Microdeletions/duplications involving TBX1 gene in fetuses with conotruncal heart defects which are negative for 22q11.2 deletion on fluorescence in-situ hybridization.

OBJECTIVES: Conotruncal heart defects (CTD) are associated with del22q11.2 syndrome, which is often diagnosed by fluorescence in-situ hybridization (FISH). However, in those negative for del22q11.2 on FISH, the etiology is usually obscure. We aimed to use high-resolution array comparative genomic hybridization (array CGH) to clarify the underlying genetic causes in these cases. METHODS: In this retrospective study, fetal samples of amniocytes or fibroblasts, taken either for prenatal diagnosis by amniocentesis or for postnatal survey after termination of pregnancy, were obtained from 45 fetuses with CTD and were investigated by cytogenetic analysis including karyotyping and FISH for del22q11.2 syndrome. Eight fetuses with no findings on karyotyping and FISH were investigated further by array CGH, real-time quantitative polymerase chain reaction (qPCR) and Sanger sequencing of TBX1. RESULTS: Array CGH revealed that three of the eight fetuses carried submicroscopic genomic imbalances. Of these, two cases showed similar small microdeletions/duplications in 22q11.2 (one 0.85 kb microdeletion and one 8.51 kb microduplication). The minimal shared region spanned exon 2 of TBX1, a candidate gene responsible for cardiovascular defects in del22q11.2 syndrome. In all eight cases, the array CGH results were confirmed by qPCR, and Sanger sequencing did not detect other molecular pathologies. CONCLUSION: Our findings indicate an association between TBX1 variations and fetal CTD. The results also demonstrate the power of array CGH to further scrutinize the critical gene(s) of del22q11.2 syndrome responsible for heart defects. Array CGH apparently has diagnostic sensitivity superior to that of FISH in fetuses with CTD associated with del22q11.2 (and dup22q11.2) syndrome.

Delivery of the second twin.

OBJECTIVE: To determine the likelihood of cesarean for the second twin after vaginal delivery of the first and the risk of vaginal delivery. METHOD: A retrospective analysis of twin deliveries was performed on 10,365 live born twin pairs (20,730 births), using birth certificate data from the State of Illinois from 1997 through 2000. RESULT: The incidence of cesarean for the second twin after vaginal delivery of the first was 10.1%. The greatest incidence of failed vaginal delivery of the second twin was in the vertex/non-vertex group. Five-minute Apgar scores <4 were significantly more frequent in vaginally delivered twins <2000 g compared to those delivered via cesarean (p<0.001). CONCLUSION: Twin presentation type is predictive of the likelihood of a failed vaginal delivery of the second twin. Cesarean appears to significantly reduce the incidence of Apgars <4 for neonates <2000 g.

Comparison of five body-composition methods in peritoneal dialysis patients.

Body-composition assessment is an important method of evaluating nutritional status in peritoneal dialysis patients. Because body-composition measurement estimates have not been fully validated in this population, we assessed five body-composition methods in 30 well-dialyzed peritoneal dialysis patients. The techniques studied included bioelectrical impedance analysis, dual-energy X-ray absorptiometry, total-body potassium counting, and anthropometry by two techniques. The dialysis patients were matched for age, race, sex, height, weight, and body mass index with 29 healthy control subjects in our laboratory database. By 5 x 2 x 2 analysis of variance, significant differences were found between results by modality (P < 0.0001) as well as by sex, with women having an increased percentage of fat (P < 0.0001). However, there was no significant intermethod difference by condition (peritoneal dialysis or control). That is, although significantly different percentage fat values were found between the body-composition techniques, this variability was independent of whether the measurement was made on control or peritoneal dialysis patients. Despite the differences between modalities, all techniques were found to correlate significantly with each other (P < 0.01 or better for men and P < 0.001 or better for women). Our experience shows that these routine techniques for measuring body composition can be readily applied to stable peritoneal dialysis patients.

Chromosomal abnormalities in the first and second polar body.

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

Body composition assessed by neutron activation analysis in dialysis patients.

Malnutrition is prevalent in end-stage renal disease (ESRD) patients treated with hemodialysis (HD) and peritoneal dialysis (PD). In addition, there is increased incidence of morbidity in this group. Evaluation of nutritional status is important. Application of body composition in the ESRD population to evaluate body compartments and to assess nutritional health has become more common in clinical practice. Neutron activation analysis (NAA) may provide data on metabolically active tissue by quantification of total body potassium (TBK) for body cell mass and assessment of protein by total body nitrogen (TBN). This method may be able to detect changes in body composition before clinical signs of malnutrition are apparent. Ten HD (5 male and 5 female) and 10 PD patients (7 male and 3 female) were evaluated by NAA, TBK, and isotope dilution. Female PD patients had an increased total body water (TBW) and increased intracellular water compared to HD females. Albumin was lower in PD women. There was no significant difference between PD men and laboratory controls in TBW, extracellular water, and TBN. The clinical application of body composition methods for evaluation of dialysis patients by serial assessment and for development of a bedside tool needs further study.

Diagnostic reliability of Mi-Mark helix technique in endometrial neoplasia.

To evaluate the diagnostic reliability of the Mi-Mark helix technique in endometrial neoplasia, 138 women with abnormal uterine bleeding underwent a prospective study of Mi-Mark sampling of the uterine cavity before dilatation and curettage. Of one hundred thirty-eight patients, 42% had postmenopausal bleeding and 18% had perimenopausal bleeding. The acceptability of this procedure by patients and physicians was remarkable. All invasive endometrial carcinomas were detected by Mi-Mark cytology. The most serious limitation of this technique was its failure to detect a large number of hyperplasias without atypia. Examination of a cell block along with cytology would facilitate the histopathologic diagnosis, especially of hyperplasia. The results of this study appear to justify the use of this procedure in high-risk patients.

The quantum origins of the free induction decay signal and spin noise.

Experiments are described that elucidate the quantum mechanical origins of the free induction decay voltage and of spin noise. It is shown that the experimentally measured FID voltage induced in a Hertzian loop receiving coil following a 90 degrees pulse is typically two orders of magnitude too large to be accounted for by the current quantum theory of signal reception-coherent spontaneous emission. An experiment is then presented in which spin noise is easily observed in a circuit with a Q-factor of order unity, thereby undermining a popular hypothesis that such noise is due to spontaneous emission and is only observable because of the enhancement in the density of the radiation field in a high Q-factor tuned circuit, the NMR probe. Both the free induction decay and the spin noise are shown to be accurately predicted by near-field Faraday induction, which is described in the theory of quantum electrodynamics by an exchange of virtual photons. A heuristic approach to understanding the nature and role of virtual photons in the signal reception process is then given. Thus current popular statements that observation of the magnetic resonance phenomenon relies on the absorption and emission of radio waves are shown to be wrong.

Effect of lamellar flap location on corneal topography after laser in situ keratomileusis.

PURPOSE: To investigate the effect of hinge position on corneal topography after laser in situ keratomileusis (LASIK) for myopia. SETTING: Academic center and refractive surgery practice. METHODS: Topography data obtained from 89 eyes of 46 patients after LASIK were analyzed. Using a system of Cartesian coordinates, data along the horizontal and vertical axes were analyzed, measuring sagittal height and power change at 1 mm intervals from the ablation zone center. Data points that were equidistant and on opposite sides of the ablation center were compared to find asymmetry along either axis relative to nasally hinged flaps. RESULTS: Along the horizontal axis, areas of the cornea closer to the hinge had a higher topography than areas farther from the hinge. Specifically, the points nearest and farthest from the hinge were significantly different in sagittal height (P <.034); the areas farthest from the hinge were reduced more after surgery (relatively lower topography). When results were stratified into low- and high-diopter corrections, this difference was significant in only the high-diopter group (P <.0006). Trends in power change were also observed. Areas of the cornea closer to the hinge were relatively flatter than areas farther from the hinge. Statistical significance was detected in only the low-diopter group at data points 2 mm from the ablation zone center in opposite directions (P <.008). No asymmetry was seen along the vertical axis in power change or sagittal height. CONCLUSIONS: The lamellar flap in LASIK may influence postoperative corneal topography. Hypothetically, the corneal flap may retract toward the hinge, producing axial asymmetry in the postoperative topography relative to the hinge. Understanding the influence of corneal flap characteristics on post-LASIK topography may improve optical results and may be particularly important in the development and effectiveness of topography-guided ablation techniques.

Photorefractive keratectomy for myopia with a 15 Hz repetition rate.

PURPOSE: To evaluate excimer laser photorefractive keratectomy (PRK) for myopia using a repetition rate of 15 Hz instead of 10 Hz. SETTING: The Cornea and Laser Eye Institute, Teaneck, and Department of Ophthalmology, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA. METHODS: Photorefractive keratectomy using a 15 Hz repetition rate was performed in 23 eyes of 14 patients by a single surgeon at 1 center. The attempted corrections ranged from -2.8 diopters (D) to -5.5 D. Preoperative and postoperative uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), predictability, corneal haze, and subjective glare/halo were evaluated over 6 months. RESULTS: At 6 months, UCVA was 20/32 or better in all eyes and at least 20/20 in 14 eyes (73.7%). Two eyes (10.5%) lost 2 or more Snellen lines of BSCVA; postoperative BSCVA was at least 20/25 in 100% of eyes and 20/20 or better in 95.0%. Fifteen eyes (78.9%) were within +/-0.5 D of attempted correction, and 19 (100%) were within +/-1.0 D. Mean spherical equivalent refraction was -4.62 D preoperatively, +0.15 D at 1 month, -0.09 D at 3 months, and -0.37 D at 6 months. At 6 months, 4 eyes (21.0%) had no corneal haze and 14 (73.7%) had trace subepithelial haze. Fifteen eyes (78.9%) had no glare/halo effect at 6 months, and 4 (21.0%) had minimal glare/halo effect. CONCLUSIONS: Clinical outcomes after excimer laser PRK for myopia using an increased repetition rate of 15 Hz were good and similar to those in studies conducted with a 10 Hz repetition rate.

Prepregnancy genetic testing for age-related aneuploidies by polar body analysis.

Current practice for prevention of chromosomal aneuploidies involves prenatal screening and termination of pregnancy, a procedure that is not universally acceptable. We introduced prepregnancy genetic testing by sampling and fluorescence in situ hybridization (FISH) analysis of the first and second polar body (PB), to avoid fertilization and transfer of embryos resulting from aneuploid oocytes. In 395 in vitro fertilization (IVF) patients of advanced maternal age, the first and second PBs were removed following their extrusion from oocytes and studied by FISH, using probes specific for chromosomes 13, 18, and 21, to detect and avoid the transfer of oocytes with common aneuploidies. Overall, 3,651 oocytes obtained from 598 IVF cycles were available for FISH analysis, with 2,952 showing interpretable FISH results (80.9%). The analysis revealed 1,271 (43.1%) oocytes with aneuploidy, which were excluded from transfer and subjected to follow-up FISH analysis to confirm PB diagnosis in the cleavage or blastocyst stage embryos. Only embryos originating from 1,681 aneuploidy-free oocytes were transferred back to patients, resulting in 119 pregnancies overall, from which 78 healthy children have already been born, 35 were spontaneously aborted, and 16 are ongoing, after confirming PB diagnosis by prenatal diagnosis. The results demonstrate that PB-based preimplantation diagnosis may be used for prepregnancy screening in women with age-related risk for common aneuploidies.

Long-term high dose intravenous calcitriol therapy in end-stage renal disease patients with severe secondary hyperparathyroidism.

We prospectively studied the long-term effects of intravenous calcitriol in 17 hemodialysis patients with severe secondary hyperparathyroidism (HPT) for 25.7 +/- 3.4 (+/- SE) months. Calcitriol was given thrice weekly after dialysis. Subsequently, changes were made every 3-4 weeks based upon serum chemistries. Total calcium and inorganic phosphorus were measured weekly; alkaline phosphatase (AP) and IRMA-PTH were measured monthly. Inorganic phosphate was controlled with calcium supplements. With calcitriol therapy both IRMA-PTH and AP decreased from 876 +/- 113 to 65 +/- 13 pg/ml (p < or = 0.001) and 432 +/- 106 to 103 +/- 15 U/ml (p < or = 0.001), respectively. Each patient had a reduction in IRMA-PTH and AP. Nadir IRMA-PTH occurred at 55.4 +/- 7.3 weeks. The maximum and mean maximum doses of calcitriol were 8.0 and 4.1 +/- 0.4 micrograms thrice weekly, respectively. Hypercalcemia tended to occur in those patients who were hypercalcemic prior to the initiation of intravenous calcitriol therapy. All hypercalcemic episodes were asymptomatic and reversed either by temporary withdrawal or lowering of the calcitriol dose. Hyperphosphatemia developed in those patients with a history of elevated serum phosphates and was mostly related to dietary and medication noncompliance. We conclude that intravenous calcitriol was uniformly effective and safe for the long-term therapy of severe HPT in ESRD. Careful attention to serum phosphate control is required.

Bioelectrical impedance analysis and dual energy x-ray absorptiometry to monitor nutritional status.

There exists an imperative to monitor changes in body composition in all dialysis patients on a regular basis to avoid overt malnutrition. In this regard, the absolute measurement of the fat-free mass assessment may not be as crucial as the serial measurement of fat-free mass with the same modality. A significant difference in measured fat and fat-free mass should be expected if different techniques are employed. Therefore, when attempting to monitor patients over time or to assess the effects of changes in therapeutic regimens, a single methodology should be employed. Our data validate the use of BIA in the stable PD patient, indicating that BIA can predict the DXA results. Considering the ease with which BIA measurements can be obtained and the lack of dependency on operator interpretation, BIA is an ideal technique for use in the clinical setting. The applicability of this technique for use in monitoring longitudinal changes in body composition has, in fact, been well established (25, 30, 31). BIA appears to be an excellent method for routine fat-free mass measurement in dialysis patients. In as much as malnutrition continues to remain a significant problem in PD patients, measuring and monitoring body composition is strongly recommended.

Sex difference in crown-rump length in first-trimester twins.

OBJECTIVE: To determine if there is a difference in the crown-rump length (CRL) between male and female fetuses in the first trimester. STUDY DESIGN: CRL was determined in 77 normal twin pairs at the time of chorionic villus sampling. The sex of each fetus was assigned based upon the results of the sampling. RESULTS: A small difference was found between the CRL of males as compared to females, but this was not statistically significant. However, if there was a difference in size between the twin pairs, the odds were 1.5:1 that the larger would be male. CONCLUSION: There is no clinically significant difference in size between male and female fetuses in the first trimester of pregnancy.

Decreasing risk of pregnancy loss following chorionic villus sampling. Elimination of transabdominal chorionic villus sampling during the ninth week of pregnancy.

Chorionic villus sampling (CVS) is a method of obtaining fetal cells in the first trimester of pregnancy for genetic analysis. The transcervical (TC) approach was the first technique to be widely used. In the National Institute of Child Health and Human Development collaborative study the absolute loss rate following CVS (the total number of spontaneous abortions and neonatal deaths following CVS) was 4%. More recently the transabdominal (TA) approach has been introduced. This study compares the loss rates for the two approaches at various gestational ages for three 6-month periods following the addition of the TA approach with each other and with the loss rates prior to the introduction of TA CVS. We found that the percentage of pregnancy losses following TA CVS during the ninth week of gestation (63-69 days) was consistently higher than for TC CVS performed at the same gestational age. The loss rate for TC CVS has steadily decreased since the introduction of TA CVS after remaining the same for the two years prior to the introduction of the TA approach. After minimizing the number of TA CVS performed during the ninth week of gestation, the overall loss rate during the most recent 6-month period has been reduced to 0.94%. We conclude that the lowest loss rate following CVS can be obtained if both the TA and TC methods are available, and that the number of TA procedures performed during the ninth week of gestation is minimized.

Creating roles for social work in changing health care organizations: organizational development perspective.

Social work has historically been influenced by and influential in periods of social change. The current health care environment poses challenges to the profession whose function is to maximize adaptation. In addition to helping patients and families adapt to a rapidly changing health delivery system, social workers can develop roles that affect the direction and impact of organizational change, substantively if not fundamentally. This includes assisting staff to work professionally and maintain client-focus during organizational stress and chaos. This article develops one example of how social work expanded its role during a time of transition through staff education of another discipline at Mount Sinai Medical Center in New York City, USA. The authors conceptualize the need for such practice, describe and analyze the program, and extrapolate practice principles for expanding social work roles in a changing work organization.

How to predict recurrent shoulder dystocia.

OBJECTIVE: Our aim was to determine the rate and risk factors for recurrent shoulder dystocia. STUDY DESIGN: A retrospective analysis of patients diagnosed with shoulder dystocia was performed by searching a computerized database from January 1, 1993, to June 30, 1999 for the following information: (1) vaginal deliveries, either spontaneous or operative, (2) shoulder dystocia, (3) birth weight, (4) duration of second stage of labor, (5) parity, and (6) gestational diabetes. Statistical analyses included chi(2) and t test. RESULTS: There were 39,681 vaginal deliveries with 602 (1.5%) complicated by shoulder dystocia. Sixty-six patients underwent a subsequent vaginal delivery, and 11 (16.7%) experienced another shoulder dystocia. The odds ratio for a recurrent shoulder dystocia was 10.98 (P <.000001). Nine of the 11 patients with recurrent shoulder dystocia compared with 28 of 55 without a recurrence were nulliparous women in their index pregnancy (P <.001). The mean fetal weights were 3885 g in the recurrent dystocia group and 3702 g in the group without recurrence (P <.03). Gestational age, operative delivery, and gestational diabetes were similar in the two groups. CONCLUSION: Factors that appear to increase the recurrence risk of shoulder dystocia include fetal weight and maternal parity. Prior shoulder dystocia is the single greatest predictive factor.

Association of parvovirus infection with isolated fetal effusions.

The association of parvovirus B19 infection and hydrops fetalis is well known. However, the association of parvovirus and fetal pleural or pericardial effusions has not been reported. We present five cases of isolated pleural or pericardial effusion with documented maternal parvovirus infection in four of these pregnancies. In the absence of structural or karyotypic abnormalities, spontaneous resolution of the effusion portends for a successful pregnancy outcome.