[Update on diagnosis of limb girdle muscular dystrophy].
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Diagnosis, Differential↗
Biomedical subjects
Y Yaron
Publications and source records attributed to Y Yaron.
Fetal muscle biopsy as a diagnostic tool in Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a relentless progressive disorder, leading to severe disability during childhood and death in adolescence or early adulthood. In most families, prenatal diagnosis is readily achieved by molecular detection of DNA deletions using chorionic villi or amniocytes, or by linkage analysis. In some cases, however, molecular methods fail to provide a definitive diagnosis and in such cases in utero fetal muscle biopsy may serve as a diagnostic option. We describe three families in whom fetal muscle biopsy was performed, focusing on the prenatal diagnostic dilemmas, the indications and timing for in utero fetal muscle biopsy, and the difficulties encountered.
Female↗
Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome.
OBJECTIVE: We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. STUDY DESIGN: A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. RESULTS: In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. CONCLUSION: Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.
Abruptio Placentae↗
Multifetal pregnancy reductions of triplets to twins: comparison with nonreduced triplets and twins.
OBJECTIVE: Multifetal pregnancy reduction has been shown to improve survival rates in high-order multifetal pregnancies (>/=4). There is, however, some controversy as to whether multifetal pregnancy reduction improves pregnancy outcomes of triplets reduced to twins. The purpose of this study was to evaluate this issue by comparing outcomes of triplet gestations undergoing reduction to twins with outcomes of nonreduced twin gestations and expectantly managed triplet gestations. STUDY DESIGN: The study included 143 triplet pregnancies that underwent reduction to twins over a 10-year period at a single center. These were compared with 12 nonreduced triplet pregnancies from the Wayne State University Perinatal Database and with 2 groups of twin pregnancies: 605 from the Wayne State University Perinatal Database and 207 from the Quest Diagnostics Database. RESULTS: The miscarriage rate for expectantly managed triplets was 25%, compared with 6.2% for triplets reduced to twins. This rate was similar to the rates for both groups of nonreduced twins: 5.8% (Quest) and 6.3% (Wayne State University). Severe prematurity occurred in 25% of nonreduced triplets compared with 4. 9% of twins after reduction. This rate was also similar to that of nonreduced twins: 7.7% (Quest) and 8.4% (Wayne State University). The mean gestational age at delivery for expectantly managed triplets (32.9 +/- 4.7 weeks) was significantly shorter than for triplets reduced to twins (35.6 +/- 3.1 weeks). By comparison, nonreduced twins had a mean gestational age at delivery of 35.8 +/- 3.9 weeks for Quest and 34.4 +/- 3.6 weeks for Wayne State University. Mean birth weights were significantly lower in expectantly managed triplets as compared with triplets undergoing reduction to twins (1636 +/- 645 g vs 2381 +/- 602 g, respectively). Nonreduced twins had a mean birth weight of 2254 +/- 653 g for Quest and 2123 +/- 634 g for Wayne State University. Pregnancy loss rates, mean length of gestation, and mean birth weight did not vary significantly between triplets who underwent reduction to twins and nonreduced twins. CONCLUSIONS: Reduction of triplets to twins significantly reduces the risk for prematurity and low birth weight and may also be associated with a reduction in overall pregnancy loss. This suggests that multifetal pregnancy reduction of triplets to twins is a medically justifiable procedure not only from an actuarial viewpoint but also from the ethical perspective of supporting patients' autonomy and respect for patients' individual circumstances.
Abortion, Spontaneous↗
Lysyl oxidase transcripts in peritoneal adhesions and incisional scars.
OBJECTIVE: To evaluate the role of lysyl oxidase in postsurgical adhesion formation and incision wound repair. STUDY DESIGN: Female New Zealand rabbits underwent a pelvic-peritoneum adhesion-inducing operation under sterile conditions. In brief, the uterine horns were removed from the abdomen and abraded with surgical gauze and a scalpel blade. The horns were then replaced into the abdominal cavity, the incision was sutured, and the animals were allowed to recover. The animals were killed before lesion development and after 2, 4, 8, and 14 days of postsurgical recovery. The abraded uterine horns, abdominal wall incisional wound and a portion of the sidewall peritoneum were then removed. Total RNA was extracted using the guanidinium thiocyanate-phenol-chloroform method. Northern blot analysis was performed with an [alpha-32P]-labeled lysyl oxidase probe. RESULTS: Lysyl oxidase was expressed during abdominal wall incision repair on days 2 and 4 of postsurgical recovery, declining thereafter (days 8 and 14). In contrast, no increase in lysyl oxidase expression was noted in the uterine horns as compared to the control sidewall peritoneum. CONCLUSION: Lysyl oxidase plays a differential role in the early stages of abdominal wall and uterine horn repair.
Animals↗
p53 tumor suppressor gene expression in the mouse ovary during an artificially induced ovulatory cycle.
OBJECTIVE: To evaluate the expression of p53 in the mouse ovary during an artificially induced ovulatory cycle. STUDY DESIGN: Ovulation induction was performed using pregnant mares' serum gonadotropin/human chorionic gonadotropin (PMSG/hCG). First, a p53 promoter-chloramphenicol acetyl transferase (CAT) transgenic mouse model was used. Protein samples from ovaries of transgenic mice were assayed for CAT activity as evidence of p53 promoter activation. Next, RNA extracted from CD-1 mouse ovaries was used for reverse transcription/polymerase chain reaction (PCR) and northern blot analysis using a p53-specific probe. RESULTS: Increased CAT activity was noted in transgenic mice treated with PMSG/hCG as compared with controls. PCR studies on transgenic mice using primers for CAT and on CD-1 mice using primers for wild type p53 substantiated this observation. Furthermore, CAT assay and northern analysis, performed on samples obtained at serial time intervals from induction, indicated that maximal p53 expression occurs around the time of ovulation, beginning 48 hours after PMSG and peaking 6-12 hours after hCG administration. CONCLUSION: The temporal expression of p53 in the ovary during a PMSG/hCG artificially induced ovulatory cycle may indicate a role for p53 in processes of differentiation of granulosa cells into luteal cells.
Animals↗
Determinants of parental decisions after the prenatal diagnosis of Down syndrome.
We evaluated demographic factors and factors specific to the current pregnancy, and their relationship to the decision to continue or terminate a pregnancy after prenatal diagnosis of Down syndrome. All cases of Down syndrome (DS) managed at a tertiary care center from 1989-1997 were retrospectively analyzed with respect to maternal age, parity, gestational age, sonographic findings, insurance status, and race. Of 145 cases of trisomy 21, 19 (13.1%) of women chose continuation of pregnancy, while 126 (86.9%) chose termination. There were no differences between groups in parity, sonographic findings, insurance status, or race at the time of diagnosis. However, patients who chose termination were significantly older and earlier in gestation than those electing to continue their pregnancy. When Down syndrome is diagnosed prenatally, the choice of termination is related to maternal age and gestational age, but only gestational age is a significant independent predictor of pregnancy termination.
Abortion, Eugenic↗
Fetal gender impact on multiple-marker screening results.
Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are used in combination with maternal age to calculate the risk for Down syndrome (DS) in pregnancy. Increased levels of hCG and decreased levels of MSAFP and uE3 are consistent with an increased risk for DS. We retrospectively evaluated second-trimester maternal serum marker levels in a large cohort of patients with known normal outcomes and documented fetal gender. These included 15,428 patients who had MSAFP measurements, 11,428 patients with both MSAFP and hCG, and 6,090 patients with all three markers including uE3. MSAFP levels in patients with female fetuses were consistently lower than those with males. Conversely, hCG was higher in pregnancies with females as compared to males. No gender-related difference was noted for uE3. These results would suggest that the computed DS risk for female fetuses is higher than for males, despite the fact that the incidence of DS is similar in both genders. This information could be useful for calculating gender-specific DS risk; however, this would require ultrasonographic determination of fetal sex.
Biomarkers↗
Combination of elevated maternal serum alpha-fetoprotein (MSAFP) and low estriol is highly predictive of anencephaly.
Increased levels of second trimester maternal serum alpha-fetoprotein (MSAFP) have long been established as a marker for neural tube defects (NTDs). In addition, decreased levels of maternal estriol in the third trimester have been reported in pregnancies with anencephalic fetuses. The purpose of this study was to evaluate whether early second trimester unconjugated serum estriol (uE3) is an independent predictor of NTDs. The study included 57,031 patients who underwent maternal serum screening with MSAFP at 14-22 weeks gestation. Of these, 23,415 also had uE3 measurements. There were 63 cases of NTD, an overall incidence of 1.1 per 1,000. Elevated MSAFP (> or =2.5 MOM) was detected in 1,346 patients, 48 of which had NTDs. Decreased uE3 (< or =0.5) was detected in 1,437 patients, 17 of which had NTDs. The incidence of NTDs was significantly higher in patients with low uE3, compared to patients with normal/high uE3 (1.15% vs. 0.09%, P < 001). Finally, 51 patients had both increased MSAFP and decreased uE3; 16 of these had NTDs, 14 of which were anencephalics. In conclusion, both elevated MSAFP and low maternal serum estriol are predictive of NTD but have a low sensitivity. The combination of abnormally elevated MSAFP and low estriol is highly predictive of NTD in particular anencephaly.
Anencephaly↗
Effect of adjustment of maternal serum alpha-fetoprotein levels in insulin-dependent diabetes mellitus.
Our objective was to determine the effect of the 20% upward adjustment of maternal serum alphafetoprotein (MSAFP) in patients with insulin-dependent diabetes mellitus (IDDM) on the number of patients that would be classified at increased risk for pregnancy complicated by either Down syndrome (DS) or neural tube defect (NTD). We retrospectively evaluated a database containing 63,110 patients who underwent multiple serum marker screening between 14 and 22 weeks gestation; 620 patients with IDDM had measurements of MSAFP of which 479 also had measurements of beta-HCG, allowing calculation of DS risk. Increased NTD risk was defined as MSAFP >2.5 MOM while increased DS risk was defined as a calculated risk > or =1/270. One IDDM patient delivered an infant with a NTD; it was not detected on serum screening. No infants were born with DS. Of the 620 patients with MSAFP determinations, 9 had values >2.5 MOM before adjustment. After upward adjustment, 7 additional patients were identified. Sixteen patients were identified at increased risk for DS before and after adjustment. Our data suggest that the 20% upward adjustment of MSAFP increases by 78%, the number of patients who would require further evaluation for NTD's. Although we were able to identify 620 women with IDDM who underwent serum screening for NTD, the low prevalence of NTD's did not allow us to demonstrate an increased detection rate. The effect of upward adjustment of MSAFP on the number of patients categorized at increased DS risk appears to be minimal.
Adult↗
Age-specific variation in aneuploidy incidence among biochemical screening programs.
OBJECTIVE: Our purpose was to compare the observed age-related incidence of Down syndrome in two large screening programs with the commonly quoted incidences used in biochemical screening programs. STUDY DESIGN: Data from two large prenatal screening programs were stratified in 5-year age groups. The age-related incidence of Down syndrome was compared with the commonly used incidence as reported by Cuckle. RESULTS: No significant differences were found in age-related incidences of Down syndrome in any age group between the screening groups or among women ages 15 through 29 in any of the three groups. However, for women 30 to 34 and > or = 40 years old, a trend was noted toward a higher incidence in the screening groups. For women ages 35 to 39, the observed incidence was significantly greater in the screening groups compared with the data of Cuckle. CONCLUSION: Our data suggest an underascertainment in Down syndrome risk built into the Cuckle model, particularly in high-risk patients.
Adolescent↗
Malignant fibrous histiocytoma with myofibroblastic differentiation of the vulva in an adolescent female.
Malignant fibrous histiocytoma is a rare sarcoma. Only seven cases in the vulva have been reported. We present a case of malignant fibrous histiocytoma of the vulva in an adolescent female. The elected treatment was local wide resection.
Adolescent↗
Multifetal pregnancy reduction.
Multifetal pregnancy reduction (MFPR) has become a mainstay of infertility therapy as its development has allowed physicians to become more aggressive in treating patients resistant to more conservative therapies. Over the course of the past decade, MFPR has become practised in a limited number of tertiary specialty centres, which have improved its performance and very substantially lowered its risks. The majority of physicians performing MFPR employ a transabdominal needle injection of potassium chloride into the fetal thorax. Risks for pregnancy losses of patients starting with triplets and/or quadruplets reduced to twins have improved over the past decade and are not substantially different from those in patients whose pregnancy began as twins. There have been no substantiated risks of coagulopathies or damage to surviving fetuses.
Ethics, Medical↗
Centromere sequences localize to the nuclear halo of human spermatozoa.
Chromatin is organized into a series of discrete nuclear matrix-associated and non-nuclear matrix-associated domains. The non-matrix-associated domains consist of loops of DNA that are attached to the proteinaceous nuclear matrix by matrix-associated regions (MARs). Although this organization is well characterized in somatic cells, comparatively little is known of this mode of organizing the genome in the human sperm nucleus. To define this relationship, the interaction of human sperm chromatin with the nuclear matrix was assessed by fluorescence in situ hybridization using specific alpha satellite probes directed to the centromeric regions of chromosomes 13 plus 21 and 18. Hybridization of the centromeric sequences was visualized as segmented, bundled structures that extended from the nuclear core into the halo.
Cell Nucleus↗
High frequency of a common Bloom syndrome Ashkenazi mutation among Jews of Polish origin.
Bloom syndrome (BS) is an autosomal recessive disorder characterized by small stature, immunodeficiency, chromosomal instability, and a predisposition to different types of cancer. Although extremely rare in the general population, BS is seen in about 1 in 48,000 Ashkenazi Jews. Mutation analysis of seven Ashkenazi BS probands has shown that all were homozygous for the same mutation in the BLM gene: 2281delATCTGAinsTAGATTC, also known as blmAsh. This finding, along with the increased incidence of BS among Ashkenazi Jews, suggests a founder effect for BS in this population. The purpose of this study was to determine the frequency of blmAsh mutation carriers in a randomly sampled Ashkenazi Jewish population in Israel. The initial study group included 1,613 Ashkenazi Jews who were referred for routine DNA screening tests (cystic fibrosis, Gaucher, Canavan, fragile X). None had a family history of BS. A group of 552 non-Ashkenazi Jews served as controls. Mutation analysis was performed by PCR amplification followed by analysis of a specific BstN1 restriction site, created by the blmAsh mutation. All positive carriers were confirmed by direct sequencing. Sixteen blmAsh carriers were detected among 1,613 Ashkenazi Jews (1 in 101), compared to none among 552 non-Ashkenazi individuals. In this study, Ashkenazi Jews of biparental Polish descent had a significantly higher proportion of the blmAsh mutation (1 in 37) compared to Ashkenazi Jews of non-Polish descent. These results provide further evidence that a founder effect is responsible for the increased incidence of Bloom syndrome among Ashkenazi Jews, particularly those of Polish descent.
Adenosine Triphosphatases↗
Oocyte donation in Israel: a study of 1001 initiated treatment cycles.
There are numerous studies concerning pregnancy rates in oocyte donation, yet only a handful report the obstetric outcome in such pregnancies. The purpose of this study was to assess factors that influence pregnancy rates, to determine the incidence of complications, and to evaluate obstetric outcome in pregnancies resulting from oocyte donation. This study included 423 oocyte recipients who underwent 1001 oocyte donation cycles at the Oocyte Donation Programme, In-Vitro Fertilization (IVF)-Embryo Transfer Unit, Herzlia Medical Center, Israel. Donors were all healthy women < 34 years old who underwent IVF themselves. In 873 cycles, fertilization occurred and embryo transfer was performed, resulting in 194 clinical pregnancies. Pregnancy rates (PR) significantly declined with the increase in number of previous attempts, and with increasing age of recipient (36.8%/embryo transfer in patients < or = 30 compared to 17.8% in patients > 40 years old). A significant increment in PR was noted with the increasing number of embryos transferred. The overall PR was 22.2%/embryo transfer. However, in young amenorrhoeic patients with normal karyotypes undergoing their first cycle, PR was 52.2%; the 'take home baby' rate was 38.3% per patient undergoing embryo transfer and 17.8% per embryo transfer cycle. A significant increase in the incidence of pregnancy-induced hypertension and a higher proportion of abortions were noted in older patients. A significantly higher incidence of prematurity and low birthweight was observed in multiple pregnancies.
Adult↗
Selective termination and elective reduction in twin pregnancies: 10 years experience at a single centre.
Selective termination is employed in multifetal pregnancies, in the presence of an abnormal fetus, in order to improve the prognosis of the normal fetuses. The term elective reduction is used to describe reduction in twin pregnancies for maternal medical conditions, psychological, or socioeconomic reasons. The purpose of this study was to evaluate the factors that influence outcome in such pregnancies. Eighty-two twin pregnancies underwent selective termination (n = 59) or elective reduction (n = 23) over a 10-year period. Early procedures, performed < or = 14 weeks (n = 31), had a pregnancy loss of 9.7% and a mean procedure-to-loss interval of 4.1 +/- 2.8 weeks; mean birthweight was 3299 +/- 395 g in survivors, with a mean gestational age at delivery of 38.4 +/- 2.3 weeks. In comparison, procedures performed > 14 weeks (n = 51) had a pregnancy loss of 7.8%, with a procedure-to-loss interval of 1.2 +/- 0.6 weeks. Mean birthweight was 2577 +/- 999 g, with a mean gestational age at delivery of 35.7 +/- 5 weeks. In conclusion, outcomes were more favourable among patients who underwent a first trimester procedure. The slight increase in pregnancy loss may be attributed to a higher than expected rate of spontaneous abortions in the first trimester, as manifested by the higher procedure-to-loss interval after a first trimester procedure. These facts underscore the importance of early detection of fetal abnormalities in twin pregnancies by ultrasonography and chorionic villus sampling.
Abortion, Spontaneous↗
What are the ethical and technical problems associated with multifetal pregnancy reduction?
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Ethics, Medical↗