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Objectives: To revise the estimates of maternal age specific live birth prevalence of Down's syndrome in the absence of antenatal screening and selective termination using newly available data. Setting and Design: Data were used from the National Down Syndrome Cytogenetic Register (NDSCR), which contains information on nearly all antenatally or postnatally diagnosed cases of Down's syndrome in which a karyotype was confirmed between 1989 and 1998 in England and Wales. It is the largest single series of data on the prevalence of Down's syndrome. Results and conclusion: The prevalence does not continue increasing at an increasing rate with age above age 45 as has been previously assumed. Above this age the rate of increase declines with increasing age. The overall age pattern is sigmoidal. A new logit logistic model is proposed which fits the data well. The risk of a Down's syndrome live birth is given by: risk=1/(1+exp(7.330-4.211/(1+exp(-0.282x(age-37.23))))). [ABSTRACT FROM AUTHOR]

STUDY DESIGN: :A paired comparison of the peak and submaximal responses of oxygen uptake and heart rate in patients with spinal cord injury (SCI) performing voluntary arm cycle exercise and functional electrical stimulation (FES) leg cycling exercise. OBJECTIVES: :To test if the blunted heart rate response and slower rate of adjustment of oxygen uptake seen in patients with SCI performing FES leg cycle exercise are also characteristic of arm exercise in these patients. METHODS: :Eight paraplegics performed incremental and constant work rate (CWR) exercise with the legs and arms. Mean response times (MRT) for V˙o2 during exercise (on) and in recovery (off) were calculated from the breath-by-breath V˙o2 profile. RESULTS: :Peak heart rate was higher during incremental arm exercise, and uncorrelated with that observed during incremental FES leg cycling. For the same increase in V˙o2, constant work rate arm exercise was associated with faster (and normal) V˙o2 kinetics, greater increase in heart rate, and lower end-exercise blood lactate, compared to FES leg cycling. CONCLUSIONS: :The consistently higher peak heart rate and V˙o2, and faster V˙o2 kinetics, for voluntary arm compared to FES leg cycle exercise suggest no intrinsic dysfunction of heart rate control in these paraplegics. Rather, these data suggest that during FES leg cycling the changes seen are due to some characteristic specific to the injury, such as reduced muscle mass and/or deconditioning of the remaining muscle. SPONSORSHIP: :This research was supported by The Department of Veterans Affairs, Rehabilitation Research and Development Project #B603-RA.Spinal Cord (2000) 38, 340–345. [ABSTRACT FROM AUTHOR]

Background: Associations between environmental hazards and the occurrence of congenital anomalies may be detectable by seeking evidence of non-random occurrence of cases (clusters). There have been a number of anecdotal reports of occurrences of clusters of Down syndrome (DS).Methods: Data from a national register of cytogenetic diagnoses of Down syndrome births and legal terminations occurring between 1989 and 1995 were used to examine the possibility of clustering. Space-time clustering at Regional Health Authority (RHA) level was examined by comparing the expected monthly number of DS pregnancies given the maternal age distribution, with the observed numbers. Knox's method was used to determine if any clustering of RHA of unexpectedly high prevalence had occurred. Seasonality was also investigated by comparing monthly expected and observed numbers of DS pregnancies. Time clustering was examined by using the scan statistic to determine whether a statistically significant excess of pregnancies in any 3-month period occurred in any individual or adjacent groups of District Health Authority (DHA).Results: The numbers of DS pregnancies were no higher than expected (P < 0.05) in the same RHA over consecutive months. There was no evidence of any seasonality of DS pregnancies (P > 0.5). Only two individual DHA and three pairs of adjacent DHA had significantly high scan statistics (P < 0.03), but as over 400 statistical tests had been completed 12 clusters would be expected to have occurred due to chance alone.Conclusion: There was no evidence of any space-time clustering in DS at DHA level. [ABSTRACT FROM AUTHOR]

In a family in which the father carried a balanced translocation between chromosomes 15 and 22 two of his children had Prader-Willi syndrome and an unbalanced chromosome complement, having lost the proximal bands from the long arm of chromosome 15. His four other surviving children were normal but carried a balanced translocation. [ABSTRACT FROM AUTHOR]

Presents an abstract of the article "Evidence for Non-Homologous Meiotic Co-orientation in Man," by Nataliya Kovaleva and D. E. Mutton.

Presents an abstract of the article "Screening for Down Syndrome(DS) Over the Past 15 Years: A Report From the National Down Syndrome Cytogenetic Register (NDSCR)," by Joan Morris, D. Mutton, and E. Alberman.

This study describes the cytological and epidemiological findings in 985 trisomy 13 and 2512 trisomy 18 compared with 10,255 trisomy 21 diagnoses between 2004 and 2009 included in the National Down Syndrome Cytogenetic Register of England and Wales. The frequency of occurrence, proportions diagnosed prenatally, sex ratios, mean maternal age, and proportions of mothers with recurrences were analyzed. Ninety-seven, 98%, and 92% were free karyotypes for trisomy 21, 18, and 13, respectively; 3% of 21, 1% of 18, and 8% of trisomy 13 were translocations; and under 1% of trisomies 21 and 18 were double or triple aneuploids. Overall 1% of each trisomy had mosaicism, but 48% of the trisomy 21 double aneuploids, and 10% of trisomy 18 multiple aneuploids had mosaicism. The proportion of livebirths was 40% of trisomy 21, 11% of 18, and 13% of 13, respectively. Free trisomies 21 and 13 had an excess of males, and 18 had an excess of females, as did mosaic free trisomies 21 and 18. Mean maternal ages were 35.9 years in trisomy 21, 36.4 years in 18, and 34.6 years in 13. During the 6 years of data collection 1% of the mothers had recurrences, most recurrent trisomy 21 or 18 were identical translocations, but hetero-trisomic recurrences included 21 and 18, and 21 and 13. There are significant differences between the trisomic karyotypes and attributes, possibly related to their variable origins. Notable are the relative excess of trisomy 13 translocations, mosaicism in cases with multiple aneuploidy, and the types of homo- and hetero-recurrences., (Copyright © 2012 Wiley Periodicals, Inc.)

This study describes the characteristics of karyotypes leading to phenotypic Down syndrome (trisomy 21) in 29,256 cases diagnosed between 1989 and 2009 in England and Wales included in the National Down Syndrome Cytogenetic Register (NDSCR). The frequency of occurrence of the different karyotypes, proportions diagnosed prenatally, sex ratios, mean maternal age, and proportions of mothers with recurrences were analyzed. Nearly 97% of all cases were free trisomy 21; 2.9% contributory trisomy 21, 0.3% double or triple aneuploidies; 1% of all were mosaics. Mean maternal age of free trisomy 21 cases was 35 years, 54% were male, and 1% of mothers had recurrences. Free trisomy 21 mosaics had a lower mean maternal age (33 years), a lower proportion of males (39.5%), and 2.5% of mothers had recurrences. The majority of contributory translocations were Robertsonian or rea (21;21). Their mothers were younger, particularly those of Robertsonian translocations (28 years). Of the Robertsonian der (14;21) translocations of known parental origin, 54% were de novo, 41% maternal and 5% paternal and 15.8% of mothers of those of maternal origin had recurrences. Multiple aneuploidies have the highest proportion of males (67%), highest proportion of mosaics (40%), a mean maternal age of 37 years, and no mothers had a recurrence. The size of this national register allowed the frequency of occurrence of the rarer karyotypes of Down syndrome to be estimated and their epidemiology described., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: Whether the introduction of antenatal screening for Down syndrome in England and Wales with serum biochemistry or ultrasound has led to improvements in patient outcomes is unknown. The purpose of this study was to relate pregnancy outcomes to the dominant method used for prenatal Down syndrome screening., Study Design: For the years 1989 through 1999, England and Wales were divided into geographically defined areas where specific hospitals, health authorities, and cytogenetic laboratories provided maternity care for well-defined populations. For each year from 1989 through 1999, the dominant Down syndrome screening method that was used in each area was determined. Outcomes for area-years that used serum biochemistry or ultrasound (first or second trimester) were compared with area-years that used advanced maternal age as the dominant screening method. The percent of Down syndrome cases that were diagnosed prenatally (effectiveness) and the number of invasive prenatal tests that were performed to diagnose each Down syndrome case prenatally (efficiency) were compared., Results: There were 5,980,519 births and 335,184 referrals for prenatal karyotyping (amniocentesis and chorionic villus sampling) that occurred in the area-years studied, of which 12,047 pregnancies were diagnosed as Down syndrome; 5393 cases of Down syndrome (45%) were diagnosed prenatally. Invasive testing increased from 4.4% of pregnancies in 1989 to 6.4% in 1997 and declined slightly in 1999 (5.8%). Prenatal diagnosis of Down syndrome cases rose from 28% in 1989 to 53% in 1999, and the number of invasive tests that were performed to diagnose each Down syndrome case fell from 89.7 to 47.7 (P [for trend]<.0001). Areas with serum or ultrasound as the dominant screening method detected 50% more Down syndrome cases in prenatally (52% and 53% vs 36%; P<.0001) and performed fewer invasive procedures to diagnose each Down syndrome case (60.7 and 52.0 vs 88.0; P<.0001) compared with areas in which advanced maternal age screening was dominant, despite serving populations with similar mean/median maternal ages., Conclusion: In clinical practice, screening programs for Down syndrome that were based on maternal serum biochemistry or ultrasound were more effective and efficient than the screening programs that used advanced maternal age alone.

Data from the New York State Chromosome Registry on over 10,000 cases of Down syndrome reported from 1977 to 1996 confirm findings in the England and Wales Cytogenetic Register that in mosaic 46/47,+21 cases of Down syndrome the male/female ratio (as inferred from XY and XY karyotypes respectively) is less than 1.0 as opposed to the ratio in nonmosaic 47,+21 cases in which the ratio is close to 1.2, or in the general background population with ratio of about 1.05. These results may reflect in part differential pairing in 47,+21 somatic cells of X and Y chromosomes with a 21 chromosome and/or in in-utero selection.

Objectives: (1) To determine if a hybrid exercise (leg plus arm) training program performed immediately after functional electrical stimulation (FES) leg cycle exercise (LCE) training would further improve aerobic capacity when compared with FES leg cycle training alone, and (2) to compare the submaximal responses occurring during both FES-LCE alone and hybrid exercise in the same SCI subjects., Design: Nonrandomized control trial whereby subjects act as their own control., Setting: Outpatient rehabilitation in a primary care hospital., Patients: A volunteer sample (n = 11) of men 20 to 50 years old with complete spinal cord injury, free from cardiovascular and metabolic disease with spasticity., Interventions: Three phases of exercise training: phase I, progressive FES-LCE to 30 minutes of exercise (n = 11); phase II, 35.2 +/- 16.2 sessions of FES-LCE (n = 11); phase III, 41.4 +/- 17.7 30-minute sessions of hybrid exercise (n = 8)., Main Outcome Measures: (1) Aerobic capacity-a further increase after hybrid exercise when compared with FES-LCE alone; (2) submaximal physiologic parameters (oxygen uptake [VO2], heart rate [HR], blood lactate [BLa-])-measurement of these during constant work rate exercise and a training effect., Results: VO2 (the body's ability to utilize oxygen) significantly improved (p < .05) after both FES-LCE and then further after hybrid training. Hybrid exercise training resulted in significantly (p < .05) greater work rates and VO2 values than both FES-LCE at baseline and training work rates., Conclusion: These subjects demonstrated that hybrid exercise performed twice a week provided sufficient intensity to improve aerobic capacity and provide a medium whereby patients with SCI can burn more calories than via FES-LCE alone. This has important implications for improving the health and fitness levels of individuals with SCI and may ultimately reduce their risk of cardiovascular disease.

We examined the ability of patients with spinal cord injury to undergo adaptations to chronic exercise training (cycle ergometry) invoked by functional electrical stimulation (FES) of the legs. Nine such patients performed incremental and constant work rate exercise before and after exercise training. Exercise sessions averaged 2.1 +/- 0.4/wk, and consisted of 30 min/session of continuous FES recumbent cycling with increasing work rate as tolerated. Peak VO2 and peak work rate significantly improved with training. Peak VO2 was significantly correlated with peak heart rate both before and after training (r = 0.97 pre and 0.85 post, P < 0.01 for both). The time course of the VO2, VCO2 and VE responses to constant-load exercise (unloaded cycling) and in recovery (mean response time MRT) were very long prior to training, and became significantly faster following training. However, there was no correlation between percentage improvement in either MRTon or MRToff for VO2 and the percentage increase in peak VO2. Exercise tolerance in these patients with spinal cord injury appears to be a direct function of the ability to increase heart rate. Further, exercise training can elicit significant improvements in both exercise tolerance and in gas exchange kinetics, even when performed only twice per week. However, these improvements may be accomplished by different mechanisms.

Eight males with spinal cord injury (SCI) participated in an exercise training program using neuromuscular electrical stimulation (NMES) leg cycle ergometry. Each subject completed a minimum of 24 (mean +/- SD = 38.1 +/- 17.2) 30-minute training sessions over a 19-week period. The initial work rate (WR) of 0 watts (W) of unloaded cycling was increased when appropriate with subjects exercising at 11.4 +/- 3.7 W (range = 6.1 W-18.3 W) at the end of the training program. Randomized block repeated measures ANOVA was used to compare pretraining and posttraining peak physiologic responses during graded NMES leg cycle tests and subpeak physiologic responses during 10 minutes of NMES leg cycle exercise at an absolute WR (0 W). A significant (P < or = 0.05) increase was observed for peak VO2; (+10%, 1.29 +/- 0.30 to 1.42 +/- 0.39 1.min-1). No other statistically significant differences were noted for any other peak variable (VCO2, VO2 ml.kg-1 min-1, VE, WR, HR, RER) pre- to posttraining. During submaximal NMES leg cycle testing, a significant decrease was noted for RER (-9.2%, 1.19 +/- 0.14 to 1.08 +/- 0.09). No other submaximal variable (VO2 1.min-1, ml.kg-1.min-1, VCO2, HR, VE) showed significant changes as a result of the training. Although the improvement in peak VO2 was not as dramatic as those reported in previous studies, it appears that NMES leg cycle training performed two times per week can significantly enhance cardiorespiratory fitness.

The pregnancy outcomes on cases of Down syndrome diagnosed prenatally in which the mother did not elect termination were evaluated in data reported to a comprehensive Register of Down syndrome for England and Wales for 1989-94. In the 168 cases in which placental biopsy was not used, the overall rate of spontaneous loss was 35%, but this figure masks considerable heterogeneity by gestational stage at ascertainment. Data on ages at diagnostic procedure and on pregnancy termination enabled a more precise survival analysis. The loss rates were approximately 50% for those fetuses ascertained at 15-17 completed wk, 43% at 18 wk, 31% at 19 wk, 25% at 20 wk, and then a leveling off at approximately 20%-25% for fetuses ascertained at 21-28 completed wk. For fetuses ascertained prior to 18 wk, there was no evidence that maternal age was associated with fetal loss, consistent with earlier reports. At 18 wk and after, however, maternal age was on the average approximately 3 years greater in fetuses that were lost. Comparison of successive gestational birth cohorts provided no evidence in these 168 cases that the diagnostic procedure itself had any effect on loss or that selective ascertainment of mothers in risk of loss had any effect on the results. In contrast, in the 21 cases in which placental biopsy had been undertaken, the overall loss rates were not only higher when appropriate comparisons could be made, but there was some evidence for selective ascertainment and/or procedure-associated losses.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the kinetics of VO2, VCO2, and VE following the onset of unloaded leg cycling, and in recovery, in six patients with spinal cord injury (SCI). Exercise was produced by functional electrical stimulation (FES) of the quadriceps, hamstrings, and gluteal muscles. End-exercise VO2 (1.03 +/- 0.16 l.min-1), VCO2 (1.20 +/- 0.22 l.min-1) and VE (41 +/- 10 l.min-1) were elevated compared to values typically seen in healthy ambulatory subjects performing similar unloaded cycling. Mean response times for the on transients (MRTon) were both long and variable across subjects for VO2 (165 +/- 62 s), VCO2 (173 +/- 58 s), and VE (202 +/- 61 s). Recovery kinetics showed much less intersubject variability, and for five of six subjects were faster than the equivalent exercise MRT for all three variables (MRToff for VO2 of 103 +/- 28 s, VCO2 136 +/- 20 s, and VE 144 +/- 34 s), but P > 0.05 for all three. Size of the O2 deficit (1.96 +/- 0.90 l) and end-exercise lactate (7.05 +/- 1.65 mmol.l-1) were similar to values reported for healthy sedentary subjects performing maximal voluntary exercise, but the end-exercise heart rate (102 +/- 16 bpm) was lower than expected for this intensity of exercise. In conclusion, FES-induced unloaded cycling leads to exaggerated responses of pulmonary gas exchange and long time constants in patients with SCI. The delayed kinetics may be due in part to a blunted increase in heart rate in addition to severe deconditioning.

Objective: To investigate changes in the numbers of Down's syndrome births and terminations of pregnancies from 1989 to 1993., Design: Data from a national register of cytogenetic diagnoses of karyotypes associated with Down's syndrome were analysed to obtain observed numbers of births and terminations of pregnancies known to be affected. Allowance was made for those cases diagnosed prenatally for whom the eventual outcome of the pregnancies had not yet been ascertained., Results: There has been an increase over the study years in the number of cytogenetic diagnoses of Down's syndrome from 1063 in 1989 to 1137 in 1993, despite an overall fall in births in England and Wales. This is largely due to the increase in antenatal screening and diagnosis, but in part also due to the rise in numbers of pregnancies at increased maternal ages. The rise in prenatally diagnosed cases, of which 92% end in termination, has been accompanied by a fall in both the estimated numbers of affected live births, from 764 in 1989 to 615 in 1993, and the rate per 1000 total live births in the same years from 1.1 to 0.9., Conclusions: Better and speedier information on the outcome of prenatally diagnosed cases of congenital anomalies such as Down's syndrome would improve the quality of information available for those auditing genetic services or those planning for the care of survivors.

The national register of chromosomal anomalies that lead to Down's syndrome has enabled the monitoring of change in prenatal diagnosis for this condition, and the factors which affect the change. The proportion of cases of cytogenetically diagnosed Down's syndrome in England and Wales detected prenatally rose to 46% in 1991-2 from 31% in 1988-9, a 1.5-fold increase (95% confidence interval 1.3 to 1.7). The increase was confined to mothers under 40 years and was due to the introduction of screening by maternal serum analysis and ultrasound. Over a quarter of affected pregnancies in women aged 25-29 were detected prenatally in 1991-2 compared with less than 10% in 1988-9. Analysis of the data showed regional differences in prenatal diagnosis rates, and in the length of time elapsing between the diagnostic test and termination of an affected pregnancy. An inexplicable finding was that this period varied with the sex of the fetus, being on average a day longer for females than for males.

The effects of 5 wk of equivalent intensity, 85-90% maximum heart rate (MHR), run-only (N = 6) vs cycle/run (N = 5) training were evaluated in moderately fit runners, mean VO2max of 55.2 ml.kg-1.min-1, 19-35 yr old, on maximal treadmill (TM) and cycle ergometer (CE) testing, 5000-m and 1609-m run performances, and submaximal measures while treadmill running. Subjects participated in either 4 d.wk-1 of run-only or alternating run and cycle training. Both groups significantly improved TM VO2max (P < 0.05), CE VO2peak (P < 0.01), and 5000-m (P < 0.01) and 1609-m (P < 0.05) run times with no significant differences between the groups. The TM VO2max pre/post values were 55.3 +/- 3.0 to 58.2 +/- 3.0 and 55.6 +/- 3.8 to 58.9 +/- 2.4 ml.kg-1.min-1 for the run group and cross-trained group, respectively. Posttraining submaximal treadmill running showed statistically significant pace increases of 18.7 (run) and 16.1 (cycle/run) m.min-1 with similar heart rate, blood lactate, and RQ values as pretraining. Results indicate that 5 wk of either mode of training can significantly improve aerobic capacity and run performance.

Physically active college age women were evaluated to determine the effects of 9 wk of stair-climbing (Stairmaster Gauntlet) vs run training on 2414-m run time and treadmill measured aerobic capacity (VO2max) and submaximal physiological parameters. Subjects were randomly assigned to a stair-climbing (STAIR N = 11) (43.8 +/- 1.5 ml.kg-1.min-1) (mean +/- SEM) or run training (RUN N = 12) (44.2 +/- 1.8) group, training 4 d.wk-1 at 70-80% of maximum heart rate (MHR) for 30 min progressing to 85-90% MHR for 45 min. The STAIR group significantly increased (P < 0.01) their VO2max by 12% and decreased (P < 0.01) their 2414-m run time of 12.8 min by 8%. The RUN group increased (P < 0.01) their VO2max 16% and decreased run time (P < 0.01) 11% from 13.1 min. Submaximal treadmill runs at the same speed and grade demonstrated significant decreases in %VO2max and % MHR (P < 0.01) for both groups. The data support the use of stair-climbing exercise as an alternative mode to running with similar treadmill and running performance results subsequent to 9 wk of training.

Flow cytometry has been used to detect in vivo expression of rubella antigens on human leucocytes. Sequential samples of peripheral blood were obtained from four volunteers with naturally acquired rubella and five persons immunised with RA27/3 rubella vaccine. Leucocytes were stained for rubella antigens using a pool of rubella monoclonal antibodies. Rubella antigens were detected on the leucocytes of all four volunteers with naturally acquired rubella between 1 and 13 days after onset of illness. Viral antigens were expressed more frequently on the monocyte (9-51%) than the lymphocyte (less than 1-4%) and granulocyte (less than 1-3%) populations. Among the vaccines, rubella antigens were detected on the leucocytes of four of the five volunteers between 5 and 12 days after immunisation. The expression of viral antigens was more transient and the proportion of cells exhibiting rubella-specific fluorescence considerably lower following vaccination (1-12%) than natural infection (9-51%). Our results demonstrate that flow cytometry provides a rapid and sensitive analytical technique for detecting viral antigens on leucocytes from infected persons. Leucocytes may play an important role in the pathogenesis of rubella infection.