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Biomedical subjects

M Choolani

Publications and source records attributed to M Choolani.

At least 19 recordsLinked to original sources
PubMed2006

The association between fibrinogen, von Willebrand Factor, antithrombin III, and D-dimer levels and survival outcome by 36 months from ovarian cancer.

Thirty-five patients diagnosed to have ovarian cancer (early FIGO stage I/II n = 11, advanced FIGO stage III/IV, n = 24) were evaluated for hemostatic parameters relating to survival outcome by 36 months of disease. Systemic plasminogen activators and inhibitors were evaluated and we found no significant association with survival outcome and eventually only fibrinogen, von Willebrand Factor (vWF), antithrombin III (ATIII), and D-dimer levels were determined for their association with disease outcome by 12 months, 24 months, and 36 months. Twenty-four patients succumbed to the disease by 36 months (early n = 2, advanced n = 22). The 11 surviving patients (advanced n = 3, including one deceased at 52 months) is still living past 36 months and 82 months at the time of analysis. Elevated fibrinogen, vWF, and D-dimer together with reduced ATIII levels were found to be associated with poor survival outcome by 12 months of disease. Moreover, elevated vWF and D-dimer with reduced ATIII levels was strongly implicated with poor survival outcome by 36 months from ovarian cancer. The overall survival rate at 36 months from ovarian cancer was 31.4%. It is therefore suggested that fibrinogen, vWF, ATIII, and D-dimer levels be used together as prognostic markers for disease outcome especially in patients with advanced ovarian cancer within 36 months of disease. An expanded study is required to confirm these findings.

Adolescent↗
PubMed2003

Identification of fetal mesenchymal stem cells in maternal blood: implications for non-invasive prenatal diagnosis.

Strategies for genetic prenatal diagnosis on fetal cells in the maternal circulation have been limited by lack of a cell type present only in fetal blood. However, the recent identification of mesenchymal stem cells (MSC) in first trimester fetal blood offers the prospect of targeting MSC for non-invasive prenatal diagnosis. We developed protocols for fetal MSC enrichment from maternal blood and determined sensitivity and specificity in mixing experiments of male fetal MSC added to female blood, in dilutions from 1 in 10(5) to 10(8). We then used the optimal protocol to isolate fetal MSC from maternal blood in the first trimester, using blood taken after surgical termination of pregnancy as a model of increased feto-maternal haemorrhage. In model mixtures, we could amplify one male fetal MSC in 2.5 x 10(7) adult female nucleated cells, yielding a 100% pure population of fetal cells, but not one fetal MSC in 10(8) nucleated cells. Fetal MSC were identified in one of 20 post-termination maternal blood samples and confirmed as fetal MSC by XY fluorescence in-situ hybridization (FISH), immunophenotyping and osteogenic and adipogenic differentiation. We report the isolation of fetal MSC from maternal blood; however, their rarity in post-termination blood suggests they are unlikely to have a role in non-invasive prenatal diagnosis. Failure to locate these cells routinely may be attributed to their low frequency in maternal blood, to sensitivity limitations of enrichment technology, and/or to their engraftment in maternal tissues soon after transplacental passage. We speculate that gender microchimerism in post-reproductive maternal tissues might result from feto-maternal trafficking of MSC in early pregnancy.

Adult↗
PubMed2003

Fetal cells in maternal blood: state of the art for non-invasive prenatal diagnosis.

In Singapore, 1 in 5 pregnancies occur in mothers > 35 years old and genetic diseases, such as thalassaemia, are common. Current methods for the diagnosis of aneuploidy and monogenic disorders require invasive testing by amniocentesis, chorion villus biopsy or fetal blood sampling. These tests carry a procedure-related risk of miscarriage that is unacceptable to many couples. Development of non-invasive methods for obtaining intact fetal cells would allow accurate prenatal diagnosis for aneuploidy and single gene disorders, without the attendant risks associated with invasive testing, and would increase the uptake of prenatal diagnosis by women at risk. Isolation of fetal erythroblasts from maternal blood should allow accurate non-invasive prenatal diagnosis of both aneuploidies and monogenic disorders. Expression of gamma-globin in maternal erythroblasts and the inability to locate fetal erythroblasts reliably in all pregnancies have prevented its clinical application. In the absence of a highly specific fetal cell marker, enrichment, identification and diagnosis--the 3 components of non-invasive prenatal diagnosis--have clearly defined objectives. Since fetal cells are rare in maternal blood, the sole purpose of enrichment is yield--to recover as many fetal cells as possible--even if purity is compromised at this stage. In contrast, the primary goal of identification is specificity; absolute certainty of fetal origin is required at this stage if the ultimate objective of diagnosis, accuracy, is to be achieved. This review summarises the current state of the art of non-invasive prenatal diagnosis using fetal erythroblasts enriched from maternal blood.

Adult↗
PubMed2001

Simultaneous fetal cell identification and diagnosis by epsilon-globin chain immunophenotyping and chromosomal fluorescence in situ hybridization.

Isolating fetal erythroblasts from maternal blood offers a promising noninvasive alternative for prenatal diagnosis. The current immunoenzymatic methods of identifying fetal cells from background maternal cells postenrichment by labeling gamma-globin are problematic. They are nonspecific because maternal cells may produce gamma-globin, give poor hybridization efficiencies with chromosomal fluorescence in situ hybridization (FISH), and do not permit simultaneous visualization of the fetal cell identifier and the FISH signal. We describe a novel technique that allows simultaneous visualization of fetal erythroblast morphology, chromosomal FISH, and epsilon-globin labeled with AMCA (7-amino-4-methylcoumarin-3-acetic acid). AMCA was chosen as the fluorescent label to circumvent the problem of heme autofluorescence because the mean difference in relative fluorescence intensity between fetal erythroblasts stained positive for antiglobin antibody and autofluorescence of unstained cells was greater with AMCA (mean 43.2; 95% confidence interval [CI], 34.6-51.9; SD = 14.0) as the reporting label compared with fluorescein isothiocyanate (mean 24.2; 95% CI, 16.4-31.9; SD = 12.4) or phycoerythrin (mean 9.8; 95% CI, 4.8-14.8; SD = 8.0). Median FISH hybridization efficiency was 97%, comparable to the 98% (n = 5 paired samples) using Carnoy fixative. One epsilon-positive fetal erythroblast was identified among 10(5) maternal nucleated cells in 6 paired mixture experiments of fetal erythroblasts in maternal blood (P <.001). Male epsilon-positive fetal erythroblasts were clearly distinguishable from adult female epsilon-negative erythroblasts, with no false positives (n = 1000). The frequency of fetal erythroblasts expressing epsilon-globin declines linearly from 7 to 14 weeks' gestation (y = -15.8 x + 230.8; R(2) = 0.8; P <.001). We describe a rapid and accurate method to detect simultaneously fetal erythroblast morphology, intracytoplasmic epsilon-globin, and nuclear FISH. (Blood. 2001;98:554-557)

Adult↗
PubMed1996

Termination of early human pregnancy with either 50 mg or 200 mg single oral dose of mifepristone (RU486) in combination with either 0.5 mg or 1.0 mg vaginal gemeprost.

Mifepristone (RU486) is licensed for use in France at a dose of 600 mg in combination with 1.0 mg of vaginal gemeprost (a prostaglandin E1 analogue) for medical termination of early pregnancy up to 7 weeks' amenorrhoea resulting in 96% complete abortion rates. This study examines if it is possible to use lower doses of mifepristone and gemeprost to achieve similar success for women with pregnancies up to 56 days' amenorrhoea. Four groups of 25 women were scheduled to be given single oral doses of either 50 mg or 200 mg of mifepristone followed 48 hours later by insertion of a single vaginal pessary of 0.5 mg or 1.0 mg gemeprost. The lowest dose combination (i.e. 50 mg mifepristone + 0.5 mg gemeprost) was found to have unacceptable efficacy with a complete abortion rate of only 82%; the highest dose combination (i.e. 200 mg mifepristone + 1.0 mg gemeprost) resulted in a satisfactory complete abortion rate of 96% which is comparable with the rates for the recommended high 600 mg mifepristone dose (+ 1.0 mg gemeprost) in routine clinical use in France. The current study shows that efficacy can be maintained using a third of the recommended dose of mifepristone.

Abortifacient Agents, Nonsteroidal↗
PubMed1995

Blood loss in termination of early pregnancy with mifepristone and gemeprost.

The combination of an antiprogestogen with prostaglandin has been shown to be an effective alternative to surgical procedures for pregnancy termination in the first 49 days of amenorrhoea and has been available in France since late 1988. Mifepristone when used alone caused poor efficacy with unacceptable vaginal bleeding. The addition of a prostaglandin analogue (sulprostone, gemeprost) produced acceptable efficacy with less bleeding. The present study provides a quantitative assessment of blood loss in a sample of 20 women undergoing medical termination of early pregnancy (amenorrhoea < or = 49 days). Vaginal bleeding occurred between days 3 and 15 of commencing therapy. The median number of days of bleeding was 4 with a median blood loss of 91.5 mL. The mean blood loss was 136.8 mL (+/- SD 159.2) but this did not adversely affect the hemoglobin level in the volunteers. Most patients describe the experience as that similar to a heavy period and viewed the procedure positively especially since they are spared the anaesthetic risks and hospitalization attendant with surgical abortion. Caution is still however advised as there may be the occasional subject with excessive haemorrhage (as in this study where one woman bled a total of 761.4 mL) and close supervision by a physician is essential.

Abortifacient Agents, Nonsteroidal↗
PubMed1995

Automated 24-hour ambulatory blood pressure monitoring in preeclampsia.

A prospective controlled study was designed to compare automated 24-hour ambulatory blood pressure monitoring with intermittent blood pressure recordings obtained using a sphymomanometer. Blood pressure was measured in 20 hospitalized preeclamptic women in the third trimester. Data obtained using the Spacelabs automated blood pressure monitor was recorded over a period of 24 hours, and thereafter stored and processed in a computer. During the same 24 hour period, blood pressure and heart rate were measured by experienced staff at 07.00, 10.00, 13.00, 15.00, 18.00 and 21.00 hours, with the patient in a semi-recumbent position using a conventional mercury sphygmomanometer with a cuff of appropriate size. Korotkoff phase 5 was used as the indicator of diastolic blood pressure in all recordings by the staff. The main outcome measures were systolic and diastolic blood pressure, mean arterial blood pressure and maternal heart rate. Automated ambulatory monitoring was well tolerated and gave 91.6% successful readings. The mean differences between the blood pressure readings recorded by the monitor and of intermittent mercury sphygmomanometry during daytime were 0.7 (95% confidence interval -2.6 to 4.0) mmHg for the mean arterial blood pressure, -1.7 (95% confidence interval -6.8 to 3.5) mmHg for the systolic blood pressure, and 1.9 (95% confidence interval -2.2 to 6.0) mmHg for the diastolic blood pressure. The mean differences between day-time and night-time monitored blood pressures were 4.3 (95% confidence interval 0.8 to 7.8) mmHg, 4.6 (95% confidence interval 2.0 to 7.2) mmHg, and 4.4 (95% confidence interval 1.5 to 7.2) mmHg, respectively. The number of patients diagnosed as being hypertensive was similar whether automated blood pressure monitor or mercury sphymomanometry was used. Mean maternal heart rate recorded by the monitor or by the staff did not differ. Automated ambulatory blood pressure monitoring is reliable and might improve our understanding of the dynamic changes in blood pressure in pre-eclamptic women and may be a more suitable method to assess the blood pressure control achieved by different drugs.

Autoanalysis↗