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Biomedical subjects

S Ratnam

Publications and source records attributed to S Ratnam.

At least 37 records · Page 2Linked to original sources
PubMed1997

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↗
PubMed1997

Ongoing normal pregnancy after transfer of zona-free blastocysts: implications for embryo transfer in the human.

Recent reports suggest that transfer of day 5 blastocysts improves implantation rates in in-vitro fertilization programmes. This paper reports a successful ongoing pregnancy after the transfer of zona-free day 6 expanded and hatching blastocysts. The patient was 37 years old and had undergone six stimulated and two thaw cycles previously, all of which had failed. Stimulation was by down-regulation and oocytes recovered transvaginally by ultrasound guidance. Two pronuclear embryos were co-cultured on Vero cells to day 6. The zonae of two hatching and two fully expanded blastocysts were removed using 0.5% pronase, and the zona-free blastocysts were then transferred. Pregnancy was confirmed on day 18 with a positive human chorionic gonadotrophin (HCG) and ultrasound at 6 weeks showed a single healthy fetal heart inside a clear sac. At 14 weeks a triple test (oestriol, J-HCG and alpha-fetoprotein) was normal and at 22 weeks a detailed ultrasound scan showed no congenital anomalies. This is the first report in the human of a normal ongoing pregnancy after the transfer of zona-free day 6 embryos.

Adult↗
PubMed1996

Prevalence of HIV infection among pregnant women in Newfoundland.

OBJECTIVE: To determine the prevalence of HIV infection among pregnant women in Newfoundland. DESIGN: Anonymous unlinked seroprevalence study. SETTING: Newfoundland. PATIENTS: A total of 14911 women receiving prenatal care or undergoing an abortion, representing nearly all pregnancies in Newfoundland from Nov. 1, 1991, to Oct. 31, 1993. OUTCOME MEASURES: HIV antibody status, as determined by enzyme immunoassay of leftover serum samples (initially obtained for routine screening) and confirmation of reactive samples by the Western blot technique, health region of residence, and age group. RESULTS: Of the 14911 serum samples 13 were positive for HIV, for an overall crude prevalence rate of 1 per 1147 or 8.7 per 10000 pregnant women (95% confidence interval [CI] 4.7 to 14.9). Seven of the positive samples were from women residing in the Eastern Health Region of the province, for a crude prevalence rate of 1 per 376 or 26.6 per 10000 pregnant women (95% CI 10.7 to 54.8) for that region. All women found to be HIV positive were 15 to 29 years of age, the peak prevalence (20.8 per 10000 pregnant women [95% CI 9.5 to 39.4]) was observed among those 20 to 24 years. CONCLUSIONS: The overall prevalence rate of 8.7 per 10 000 pregnant women in Newfoundland is the highest provincial rate recorded among those from similar studies in Canada. Although it may be concluded that there are an estimated 125 HIV-positive women of childbearing age in Newfoundland (95% CI 67 to 213), the age-adjusted estimate is 84 (95% CI 36 to 131). This study provides an independent confirmation of an outbreak of HIV infection among women in the Eastern Health Region of the province.

Adolescent↗
PubMed1996

Management of non-immune hydrops: 8 years' experience.

During a period of 8 years (1985-92), 100 fetuses were diagnosed to have non-immune hydrops on the basis of ultrasonographic findings and absence of rhesus isoimmunization. Both the mother and the fetus were thoroughly evaluated by a set protocol that included a detailed fetal abnormality scan with echocardiography and fetal blood sampling. A cause for non-immune hydrops could be identified in 81% of the fetuses. Cardiovascular abnormalities (23%) and alpha(1)-thalassemia (22%) were almost equally common etiological factors in the South-East Asian population under investigation. A chromosomal abnormality was detected in 10% of the fetuses with non-immune hydrops. Twenty-six fetuses were found to be suitable for in utero therapy. In utero therapy included one or more of the following: (1) fetal intravascular blood transfusion; (2) direct fetal drug therapy; and (3) fetal pleuroamniotic shunting. Eighteen of the 26 babies (69.2%) were alive and well at 1 month after delivery. It is concluded that in well-selected cases appropriate in utero fetal therapy can lead to significant improvement in fetal salvage.

Evaluation Studies as Topic↗
PubMed1996

Safety and tolerability of combined treatment with moclobemide and SSRIs: a systematic study of 50 patients.

Fifty major depressed patients, resistant to multiple pharmacotherapies, were treated by the addition of moclobemide (up to 600 mg/day) to paroxetine or fluoxetine (20 mg/day) for 6 weeks in an open study to assess tolerability. There were 188 adverse events: insomnia, dizziness, headache, nausea, dry mouth and myoclonic jerks were the most common. Many events were rated as severe. The high rate of adverse events suggest that there are clinically significant pharmacodynamic interactions between moclobemide and SSRIs. However the uncontrolled data on effectiveness is encouraging and the combination deserves further consideration as a strategy for treating intractable depression.

Adult↗
PubMed1996

Heterogeneity in phenotypic and genotypic characteristics among strains of Hafnia alvei.

Hafnia alvei is an emerging human pathogen associated with sporadic cases and outbreaks of diarrhea. Bangladeshi isolates of H. alvei possess the Escherichia coli attaching and effacing (eaeA) gene and demonstrate an attaching and effacing phenotype. In the present study we examined 11 Canadian H. alvei isolates and strain 19,982 from Bangladesh to determine if the formation of attaching and effacing lesions is a property shared among multiple isolates. Attaching and effacing lesions were detected by induction of tyrosine kinase protein phosphorylation and cytoskeletal rearrangements in infected tissue culture epithelial cells with immunofluorescence microscopy and by the examination of infected cells with transmission electron microscopy. The presence of the eaeA gene was examined by PCR and colony blot hybridization. Profiles of outer membrane protein extracts, chromosomal macrorestriction fragments, and plasmids were also examined. Accumulation of host phosphotyrosine proteins and rearrangement of the cytoskeletal protein alpha-actinin were both observed in HEp-2 cells infected with H. alvei 19,982. In contrast, none of the other 11 clinical H. alvei isolates demonstrated either of these responses, nor did they form attaching and effacing lesions under electron microscopy. Consistent with the absence of the attaching and effacing phenotype, these clinical isolates did not possess the eaeA gene. The outer membrane protein profiles of all the Canadian isolates were identical but differed from that of H. alvei 19,982. Pulsed-field gel electrophoresis and plasmid profile analyses of the clinical H. alvei isolates differed substantially from those of the Bangladeshi strain. These results indicate that there is heterogeneity among H. alvei strains with respect to signal transduction, attaching and effacing adhesion, outer membrane constituents, and genotype. Epidemiological studies on enteropathogenic H. alvei thus need to go beyond simple species designations and require specific identification of the virulent clones.

Actinin↗
PubMed1996

Randomised controlled trial of methyldopa and isradipine in preeclampsia--effects on uteroplacental and fetal hemodynamics.

This is a prospective randomised controlled study in 21 women admitted with preeclampsia in the third trimester. The mean arterial blood pressure decreased by 11.1 mmHg (95% confidence interval -14.9 to -7.3 mmHg) in the methyldopa group, and by 9.3 mmHG (95% confidence interval-14.4 to -4.2 mmHG) in the isradipine group. The maternal heart rate decreased by 6.9 beats per min (95% confidence interval -11.6 to -2.2 bpm) during methyldopa treatment, and by 2.5 beats per min (95% confidence interval -9.2 to 4.3) during isradipine treatment. Pulsatility index in maternal and fetal vessels was not affected by either of the two drugs. The birth weight and placental weight and neonatal outcome were similar and uneventful. The hypotensive effect was similar for methyldopa and isradipine. Except reduced maternal heart rate on methyldopa, fetal and uteroplacental hemodynamics were not altered during treatment of preeclampsia with methyldopa or isradipine.

Antihypertensive Agents↗
PubMed1996

Effectiveness of vaccination at 6 to 11 months of age during an outbreak of measles.

HYPOTHESIS: Monovalent measles vaccine can be administered to children 6 to 11 months of age during an outbreak. Efficacy and effectiveness of this control measure still have to be assessed. METHODS: During and outbreak of measles, monovalent measles vaccine was administered as part of outbreak control to children aged 6 to 11 months. Active surveillance was used to detect cases of measles occurring during the following month. Children who did not develop measles were tested for measles antibody before their revaccination at 15 months of age. RESULTS: Of 81 children 6 to 11 months of age, 56 were vaccinated and two received immunoglobulins; the latter were excluded from the analysis. Measles occurred in 15 of the 79 children during and after the vaccination campaign, for an overall attack rate of 19%. The attack rate among unvaccinated children was 39% (9 of 23), compared with 11% (6 of 56) among those vaccinated (relative risk = 3.6, 95% confidence interval [CI] = 1.5 to 9.1). All of those who sustained measles in the vaccinated group developed the disease within 10 days after vaccination. The overall vaccine effectiveness was 73% (95% CI = 32% to 89%) when children were classified as vaccinated as soon as they were given measles vaccine. It rose to 96% (95% CI = 72% to 99%) when children were considered vaccinated 1 week postimmunization. Nineteen infants who were vaccinated and who did not develop measles during the outbreak were tested for measles antibody status at 15 months of age before revaccination. All had plaque reduction neutralizing antibody titers greater than 120. CONCLUSION: This study confirms that measles vaccination of infants aged 6 to 11 months is an effective intervention measure during measles outbreaks.

Antibodies, Viral↗
PubMed1996

Leptospiral antibodies in patients with recurrent ophthalmic involvement.

Leptospiral antibodies could be demonstrated by microscopic agglutination test in 14 of 15 (93%) patients with acute panuveitis and retinal vasculitis in a preliminary study undertaken during the postmonsoon period at Madurai in Tamilnadu, India. The predominant serogroup was Pomona followed by Autumnalis, Australis and Javanica, the titres being between 1:160 and 1:10240. Titres in the normal controls were 1:20 to 1:80 in 8 of 20 mostly to the endemic serogroup Autumnalis. The involvement of leptospires particularly Pomona as a cause of ophthalmic complications in the patients studied is likely.

Adult↗
PubMed1996

An investigation of leptospirosis in a laboratory animal house.

A study was undertaken to investigate the possible involvement of leptospires in causing infection and persistent deaths among albino mice and wistar rats of a laboratory animal house. The serological study revealed that 79.2% of mice, 90% of wistar rats, 71.4% of guinea pigs and 81.8% of rabbits had leptospiral antibodies to one or more of serogroups. Autumnalis predominated in guinea pigs and mice, while Javanica predominated in wistar rats. Rabbits exhibited equal seroprevalence of Autumnalis and Javanica. The animal house workers had 91.0% sero positivity, predominantly Autumnalis while control human group had only 20%. All isolations made from a mice (M2) and six wistar rats (W1, W4, W8 W9, W12 & W13) were serovar javanica and incidentally the isolate from a trapped house rat (R1) also belonged to the same serovar javanica. The house rat was perhaps the source of virulent leptospires for causing infection and mortality among laboratory animals like mice and wistar rats.

Animals↗
PubMed1995

Early increase in choline kinase activity upon induction of the H-ras oncogene in mouse fibroblast cell lines.

The effects of expression of the H-ras oncogene on phosphatidylcholine metabolism were examined in C3H10T1/2 and NIH3T3 cells expressing ras constitutively or under the control of inducible promoters. Cell lines expressing ras under the control of the mouse metallothionein promoter and the Escherichia coli lac operator/repressor system and an NIH3T3 cell line stably transfected with the ras oncogene were studied. Phosphocholine levels were elevated in the cells constitutively expressing ras and were increased 4-6 h upon induction in the inducible cell lines. Glycerophosphocholine, which is elevated five- to sixfold in constitutively transfected ras cells, did not increase at early times of induction, suggesting the absence of increased phosphatidylcholine degradation via a phospholipase A. Choline kinase activity increased within 4-6 h upon induction and correlated well with the increase in phosphocholine levels. This increase in phosphocholine levels could be prevented by the addition of hemicholinium-3, a competitive inhibitor of choline kinase. Expression of activated c-raf or v-raf also increased choline kinase activity, suggesting that the induction of choline kinase by ras is downstream of the ras/raf interaction. Long-term and short-term labeling experiments failed to detect evidence for increased phospholipase C activity. These results suggest that the increase in choline kinase activity observed in cells expressing ras is an early, integral part of ras transformation and is the main contributor to increased phosphocholine levels accompanying morphological changes.

3T3 Cells↗
PubMed1995

Cloning, nucleotide sequence and expression of the bifunctional dihydrofolate reductase-thymidylate synthase from Glycine max.

cDNAs encoding the bifunctional dihydrofolate reductase-thymidylate synthase from Glycine max were isolated and sequenced. The 1794 base full length cDNA contains a single open reading frame of 1593 bases. The predicted size of the encoded protein is 530 amino acids with a molecular weight of 59,707. The protein has two domains: a 226 residue DHFR domain in the N-terminus, which is over 30% identical to human DHFR or the DHFR domain of protozoal DHFR-TS, and a 304 residue thymidylate synthase (TS) domain, which is over 60% identical to eukaryotic TS enzymes. The whole protein sequence is greater than 75% identical to DHFR-TS sequences from two other plants, Daucus carota and Arabidopsis thaliana. The sequence of two tryptic peptides obtained from DHFR preparations matched the predicted amino acid sequence, one peptide lying in the DHFR domain and the other in the TS domain. These results indicate that DHFR and TS exist in a bifunctional polypeptide in Glycine max. The coding region of the cDNA was inserted downstream of the T7 promoter and translation initiation signals in the vector pET-3a. This construct (pDR-TS) was transformed into Escherichia coli BL21 (DE) [plysS] which produces T7 RNA polymerase upon induction by isopropyl-beta-D-thiogalactopyranoside (IPTG). The expression of the bifunctional enzyme was confirmed by detection of both DHFR and TS activities. The purified enzyme has a subunit molecular mass of 60 kDa. This is the first report of expression of a plant DHFR-TS cDNA.

Amino Acid Sequence↗
PubMed1995

Measles, mumps, and rubella antibodies in children 5-6 years after immunization: effect of vaccine type and age at vaccination.

The levels of antibody against measles, mumps, and rubella were determined at 5-6 years postimmunization in 468 children vaccinated with two different trivalent vaccines. The proportions of children without detectable antibody levels were 12 and 3.6% for measles (p < 0.001), 14.9 and 7% for mumps (p = 0.006), and 3.3 and 3.1% for rubella (p = 0.88), respectively, in MMR II and Trivirix recipients. A higher proportion of those vaccinated at younger ages had undetectable or low levels of measles antibody. These data indicate that a large proportion of children vaccinated under routine conditions do not have detectable measles and mumps antibody.

Age Factors↗
PubMed1995

Measles and rubella antibody response after measles-mumps-rubella vaccination in children with afebrile upper respiratory tract infection.

The effect of concurrent afebrile viral upper respiratory tract infection (URI) on measles and rubella serum antibody response after measles-mumps-rubella (MMR) vaccination was determined in 580 1-year-old children, 369 with URI and 211 without URI, with the use of preimmunization and postimmunization sera. The presence of URI during the preceding 28 days, at the time of, or up to 7 days after immunization had no effect on the antibody response to either the measles or the rubella component of the vaccine. These findings support the recommendation that MMR vaccine be give to children at the recommended age regardless of the presence of afebrile viral URI.

Antibodies, Viral↗
PubMed1995

Continuous maternal glucose infusion during labor: effects on maternal and fetal glucose and lactate levels.

Fetal and neonatal glucose and lactate levels and acid-base balance after continuous maternal infusion of 5% dextrose at 180 mL/h (9 g/h) was compared with 0.9% saline solution in a prospective, randomized study from selected monitored labors. An infusion of 5% dextrose produced significantly increased glucose levels in maternal (p < 0.01), cord artery (p < 0.01), and cord vein (p < 0.001) blood. An increased maternal insulin level was also present (p < 0.05), but no differences in cord insulin levels were observed. beta-Hydroxybutyrate was lower in maternal (p < 0.05) and cord vein (p < 0.01), but not in cord artery blood, after maternal dextrose infusion. No significant changes occurred in blood lactate levels between the two groups in either mother, fetus, cord, or neonate. Acid-base balance in cord blood did not differ between the two groups. Maternal infusion of 5% dextrose at 180 mL/h (9 g/h), compared with saline solution, produces higher glucose levels in both mother and fetus, but increased insulin concentrations only in the mother. Dextrose infusion also lowers beta-hydroxybutyrate in maternal and cord vein blood. No differences were seen in lactate levels or cord acid-base balance. Both regimens seem safe according to risks for lactacidosis and neonatal hypoglycemia in the normoxemic, normal size fetus.

3-Hydroxybutyric Acid↗
PubMed1995

Alpha-actinin accumulation in epithelial cells infected with attaching and effacing gastrointestinal pathogens.

Fluorescent F-actin staining utilizing phalloidin, a highly toxic mushroom poison, is used as an indirect test to detect attaching and effacing (AE) bacteria. A study was done to determine if accumulation of alpha-actinin in infected tissue culture cells is a consistent feature and whether it corresponds with the AE response. Rearrangement of alpha-actinin was detected using immunofluorescence microscopy by incubation of infected cells with a murine monoclonal anti-alpha-actinin antibody. Foci of alpha-actinin-specific fluorescence corresponding to areas of bacterial adhesion were detected by transmission electron microscopy in HEp-2 and gastric KATO-III cells infected with only those bacterial strains that formed AE lesions. Therefore, this study shows that alpha-actinin accumulation is a consistent, specific manifestation of the AE phenotype and forms the basis for the development of a safe alternative test for detecting AE bacteria.

Actinin↗
PubMed1995

Cellular immunity in measles vaccine failure: demonstration of measles antigen-specific lymphoproliferative responses despite limited serum antibody production after revaccination.

Measles antigen-specific immune responses were evaluated 1 and 6 months after revaccination in 60 previously vaccinated subjects (9.4 +/- 3.4 years of age) who had either undetectable or low plaque reduction neutralization (PRN) titers (< 200). PRN titers were increased in all subjects at 1 month (590 +/- 61; range, 129-2513) but fell again in 66% of subjects by 6 months (214 +/- 29; range, 30-794). At 6 months, 23 (38%) had subprotective (< 120) or borderline (< 200) PRN titers. Lymphoproliferative responses to measles virus antigens were low overall before revaccination (mean stimulation index [SI], 2.6 +/- 0.4; range, 0.5-13.5) but were readily detectable at 1 (SI, 145.8 +/- 2.6; range, 1.4-80) and 6 months after revaccination (SI, 9.4 +/- 1.8; range, 1.1-87). Before revaccination, 10 of the subjects (50%) with low positive PRN titers had SIs > or = 3. At 6 months after revaccination, 18 subjects (78%) with PRN titers < or = 200 had SIs > or = 3. These data suggest that cellular responses to measles virus may be better sustained than antibody titers after vaccination and revaccination in some subjects.

Antibodies, Viral↗