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Chris Meier

Publications and source records attributed to Chris Meier.

29 records · Page 2Linked to original sources
PubMed2003

Accuracy of trisomy 18 screening using the second-trimester triple test.

OBJECTIVE: To assess the accuracy of the calculated risk for trisomy 18 assigned to individual women screened with the second-trimester triple test. METHODS: The study was based on 382598 women screened in the Ontario Maternal Serum Screening Programme between October 1993 and September 2000. Of the women screened, 111 cases of trisomy 18 were identified. Originally, 92874 women were screened using a risk cut-off level method. Estimated risks of trisomy 18 were calculated by applying published population parameters for the remaining women screened using a fixed analyte cut-off method. Women were ranked according to their individual risk for trisomy 18 syndrome in decreasing order and divided into 12 groups. The mean calculated risks of having an affected pregnancy at term for each group were compared with the birth prevalence of the corresponding group after allowing for spontaneous fetal losses. RESULTS: Agreement between the mean calculated risks and the observed prevalence was seen across the entire risk range, although women identified as having high-risk pregnancies had an actual prevalence that was somewhat lower than that estimated by the screen. CONCLUSION: The calculated risk for trisomy 18 syndrome assigned to the individual woman on the basis of the risk cut-off method accurately reflects their risk of having a term trisomy 18 syndrome pregnancy.

Adult↗
PubMed2003

The implications of a false positive second-trimester serum screen for Down syndrome.

OBJECTIVE: To investigate the genetic and obstetric implications of false positive Down syndrome serum screening results. METHODS: The study population comprised 162774 women underwent triple marker screening in the Ontario Maternal Serum Screening program between October 1995 and September 1998, with outcomes obtained from the Canadian Institute of Health Information. The study compares the incidence of chromosomal abnormalities other than Down syndrome in screen positive women with background incidence from the literature. It also compares the risks of having a fetus with congenital abnormalities or of developing obstetric complications in 11549 screen positive women with their matched controls. RESULTS: A higher incidence of trisomy 13 (12.4 per 10000) was seen in screen positive women; the incidence of other chromosomal abnormalities in screen positive women was not increased relative to the general population. The higher incidence of trisomy 13 may have been biased by the selective uptake of amniocentesis in women who had high risks for Down syndrome or abnormal ultrasound findings. Incidences of fetal congenital abnormality in screen positive and negative women were similar. Women who screened positive for Down syndrome had increased risk of spontaneous fetal loss (odds ratio 1.80; 95% confidence interval 1.54, 2.07) but no other obstetric complications. CONCLUSION: Among women who screened positive for Down syndrome, we found a higher number of spontaneous fetal losses and a possibly higher risk of having a fetus with trisomy 13. We did not find an increased risk for other chromosomal abnormalities, congenital abnormalities, or other adverse obstetric outcomes.

Abortion, Spontaneous↗
PubMed2003

Association between folic acid food fortification and congenital orofacial clefts.

By January 1998, most of Canada's cereal grain products were being fortified with folic acid. Among 336963 women who underwent antenatal maternal serum screening, the prevalence of orofacial clefts did not change from before (1.15 per 1000) to after (1.21 per 1000) food fortification (prevalence ratio, 1.06; 95% confidence interval, 0.86-1.30).

Canada↗
PubMed2002

CycloSal-BVDUMP pronucleotides: how to convert an antiviral-inactive nucleoside analogue into a bioactive compound against EBV.

Novel cycloSal-BVDUMP triesters 2-4 5-[(E)-2-bromovinyl]-2'-deoxyuridine (BVDU, 1) have been studied with regard to their potential anti-EBV activity. In addition to the 3'-unmodified cycloSal-BVDUMP triesters 2a-f, the 3'-hydroxyl function has been esterified with different aliphatic carboxylic acids (3a-g) and alpha-amino acids having natural and nonnatural Calpha-configuration (4a-m). In addition to the synthesis of these compounds, different physicochemical properties of the new derivatives will be reported, i.e., lipophilicity and hydrolysis behavior. It could be proven that the monophosphate BVDUMP and not 3',5'-cyclic BVDUMP was delivered from most of the compounds by chemical hydrolysis in phosphate buffers at pH 6.8 and 7.3 as well as P3HR-1 cell extracts. Finally, the new compounds were tested for their anti-EBV activity. As a result, the prototype compounds and particularly triesters 2c,d exhibited pronounced anti-EBV activity making these compounds promising candidates for further development. However, the 3'-ester derivatives were devoid of any antiviral activity while the 3'-aminoacyl derivatives showed an antiviral activity dependent upon the amino acid and the Calpha-configuration

Antiviral Agents↗
PubMed2002

Double-positive maternal serum screening results for down syndrome and open neural tube defects: An indicator for fetal structural or chromosomal abnormalities and adverse obstetric outcomes.

OBJECTIVE: The study was designed to evaluate whether double positive maternal serum screening results for Down syndrome and open neural tube defects indicate an increased risk of adverse perinatal outcome. STUDY DESIGN: A retrospective case-control study was conducted. In a cohort of 170,394 women who underwent maternal serum triple screening in Ontario, Canada, between October 1995 and September 1998, 189 women received positive screening results for both Down syndrome and neural tube defects. Each case was matched to 5 control subjects who had negative screening results for test center, maternal age, and specimen date. The risks for adverse perinatal outcomes were compared. RESULTS: Women with double-positive screening results had significantly higher risks of having fetuses with structural abnormalities (odds ratio, 14.5) and chromosomal anomalies (odds ratio, 36.3). They also had higher risks of having preeclampsia (odds ratio, 6.7), small-for-gestational age (odds ratio, 9.7), preterm delivery (odds ratio, 5.9), miscarriage, and intrauterine fetal death (odds ratio, 11.8). CONCLUSION: Double-positive maternal serum screening results are associated with fetal structural and chromosomal abnormalities and/or adverse pregnancy outcomes. Close fetal and maternal surveillance are indicated when such pregnancies are identified.

Case-Control Studies↗
PubMed2002

Comparative study of bis(benzyl)phosphate triesters of 2',3'-dideoxy-2',3'-didehydrothymidine (d4T) and cyclosal-d4TMP--hydrolysis, mechanistic insights and anti-HIV activity.

A comparative study of three cycloSal-d4TMP 1, 2 and 3 and a variety of bis(benzyl) phosphate triester 4-8 of the antivirally active nucleoside analogue 2',3'-dideoxy-2',3'-didehydrothymidine (d4T) will be described. This study has been initiated by the observation that the introduction of a simple 7-methyl group in the cycloSal-structure (2) led to a completely different hydrolysis pattern as compared to the prototype cycloSal-d4TMP 1. Instead of the selective formation of d4TMP, a phenyl phosphate diester was formed in the case of the 7-methyl-substituted compound 2. The difference in degradation pathway was caused by a change of the reaction mechanism. The phenyl phosphate diester was chemically and enzymatically inert to further cleavage to yield d4TMP. For comparison bis(benzyl)-d4TMP 4, bis(alpha-methylbenzyl)-d4TMP 5, bis(alpha-methoxycarbonylmethyl [MCM]-benzyl)-d4TMP 6 as well as the enzyme-cleavable bis(4-acetoxybenzyl)-d4TMP [bis(AB)-d4TMP(7 and bis(alpha-methoxycarbonylmethyl-4-acetoxybenzyl)-d4TMP [bis(alpha-MCM-AB)-d4TMP] 8 were synthesized. Chemical hydrolysis studies proved that all bis(benzyl) triesters hydrolyze to give the intermediate benzyl phosphate diesters. Moreover, the latter two triesters 7,8 and cycloSal-d4TMPs 1 and 3 led finally to the delivery of d4TMP. The chemical hydrolysis studies allowed a detailed mechanistic interpretation of the degradation pathways of triesters 1-8. Cell extract studies of the bis(benzyl) triesters 4-8 confirmed that only triesters 7 and 8 released d4TMP although with a considerable increase of the reaction rate. Anti-HIV evaluation of the compounds showed that cycloSal-d4TMP 1 and the bis(AB) triesters 7,8 were entirely independent of the presence of cellular thymidine kinase (TK).

Anti-HIV Agents↗
PubMed2002

Aryl-substituted and benzo-annulated cyc/osal-derivatives of 2',3'-dideoxy-2',3'-didehydrothymidine monophosphate--correlation of structure, hydrolysis properties and anti-HIV activity.

The synthesis of phenyl-substituted and benzoannulated cycloSal phosphate triesters of the nucleoside analogue 2',3'-dideoxy-2',3'-didehydrothymidine (d4T, Zerit) as lipophilic, membrane-soluble pronucleotides is described. The cycloSal moiety was introduced by using cyclic chlorophosphite agents prepared from phenyl-substituted saligenin derivatives and ortho-hydroxymethylated naphthols, respectively. Hydrolysis studies (HPLC analysis) of the triesters 2, 3 showed a range of hydrolytic stability from 1.4 h up to 5.1 h and the stability could be correlated with the substitution pattern in the cycloSal moiety. A slight decrease of their stability was observed, if phenyl-substituted derivatives were hydrolyzed in human CEM/O cell extracts. D4T and thymine, possible products of enzymatic cleavage of the pronucleotides, were not detected in the cell extracts. A further investigation of the hydrolysis process was performed by 31P-NMR spectroscopy. This technique allowed a precise monitoring of the degradation products and the exact determination of the product ratio. Finally, the newly synthesized compounds were tested concerning their antiviral activity against HIV in vitro. A strong correlation of the hydrolysis properties and the antiviral activity was found. 3-phenyl-cycloSal-d4TMP showed a threefold increase in its anti-HIV-1 activity and retained full activity in thymidine kinase (TK) deficient cells, indicative of a successful TK-bypass.

Anti-HIV Agents↗
PubMed2002

cycloSal-pronucleotides design of chemical trojan horses.

Pronucleotides represent a promising alternative to improve the biological activity of nucleoside analogues against different viral diseases. The basic idea is to achieve nucleotide delivery into cells bypassing limitations encountered during the intracellular formation of nucleotides. The cycloSal-concept is one of several pronucleotide systems reported so far. For some nucleoside analogues, the cycloSal-approach improved antiviral potency thus broadening the applicability of nucleosides. The initial design, chemistry, the proof-of-principle and different applications of the cycloSal-strategy will be discussed in this review.

Animals↗
PubMedDate not supplied

Association of neural tube defects and folic acid food fortification in Canada.

Many women do not receive folic acid supplements before conception. In response, most of Canada's cereal grain products were being fortified with folic acid by January, 1998, thereby providing an additional 0.1-0.2 mg per day of dietary folate to the Canadian population. We assessed the effect of supplementation on prevalence of open neural tube defects in the province of Ontario. Among 336 963 women who underwent maternal serum screening over 77 months, the prevalence of open neural tube defects declined from 1.13 per 1000 pregnancies before fortification to 0.58 per 1000 pregnancies thereafter (prevalence ratio 0.52, 95% CI 0.40-0.67, p<0.0001). At a population level, folic acid food fortification is associated with a pronounced reduction in open neural tube defects.

Adult↗
PubMedDate not supplied

Alpha-hydroxybenzylphosphonate modified oligonucleotides: synthesis, properties, and a novel route via monomer building blocks.

In general, alpha-hydroxybenzylphosphonate modified 2'-deoxyadenosine-thymidine dimer building blocks 1, 2 are utilized for the incorporation into alpha-hydroxybenzylphosphonate pro-oligonucleotides. For a universal application of our pro-oligonucleotide concept on biologically relevant oligonucleotides a route for the synthesis of modified monomer building blocks 3 was developed and is presented herein.

Indicators and Reagents↗