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P S Bernstein

Publications and source records attributed to P S Bernstein.

At least 19 recordsLinked to original sources

Identification and quantitation of carotenoids and their metabolites in the tissues of the human eye.

There is increasing evidence that the macular pigment carotenoids, lutein and zeaxanthin, may play an important role in the prevention of age-related macular degeneration, cataract, and other blinding disorders. Although it is well known that the retina and lens are enriched in these carotenoids, relatively little is known about carotenoid levels in the uveal tract and in other ocular tissues. Also, the oxidative metabolism and physiological functions of the ocular carotenoids are not fully understood. Thus, we have set out to identify and quantify the complete spectrum of dietary carotenoids and their oxidative metabolites in a systematic manner in all tissues of the human eye in order to gain better insight into their ocular physiology. Human donor eyes were dissected, and carotenoid extracts from ocular tissues [retinal pigment epithelium/choroid (RPE/choroid), macula, peripheral retina, ciliary body, iris, lens, vitreous, cornea, and sclera] were analysed by high-performance liquid chromatography (HPLC). Carotenoids were identified and quantified by comparing their chromatographic and spectral profiles with those of authentic standards. Nearly all ocular structures examined with the exception of vitreous, cornea, and sclera had quantifiable levels of dietary (3R,3'R,6'R)-lutein, zeaxanthin, their geometrical (E / Z) isomers, as well as their metabolites, (3R,3'S,6'R)-lutein (3'-epilutein) and 3-hydroxy-beta,epsilon-caroten-3'-one. In addition, human ciliary body revealed the presence of monohydroxycarotenoids and hydrocarbon carotenoids, while only the latter group was detected in human RPE/choroid. Uveal structures (iris, ciliary body, and RPE/choroid) account for approximately 50% of the eye's total carotenoids and approximately 30% of the lutein and zeaxanthin. In the iris, these pigments are likely to play a role in filtering out phototoxic short-wavelength visible light, while they are more likely to act as antioxidants in the ciliary body. Both mechanisms, light screening and antioxidant, may be operative in the RPE/choroid in addition to a possible function of this tissue in the transport of dihydroxycarotenoids from the circulating blood to the retina. This report lends further support for the critical role of lutein, zeaxanthin, and other ocular carotenoids in protecting the eye from light-induced oxidative damage and aging.

Carotenoids↗

Ligand-binding characterization of xanthophyll carotenoids to solubilized membrane proteins derived from human retina.

The macula of the human retina contains extraordinarily high concentrations of lutein and zeaxanthin, xanthophyll carotenoids that appear to play an important role in protecting against age-related macular degeneration, the leading cause of blindness among the elderly. It is likely that the uptake and stabilization of these carotenoids is mediated by specific xanthophyll-binding proteins. In order to purify and characterize such a binding protein, a carotenoid-rich membrane fraction derived from human macula or peripheral retina was prepared by homogenization, differential centrifugation, and detergent solubilization. Further purification was carried out using ion-exchange chromatography and gel-filtration chromatography coupled with continuous photodiode-array monitoring for endogenously associated xanthophyll carotenoids. The most highly purified preparations contained two major protein bands at 25 and 55 kDa that consistently co-eluted with endogenous lutein and zeaxanthin. The visible absorbance spectrum of the binding protein preparation closely matches the spectral absorbance of the human macular pigment, and it is bathochromically shifted about 10 nm from the spectrum of lutein and zeaxanthin dissolved in organic solvents. Binding of exogenously added lutein and zeaxanthin is saturable and specific with an apparent Kd of approximately 1 microM. Canthaxanthin and beta-carotene exhibit no significant binding activity to solubilized retinal membrane proteins when assayed under identical conditions. Other potential mammalian xanthophyll-binding proteins such as albumin, tubulin, lactoglobulin and serum lipoproteins possess only weak non-specific binding affinity for carotenoids when assayed under the same stringent binding conditions. This investigation provides the first direct evidence for the existence of specific xanthophyll-binding protein(s) in the vertebrate retina and macula. The possible roles of xanthophyll-binding proteins in normal macular function and in the pathogenesis of age-related macular degeneration remain to be elucidated.

Carrier Proteins↗

Assessment of mutations in the Best macular dystrophy (VMD2) gene in patients with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and bull's-eye maculopathy.

PURPOSE: To study the presence of Best macular dystrophy (VMD2) gene mutations in patients diagnosed with maculopathies other than classic Best disease and to describe the clinical characteristics of these subjects. DESIGN: Case-comparison study of phenotype-genotype correlations. METHODS: Patients with either age-related maculopathy (ARM; n = 259) or maculopathies other than classic Best disease (n = 28) were screened for mutations in the Best gene (VMD2; OMIM 153700). These cases were compared with ethnically similar subjects in the same age range without maculopathy (n = 196). All patients underwent a complete dilated ocular examination, and all affected individuals underwent fundus photography. Phenotype-genotype comparisons were made. MAIN OUTCOME MEASURES: Presence of mutations in the Best gene (VMD2; OMIM 153700) and the clinical phenotype. RESULTS: Three of 259 patients (1%) with ARM and 2 of 28 patients (7%) with other maculopathies including 1 of 3 patients with adult-onset foveomacular vitelliform dystrophy and 1 of 5 patients with a bull's eye maculopathy, but none of the controls, were found to possess amino acid-changing variants in the VMD2 gene. These included a man with confluent drusen and retinal pigment epithelial detachments (variant in exon 6; T216I), a man with geographic atrophy and numerous soft drusen (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations resembling bull's-eye maculopathy (variant in exon 4; E119Q), and a woman diagnosed with adult-onset foveomacular vitelliform dystrophy (variant in exon 4; A146K). CONCLUSIONS: Novel mutations in the VMD2 gene were found in patients diagnosed with maculopathies other than classic Best disease. Some cases diagnosed as adult-onset vitelliform foveomacular dystrophy may represent a variant of Best disease with delayed onset. The VMD2 gene does not play a major role in the development of ARM.

Aged↗

Cardiomyopathy in pregnancy: a retrospective study.

Women with dilated cardiomyopathies (DCM) have traditionally been advised not to attempt to carry pregnancies. This is largely based on data derived from studies of the course of peripartum cardiomyopathy (PPCM) and it is not clear that this extrapolation is appropriate. Our objective was to compare maternal and obstetric outcomes of pregnancies in women with preexisting DCM to women with PPCM. A 10-year retrospective comparative cohort study was undertaken of women between the ages of 15 and 40 discharged from two university medical centers with the diagnosis of cardiomyopathy (CM). Patients were included in the study if CM was diagnosed prior to pregnancy (DCM group) or if CM developed during pregnancy or within 5 months postpartum (PPCM group), and follow-up data was available. Thirty-one subjects were included in the study. Twenty-three women with the diagnosis of PPCM were compared with 8 women with DCM of other etiologies. There were no significant differences in maternal age, race, parity, tobacco or other substance use, or other risk factors between the two groups. Maternal outcomes in the PPCM group were significantly worse than in the DCM group, with three maternal deaths and four women undergoing heart transplants (p = 0.05). In the DCM group, one woman with a prepregnancy ejection fraction of 16% underwent transplantation after termination of pregnancy for genetic indications. None of the other women in the DCM group had a significant decline in cardiac status. Infant outcomes in both groups were uniformly good. PPCM represents an acute, evolving insult to the pregnant or postpartum woman. The prognosis of this condition should not be used for counseling women with DCM considering pregnancy. Women with stable DCM may do well during pregnancy without significant deterioration in their cardiac status.

Adult↗

Evaluation of the ELOVL4 gene in patients with age-related macular degeneration.

Stargardt-like macular degeneration (STGD(3)) and autosomal dominant macular degeneration (adMD) share phenotypic characters with atrophic age-related macular degeneration (AMD). Mutations in a photoreceptor cell-specific factor involved in the elongation of very long chain fatty acids (ELOVL(4)) were shown to be associated with STGD(3), adMD, and pattern dystrophy. We screened 778 patients with AMD and 551 age-matched controls to define the role of sequence variants in the ELOVL(4) gene in age-related macular degeneration. We detected three sequence variants in the non-coding region and eight variants in the coding region. No statistically significant association was observed between sequence variants in the ELOVL(4) gene and susceptibility to AMD. However, for the detection of modest effects of multiple alleles in a complex disease, the analysis of larger cohorts of patients may be required.

Age Factors↗

Evaluation of the G protein coupled receptor-75 (GPR75) in age related macular degeneration.

BACKGROUND: A long term project was initiated to identify and to characterise genes that are expressed exclusively or preferentially in the retina as candidates for a genetic susceptibility to age related macular degeneration (AMD). A transcript represented by a cluster of five human expressed sequence tags (ESTs) derived exclusively from retinal cDNA libraries was identified. METHODS: Northern blot and RT-PCR analyses confirmed preferential retinal expression of the gene, which encodes a G protein coupled receptor, GPR75. Following isolation of the full length cDNA and determination of the genomic organisation, the coding sequence of GPR75 was screened for mutations in 535 AMD patients and 252 controls from Germany, the United States, and Italy. Employed methods included single stranded conformational polymorphism (SSCP) analysis, denaturing high performance liquid chromatography (DHPLC), and direct sequencing. RESULTS: Nine different sequence variations were identified in patients and control individuals. Three of these (-30A>C, 150G>A, and 346G>A) likely represent polymorphic variants. Each of six alterations (-4G>A, N78K, P99L, S108T, T135P, and Q234X) were found once in single AMD patients and were considered variants that could affect the protein function and potentially cause retinal pathology. CONCLUSION: The presence of six potential pathogenic variants in a cohort of 535 AMD patients alone does not provide statistically significant evidence for the association of sequence variation in GPR75 with genetic predisposition to AMD. However, a possible connection between the variants and age related retinal pathology cannot be discarded. Functional studies are needed to clarify the role of GPR75 in retinal physiology.

Adult↗

Diverse macular dystrophy phenotype caused by a novel complex mutation in the ELOVL4 gene.

PURPOSE: A 5-bp deletion in ELOVL4, a photoreceptor-specific gene, has been associated with autosomal dominant (ad) macular dystrophy phenotypes in five related families, in which phenotypes range from Stargardt-like macular dystrophy (STGD3; Mendelian Inheritance in Man 600110) to pattern dystrophy. This has been the only mutation identified in ELOVL4 to date, which is associated with macular dystrophy phenotypes. In the current study, the potential involvement was investigated of an ELOVL4 gene variation in adSTGD-like and other macular dystrophy phenotypes segregating in a large unrelated pedigree from Utah (K4175). METHODS: The entire open reading frame of the ELOVL4 gene was analyzed by direct sequencing in a proband from the K4175 family. The combination of denaturing high-performance liquid chromatography (DHPLC) analysis and direct sequencing of all available family members was used to further assess segregation of identified ELOVL4 variants in the pedigree. RESULTS: A complex mutation, two 1-bp deletions separated by four nucleotides, was detected in all affected members of the family. The mutation results in a frameshift and the truncation of the ELOVL4 protein, similar to the effect of the previously described 5-bp deletion. CONCLUSIONS: The discovery of a second mutation in the ELOVL4 gene segregating with macular dystrophy phenotypes confirms the role of this gene in a subset of dominant macular dystrophies with a wide range of clinical expressions and suggests a role for modifying genes and/or environmental factors in the disease process.

Adolescent↗

Risk factor scoring for predicting venous thromboembolism in obstetric patients.

OBJECTIVE: The aim of this study was to develop a risk factor scoring system for the prediction of venous thromboembolism in obstetric patients. STUDY DESIGN: We conducted a retrospective case-control study of all pregnant or postpartum women admitted to the Jack D. Weiler Hospital from 1987 through 1998 with a discharge diagnosis indicating thromboembolism. For each study subject the three women who were delivered immediately before that index patient were selected for the control group. Data collected included the following: history of thrombosis, age, body mass index, previous abdominal surgical procedures, presence of systemic diseases, and blood type. Each patient was assigned a score that was based on the risk factors identified. RESULTS: We identified 21 patients who had sustained thromboembolic events during pregnancy or 6 weeks post partum. Nineteen of the thromboembolic events (90%) were diagnosed during pregnancy, and these cases were distributed throughout gestation-8 (42%) in the first trimester, 2 (10%) in the second trimester, and 9 (48%) in the third trimester. Six (28%) of these patients had pulmonary embolisms. Two cases of postpartum thromboembolic events were documented. Both were cases of pulmonary embolism. There was 1 maternal death. Patients with a score >2 were at significantly increased risk for having a thromboembolism, with an odds ratio of 4.8 (P <.05). The sensitivity, specificity, positive predictive value, and negative predictive value of this cutoff point were 21%, 95%, 57%, and 78%, respectively. CONCLUSION: Obstetric patients with high risk factor scores were at increased risk for thromboembolism.

ABO Blood-Group System↗

Improving preconception care.

OBJECTIVE: To improve the documentation and delivery of preconception care to all women of reproductive age attending an inner city hospital's outpatient gynecology clinic. A secondary goal was to evaluate the knowledge and awareness of providers regarding preconception care. STUDY DESIGN: A preintervention chart review of a convenience sample of non-pregnant women with reproductive potential who attend an inner city hospital gynecology clinic (n = 100) was conducted to evaluate delivery of preconception care. Items screened for included: family planning services, domestic violence, nutrition and medical risk factors, medication use, appropriate counseling and use of referral services. All providers in the clinic were surveyed to assess their knowledge of and attitudes toward preconception care. A two-part intervention was then carried out: (1) a one-hour lecture for all providers, and (2) a standardized preconception care form inserted in all charts. A postintervention chart review of a second convenience sample (n = 100) and repeat provider survey were then conducted to evaluate the effectiveness of the two interventions. RESULTS: Following the two-pronged intervention, there was evidence of improved documentation of the delivery of preconception care. Documentation of screening in almost all categories was significantly improved (P < .05). The greatest improvements were noted in complete screening for medical risk factors (from 15% to 44%), for over-the-counter and prescription medication use (from 10% to 70% and 30% to 77%, respectively), domestic violence (from 10% to 57%) and nutrition (from 9% to 50%). However, provider knowledge of and attitudes toward preconception care were not significantly changed. CONCLUSION: The combination of education about preconception care and insertion of a standardized form into a patient's chart led to a clear improvement in the documentation of preconception care. Given the significance of preconception care, insertion of a standardized form should be considered to help providers complete and appropriate care to their patients.

Adult↗

Maintenance of retinoid metabolism in human retinal pigment epithelium cell culture.

If transplantation of cultured retinal pigment epithelium (RPE) or iris pigment epithelium (IPE) is to be successful in the treatment of ocular disease, it is imperative to demonstrate that these cells can perform all of their necessary metabolic functions. Unfortunately, a critical function of the RPE, retinoid metabolism, is often lost rapidly in culture. We have examined whether or not nonspecific proteolytic enzymes commonly used in cell isolation and serial passaging may be responsible for this loss of function, and we have investigated novel isolation and passaging techniques which can alleviate this loss of retinoid metabolism.RPE cells were obtained from human donor eyes by enzymatic and nonenzymatic methods. Cells were cultured either on control tissue culture inserts or on inserts coated with a layer of thermally responsive poly(N -isopropylacrylamide-co-cinnamoylcarbamidemethylstyrene). Upon confluence, cells were detached either by trypsinization or by lowering dish temperature. Retinoid metabolism of cells was assessed after isolation and culture by incubating membrane fractions with3H-all- trans -retinol. Retinoid metabolism was also measured in freshly isolated IPE, corneal endothelium (CE), an RPE cell line (D407), and two hepatocyte cell lines (Hepa 6 and HepG2). Membrane fractions from cells isolated nonenzymatically or using collagenase/hyaluronidase formed 11- cis -retinol, retinal isomers and retinyl esters. Retinoid metabolism of RPE cells freshly isolated by trypsinization showed no 11- cis -retinal and little 11- cis -retinol formation. Nondamaged cells cultured on thermally responsive surfaces detached in sheets upon temperature change. They showed metabolism similar to that of cells freshly isolated by nonenzymatic means. After trypsinization, confluent cultures dissociated into individual cells, but these cells showed poor retinoid metabolism, including no detectable retinyl esters or 11- cis -retinoid isomers. IPE, CE and Hepa 6 did not show any retinoid metabolism. D407 and HepG2 produced retinals, but not the 11- cis isomer.RPE cells isolated using trypsin lose the ability to form critical intermediates in the visual cycle. Collagenase/hyaluronidase or nonenzymatic cell isolation techniques enable these functions to be maintained. After cell culture, thermally responsive surfaces allow nonenzymatic cell detachment and excellent maintenance of retinoid metabolism.

Adolescent↗

Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies.

Vitelliform macular dystrophy (VMD2, Best disease, MIM153700) is an early onset, autosomal, dominant macular degeneration characterized by the deposition of lipofuscin-like material within and below the retinal pigment epithelium (RPE); it is associated with degeneration of the RPE and overlying photoreceptors. Recently, we cloned the gene bestrophin, which is responsible for the disease, and identified a number of causative mutations in families with VMD2. Here, we report that the analysis of bestrophin in a collection of 259 age-related macular degeneration (AMD) patients provides evidence that mutations in the Best disease gene do not play a significant role in the predisposition of individuals to AMD. However, our results suggest that, in addition to Best disease, mutations within the bestrophin gene could be responsible for other forms of maculopathy with phenotypic characteristics similar to Best disease and for other diseases not included in the VMD category.

Adult↗

Second-trimester molecular prenatal diagnosis of sporadic Apert syndrome following suspicious ultrasound findings.

Apert syndrome, an autosomal dominant disorder characterized by craniosynostosis, mid-facial malformations, symmetric bony syndactyly of hands and feet, and varying degrees of mental retardation, is most frequently caused by a de novo mutation. Two missense mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have been found to account for the disorder in approximately 98% of affected patients. Seven cases of prenatal ultrasound diagnosis have been reported. Although one earlier diagnosis has been made in a familial case, sporadic cases have not been definitively diagnosed until the third trimester when craniosynostosis is usually detected. We report a second-trimester molecular diagnosis of a sporadic case, based on the ultrasound observation of fetal 'mitten hands' and craniosynostosis. We discuss the approach to such ultrasound features, given the current availability of molecular diagnosis for Apert syndrome.

Abortion, Therapeutic↗

Utilization of real-time ultrasound on labor and delivery in an active academic teaching hospital.

OBJECTIVE: Ultrasound (US) is currently available on most if not all Labor and Delivery (L+D) services. Our objective was to survey utilization of real-time US on L+D in an active academic teaching hospital. STUDY DESIGN: Between April 1, and July 31, 1998, all US examinations performed for clinical purposes on patients presenting to L+D, were documented. Data collected included: gestational age, whether or not the patient was in labor, number of fetuses, and indication for US. All US examinations were performed by OB/GYN housestaff at the PGY 2-3 level, and fellows in Maternal-Fetal Medicine. Statistical analysis included Student's t-test and chi2 when appropriate, with p < 0.05 considered significant throughout. RESULTS: During the 4-month study period, 1316 patients delivered and 1363 were discharged from L+D, not in labor. Of 630 US examinations 31.64% (192 of 630) and 67.69% (418 of 630) were performed in laboring versus nonlaboring patients, respectively. Of all patients delivered during the study period, 14.5% (192 of 1316) underwent intrapartum US, and of all nonlaboring patients, 30.66% (418 of 1363) underwent US on L+D. The mean gestational age at the time of assessment was 37.32 +/- 4.23 weeks' versus 35.74 +/- 5.76 weeks' gestation, in laboring versus nonlaboring patients respectively, p < 0.05. Main indications for US in patients in labor were; fetal presentation in patients with spontaneous rupture of membranes (SROM) 34.4% (n = 66), confirmation of vertex presentation 20.3% (n = 39), preterm labor 12% (n = 23), multiple gestation 7.3% (n = 14), and malpresentation 7.3% (n = 14). Main indications for patients not in labor were; amniotic fluid index 15.8% (n = 66), SROM 15.6% (n = 65), postdates 9.8% (n = 41) placental location 9.6% (n = 40), and decreased fetal movement 9.3% (n = 39). Ultrasound-guided interventions included: all deliveries of multiple gestations (n = 9), version in nonlaboring patients (n = 10), and postpartum curettage for retained placental tissue in conjuction with severe early postpartum hemorrhage (n = 2). The incidences of each separate indication for US were significantly different between laboring versus nonlaboring patients, p < 0.05, respectively. CONCLUSION: US examination is performed in 15% of patients in labor and 31% of patients not in labor assessed on L+D, constituting a widely applied diagnostic tool in this environment.

Delivery, Obstetric↗

Beta-human chorionic gonadotropin in cervicovaginal secretions as a predictor of preterm delivery.

OBJECTIVE: This study's objective was to determine whether the concentrations of beta-human chorionic gonadotropin in the secretions of the cervix and vagina could be used to predict preterm delivery in a group of women at high risk for this complication. STUDY DESIGN: Women attending a prematurity prevention clinic at an inner-city hospital July 1, 1996-October 1, 1997, were invited to participate. From those who consented, secretions from the cervix and posterior vaginal fornix were sampled every 2 weeks until delivery, beginning at 24 weeks' gestation. Concentrations of beta-human chorionic gonadotropin were measured with a commercially available enzyme-linked immunosorbent assay. Providers of obstetric care were blinded to the results. Levels of beta-human chorionic gonadotropin in those who were delivered before 34 weeks' gestation and those who were delivered at term were compared. A value >50 mIU/mL was considered elevated. This cutoff value was determined according to beta-human chorionic gonadotropin values obtained during pregnancies that were delivered at term. RESULTS: Of the 146 women asked to participate, 77 consented. There was no difference between participants and nonparticipants with respect to age, race, indication for enrollment in the clinic, gestational age at delivery, or parity. Of the 77 participants, 24 (31%) were delivered before 37 weeks' gestation and 12 (16%) were delivered before 34 weeks' gestation. A single beta-human chorionic gonadotropin value >50 mIU/mL obtained between 24 and 28 weeks' gestation was associated with a significant increase in the incidence of delivery before 34 weeks' gestation (P = .03). This cutoff value had sensitivity, specificity, and positive and negative predictive values for predicting delivery before 34 weeks' gestation of 50%, 87%, 33%, and 93%, respectively. CONCLUSION: These data suggest that the concentration of beta-human chorionic gonadotropin in cervicovaginal secretions may be a useful predictor of preterm delivery.

Adult↗

Abortion and maternal health.

Since the beginning of recorded history, women have attempted to terminate unwanted pregnancies. Despite the safety of modern techniques of abortion, many women throughout the world still have to resort to unsafe abortions, placing themselves at considerable risk. The World Health Organization estimates that there are approximately 20 million unsafe abortions performed each year, and estimates of maternal deaths as a result of abortion range between 60,000 and 100,000 per year. With free and legal access to safe abortions, rates of complications and mortality drop dramatically. There is an urgent need for efforts to prevent unwanted pregnancies in order to reduce the need for abortion; for the early identification of abortion complications and easy access to treatment for women suffering those complications; for expansion of safe abortion availability; and for proper training and resources for providers of abortion services.

Abortion, Legal↗

Uncomplicated baseline fetal tachycardia or bradycardia in postterm pregnancies and perinatal outcome.

OBJECTIVE: to assess perinatal outcome in post-term pregnancies in which fetal heart rate (FHR) monitoring revealed either uncomplicated baseline fetal tachycardia (> or = 160 bpm) or fetal bradycardia (< or = 120 bpm). STUDY DESIGN: We performed a case-control study of patients who underwent fetal assessment between July 1989 and June 1995, as part of post-term evaluation. Inclusion criteria consisted of nonlaboring afebrile patients with singleton post-term pregnancies > or = 41 weeks of gestation by strict dating criteria (last menstrual period consistent with ultrasound biometric parameters obtained prior to 20 weeks' gestation), normal fetal anatomy, intact membranes, and reactive nonstress test with no evidence of chorioamnionitis. Patients with fetal tachy or brady arrhythmias, FHR decelerations, or loss of short-term beat-to-beat variability were excluded. Baseline FHR was recorded retrospectively by an observer blinded to maternal and neonatal clinical outcome. For each case of uncomplicated baseline fetal tachycardia (> or = 160 bpm) or bradycardia (< or = 120 bpm), either two or three control cases (matched for maternal age and parity), with FHR > 120 bpm and < 160 bpm, were identified. Outcome variables assessed included: incidence of cesarean delivery, nuchal cord at delivery, meconium-stained amniotic fluid (AF), 5-min Apgar score < 7, fetal growth restriction (< 10th percentile for 41 weeks' gestation), meconium aspiration syndrome, and neonatal intensive care unit (NICU) admission. Statistical analysis included two-tailed t-test and chi2 test when appropriate, with p < 0.05 considered significant throughout. RESULTS: During the study period 1390 post-term patients (6.81% of the general population) were assessed. Of these, 31 (2.23%) fetuses exhibited baseline FHR > or = 160 bpm, and 76 fetuses (5.46%) exhibited baseline FHR < or = 120 bpm. No significant differences were noted in the incidence of cesarean delivery, presence of nuchal cord at delivery, meconium-stained AF, 5-min Apgar scores < 7, fetal growth restriction, meconium aspiration syndrome, or the incidence of NICU admissions between the groups of patients with fetal tachycardia, bradycardia, and their respective controls. CONCLUSIONS: Uncomplicated baseline fetal tachycardia or bradycardia in postterm patients are not associated with an increase in the incidence of adverse perinatal outcome.

Bradycardia↗

Raman detection of macular carotenoid pigments in intact human retina.

PURPOSE: To develop and test a novel noninvasive optical technique suitable for the objective measurement of macular carotenoid levels in human retina. METHODS: A resonance Raman scattering apparatus was constructed to measure carotenoid levels in flat-mounted human retinas and eyecups and in experimental animal eyes. Light from an argon laser was used to resonantly excite the electronic absorption of the carotenoid pigments, and scattered light was collected and analyzed by a Raman spectrometer. After carotenoid Raman measurements were completed on the retinal samples, macular carotenoid levels were determined by high-performance liquid chromatography (HPLC). RESULTS: Carotenoid resonance Raman scattering proved to be a highly sensitive and specific method for the noninvasive measurement of macular pigments in the human retina. Signal strength scaled linearly with actual macular carotenoid content as measured by HPLC. Our apparatus was also used to record resonance Raman signals from xanthophyll carotenoids stored in the retinal pigment epithelium of intact frog eyes. CONCLUSIONS: This new noninvasive optical method will facilitate studies of ocular carotenoid distributions and their role in degenerative diseases of the eye and may allow for the rapid screening of carotenoid levels in large populations at risk for vision loss from age-related macular degeneration, the leading cause of blindness in the elderly in the United States. A prototype clinical instrument is under development.

Animals↗

Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of severe central visual impairment among the elderly and is associated both with environmental factors such as smoking and with genetic factors. Here, 167 unrelated AMD patients were screened for alterations in ABCR, a gene that encodes a retinal rod photoreceptor protein and is defective in Stargardt disease, a common hereditary form of macular dystrophy. Thirteen different AMD-associated alterations, both deletions and amino acid substitutions, were found in one allele of ABCR in 26 patients (16%). Identification of ABCR alterations will permit presymptomatic testing of high-risk individuals and may lead to earlier diagnosis of AMD and to new strategies for prevention and therapy.

ATP-Binding Cassette Transporters↗