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Biomedical subjects

C Strom

Publications and source records attributed to C Strom.

At least 19 recordsLinked to original sources
PubMed2001

Chromosomal abnormalities in the first and second polar body.

Aneuploidy free oocytes may be pre-selected by testing the first and second polar bodies removed from oocytes following their maturation and fertilization. We present here our experience on the application of the method in IVF cycles from patients of advanced maternal age. Overall, 5590 oocytes were obtained from 917 cycles and tested by polar body sampling and fluorescent in situ hybridization (FISH) analysis using specific probes for chromosomes 13,16,18,21 and 22. FISH results were available in 4599 (82.2%) of 5590 oocytes studied, from which 2077(45.2%) were with aneuploidies. Thirty six point one percent of aneuploidies were of the first meiotic origin, and 29.3% of the second meiotic origin. Most errors in the first meiotic division were represented by chromatid errors. The transfer of embryos deriving from 2014 of 2520 aneuploidy free oocytes in 821 treatment cycles resulted in 182 (22.2%) clinical pregnancies and 140 healthy children born after confirmation of the polar body diagnosis. Polar body testing of oocytes provides an approach for pre-selection of aneuploidy free embryos, improving pregnancy rate in IVF patents of advanced maternal age.

Adult↗
PubMed2001

Preembryonic diagnosis for sickle cell disease.

Embryos found to be abnormal during preimplantation genetic diagnosis are discarded or analyzed to confirm the diagnosis. The destruction of affected embryos is ethically unacceptable to some couples. We developed a preembryonic genetic diagnosis, that uses sequential first and second polar body removal, followed by oocyte freezing at the pronuclear stage. This was applied in a patient at risk of having a child with sickle cell disease, who suffered hyper-stimulation syndrome. Fourteen oocytes were obtained and tested for the maternal sickle cell allele by PCR analysis of the first and second polar body. Immediately after procedure of polar body removal, the pronuclear-stage oocytes were frozen. Six mutation-free oocytes detected by polar body analysis were then thawed, allowed to cleave, and transferred in the two consecutive clinical cycles, both resulting in clinical pregnancies, one of which resulted in birth of a healthy child. The oocytes predicted to contain abnormal beta-globin gene were not further cultured, to avoid formation and discard of the affected embryos. The results demonstrate feasibility of preembryonic diagnosis for single gene disorders, avoiding the establishment and destruction of mutant embryos.

Adult↗
PubMed2001

Reliability of preimplantation diagnosis for single gene disorders.

Reliability of preimplantation genetic diagnosis (PGD) depends on controlling one of the most important limitations of single cell PCR, undetected allele drop out (ADO), which may lead to misdiagnosis. To avoid this we introduced mutation analysis simultaneously with linked polymorphic markers, pre-selecting only those embryos whose unaffected status could be confirmed by at least one linked polymorphic marker. We applied this strategy for testing 1047 oocytes, from which 237 unaffected ones were pre-selected for transfer back to patients, resulting in 34 unaffected pregnancies and birth of 23 healthy children. Embryos originating from mutant oocytes and those with insufficient marker information were followed up by multiplex PCR to confirm single cell PCR diagnosis. Of 75 (8.5%) detected ADO, only seven (under 1%) were missed in the actual PGD, demonstrating high reliability of PGD (98%) based on multiplex single cell PCR.

Alleles↗
PubMed2001

Preimplantation diagnosis for Fanconi anemia combined with HLA matching.

CONTEXT: The advent of single-cell polymerase chain reaction (PCR) has presented the opportunity for combined preimplantation genetic diagnosis (PGD) and HLA antigen testing. This is a novel and useful way to preselect a potential donor for an affected sibling requiring stem cell transplantation. OBJECTIVE: To perform in vitro fertilization (IVF) and preimplantation HLA matching combined with PGD for Fanconi anemia (FA). DESIGN: DNA analysis for the IVS 4 + 4 A-->T (adenine to thymine) mutation in the FA complement C (FANCC) gene in single blastomeres, obtained by biopsy of embryos, to identify genetic status and HLA markers of each embryo before intrauterine transfer. SETTING: In vitro fertilization programs at large medical centers in Chicago, Ill, and Denver, Colo. PARTICIPANTS: A couple, both carriers of the IVS 4 + 4 A-->T mutation in the FANCC gene with an affected child requiring an HLA-compatible donor for cord blood transplantation. MAIN OUTCOME MEASURES: DNA analysis of single blastomeres to preselect unaffected embryos representing an HLA match for the affected sibling. RESULTS: Of 30 embryos tested in 4 IVF attempts, 6 were homozygous affected and 24 were unaffected. Five of these embryos were also found to be HLA-compatible, of which 2 were transferred in the first and 1 in each of the other 3 cycles, resulting in a pregnancy and birth of an unaffected child in the last cycle. CONCLUSION: To our knowledge, this is the first PGD with HLA matching, demonstrating feasibility of preselecting unaffected embryos that can also be an HLA-compatible source for stem cell transplantation for a sibling.

Blastomeres↗
PubMed2001

Preimplantation testing for phenylketonuria.

OBJECTIVE: To use preimplantation genetic diagnosis to achieve a phenylketonuria-free pregnancy in a couple at 50% risk for producing an affected child. DESIGN: DNA analysis of the first and second polar bodies (PB1 and PB2) obtained from oocytes of a heterozygous mother in IVF-ET, with the goal of identifying and transferring back to the patient the embryos resulting from mutation-free oocytes. SETTING: IVF program of Reproductive Genetics Institute, Chicago, Illinois. PATIENT(S): A mother carrying the R408W mutation and a father with compound heterozygosity for R408 and Y414C mutations in phenylalanine hydroxylase (PAH) gene. INTERVENTION(S): Removal and testing for maternal mutation in PB1 and PB2 from each oocyte after standard IVF. MAIN OUTCOME MEASURE(S): DNA analysis of PB1 and PB2 indicating whether corresponding oocytes were mutation-free, for the purposes of transferring only unaffected embryos resulting from these oocytes. RESULT(S): Of 11 zygotes with both PB1 and PB2, 6 were predicted to be free of phenylketonuria. Of these, 4 were transferred, resulting in an unaffected twin pregnancy and birth of two healthy children. CONCLUSION(S): Preimplantation genetic diagnosis of phenylketonuria resulted in the birth of phenylketonuria-free children. Preimplantation genetic diagnosis by PB analysis in couples with a compound heterozygous male partner is clinically useful.

Adult↗
PubMed2001

Crown-rump lengths in missed miscarriages and trisomy 21.

OBJECTIVES: To compare crown-rump lengths with karyotypes of missed miscarried fetuses and to determine a relationship between crown-rump length and trisomy 21. STUDY DESIGN: Chorionic villus sampling was performed on 129 consecutive missed miscarriages between 10 and 12 weeks by last menstrual period in patients >or= 35 years of age. Crown-rump length was correlated with the karyotype. Statistical analysis was performed using Student's t-test. RESULTS: Twenty-one of 129 missed miscarriages involved fetuses affected by trisomy 21. The crown-rump length was < 22 mm in 77% of missed miscarriages. Using a crown-rump length of >or= 22 mm for the prediction of trisomy 21 had a sensitivity of 86%, specificity of 89%, positive predictive value of 60% and negative predictive value of 97%. At 10-12 weeks, the crown-rump lengths of missed miscarried fetuses with trisomy 21 was significantly larger (P or= 35 years of age, with a missed miscarriage, in whom pregnancies reached >or= 10 weeks from the last menstrual period, a fetal crown-rump length of >or= 22 mm has a high probability that the etiology of the loss will be secondary to trisomy 21.

Abortion, Missed↗
PubMed2001

[Perioperative antiarrhythmic drug management].

Perioperative arrhythmias are common. In 2.5 % they result in a severe adverse outcome. This review discusses the normal physiology of the myocardial conduction system and the etiology and pathophysiology of the most common perioperative dysrhythmias. Subsequently some important antiarrhythmic drugs are described and treatment plans for the most frequent dysrhythmias are presented.

Anti-Arrhythmia Agents↗
PubMed2000

Preimplantation diagnosis for ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) deficiency is a severe X-linked metabolic disorder leading to hyperammonaemia and death shortly after birth. Prenatal diagnosis for OTC deficiency is available, but may require termination of pregnancy if affected. Thus there is a need for an option for pre-pregnancy testing, to pre-select OTC deficiency-free embryos for transfer, thus avoiding prenatal diagnosis and pregnancy termination. Preimplantation genetic diagnosis (PGD) for OTC deficiency has been developed, using sequential first and second polar body analysis; it was applied in a woman carrying the R26Q mutation in the exon 1 of OTC gene. The first and second polar bodies were removed following maturation and fertilization of oocytes in a standard IVF protocol, and analysed using a multiplex nested PCR. R26Q mutation was tested simultaneously with linked markers in six zygotes, resulting in detection of the embryos with a mutation-free maternal contribution; these were transferred back to the patient, yielding pregnancy and birth of a healthy child. This is the first PGD for OTC deficiency resulting in the birth of an unaffected child.

Journal Article↗
PubMed2000

Intermittent atrial level right-to-left shunt with temporary hypoxemia in a patient during support with a left ventricular assist device.

We report a 56-year-old male patient developing hypoxemia after surgical replacement of infected valves of a left ventricular assist device (LVAD, Novacor) which had supported him during the previous 15 months. Contrast transesophageal echocardiography (TEE) revealed an atrial septal defect with intermittent right-to-left shunt across a patent foramen ovale. We postulate that the shunt detected in this patient occurred as a consequence of reduced pulmonary vascular compliance due to positive end-expiratory pressure (PEEP) and an increase of mean intrathoracic pressure. Furthermore, we hypothesize that synchronized LVAD operation exacerbates any potential right-to-left shunt due to the profound left ventricular unloading which occurs during LVAD support. In this first report of a right-to-left shunt from a previously unrecognized patent foramen ovale in a Novacor patient, the subsequent transient hypoxemia could be managed by avoiding PEEP of more than 3 mmHg, and mean airway pressure of more than 11 mmHg and by careful volume replacement in order to prevent the pump from completely emptying the left ventricle (LV) and the left atrium (LA). Thus, prior to every LVAD implantation a transesophageal contrast echocardiography with Valsalva maneuver should be performed to identify intracardiac right-to-left shunt.

Heart Septal Defects, Atrial↗
PubMed1999

Prenatal diagnosis of 46,XX male fetuses.

Ultrasonography can accurately determine phenotypic sex differences from those of the genetic sex. Two cases were identified; they were the result of a translocation of the SRY gene from the Y chromosome to the X chromosome during meiosis. An ultrasonographic difference may represent an otherwise unsuspected genetic abnormality.

Adult↗
PubMed1999

Prevention of age-related aneuploidies by polar body testing of oocytes.

PURPOSE: We previously demonstrated that aneuploidy-free oocytes may be preselected by testing the first and second polar bodies removed from oocytes following their maturation and fertilization. The present paper describes the results of the application of the method in 659 in vitro fertilization cycles from patients of advanced maternal age. METHODS: Using micromanipulation techniques, 3943 oocytes were tested by polar body sampling and fluorescent on situ hybridization analysis using specific probes for chromosomes 13, 18, and 21. RESULTS: Fluorescent in situ hybridization results were available for 3217 (81.6%) of 3943 oocytes studied, of which 1388 (43.1%) had aneuploidies; 35.7% of the aneuploidies were of first meiotic division origin, and 26.1% of second meiotic division origin. Most errors in the first meiotic division were represented by chromatid malsegregation. The transfer of embryos deriving from 1558 of 1829 aneuploidy-free oocytes in 614 treatment cycles resulted in 131 clinical pregnancies and 88 healthy children born after confirmation of the polar body diagnosis. CONCLUSIONS: Polar body testing of oocytes provides an accurate and reliable approach for prevention of age-related aneuploidies in in vitro fertilization patients of advanced maternal age.

Adult↗
PubMed1999

Accuracy of preimplantation diagnosis of single-gene disorders by polar body analysis of oocytes.

PURPOSE: A number of pitfalls in single-cell DNA analysis, including undetected DNA contamination, undetected allele drop out, and preferential amplification, may lead to misdiagnosis in preimplantation genetic diagnosis of single-gene disorders. METHODS: Preimplantation genetic diagnosis was performed by sequential first and second polar body analysis of oocytes in 26 couples at risk for having children with various single-gene disorders. Mutant genes were amplified simultaneously with linked polymorphic markers, and only embryos resulting from the mutation-free oocytes predicted by polar body analysis with confirmation by polymorphic marker testing were transferred back to patients. RESULTS: Overall 529 oocytes from 48 clinical cycles (26 patients) were tested, resulting in the transfer of 106 embryos in 44 clinical cycles. As many as 46 (9.6%) instances of allele dropout were observed, the majority (96%) of which were detected. Seventeen unaffected pregnancies were established, of which nine resulted in the birth of an unaffected child, and the rest are ongoing. CONCLUSIONS: A high accuracy of preimplantation genetic diagnosis of single-gene disorders is achieved by application of sequential analysis of the first and second polar body and multiplex polymerase chain reaction.

Alleles↗
PubMed1999

Birth of healthy children after preimplantation diagnosis of thalassemias.

BACKGROUND: Preimplantation genetic diagnosis (PGD) allows couples at risk of having children with thalassemia to ensure the healthy outcome of their pregnancy. METHODS: Seventeen PGD clinical cycles were initiated for Cypriot couples at risk of having children with different thalassemia mutations, including IVSI-110, IVSI-6, and IVS II-745. Unaffected embryos for transfer were selected by testing oocytes, using first and second polar body (PB) removal and nested polymerase chain reaction analysis followed by restriction digestion. RESULTS: Unaffected embryos were selected in 16 of 17 PGD cycles. Of 166 oocytes studied from these cycles, 110 were analyzed by sequential analysis of both the first and the second PB, resulting in preselection and transfer of 45 unaffected embryos. This resulted in seven pregnancies and in the birth of five healthy thalassemia-free children. The embryos predicted to have inherited the affected allele were not transferred. Analysis of these embryos confirmed the PB diagnosis. CONCLUSIONS: Sequential first and second PB testing of oocytes is reliable for PGD of thalassemia and is a feasible alternative to prenatal diagnosis in high-risk populations.

Alleles↗
PubMed1999

Construction and sequence analysis of subtraction complementary DNA libraries from human preimplantation embryos.

PURPOSE: Because stage-specific genetic expression in human preimplantation development is not sufficiently studied, we have undertaken the construction of a subtraction complementary DNA (cDNA) library enriched for transcripts specific for human blastocysts. METHODS: For this purpose individual pools of cDNAs synthesized from four hatched blastocysts and three cleaving 8- to 10-cell embryos were exposed to suppression subtractive hybridization to minimize the presence of transcripts of housekeeping genes and other genes of maternal origin known to be expressed earlier in preimplantation development. Random clones of this library were sequenced and analyzed using the BLAST algorithm. RESULTS: The resulting subtraction library had a complexity of 3 x 10(5) and an average size of inserts of about 0.8 kb. Sequencing of random library clones revealed the following human genes: CD9 antigen, fatty acid binding protein, ferritin heavy chain, amyloid precursor, MAP kinase messenger RNAs, DNA clone 127H14, messenger RNA for diacylglycerol kinase, a sequence homologous to C1 inhibitor, messenger RNA for the KIAA0145 gene, and others. CONCLUSIONS: The presence of these genes in human preimplantation development suggests expression specific to the blastocyst stage.

Algorithms↗
PubMed1999

Prepregnancy testing for single-gene disorders by polar body analysis.

Preventive measures for single-gene disorders are currently based on carrier screening in pregnancy and prenatal diagnosis. Although this has been extremely effective for preventing new cases of common inherited conditions, the major limitation is still termination of 25% of wanted pregnancies following detection of affected fetuses. To overcome this important problem, we developed a method for prepregnancy genetic testing that involves DNA analysis of the first and second polar bodies, which are extruded during maturation and fertilization of oocytes. We offered this option to 28 couples at risk for having children with single-gene disorders. Fifty clinical cycles were performed from these patients for the following conditions: 20 for cystic fibrosis, 18 for thalassemia, 6 for sickle cell disease, 2 each for Gaucher disease and LCHAD (long-chain 3-hydroxyacyl-COA dehydrogenase deficiency), and 1 each for hemophilia B and phenylketonuria. Oocytes obtained from these patients using in vitro fertilization procedures (IVF) were tested by a sequential multiplex nested PCR analysis of the first and second polar body to detect the gene involved simultaneously with linked polymorphic markers. A total of 191 of 399 oocytes with predicted genotype were mutation free and preselected for fertilization and transfer. In all but three cycles, one to three unaffected embryos with predicted unaffected genotypes were transferred, resulting in 20 pregnancies, from which 19 healthy children have been born. The follow-up analysis of embryos resulting from oocytes with predicted affected genotype, confirmed the diagnosis in 97% of cases, demonstrating the reliability of prepregnancy diagnosis of single-gene defects by polar body analysis.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1998

[The role of echocardiography in preoperative diagnosis of cardiac risk in patients before non-cardiac surgical interventions].

Echocardiography is a noninvasive method for cardiac evaluation. A review of the current literature shows that the routine use of echocardiography for assessing perioperative cardiac risk in patients undergoing noncardiac surgery can not be supported. Only patients with suspected relevant heart valve diseases, acute heart failure, cardiomyopathy or condition after heart or heart-lung transplantation may benefit from preoperative echocardiography. In patients with suspected or proven coronary artery disease stress echocardiography offers the most relevant additional information for the anaesthesiologist. However, because of the high financial and personal implications it should be reserved to those patients who are not able to perform a normal stress test. Besides in patients in whom transthoracic echocardiography doesn't offer sufficient information or is not possible transesophageal echocardiography plays only a minor role in preoperative cardiac evaluation.

Echocardiography↗
PubMed1998

Sequence analysis of libraries from individual human blastocysts.

PURPOSE: It has recently become possible to construct cDNA libraries from individual human blastocysts to investigate the expression of embryonic genes in human preimplantation development. We have previously reported the expression of beta-actin, CD-59, and homeobox OCT-3 and identified almost-complete homology of sequences to human histone 3.1 and human ribosome protein S25. In the present paper, our further sequencing analysis of cDNA libraries from single human blastocysts is described. METHODS: cDNA libraries were constructed from 13 blastocysts. Sequence analysis was performed in 120 clones from one of these cDNA libraries with fragments of 50 to 1000 bp. Their sequence identity was analyzed using the expressed sequence tag (EST) database. RESULTS: The presence of two housekeeping genes, hexokinase I and serine/threonine phosphorylase, and four other ESTs was demonstrated, the identity of which, with particular gene expression in preimplantation development, has not yet been established. CONCLUSIONS: The data demonstrate the usefulness of constructing cDNA libraries from individual human blastocysts and their values in the analysis of genetic expression in human preimplantation development.

Blastocyst↗