twin pregnancies. The first patient developed antepartum haemorrhage of unknown origin at 34 weeks of gestation preceding preterm premature rupture of membranes and subsequently had preterm labour. The second patient developed proteinuric hypertension at 33 weeks of gestation. Both ended in a lower segment cesarean section. Both sets of twins and their mothers were discharged well.

Adult↗

Enhanced secretory production of a single-chain antibody fragment from Bacillus subtilis by coproduction of molecular chaperones.

Formation of inclusion bodies is a major limiting factor for secretory production of an antidigoxin single-chain antibody (SCA) fragment from Bacillus subtilis. To address this problem, three new strains with enhanced production of molecular chaperones were constructed. WB600BHM constitutively produces the major intracellular molecular chaperones in an appropriate ratio without any heat shock treatment. This strain reduced the formation of insoluble SCA by 45% and increased the secretory production yield by 60%. The second strain, WB600B[pEPP], overproduces an extracytoplasmic molecular chaperone, PrsA. An increase in the total yield of SCA was observed. The third strain, WB600BHM[pEPP], coproduces both intracellular and extracytoplasmic molecular chaperones. This led to a further reduction in inclusion body formation and a 2.5-fold increase in the secretory production yield. SCA fragments secreted by this strain were biologically active and showed affinity to digoxin comparable to the affinity of those secreted by strains without overproduction of molecular chaperones. Interestingly, accumulation of a pool of periplasmic SCA was observed in the PrsA-overproducing strains. This pool is suggested to represent the secreted folding intermediates in the process of achieving their final configuration.

Antigen-Antibody Reactions↗

Azoospermia associated with a mutation in the ligand-binding domain of an androgen receptor displaying normal ligand binding, but defective trans-activation.

Although male infertility affects a significant proportion of couples trying to conceive, the cause of defective spermatogenesis is not known in a large number of cases. Ligand binding studies indicate that a number of these subjects may have defects of the androgen receptor (AR). Genetic screening in subjects with defective spermatogenesis and in 110 fertile controls identified an azoospermic (no sperm in any ejaculates) patient with an amino acid substitution (Gln-->Glu) in residue 798 of the AR gene. This germline mutation was pathogenic because it was not observed in fertile controls, was associated with features of minimal androgen insensitivity in our patient, has been related to more severe grades of androgen insensitivity, and caused a subtle, but significant, decrease in receptor trans-activation function in vitro that is consistent with the phenotype. Despite being located in the middle of the ligand-binding domain of the receptor, the Q798E mutation did not cause any ligand binding defect, indicating that this highly conserved residue has a trans-activation function but does not directly form part of the ligand binding pocket of the receptor. The trans-activation defect of the mutant receptor can be rectified in vitro with the androgenic drug, fluoxymesterone, but not with mesterolone or nortestosterone. Further studies are required to determine the therapeutic relevance of this finding.

Adult↗

Androgen receptor transactivation domain and control of spermatogenesis.

Male sex steroids (androgens) are important for maintaining sperm production and growth of the accessory sex organ, the prostate gland. This article examines the role of the androgen receptor (AR) in the control of spermatogenesis and focusses on the N-terminal transactivation domain of the receptor, a poorly studied region that is essential for receptor function. This domain is of great interest because of its causative relationship to a fatal neuromuscular disease, spinal bulbar muscular atrophy (Kennedy's syndrome). Genetic screening of the transactivation domain of the AR gene of 153 patients presenting solely with defective spermatogenesis and male infertility, and of over 72 healthy fertile controls was performed. Up to 20% of infertile males have reduced androgenicity caused by an increase in length of a polymorphic trinucleotide (CAG) repeat segment, encoding a polyglutamine tract, of the androgen receptor. The increased risk of male infertility associated with long CAG lengths is associated with reduced risk of prostate cancer. Conversely, short polyglutamine tracts are associated with increased risk of prostate cancer but a reduced risk of male infertility. Thus depressed spermatogenesis and prostate cancer represent opposite ends of the spectrum of androgen receptor transactivation function. Improved understanding of androgen receptor action in these two important public health concerns could lead to rational and effective prevention and therapy.

Humans↗

Laparoscopic adhesiolysis for subfertility.

AIM: Laparoscopic adhesiolysis has been associated with pregnancy rates of 12% to 58%. This study looks at our experience with laparoscopic adhesiolysis in the management of subfertile patients. METHOD & RESULTS: Between January 1992 and March 1995, 27 subfertile patients who had laparoscopic adhesiolysis done were studied. Four patients (15%) had a second look laparoscopy. The overall pregnancy rate (after excluding 6 patients with bilateral tubal blockage or severe male factor) was 33% (7/21). The take home baby rate was 14.3% (3/21) and the ectopic pregnancy rate was 4.7% (1/21). CONCLUSION: Laparoscopic adhesiolysis still remains a useful and effective procedure for infertile couples with pelvic adhesions.

Adnexal Diseases↗

Imaging of thoracic manifestations of scleroderma.

Radiographs illustrating the various thoracic manifestations of systemic sclerosis are shown. These include pulmonary parenchymal disease e.g. interstitial pneumonitis and pneumonia, pleural disease (pneumothorax), cardiac involvement, oesophageal disease, bony changes and soft tissue calcification. The use of chest radiography and other imaging modalities such as high resolution computerised tomography (HRCT) of the thorax is discussed.

Adult↗

A case of sulindac-induced enteropathy resulting in jejunal perforation.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for rheumatic conditions. Their effects on the upper gastrointestinal tract are well recognised. Clinically important damage to the small intestines is less common and often unrecognised. We report a case of sulindac-induced jejunal perforation in a rheumatoid arthritis (RA) patient with previous gastrectomy for gastric carcinoma. The prevalence, diagnosis, pathogenesis and treatment options of NSAID-induced enteropathy will be discussed.

Anti-Inflammatory Agents, Non-Steroidal↗

Are antacids necessary as routine prescriptives with non-steroidal anti-inflammatory drugs?

In Singapore, there exists a local habit to routinely prescribe antacids with non-steroidal anti-inflammatory drugs (NSAIDs) perhaps in the belief that gastrointestinal (GI) symptoms and complications are common, and that antacids protect from them. We prospectively studied 140 adults in an orthopaedic clinic who were prescribed a short course of NSAIDs (1 to 4 weeks) without antacids to determine the frequency and severity of GI symptoms. Symptomatic patients were then given antacids to determine their effect on the GI symptoms and followed up by telephone interview. These patients had mild inflammation, soft tissue rheumatism, injury or degenerative disease. All were otherwise well with no known peptic ulcer disease or major illness and were not on ulcerogenic drugs. Only 13 (9.3%) had significant GI symptoms, of which 6 (4.2%) of the total took antacid and 5 (3.5%) had partial or total relief. In this study, GI symptoms were not common with short course NSAIDs in otherwise well patients. Antacids may afford symptomatic relief for GI symptoms. However, because antacids may offer no significant protection against NSAID-induced peptic ulcer, may dangerously mask symptoms of GI irritation, may be troublesome to take and costly on a large scale, we should stop routine prescription of antacids in patients requiring only short-term NSAIDs and not at risk for peptic ulcer disease.

Adolescent↗

Idiopathic pulmonary haemosiderosis--a case report.

Idiopathic pulmonary haemosiderosis (IPH) is a disorder characterised by the triad of haemoptysis, diffuse parenchymal infiltrates on chest roentgenogram and iron-deficiency anaemia. It is a diagnosis of exclusion and the prognosis is bleak despite the varied management options. We report a case of IPH occurring in a child who presented at four months of age with cough, wheeze, haemoptysis and pallor and whose symptoms are currently controlled with high-dose inhaled budesonide and low-dose oral prednisolone.

Anti-Inflammatory Agents↗

Case report of ruptured endometriotic cyst in pregnancy treated by laparoscopic ovarian cystectomy.

Pregnancy is thought to have an ameliorating effect on endometriosis, inducing a state of quiescence. We report a case of ruptured endometriotic cyst in pregnancy successfully treated by laparoscopic ovarian cystectomy. Our patient subsequently progressed uneventfully to deliver a healthy baby girl at term. Laparoscopic ovarian cystectomy in pregnancy, even with ruptured cysts, appeared to be safe in trained hands with similar benefits of reduced post-operative morbidity.

Adult↗

Apoptotic program is initiated but not completed in LNCaP cells in response to growth in charcoal-stripped media.

BACKGROUND: Morphological, proliferative, and genetic changes were studied in androgen-responsive LNCaP cells in response to growth in charcoal-stripped (CS) media. METHODS AND RESULTS: Within 5 days of treatment, there were dramatic changes in the morphology and organization of LNCaP cells. The cells unclumped and acquired a distinct neuronal-like appearance with small cell bodies and multiple long, thin processes. Despite this appearance, the cells stained negative to monoclonal antibodies to neuronal markers such as microtubule-associated protein-2 (MAP-2) and glial fibrillary acidic protein (GFAP). In situ end-labeling assay indicated that the number of cells showing signs of apoptosis (DNA fragmentation) increased dramatically in CS media compared to the control. However, ultrastructural changes and the fragmented DNA ladder that are used to define apoptosis were not observed. Instead of cell death, the cells became cytostatic, which can be reversed, although not completely, by exogeneous addition of dihydrotestosterone in a dose-dependent manner. Presence of mRNA of several genes involved in the apoptotic process, i.e., Bcl-2, Bcl-X, ICE, Ich-1, and DAD-1, was studied in response to normal and CS media. We detected mRNA of Bcl-2, Bcl-XL, Bcl-XS, Ich-1L and DAD-1, while ICE and Ich-1S were not expressed in LNCaP cells. CONCLUSIONS: This suggests that certain signals that may be essential for complete execution of the apoptotic program may be missing in this in vitro model. This may explain our observation that the growth of LNCaP cells in CS media does not fully mimic castration-mediated regression of the prostate gland in vivo.

Apoptosis↗

The single sperm curling test, a modified hypo-osmotic swelling test, as a potential technique for the selection of viable sperm for intracytoplasmic sperm injection.

OBJECTIVE: To develop a technique for the selection of viable sperm for intracytoplasmic sperm injection (ICSI), based on the phenomenon of sperm tail curling in a hypo-osmotic environment, through modification of the hypo-osmotic swelling test. DESIGN: Individual sperm were exposed to single sperm curling (SSC) medium and then injected into hamster oocytes to study the effect of SSC medium on fertilization. SETTING: All materials were collected from the National University Hospital in Singapore. PATIENT(S): Semen of proven donors and hamster oocytes with intact zonae were used. INTERVENTION(S): ICSI and the SSC test. MAIN OUTCOME MEASURE(S): Sperm head decondensation and male pronucleus formation. RESULT(S): Sperm head decondensation and male pronucleus formation were present in 59.4% and 42.4%, respectively, of the oocytes injected with sperm that had been exposed to SSC medium. These rates were 70% and 48.8%, respectively, when the sperm were washed thoroughly after exposure to SSC medium. In the control group (sperm that were not exposed to SSC medium), these rates were 68.8% and 46.2%, respectively. CONCLUSION(S): The SSC test is useful for the selection of viable sperm for ICSI. It allows the behavioral study of a single sperm in hypo-osmotic conditions. Thorough washing of the exposed sperm is important. This procedure would be of benefit especially in testicular biopsies or very severe cases of low sperm count in which only a few sperm are found among many other cells and artifact.

Animals↗

Responses of polycystic ovarian syndrome and related variants to low-dose follicle stimulating hormone.

OBJECTIVE: To determine whether patients with classical polycystic ovarian syndrome (PCOS) respond differently to low-dose FSH therapy in comparison with anovulatory patients (PCOS-like) where only some features of PCOS are present. METHODS: Two groups of patients were studied. The PCOS group (25 patients, 51 cycles) and the PCOS-like group (38 patients, 57 cycles) were treated with the same protocol of purified FSH, commencing with an initial dosage of 75 IU/day and increasing by 37.5 IU/day after 14 days, where necessary. Estradiol levels and ultrasonographic evidence of follicular development were used for monitoring. RESULTS: PCOS patients required more ampules of FSH, needed more days of gonadotropin stimulation, secreted higher levels of E2 and had increased numbers of intermediate follicles compared to the PCOS-like group. CONCLUSIONS: This study demonstrated significant differences between PCOS and other PCOS-like conditions when treated with low-dose FSH. Classification of the subvariants of PCOS may have therapeutic implications.

Adult↗

Processing of hydroxyapatite via microemulsion and emulsion routes.

Hydroxyapatite powders have been prepared by reacting CaCl2 and (NH4)2HPO4 in bicontinuous microemulsion, inverse microemulsion and emulsion, which have the same components as cyclohexane, non-ionic surfactant (NP5 + NP9) and aqueous solution. The characteristics of the resulting hydroxyapatite powders, such as the particle size, particle size distribution, chemical homogeneity and the degree of particle agglomeration, are strongly affected by the structure of the reaction medium. Both bicontinuous and inverse microemulsions led to the formation of much finer hydroxyapatite powders than that prepared from the emulsion composition. The two fine hydroxyapatite powders are sintered to a relative density of >95% theoretical density at 1000 degrees C, compared with a relative density of <73% theoretical density for the emulsion-derived one. The two microemulsion-derived hydroxyapatites also exhibit a higher sintered density and are more refined in grain size than that of the emulsion-derived one when sintered at 1200 degrees C for 2h.

Ceramics↗