Search

Beare–Stevenson syndrome (BSS) is a rare FGFR2-associated craniosynostosis syndrome with a higher rate of sudden unexplained death than related conditions such as Apert, Pfeiffer, and Crouzon syndromes. BSS presents with craniosynostosis, cutis gyrata, and significant developmental delay in most patients who survive infancy. There have only been 21 reported patients with BSS, which limits prognostication for clinicians and likely does not capture the full extent of the phenotype. Here we report on two additional patients with molecularly confirmed BSS, one each with p.Ser372Tyr and p.Tyr375Cys mutations in FGFR2. Cloverleaf skull was identified prenatally in one patient, with initial concern for Crouzon syndrome. Prenatal 3D ultrasound was performed, but cutis gyrata was only visible on retrospective examination following the clinical diagnosis of BSS after birth. Due to phenotypic overlap with Crouzon syndrome, but worse prognosis, we recommend consideration of prenatal 3D ultrasound and mutation testing for patients with suspected Crouzon to allow for prenatal diagnosis of BSS and to enable appropriate genetic counseling and postnatal care. One of our patients was noted to have a tracheal cartilaginous sleeve, which if present could explain sudden death. Of note, tracheal cartilaginous sleeves have been reported in other FGFR2-related craniosynostosis syndromes, and are associated with 90% risk of death by two years of age without tracheostomy. Tracheal cartilaginous sleeves are often only found incidentally at autopsy as they are difficult to diagnose without direct visualization of the trachea. This association and our experience suggests that BSS patients be evaluated for tracheal cartilaginous sleeve to prevent airway compromise. © 2015 Wiley Periodicals, Inc.

Objectives The objective of this study was to identify maternal characteristics associated with a failed cell-free DNA (cfDNA) test due to a low fetal fraction (FF). Method Retrospective cohort study of women with singleton pregnancies who had cfDNA screening at 10-25 weeks gestation between October 2011 and January 2016. cfDNA screening was performed using methylation techniques until October 2013; thereafter, samples were run with massively parallel sequencing. Multivariable logistic regression was performed to identify maternal characteristics associated with no cell free DNA result secondary to low FF. Results Thirty-three (1.2%) of 2890 eligible women had a failed cfDNA test, including 18 (0.6%) cases with a low FF. A failed cfDNA test due to a low FF was associated with obesity (aOR 1.11, CI 1.05-1.18, p = 0.0003) and treatment with enoxaparin (aOR 37.5, 11.19 – 125.87, p

Cell-free DNA testing is increasingly being used to screen pregnant women for fetal aneuploidy. This technology may also identify microdeletion syndromes, including 22q11.2 deletion syndrome, the most common microdeletion syndrome, and the 22q11.2 duplication syndrome. The purpose of this paper is to provide an overview of the 22q11.2 deletion syndrome, to review the early experience with cell-free DNA screening for this deletion and to consider the potential benefits that may be associated with prenatal detection of the deletion. © 2016 John WileySons, Ltd.

Studies performed in selected populations have shown a poor utilization of triptans for migraine. Our study was aimed at establishing patterns of triptans utilization in a large community using the pharmaceutical prescriptions database of two consecutive years in a regional Health Authority in Italy. About 0.5% of the population observed received triptans prescriptions in a year, but > 50% of the cases received only one prescription. On the other hand, 46% of triptan users did not receive a triptan prescription in the following year (past users): in 80% of cases, patients received only 1–2 triptan packages. The evaluation of the discontinued triptan type has shown percentages varying between 30 and 70%. The percentage of triptan users who received a triptan prescription for the first time in the successive year of study (new users) was 52%. These findings together highlight a high turnover in triptans utilization. Less than 15% of subjects received more than one triptan product in the 2 years. In conclusion, we observed a low percentage of triptan users and a low rate of utilization, associated with a high percentage of discontinuation and new utilization (high turnover), without any substantial increase in triptans utilization during the years. All these data probably do not support optimal satisfaction with triptan therapy.

A normocephalic, severely retarded boy with a family history suggesting aqueductal stenosis was found by computerized tomography to have aqueductal stenosis. His parents' concurrent pregnancy was monitored by ultrasonography and amniocentesis; these disclosed a male fetus which developed marked hydrocephalus after the 20th week. The pregnancy was terminated and an autopsy of the fetus demonstrated several major CNS malformations in addition to a very narrowed aqueduct. This case illustrates the diffuse CNS disease present in at least some cases of X-linked aqueductal stenosis (XLAS) and the importance of considering this variable syndrome in normocephalic, non-dysmorphic mentally retarded males. Important aspects of the prenatal diagnosis of XLAS are also illustrated.

Objective To provide an evidence-based review of measures of psychosocial adjustment and psychopathology, with a specific focus on their use in the field of pediatric psychology. Methods As part of a larger survey of pediatric psychologists from the Society of Pediatric Psychology e-mail listserv (American Psychological Association, APA, Division 54), 37 measures were selected for this psychometric review. Measures that qualified for the review fell into one of the following three categories: (a) internalizing or externalizing rating scales, (b) broad-band rating scales, and (c) self-related rating scales. Results Psychometric characteristics (i.e., three types of reliability, two types of validity) were strong for the majority of measures reviewed, with 34 of the 37 measures meeting “well-established” evidence-based assessment (EBA) criteria. Strengths and weaknesses of existing measures were noted. Conclusions Recommendations for future work in this area of assessment are presented, including suggestions that more fine-grained EBA criteria be developed and that evidence-based “profiles” be devised for each measure.

Genetic screening is used to identify individuals who have genetic variations or mutations that are associated with a particular disorder. Genetic screening may be useful to plan for periodic evaluation, implementation of preventive strategies, or initiation of therapeutic interventions. Current practice is to offer carrier screening for certain genetic diseases during the preconception encounter or more commonly as part of early prenatal care.

Background. Myocardial stunning has recently been demonstrated by use of stress gated technetium 99m sestamibi single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. However, its prognostic value is less well determined. The aim of this study was to investigate the prognostic value of reversible regional wall motion abnormalities (RWMAs). Methods and Results. We studied 303 consecutive subjects with known or suspected coronary artery disease who underwent 2-day stress-rest gated Tc-99m sestamibi SPECT and were followed up for 19 ± 16 months. Clinical and test-derived variables were evaluated to predict cardiac death, nonfatal myocardial infarction (MI), unstable angina, and early or late coronary revascularization. Reversible RWMAs were identified in 102 patients. On Cox analysis, the presence, site, degree, and extent of reversible RWMAs did not identify an adverse outcome, except in patients without prior ML After adjustment for prescan data, the strongest predictors of hard events and all cardiac events were poststress RWMAs and the amount of ischemia. The addition of poststress RWMAs to the combined model of prescan and perfusion data yielded incremental prognostic value. Conclusion. Poststress RWMAs and ischemia by perfusion were the most powerful predictive parameters of cardiac events. However, myocardial stunning should always be considered, particularly in patients without prior MI and in the referral of patients for early revascularization. (J Nucl Cardiol 2005;12:20-31.)

Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel

Parent-child reminiscing about negative experiences influences children's developing "emotional self-concept", which comprises three interrelated functions: self-defining (this is the kind of emotional person I am), self-in-relation (this is how I express and share my emotions with others), and coping (this is how I cope with and resolve negative emotion). In this study, we examined how 70 mostly white, middle-class mothers discuss three negative experiences (fear, anger, and sadness) with their 4-year-old children. Conversations about fear elaborate on the facts of the event and emotional resolutions, thus focusing on coping. Conversations about sadness contain evaluative feedback and emotional resolutions, thus focusing on self-in-relation and coping. Finally, conversations about anger highlight the emotional state itself, thus focusing on self-definition. Mothers are also more elaborative and more evaluative with daughters than with sons, and place emotional events in a more interpersonal context with daughters than sons. Thus girls may be forming a more elaborated and more interpersonal emotional self-concept than boys.

The simultaneous assessment of perfusion and function with the use of technetium 99m sestamibi gated single photon emission computed tomography (SPECT) is helpful for the detection of myocardial viability, but its value in comparison with more established methods is not yet defined. This study compared low-dose dobutamine (LDD) nitrate-enhanced gated SPECT with LDD echocardiography for predicting recovery of regional ventricular function after revascularization in 25 patients with ischemic cardiomyopathy. In both studies, regional function (wall motion and thickening) at rest, during inotropic stimulation, and after revascularization was scored by a 4-point scale. In LDD echocardiography, the prediction of reversible dysfunction was based on the recognition of contractile reserve in asynergic (hypokinetic or a-dyskinetic) segments. In LDD gated sestamibi SPECT, reversible dysfunction was predicted on the basis of perfusion quantification (sestamibi uptake > 50%) in a-dyskinetic segments and on the basis of contractile reserve in hypokinetic segments. LDD echocardiography predicted reversible dysfunction with sensitivity, specificity, and global accuracy of 57%, 85%, and 75%, respectively. The sensitivity and specificity of LDD gated SPECT for identifying dysfunctional segments capable of functional recovery were 77% and 88%, respectively, with a diagnostic accuracy of 84% (P < .02 vs LDD echocardiography). The combined use of 2 different markers of viability, such as cellular integrity in a-dyskinetic segments and contractile reserve in hypokinetic segments, as permitted by LDD gated sestamibi SPECT, showed higher predictive accuracy for reversible dysfunction than the assessment of contractile reserve in all asynergic segments with LDD echocardiography. (J Nucl Cardiol 2002;9:402-6.)

Cell-free DNA (cfDNA) testing is increasingly being used to screen pregnant women for fetal aneuploidies. This technology may also identify fetal sex and can be used to screen for sex chromosome aneuploidies (SCAs). Physicians offering this screening will need to be prepared to offer comprehensive prenatal counseling about these disorders to an increasing number of patients. The purpose of this article is to consider the source of information to use for counseling, factors in parental decision-making, and the performance characteristics of cfDNA testing in screening for SCAs. Discordance between ultrasound examination and cfDNA results regarding fetal sex is also discussed.

The value of gated single photon emission computed tomography (SPECT) in the assessment of wall motion (WM) in patients with severe perfusion defects and in the evaluation of low-dose dobutamine (LDD)-induced changes is not yet established. In patients with chronic coronary artery disease who have left ventricular (LV) dysfunction, the results of nitrate-enhanced technetium 99m sestamibi (sestamibi) gated SPECT for the evaluation of resting and LDD WM were compared with those of baseline and LDD echocardiography (LDDE).Thirty-seven patients underwent echocardiography and nitrate-enhanced sestamibi gated SPECT within 1 week at rest and during LDD infusion. WM was scored from 1 (normal) to 4 (dyskinetic) by using a 16-segment model. Segments with sestamibi uptake less than 30% were considered unsuitable for WM analysis (36 of 592 segments). Echocardiography was technically unreliable in 10 of 592 segments. The precise agreement between echocardiography and gated SPECT for baseline regional WM was 68.4% (kappa = 0.54), without significant differences for the involved coronary artery territory. The agreement for +/- 1 WM scoring was 96.5% (kappa = 0.94). Contractile reserve during LDD was detected by means of echocardiography in 36% and by means of sestamibi gated SPECT in 33% of baseline asynergic segments. Agreement for detection of WM improvement in response to LDD was 74% (kappa = 0.41). The overall and +/-1 WM score agreement for LDD WM was 67.5% (kappa = 0.50) and 94.7% (kappa = 0.91), respectively. A significant correlation between echocardiography and gated SPECT was observed for both baseline (p = 0.78) and LDD (p = 0.74) WM score index.In patients with coronary artery disease who have LV dysfunction, nitrate-enhanced sestamibi gated SPECT allows a reliable WM evaluation, both at rest and during LDD infusion, in almost all segments and provides results in agreement with LDDE.

National strategies to control health care costs have resulted in earlier hospital discharge of many patient groups. Earlier discharge may reduce hospital charges and return patients to their families sooner. However, complications after discharge may go undetected and require readmittance to the hospital and more acute care visits (Britton & Britton, 1984; Jansson, 1985; Rogers et al., 1990; Schwartzberg, 1982). To maintain good patient outcomes while lowering hospital charges, a number of programs of early hospital discharge and home follow-up have been developed for groups of patients at high risk who use a high volume of services (Brooten et al., 1986; McCorkle et al., 1989). Women delivering by unplanned cesarean birth represent such a group. Almost one in four women who give birth in the United States do so by cesarean birth (Taffel, Placek, & Korsary, 1992). The hospital stay after cesarean birth has decreased from a mean of 6.1 days in 1982 to 4.0 days in 1992 (Commission on Professional & Hospital Activities, 1991; 1993). One recent report suggested a 2-day length of stay for women after delivery by cesarean birth, provided they had no complications during pregnancy and delivery and after delivery (Strong, Brown, Brown, & Curry, 1993). Many early discharge programs for high-risk groups have home follow-up services that differ in length, services, and provider (Meissier, 1993). Data are needed on the nurse's time required for home follow-up of childbearing women at high risk when care is based on patient need and provider judgment rather than the reimbursement plan. For women delivering by cesarean birth, most follow-up services have' included one or more home visits by a nurse. The number and length of visits often are dictated by reimbursement systems (Brooten, 1995). Institutions or agencies providing these services usually have a standard fee and maximum time for the visit based on the projected needs of that patient population. However, home visits of varying lengths of time may be necessary, depending on the needs of individual patients and the complexity of their care. Currently, little data are available on the following: (a) the time required by nurses to provide home care to different patient groups; (b) differences in nursing time required within those groups, depending on patient morbidity; and (c) the number and length of home visits or other contacts when dictated by patient need and provider judgment rather than patterns of reimbursement. The purpose of this study was to examine the average time nurses spent planning for early hospital discharge and providing home care to women who delivered by unplanned cesarean birth. It also examined differences in nursing care time required for patients with and without morbidity when dictated by patient need and provider judgment.

Testing cell-free DNA (cfDNA) in maternal blood samples has been shown to have very high sensitivity for the detection of fetal aneuploidy with very low false-positive results in high-risk patients who undergo invasive prenatal diagnosis. Recent observation in clinical practice of several cases of positive cfDNA tests for trisomy 18 and trisomy 13, which were not confirmed by cytogenetic testing of the pregnancy, may reflect a limitation of the positive predictive value of this quantitative testing, particularly when it is used to detect rare aneuploidies. Analysis of a larger number of false-positive cases is needed to evaluate whether these observations reflect the positive predictive value that should be expected. Infrequently, mechanisms (such as low percentage mosaicism or confined placental mosaicism) might also lead to positive cfDNA testing that is not concordant with standard prenatal cytogenetic diagnosis. The need to explore these and other possible causes of false-positive cfDNA testing is exemplified by 2 of these cases. Additional evaluation of cfDNA testing in clinical practice and a mechanism for the systematic reporting of false-positive and false-negative cases will be important before this test is offered widely to the general population of low-risk obstetric patients. In the meantime, incorporating information about the positive predictive value in pretest counseling and in clinical laboratory reports is recommended. These experiences reinforce the importance of offering invasive testing to confirm cfDNA results before parental decision-making.

Periconceptional folic acid supplementation has been shown to decrease the first occurrence of isolated neural tube defects (NTDs) by as much as 50%, and to decrease the recurrence risk for NTDs by more than 70%. The possible mechanisms of vitamin supplementation in the prevention of NTDs are discussed, as are the current recommendations for reproductive-age women. Further, the limitations of dietary and pharmacological recommendations with regard to patient compliance as well as the possibility of grain fortification are reviewed.

Gaucher disease carrier screening is controversial in the medical community. The goal of this study was to explore current Gaucher disease carrier screening practices of prenatal healthcare providers. Prenatal healthcare providers were invited by email to complete an electronic-based survey. A total of 1,454 prenatal healthcare providers, including 209 genetic counselors, 450 midwives, and 795 physicians, completed the study. The majority of genetic counselors (n = 208/209, >99%), physicians (n = 415/450, 92%), and midwives (n = 634/795, 80%) currently offer Jewish ancestry disease carrier screening to couples in whom one or both partners are Jewish. Of providers who offer Jewish ancestry disease screening, the majority of genetic counselors (n = 199/208, 96%) and physicians (n = 352/415, 85%) always or sometimes offer Gaucher disease screening whereas the majority of midwives (n = 357/634, 56%) never offer Gaucher disease screening. This study presents the first report of Gaucher disease carrier screening practices of the prenatal healthcare providers in North America. Our results indicate that Gaucher disease carrier screening is being offered at a high rate within the scope of Jewish ancestry-based carrier screening. This may highlight a need to move away from the debate as to whether Gaucher disease carrier screening should be offered and, instead, focus on how best to provide Gaucher disease carrier screening services. Genet Med 2012:14(10):844–851

OBJECTIVE: Our purpose was to determine the detection and false-positive rates for maternal serum α-fetoprotein measurement to screen for fetal Down syndrome and other chromosomal abnormalities in women ≥35 years old. STUDY DESIGN: A total of 3896 women had serum maternal serum α-fetoprotein levels measured routinely before amniocentesis for the indication of advanced maternal age. RESULTS: Eighty-five percent (28/33) of fetal Down syndrome pregnancies had second-trimester risks of ≥1:270 on the basis of a combination of maternal serum α-fetoprotein measurement and maternal age. Risks were also ≥1:270 in 63% of the unaffected pregnancies. Sex chromosome aneuploidies, translocations, and other nonautosomal chromosome abnormalities in this study population were not associated with altered maternal serum α-fetoprotein levels; 51.9% (14/27) of these, however, were also assigned risks of ≥1:270. CONCLUSIONS: Maternal serum α-fetoprotein screening is more accurate than age alone for assigning individual Down syndrome risk in pregnant women ≥35 years old. Counseling for women in this age group should include information regarding the lower sensitivity of maternal serum α-fetoprotein screening for detecting fetal Down syndrome and other chromosomal abnormalities (especially sex chromosome aneuploidies) compared with offering amniocentesis to these women. (AM J OBSTET GYNECOL 1994; 170:80.)

The recent discovery of the cystic fibrosis gene has offered the possibility of population-based cystic fibrosis carrier screening. Although > 100 distinct mutations have been identified, five of these in aggregate represent about 85% of the alleles in Britain and the United States. Screening programs that test for these five mutations can be designed to offer several alternative ways to communicate the risk to a pregnancy and several alternative ways to manage a pregnancy. At this time we favor a strategy of screening partners in a couple in sequence, screening the second partner only if the first is positive; nevertheless, different strategies will appeal to different couples.

The "Continuity of Care Hospital", which is now realized in the Santa Verdiana Hospital, Castelfiorentino (Italy), is aimed at solving the existing gap between hospitalists and primary care physicians. This new model of care could represent an effective tool for solving the emerging medical and teaching needs of a population characterized by advanced age and comorbidities.

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery.

The incremental prognostic value of combined regional wall motion and perfusion over perfusion alone by gated single-photon emission computed tomographic myocardial perfusion scintigraphy has not been evaluated. Of the 402 consecutive patients who underwent stress single-photon emission computed tomographic myocardial perfusion scintigraphy for suspected myocardial ischemia, we identified 333 patients (217 men, mean age 63 +/- 10 years; exercise in 249 and dipyridamole adminstered to 84). Visual scoring of perfusion images and regional wall motion used 20 segments and a scale of 0 to 4. Resting and poststress left ventricular ejection fraction was automatically generated. On follow-up (median 13 months), 30 hard cardiac events (17 cardiac deaths, 13 nonfatal acute myocardial infarctions) and 66 total cardiac events (including hard events, 26 with unstable angina, and 10 who underwent late revascularization) occurred. After adjustment for prescan information, the best independent predictors of hard events were summed stress score for wall motion (Wald's chi-square 8.3, p0.004) and several vascular territories with ischemia by perfusion/function (Wald's chi-square 6.2, p0.01). The strongest predictors of all cardiac events were the number of ischemias (Wald's chi-square 32.1, p0.0001) and the number of ischemic vascular territories by perfusion (Wald's chi-square 13.1, p0.0001). Addition of function data to the combined model of perfusion data yielded an incremental value of 26% for predicting hard events but not for all events. In conclusion, the assessment of combined perfusion/function provides incremental prognostic information for further hard events with perfusion data alone; perfusion data best predict all cardiac events.

Preserved thrombolysis in myocardial infarction (TIMI) flow before percutaneous coronary intervention (PCI) in acute myocardial infarction is related to improved outcome. Gated single-photon emission computed tomography (SPECT) allows the simultaneous assessment of left ventricular perfusion and function. We evaluated the initial risk area and subsequent evolution of perfusion and function according to TIMI flow before successful primary PCI.In 36 patients, treated with abciximab, primary PCI and stenting, 99mTc-sestamibi was injected before PCI and gated SPECT acquired thereafter. Gated SPECT was repeated 7 and 30 days later. Perfusion defect, wall motion score index, left ventricular ejection fraction and volumes were examined.Before PCI, 14 patients (group A) showed TIMI flow 2-3 and 22 (group B) TIMI flow 0-1, but no differences in clinical variables, initial risk area, wall motion score, ejection fraction or volumes. Perfusion defect was smaller in group A at 7 (9%+/-11% vs 19%+/-14%, p0.02) and 30 days (7%+/-7% vs 16%+/-12%, p0.02) and the salvage index was higher at 30 days (77%+/-22% vs 55%+/-28%, p0.02). Wall motion score was lower in group A at 30 days (p0.05). Ejection fraction significantly improved in both groups at 7 and 30 days. End-diastolic volume showed a trend towards a reduction in group A, whilst it was significantly increased in group B. Conversely, end-systolic volume was significantly decreased in group A but remained unchanged in group B.In the setting of optimal myocardial reperfusion for myocardial infarction, preserved TIMI flow before PCI does not limit the initial risk area but it does improve myocardial salvage and functional recovery.

In patients with ischemic cardiomyopathy, the differentiation of dysfunctional myocardium in scarred versus hibernating is oversimplified. We evaluated a more complex classification using an imaging technique currently employed for viability detection, having as reference the postrevascularization outcome of dysfunctional segments.In 35 patients, we performed gated single-photon emission computed tomography (SPECT) (resting and nitrate-enhanced study, the latter with baseline and dobutamine acquisition) before revascularization. The outcome after revascularization was assessed by repeating resting gated SPECT. Dysfunctional segments without functional recovery in postrevascularization gated SPECT were defined scar (either nontransmural or transmural according to tracer activity); those with recovery were divided in stunned (unchanged uptake) or hibernating (improved postrevascularization activity). This reference classification was compared with the categorization based on prerevascularization gated SPECT.Contractile reserve in dobutamine gated SPECT differentiated scarred from viable segments with 78% accuracy. Tracer activity in nitrate imaging distinguished the degree of transmurality. Nitrate-induced activity increase was significantly higher (p0.0001) in the hibernating segments (14.9+/-20.4%) than in transmural (4.8+/-13.4%) nontransmural scars (3.3+/-13%), or stunned segments (2.2+/-8%). The presence or absence of nitrate-induced activity increase predicted the postrevascularization perfusion changes in viable myocardium and differentiated hibernating from stunned segments. The prerevascularization classification showed a good agreement with the reference categorization (kappa=0.50). Conclusion. Combining contractile reserve evaluation and perfusion quantification within a single study with baseline-nitrate gated SPECT and dobutamine test it is possible to achieve a comprehensive classification of dysfunctional segments.

Using gated SPECT, we evaluated the relationship between admission troponin I, risk area, and myocardial salvage in patients with a first myocardial infarction treated with abciximab and primary percutaneous coronary intervention within 6 h.In 43 patients, (99m)Tc-sestamibi was injected before primary percutaneous coronary intervention. Gated SPECT was acquired immediately thereafter and was repeated 7 and 30 d later. The initial risk area and subsequent infarct size were expressed as a percentage of the left ventricle; salvage index was the ratio between salvaged myocardium and initial risk area; left ventricular ejection fraction was calculated using the quantitative gated SPECT software.On admission, 20 patients showed elevated troponin I and had a larger risk area (P0.03) than did the group with normal troponin I. Infarct size at 30 d (15% +/- 12% vs. 13% +/- 13%) and salvage index (0.63 +/- 0.27 vs. 0.60 +/- 0.28) were not significantly different between the 2 groups. Ejection fraction was lower in the group with high troponin I on admission (36% +/- 10% vs. 41% +/- 11%, P0.05) and at 7 d (41% +/- 11% vs. 48 +/- 10, P0.03). At 30 d, improvement was greater in the group with high troponin I, and ejection fraction became comparable.Patients with high troponin I on admission have a larger initial risk area, but if they undergo primary percutaneous coronary intervention within 6 h and are treated with abciximab, myocardial salvage and functional recovery are similar to those observed in patients with normal troponin I, and no unfavorable relationship between high troponin I values on admission and myocardial salvage is registered.

The aim of this study was to calculate the risk for aneuploidy in twin pregnancies between 9-14 weeks utilizing maternal age, race and dizygotic twinning rates. Using previously published risks for aneuploidy in singletons and twins at the time of amniocentesis and at term, we calculated new risk estimates for twins at 9-14 weeks gestation or at the time of chorionic villus sampling. Using these tables, the risk for trisomy 21 in at least one fetus of a twin gestation in a 32-year-old at 9-14 weeks is 1/285 for Whites and for African-Americans. This is equivalent to the risk for trisomy 21 (1/265) in a 35-year-old woman with a singleton at the same gestational age. The risks for trisomies 18 and 13 also follow similar trends. In counseling women with twin pregnancies at the time of first trimester nuchal translucency screening or chorionic villus sampling, it should be noted that the maternal age-related risk for aneuploidy for a 32-year-old is equivalent to that of a 35-year-old woman with a singleton gestation.

We describe a second family with mother to son transmission of omodysplasia, a rare skeletal dysplasia characterized by shortened humeri, shortened first metacarpals and craniofacial dysmorphism. The mother in this family had been diagnosed previously with Robinow syndrome; subsequently, her diagnosis was reclassified. Her pregnancy was closely monitored antenatally with serial ultrasound examinations. Delayed ossification of the humerus was noted prenatally. Her son had ambiguous genitalia and similar skeletal manifestations as his mother. A comparison to other known and suspected cases of dominant omodysplasia is presented. Our observations confirm the existence of a dominant variant of omodysplasia, document genital hypoplasia as an important feature of this syndrome in males and highlight the need to differentiate this entity from Robinow syndrome.

The role of gated single photon emission computed tomography (SPECT) in improving viability detection with the use of perfusion imaging is uncertain. This study aimed to verify whether the classification of baseline regional dysfunction with gated SPECT helps to predict functional recovery with the use of quantitative perfusion imaging. Resting nitrate-enhanced sestamibi gated SPECT was performed in 31 patients with left ventricular dysfunction, who later underwent coronary revascularization. With the use of a 16-segment model, tracer activity was quantified, and wall motion and thickening were estimated with a 4-point scoring scheme. Reversible dysfunction was assessed with follow-up gated SPECT. According to receiver operating characteristic curve analysis, the best overall cutoff for predicting reversible dysfunction in asynergic segments was 50% of peak activity or greater, with 83% sensitivity, 54% specificity, and 64% accuracy. When the segments were divided according to wall motion in resting gated SPECT, the optimal activity cutoff was greater than 68% for hypokinetic and 50% or greater for adyskinetic segments. With the use of 2 thresholds, the overall sensitivity remained good (76%), whereas specificity increased to 73% (P < .0005) and accuracy to 74% (P < .02). Regional dysfunction assessment directly on perfusion images permits use of different activity thresholds with an improvement over a single cutoff for all asynergic segments. Therefore combining perfusion and functional data with nitrate-enhanced gated SPECT at rest appears to be a promising approach for viability detection.

We report the mid-trimester prenatal diagnosis of Neu-Laxova syndrome (NLS) in two at risk families utilizing serial sonographic examinations. Ultrasound and pathologic findings from seven affected pregnancies, the largest case series of NLS to date, are presented. One fetus had anencephaly and incomplete rachischisis, an anomaly that has not been previously reported in association with NLS. Ultrasonographic detection of severe intrauterine growth restriction (IUGR), abnormally postured limbs, microcephaly, and edema allowed prenatal diagnosis of NLS in five of these at risk pregnancies during the mid-trimester. Growth curves derived from serial sonograms reveal abnormalities of all standard biometric measurements. The growth discrepancy was most pronounced in the measurements of the biparietal diameter, which were consistently less than two standard deviations below the mean across all gestational ages. This case series confirms that aberrant growth and anomalies may be detected sufficiently early in gestation to permit prenatal diagnosis of NLS.

This study aimed to assess whether contractile reserve evaluation using dobutamine gated single-photon emission computed tomography (SPECT) improves the capability of quantitative perfusion analysis to predict functional recovery of viable hibernating myocardium. Resting and dobutamine nitrate-enhanced technetium-99m sestamibi (sestamibi) gated SPECT studies were performed in patients with coronary artery disease who had left ventricular dysfunction. Tracer activity was quantified, and wall motion and thickening visually scored. Reversible dysfunction was identified with gated SPECT repeated after coronary revascularization. Using the best activity threshold, perfusion quantification achieved 85% sensitivity and 55% specificity. Contractile reserve detection was significantly less sensitive (64%, p

We describe monozygotic twins with partially discordant phenotypes who were found to have a duplication of chromosome region 4q28.3-qter. The duplicated region of chromosome 4 resulted from an unbalanced segregation of a balanced maternal (4;22)(q28.3;p13) translocation. Duplication of the long arm of chromosome 4 has been described in60 patients; however, it usually results from the unbalanced segregation of a parental balanced translocation and has an associated monosomy. Twenty cases of dup 4q without an associated monosomy have been reported, and this is the only case of dup 4q28. 3-qter. All cases of dup 4q are reviewed, and phenotypic aspects are analyzed. Issues of monozygotic twinning and other birth defects also are addressed.

Injection of sestamibi during low-dose dobutamine (LDD) infusion might improve tracer ability to detect viable myocardium. This study investigated the potential value of LDD technetium-99m sestamibi (sestamibi) single-photon emission computed tomography (SPECT) in predicting functional recovery after revascularization by comparing its results with those of sestamibi SPECT at rest and of LDD echocardiography. Before revascularization, 23 patients with chronic coronary artery disease and regional left ventricular dysfunction underwent sestamibi SPECT at rest and, on a separate day, LDD echocardiography and sestamibi SPECT with tracer injection during LDD infusion. Echocardiography at rest was repeated after revascularization. Semiquantitative sestamibi uptake results (grading from 0 = normal to 4 = absent) and wall motion (grading from 1 = normal to 4 = dyskinesia) were evaluated with a 16-segment model. The ventricular wall was divided into 3 vascular territories. At follow-up, 20 of 32 asynergic vascular territories showed functional recovery, whereas 12 showed no changes. For prediction of functional recovery, LDD SPECT achieved better accuracy than SPECT at rest (87% vs 65%, p

Carrier screening for cystic fibrosis as part of reproductive health care, including prenatal care, is not the standard of practice at this time. However, a recent National Institutes of Health Consensus Development Conference recommended that cystic fibrosis carrier screening should be offered to adults with a family history of cystic fibrosis, partners of individuals with cystic fibrosis, couples planning a pregnancy, and couples seeking prenatal testing. A workshop convened to discuss the implementation of these recommendations concluded that several issues must be resolved before these recommendations can be implemented. This commentary reviews the discussions that occurred and the conclusions that were reached at this workshop. Some of the subjects considered by the workshop participants were: the goals and outcomes of carrier screening; the continuum from making a test available to offering that test; to whom, when, and how cystic fibrosis testing should be offered; laboratory practice and quality assurance; provider and patient education; and insurance issues. The workshop participants concluded that those populations to whom carrier screening should be offered might include individuals and couples in high-risk groups who seek preconception counseling, infertility care, or prenatal care. High-risk groups include individuals of white northern European or of Ashkenazi-Jewish descent, those whose partners have cystic fibrosis, and those with a family history of cystic fibrosis. Before screening can be offered systematically to these individuals or couples, practice guidelines, educational materials for providers and patients, informed-consent protocols, and laboratory standards for testing must be developed.

Neuroblastoma, a tumor of primitive neuroectodermal cells, is one of the most common solid malignancies of neonates. Placental metastases have been described in rare cases of congenital neuroblastoma, usually in association with hydrops fetalis, placentomegaly, and widespread disease in the neonate. We report a case in which the unexpected diagnosis of neuroblastoma was made based on the postnatal finding of tumor emboli confined to fetal vessels of the placenta. Radiation and chemotherapy were given based on this diagnosis, obviating the need for an invasive diagnostic procedure.

The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid alpha-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included. A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained. Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7-27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47-128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1-38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4-80.9). MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and unaffected patients.

Background Lymphedema-cholestasis syndrome (LCS; Aagenaes syndrome) is a rare autosomal recessive disorder, characterized by 1) neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age, and 2) severe chronic lymphedema, mainly lower limb. LCS was originally described in a Norwegian kindred in which a locus, LCS1, was mapped to a 6.6cM region on chromosome 15. Mutations in CCBE1 on chromosome 18 have been reported in some cases of lymphatic dysplasia, but not in LCS. Methods Consanguineous parents of Mexican ancestry had a child with LCS who did not exhibit extended homozygosity in the LCS1 region. A subsequent pregnancy was electively terminated due to fetal hydrops. We performed whole-genome single nucleotide polymorphism genotyping to identify regions of homozygosity in these siblings, and sequenced promising candidate genes. Results Both siblings harbored a homozygous mutation in CCBE1, c.398 T>C, predicted to result in the missense change p.L133P. Regions containing known ‘cholestasis genes’ did not demonstrate homozygosity in the LCS patient. Conclusions Mutations in CCBE1 may yield a phenotype not only of lymphatic dysplasia, but also of LCS or fetal hydrops; however, the possibility that the sibling with LCS also carries a homozygous mutation in an unidentified gene influencing cholestasis cannot be excluded.

Recent data suggest that contractile reserve in dysfunctional but viable myocardium during low-dose dobutamine infusion might be elicited not only by a direct inotropic stimulation but also by an increase in coronary blood flow. Aim of the study was to evaluate the effects of low-dose dobutamine on myocardial perfusion and function in asynergic but viable myocardium.Nineteen patients with coronary artery disease and severe regional dysfunction were studied. Both regional ventricular function and myocardial perfusion were assessed at rest (PRE), during low-dose dobutamine (DOB) and, in twelve patients, after revascularization (POST). Regional ventricular function was evaluated with two-dimensional echocardiography using a score index ranging from 1 to 4. Myocardial perfusion was studied using Tc-99m-sestamibi Single Photon Emission Tomography (SPET); uptake defects were graded from 0 (normal) to 4 (absent uptake). For both evaluations the left ventricle was divided in 16 segments and two vascular territories were considered.Low-dose dobutamine elicited contractile reserve in 12 of 24 asynergic vascular territories (DOB+). Compared with PRE scintigraphy, DOB SPET showed perfusion improvement in 10/12 DOB+ and in 3/12 DOB- asynergic territories (p = 0.006). Mean uptake score decrease significantly in DOB+ (from PRE SPET 21.0 +/- 7.2 to DOB SPET 17.6 +/- 7.1; p = 0.0005) but not in DOB- (from SPET PRE 19.0 +/- 5.3 to SPET DOB 19.5 +/- 6.8, p = NS) abnormal territories. Fourteen asynergic territories underwent revascularization. Among them, 9 showed functional recovery after intervention (viable myocardium) and 5 showed no changes (fibrotic myocardium). A functional improvement under dobutamine was observed in 7 viable and in 1 fibrotic territories. Conversely, perfusion improved under dobutamine in 8 viable and in one fibrotic territory. After revascularization the perfusion defect score decreased significantly in viable territories (from PRE SPET 22.1 +/- 7.9 to POST SPET 13.3 +/- 6.6; p = 0.00001) but not in fibrotic regions (from PRE SPET 17.8 +/- 6.0 to POST SPET 15.6 +/- 4.9).In asynergic myocardium contractile reserve elicited by low-dose dobutamine is associated in most cases with an improvement in Tc-99m-sestamibi uptake. This suggests a possible link between increased blood flow and functional improvement during dobutamine in viable myocardium.

OBJECTIVES: This paper explores several critical assumptions and methodological issues arising in cost-effectiveness analyses of genetic screening strategies in the reproductive setting. METHODS: Seven issues that arose in the development of a decision analysis of alternative strategies for cystic fibrosis carrier screening are discussed. Each of these issues required a choice in technique. RESULTS: The presentations of these analyses frequently mask underlying assumptions and methodological choices. Often there is no best choice. In the case of genetic screening in the reproductive setting, these underlying issues often touch on deeply felt human values. CONCLUSIONS: Space limitations for published papers often preclude explaining such choices in detail; yet these decisions determine the way the results should be interpreted. Those who develop these analyses need to make sure that the implications of important assumptions are understood by the clinicians who will use them. At the same time, clinicians need to enhance their understanding of what these models truly mean and how they address underlying clinical, ethical, and economic issues.

Among 179,663 prenatal diagnosis cases collected from ten institutions and two publications, 555 (0.3 per cent) were diagnosed as having chromosome mosaicism. Of these, 57 (10.3 per cent) were mosaic for an autosomal structural abnormality, 28 (5 per cent) for a sex chromosome structural abnormality, and 85 (15.3 per cent) were mosaic for a marker chromosome. Ninety-five cases of prenatally diagnosed mosaicism with a structural abnormality in an autosome and a normal cell line, and with a known phenotypic outcome, were collected for karyotype-phenotype correlations through our collaboration (40 cases), a prior survey (26 cases), and published reports (29 cases). They included 13 balanced reciprocal translocations, one unbalanced reciprocal translocation, four balanced Robertsonian translocations, four unbalanced Robertsonian translocations, four inversions, 17 deletions, three ring chromosomes, 19 i(20q), seven +i(12p), six other isochromosomes, and 17 partial trisomies resulting from a duplication or other rearrangement. All cases mosaic for a balanced structural rearrangement resulted in a normal phenotype. All cases of 46/46,i(20q) resulted in normal liveborns. Five of seven cases with 46/47,+i(12p) had an abnormal phenotype compatible with Killian-Pallister syndrome. The overall risk for an abnormal outcome for a mosaic case with an unbalanced structural abnormality, excluding 46/46,i(20q) and 46/47,+i(12p), is 40.4 per cent. In the same category, the study also suggested a correlation between the percentage of abnormal cells and an abnormal phenotype. For mosaicism involving a terminal deletion, the possibility of a familial fragile site should be considered.

To evaluate quantitative hCG measurements and transvaginal ultrasound in the diagnosis of ectopic pregnancy in patients presenting to the emergency department.A discriminatory zone for detecting the presence or absence of an intrauterine pregnancy by transvaginal ultrasound was established prospectively. Women presenting to the emergency department were evaluated prospectively using a diagnostic algorithm consisting of clinical examination, quantitative serum hCG, and transvaginal ultrasound. Finally, ectopic pregnancies diagnosed over a 22-month period were evaluated prospectively.All viable intrauterine pregnancies were identified in those subjects with hCG levels of 1500 mIU/mL (First International Reference) or greater. One thousand two hundred sixty-three subjects were evaluated prospectively; 59.8% were diagnosed with intrauterine pregnancy, 26.8% with spontaneous abortion, and 7.8% with ectopic pregnancy. At presentation, 13.2% of intrauterine pregnancies were diagnosed by clinical examination, whereas 82.9% were diagnosed by transvaginal ultrasound. Only 4% of normal intrauterine pregnancies were not confirmed on initial visit. Of 205 ectopic pregnancies diagnosed, 81.5% were hemodynamically stable; of these, 49.1% were diagnosed on initial presentation. Of all ectopics, 59% never reached an hCG level of 1500 mIU/mL and 35.8% had an hCG lower than the level at presentation. This protocol diagnosed ectopic pregnancies with a sensitivity of 100% and a specificity of 99.9%.A protocol of quantitative hCG levels (available within hours of presentation to an emergency department) combined with transvaginal ultrasound is effective in diagnosing ectopic pregnancy.

To determine the safety, efficacy, and cost savings of early hospital discharge of women delivered by unplanned cesarean delivery.Using randomized assignment, 61 postpartum women were discharged from the hospital at the usual time, and 61 were discharged early and had nurse specialist home follow-up care. The latter group received comprehensive discharge planning, instruction, counseling, home visits, and daily on-call availability from the nurse specialists. Both groups were followed from delivery to 8 weeks postpartum.Women who were discharged early and received transitional home care services by clinical nurse specialists were sent home a mean of 30.3 hours earlier than the control group (P.001). They had significantly greater satisfaction with care, more of their infants had timely immunizations at the end of follow-up, and they had a 29% reduction in health care charges compared to the control group receiving routine care. Although there were no statistically significant differences in maternal and infant rehospitalizations and acute-care visits, there were more maternal rehospitalizations in the control group than in the nurse specialist-followed group (three versus zero). No statistically significant differences were found between the groups in the outcomes of maternal affect and overall functional status.Early hospital discharge of women after unplanned cesarean birth, using the model of nurse specialist transitional home care, is safe, feasible, and cost-effective.