Prediction of obstructive sleep apnoea in children and adolescents with Down syndrome.

BACKGROUND: Obstructive sleep apnoea (OSA) is common in children and adolescents with Down syndrome (DS). Clinical guidelines recommend that all children with DS have polysomnography (PSG) for assessment of OSA by the age of 4 years, but access is limited and testing may be burdensome for children and families. METHODS: The purpose of this prospective cross-sectional cohort study was to identify a model to predict OSA in this group that could be tested in an external population to triage children and adolescents with DS for PSG. These models were based on a comprehensive set of potential predictive demographic, anthropometric, quality of life and sleep-related variables. RESULTS: The results of this study show the predictive power of a model based on the sleep disordered breathing subscale of the Pediatric Sleep Survey Instrument and sleep fragmentation quantified using actigraphy in determining moderate-severe OSA in children and adolescents with DS. This model exhibits high sensitivity (82%), specificity (80%), positive predictive value (75%) and negative predictive value (86%). CONCLUSIONS: We demonstrate the utility of a tool containing the sleep disordered breathing subscale of the Pediatric Sleep Survey Instrument and sleep fragmentation quantified using actigraphy in identifying children and adolescents with DS who have moderate/severe OSA.

Resurfacing hip arthroplasty better preserves a normal gait pattern at increasing walking speeds compared to total hip arthroplasty.

Background and purpose - Gait analysis performed under increased physical demand may detect differences in gait between total (THA) versus resurfacing hip arthroplasty (RHA), which are not measured at normal walking speed. We hypothesized that patients after RHA would reach higher walking speeds and inclines compared with THA. Additionally, an RHA would enable a more natural gait when comparing the operated with the healthy contralateral hip. Patients and methods - From a randomized controlled trial comparing THA with RHA with at least 5 years' follow-up patients with a UCLA score of more than 3 points (n = 34) were included for an instrumented treadmill gait analysis. 25 patients with a unilateral implant (primary analysis-16 THA versus 9 RHA) and 9 patients with a bilateral implant (sub-analysis-n = 5 RHA + THA; n = 4 THA + THA). Spatiotemporal parameters, ground reaction forces, and range of motion were recorded at increasing walking speeds and inclines. Functional outcome scores were obtained. Results - At a normal walking speed of 1.1 m/s and at increasing inclines no differences were recorded in gait between the 2 groups with a unilateral hip implant. With increasing walking speed the RHA group reached a higher top walking speed (TWS) (adjusted difference 0.07 m/s, 95% CI -0.11 to 0.25) compared with THA. Additionally, RHA patients tolerated more weight on the operated side at TWS (155 N, CI 49-261) and as such weight-bearing approached the unaffected contralateral side. For the RHA group a "between leg difference" of 8 N (CI 3-245) was measured versus -129 N (CI -138 to -29) for THA (adjusted difference 144 N, CI 20-261). Hip flexion of the operated side at TWS was higher after RHA compared with THA (adjusted difference 8°, CI 1.7-14). Interpretation - In this study RHA patients reached a higher walking speed, and preserved a more normal weight acceptance and a greater range of hip flexion against their contralateral healthy leg as compared with patients with a THA.

High incidence of intraoperative calcar fractures with the cementless CLS Spotorno stem.

INTRODUCTION: This study reports on the incidence of intraoperative calcar fractures with the cementless Spotorno (CLS) stem, and the potential role of a learning curve and implant positioning is investigated. METHODS: After introduction of the CLS stem, 800 consecutive cementless total hip arthroplasties (THA) were analyzed. The incidence of calcar fracture in the first 400 THA was compared with the second 400 THA, in order to study a potential learning curve effect. According to the instruction for users, varus positioning of the stem was avoided and a femoral neck osteotomy was aimed relatively close to the lesser trochanter since these are assumed to be correlated with calcar fractures. Implant positioning (neck-shaft angle, femoral offset and osteotomy-lesser trochanter distance) was measured on postoperative pelvic radiographs of all THA with calcar fractures and 100 randomly selected uncomplicated control cases. RESULTS: Seventeen (2.1%) intraoperative calcar fractures were recorded. The incidence of calcar fracture differed between the first 400 THA (n = 11) and the second 400 THA (n = 6). This difference was not statistically significant (p = 0.220); however, these numbers indicate a trend toward a learning effect. No significant difference in stem positioning nor the height of the femoral neck osteotomy was measured between THA with a calcar fracture (n = 17) and the control cases (n = 100). CONCLUSIONS: We report on a high incidence of intraoperative calcar fractures with the use of a CLS stem. The risk for calcar fractures remains clinically significant even after adequate implant positioning in the hands of experienced hip surgeons. Surgeons should be aware of this implant related phenomenon and be alert on this phenomenon intraoperatively.

Bone mineral density changes in the graft after acetabular impaction bone grafting in primary and revision hip surgery.

Background and purpose - Impaction bone grafting (IBG) is an established method in hip revision surgery to reconstruct loss of bone stock. There is limited knowledge concerning the actual bone remodelling process within the allograft. We investigated with repeated bone mineral density (BMD) measurements the biological process of bone remodelling in the allograft in vivo. We hypothesized that an initial decrease in BMD would be followed by an increase towards baseline values. Patients and methods - Dual-energy X-ray absorptiometry (DXA) was used to measure BMD values in 3 regions of interest (ROI) in 20 patients (average age at surgery 70 years, 11 males) after an acetabular reconstruction with IBG and a cemented cup. A postoperative DXA was used as baseline and DXA was repeated at 3 and 6 months and at 1 and 2 years. The Oxford Hip Score (OHS), the 12-Item Short Form Health Survey (SF12), and a 0 to 100 mm visual analogue scale (VAS) for pain and satisfaction were obtained simultaneously. Results - The overall mean BMD in the IBG regions increased significantly by 9% (95% CI 2-15) at 2 years' follow-up. In the cranial ROI BMD increased 14% (CI 6-22), whereas the BMD in the medial and caudal ROI showed an increase of 10% (CI 1-18) and 4% (CI -6-16), respectively. The OHS, SF12-mental, and VAS for pain all improved statistically significantly 2 years after surgery, with a mean VAS for satisfaction of 77 (CI 63-90) out of 100 points. The SF12-physical showed non-significant improvement. Interpretation - The BMD in the allograft gradually increased after IBG for acetabular reconstruction arthroplasties, particularly in the cranial ROI. An initial decrease in the BMD was not encountered. These BMD changes, as proxy measurements for bone remodeling, may indicate progressive apposition of vital new host bone in the grafted area.

Increase in physical activity after resurfacing hip arthroplasty is associated with calcar and acetabular bone mineral density changes.

PURPOSE: Bone preservation is an important advantage of the resurfacing hip arthroplasty (RHA) concept. We hypothesised that patients' increase in physical activity level after RHA would positively relate with periprosthetic bone mineral density (BMD) changes and thus facilitate bone preservation. METHODS: BMD-changes were prospectively recorded in 38 patients after RHA. Dual-energy absorptiometry was used to quantify BMD-changes in 6 periprosthetic regions of interest preoperatively, at 6 months, 1, 2 and 3 years postoperative. The effect estimates of patients' physical activity, according to their Harris Hip Score (HHS) and University of California at Los Angeles (UCLA) Activity Score, on these BMD changes were assessed in linear mixed models. RESULTS: The UCLA (coefficient = 0.02 (95% CI, 0.010-0.034); p<0.001) and HHS (coefficient = 0.002 (95% CI, 0.001-0.003); p<0.001) were associated with the BMD in the calcar region. As for BMD changes in the femoral neck only the HHS was associated (coefficient = 0.0006 (95% CI, <0.0001-0.001); p = 0.04). Both the UCLA and the HHS were inversely associated with BMD in the medial acetabular region (UCLA: coefficient = -0.02 (95% CI, -0.038 to -0.007); p = 0.005, HHS: coefficient = -0.002 (95% CI, -0.003 to -0.001), the same accounted for the HHS to BMD-change cranial to the acetabulum (-0.001 [95% CI, -0.0018 to -0.0001]; p = 0.03). For the caudal acetabular and femoral subtrochanteric region no relation with BMD-changes was found. CONCLUSIONS: The increase in activity scores after RHA was indeed associated with an increase in BMD in the calcar region, however unexpectedly also with a BMD decrease on the acetabular side. Stress shielding from the implant is the most likely causative factor.

Changes in bone mineral density and femoral neck narrowing in the proximal femur three to five years after hip resurfacing versus conventional total hip arthroplasty.

We studied whether bone mineral density (BMD) is preserved without significant femoral neck narrowing (FNN) after hip resurfacing (RHA) (n=42) versus small diameter metal-on-metal total hip arthroplasty (MoM THA) (n=40). In this three to five year randomized trial BMD was measured in the calcar with dual energy absorptiometry (DXA) preoperatively, at three and six months, one, two, three and five years postoperatively. Four additional BMD regions of interest (ROIs) and femoral neck narrowing (FNN) were measured after RHA. BMD in the calcar increased to 107% (P<0.001) at one year and remained stable. Additional ROIs in the femoral neck and trochanter-area BMD changes fluctuated between 99.9% and 104.1%. FNN was minimal with a mean of 1.3% at three years. After THA BMD decreased in the calcar to 80% at one year (P<0.001) and stabilized. This bone stock preserving nature of RHA must be weighed against potential disadvantages caused by specific metal-on-metal bearing problems.

Excessive polyethylene wear and acetabular bone defects from standard use of a hooded acetabular insert in total hip arthroplasty.

PURPOSE: In total hip arthroplasty (THA) the use of a polyethylene (PE) insert with a hooded rim can be considered to reduce dislocation risks. This benefit has to be balanced against the potential introduction of impingement of the femoral component on this rim. We present a case series of early acetabular revisions for excessive PE wear and acetabular bone defects from overuse of such a hooded rim insert. MATERIAL AND METHODS: Twenty-eight patients with 34 consecutive early acetabular revisions were evaluated on failure mechanism. One type of implant was used in all cases. Standard pelvic radiographs and pre-operative CT scans were used to quantify PE wear, implant positioning and acetabular bone defects. RESULTS: An acetabular revision with impaction grafting was performed in all cases with a mean cup survival of ten years (range 1.3-19.3). No concurrent stem revisions were necessary. Overall implant positioning was adequate with a mean cup inclination of 45° (range 39-57) and anteversion of 25° (range eight to 45). The mean PE wear was 0.24 mm/year (range 0.00-1.17). The mean acetabular bone defect on pelvic CT scans was calculated as 352 mm² (range zero to 1107) and 369 mm² (range zero to 1300) in the coronal and transversal planes, respectively. A hooded acetabular insert was retrieved in all cases and profound PE wear, typically from the posterior hooded rim, was encountered. CONCLUSION: The use of hooded acetabular inserts may be considered to improve implant stability intra-operatively. This case series clearly presents that together with these devices, component impingement with concordant complications such as accelerated PE wear may be introduced. Standard use of these stabilizing inserts should thus be avoided.

Modular necks in primary hip arthroplasty without anatomical deformity: no clear benefit on restoration of hip geometry and dislocation rate. An exploratory study.

Modular necks were introduced in total hip arthroplasty (THA) to improve restoration of hip-geometry and reduce dislocation-rates. This presumed advantage was evaluated retrospectively for patients with arthritis in otherwise anatomically normal hips. Restoration of hip-geometry was assessed on preoperative and postoperative calibrated radiographs in 95 consecutive primary THAs with a modular neck design and compared with 95 match controlled THAs with a similar monoblock stem. No significant differences were seen in restoration of body moment arm, leg length and cupangle. Offset restoration revealed a borderline significant difference (P = 0.48) with higher values for the monoblock stem. In both groups 4 dislocations within one year were encountered. In this study modular necks did not reveal a clear benefit in restoring hip geometry and dislocation rate after straightforward THA.

Can actigraphy measure sleep fragmentation in children?

OBJECTIVE: The gold standard assessment for sleep quality is polysomnography (PSG). However, actigraphy has gained popularity as an ambulatory monitor. We aimed to assess the value of actigraphy in measuring sleep fragmentation in children. METHODS: 130 children aged 2-18 years referred for assessment for sleep disordered breathing (SDB) were recruited. The arousal index (AI) scored from PSG was compared to the actigraphic fragmentation index (FI) and number of wake bouts/h. RESULTS: The ability of actigraphic measures to correctly classify a child as having an AI>10 events/h rated as fair for the FI and poor for wake bouts/h (area under the receiver operator characteristic curve, 0.73 and 0.67, respectively). CONCLUSION: Actigraphy provides only a fair indication of the level of arousal from sleep in children. While the limitations of actigraphy prevent it from being a diagnostic tool for SDB, it still has a role in evaluating sleep/wake schedules in children.

Investigation of sleep disorders.

Polysomnography or sleep study is the main investigation for paediatric sleep disorders. It involves the continuous and simultaneous recording of multiple physiological parameters evaluating sleep and respiration. It is most commonly used to diagnose obstructive sleep apnoea and to monitor nocturnal non-invasive ventilation requirements of children. Its role in other sleep related breathing disorders, narcolepsy and parasomnias is discussed.

Accuracy of emergency department bedside ultrasonography.

OBJECTIVES: To determine which focused ultrasound examinations can be interpreted accurately by emergency physicians who have limited training and experience. To determine whether image quality and/or the operator's level of confidence in the findings correlates with accurate scan interpretation. METHODS: A prospective sample of consenting adult emergency department patients with the conditions was selected for study. Scans were performed by emergency physicians who had attended a 3-day focused ultrasound examinations instruction course. All scans were videotaped and subsequently reviewed by a radiologist. Accuracy was determined by comparing the emergency physicians scan interpretation with preselected gold standards. Chi-squared tests were employed to determine if the individual performing the scan, the type of scan, patient's body habitus, image quality and/or operator confidence were reliable predictors of accuracy. RESULTS: Between September 1997 and January 1999, 221 scans were studied. Accuracy varied widely depending on the type of scan performed: aortic scans were 100% accurate whereas renal scans had 68% accuracy. On bivariate analyses, there was little variation in the various operators' levels of proficiency and accuracy of interpretation was not associated with patient body habitus, image quality or operator confidence. CONCLUSIONS: Neophytes can accurately perform and interpret aortic scans; additional training and/or experience appear to be necessary to achieve proficiency in conducting most of the other scans studied. Inexperienced operators are unable to discern whether their scan interpretations will prove accurate.

Emergency department ultrasound scanning for abdominal aortic aneurysm: accessible, accurate, and advantageous.

STUDY OBJECTIVE: This study was conducted to determine whether emergency physicians with relatively limited training and experience can accurately identify the presence or absence of abdominal aortic aneurysms (AAAs) by performing bedside ultrasound scanning, and to assess the potential impact of ultrasound scanning on clinical management. METHODS: Patients in whom AAAs were suspected, including those patients older than 50 years presenting with abdominal/back pain of unclear origin or presumed renal colic, were eligible for study entry. Consenting adults had ultrasound scanning by an emergency physician who was not responsible for their primary care. Treating physicians remained blinded to the results unless an unexpected AAAs was discovered. Scan accuracy was ascertained by comparing our ultrasound results with preselected gold standards. The clinical impact of the ultrasound studies was determined by comparing the preultrasound and postultrasound assessment sheets that detailed the presumed diagnosis, proposed investigations and therapies, and patient disposition. RESULTS: Our convenience sample includes 68 scans for AAAs; findings of 26 scans were positive, 40 scans yielded negative findings, and 2 scans were indeterminate. Scan interpretations were 100% accurate. The ultrasound results would have improved the care of 46 patients without adverse sequelae. Ultrasound scanning served primarily to exclude AAA in patients who proved not to have aneurysms; however, scans also provided significant benefits for those with AAAs and improved patient management plans. CONCLUSION: Relative neophytes can perform aortic ultrasound scans accurately. These scans appear useful as a screening measure in high-risk emergency department patients; they may also aid in rapidly verifying the diagnosis in patients who require immediate surgical intervention.

Mechanisms of DNA replication.

Advances in recent years have led to exciting new ideas about the initiation, regulation and coordination of DNA replication. Structural studies have yielded fascinating glimpses of replisome action. In addition, the involvement of replication proteins in other cellular processes has blurred the lines between replication, repair and recombination.

Replisome assembly at oriC, the replication origin of E. coli, reveals an explanation for initiation sites outside an origin.

This study outlines the events downstream of origin unwinding by DnaA, leading to assembly of two replication forks at the E. coli origin, oriC. We show that two hexamers of DnaB assemble onto the opposing strands of the resulting bubble, expanding it further, yet helicase action is not required. Primase cannot act until the helicases move 65 nucleotides or more. Once primers are formed, two molecules of the large DNA polymerase III holoenzyme machinery assemble into the bubble, forming two replication forks. Primer locations are heterogeneous; some are even outside oriC. This observation generalizes to many systems, prokaryotic and eukaryotic. Heterogeneous initiation sites are likely explained by primase functioning with a moving helicase target.

Modulation of the P1 plasmid partition protein ParA by ATP, ADP, and P1 ParB.

ParA is an essential P1 plasmid partition protein. It represses transcription of the par genes (parA and parB) and is also required for a second, as yet undefined step in partition. ParA is a ParB-stimulated ATPase that binds to a specific DNA site in the par promoter region. ATP binding and hydrolysis by ParA affect ParA activities in vitro. ATP and ADP binding stimulate ParA DNA binding and dimerization; however, ATP hydrolysis has a negative effect on DNA binding. Our current experiments reveal that ATP binding and hydrolysis affect ParA conformation and ParA sensitivity to ParB. Nucleotide binding assays show that ParA binds ATP better than ADP (Kd values of 33 and 50 microM, respectively). Interaction with these nucleotides as well as ATP hydrolysis by ParA alter ParA conformation as established by CD and ParA sensitivity to heat denaturation. Finally, we show that ParB stimulates ParA DNA binding. This stimulation requires ATP hydrolysis in vitro, suggesting that one role for ATP hydrolysis in vivo is to make ParA repressor sensitive to ParB. Our observations lead to the suggestion that ATP binding and hydrolysis have separable roles in ParA repressor function and perhaps in ParA partition functions as well.

The P1 plasmid partition protein ParA. A role for ATP in site-specific DNA binding.

ParA, a P1 protein required for partition of the prophage plasmid, regulates expression of its own gene and another partition gene, parB, from a promoter upstream of parA. The ATP-dependent ParA DNA binding activity to the par promoter is thought to mediate this regulation. An alternate purification for ParA is presented. This highly purified ParA was used to examine ParA DNA binding activity using DNase I protection assays. At high concentration, ParA bound to the par promoter in the absence of ATP, demonstrating that although ATP stimulates, it is not required for DNA binding. Non-hydrolyzable ATP analogues as well as ADP stimulated binding more than ATP, suggesting that the act of hydrolysis is coupled to release of the DNA. Glycerol gradient sedimentation and chemical cross-linking experiments suggest that ParA exists in an monomer-dimer equilibrium that is shifted toward dimer formation by adding ATP or ADP. These observations lead to the proposal that the more active DNA binding form of ParA is a dimer and that the effects of ATP and ParA concentration on DNA binding are a direct result of their effects on oligomerization.

Environmental enrichment following brain damage: an aid to recovery or compensation?

Postoperative environmental enrichment (EC) in rats with brain lesions has been hailed as a potential agent of recovery of function following brain damage. However, most such claims are based on examining the effects of EC on acquisition of a new task following brain injury. Elsewhere we have argued that since this paradigm fails to establish a preoperative behavioural baseline against which to compare subsequent performance it may demonstrate compensation but cannot provide evidence of recovery. The present study directly addresses this issue by examining the effects of postoperative EC both on performance of a preoperatively acquired water maze escape response as well as on de novo acquisition of such a response in rats with bilateral occipital and sham lesions. In terms of swim times postoperative EC was found to significantly improve the performance of subjects which had not been preoperatively trained but not the performance of those subjects which had. However, in terms of a trials to criterion measure postoperative EC benefitted animals in both the preoperative and postoperative training conditions. The results, therefore, support the view that what has been observed in most previous studies is EC-induced compensation rather than recovery and also help to define the conditions under which this occurs. However, they also argue for further investigation of the hypothesis that postoperative EC may enhance recovery of lesion-impaired performance consistency.

How does environmental enrichment aid performance following cortical injury in the rat?

Understanding how postoperative environmental brain damage in animals may help in devising treatment regimes for brain injured humans. This study tests Finger's hypothesis that EC increases the animal's ability to switch to alternative cues when brain damage renders the cues normally used in performing the task less salient or unavailable. Following preoperative water maze training to visual cues, rats were given either bilateral occipital lesions or sham operations, housed in either EC or standard conditions and then tested in the water maze in alternating visual and non-visual cue conditions. We found no evidence that postoperative EC helped lesioned rats to switch to non-visual cues when visual cues were unavailable.

Maternal hypothyroxinemia and brain development: II. Biochemical, metabolic and behavioural correlates.

Using a rat model, we have investigated the influence of maternal hypothyroxinemia throughout pregnancy on brain development in young and adult progeny. Although no consistent change was observed in whole brain total protein concentration, the subcellular distribution of protein was adversely affected. Isolation of glycoprotein from developing brain by concanavalin A-affinity chromatography and subsequent resolution by gel electrophoresis revealed the selective compromise of particular glycoprotein species. Furthermore, both control and experimental progeny expressed unique glycoprotein species which either persisted over the period studied or were transient. Calcineurin, a regulator of neurite elongation, was compromised in young progeny, as were a number of lysosomal enzymes (beta-D-glucosidase and aryl sulphatase). In adult progeny, the content of cerebroside sulphate (a major myelin galactolipid) was reduced in midbrain and paleocortex, and brain region-specific compromise was observed for acetylcholine metabolic enzymes. These changes were associated with alterations in behavioural output. We conclude that the availability of maternal thyroxine to the fetus may be a critical determinant for normal brain development and function.

Pharmacologic basis for the use of doxazosin in the treatment of essential hypertension.

The drug treatment of mild hypertension has been shown to afford protection against fatal and nonfatal strokes, congestive heart failure, progression to more severe levels of hypertension, and all-cause mortality, but not against the complications of coronary artery disease. The lack of benefit against coronary artery disease may result from failure to reduce other risk factors or because the drugs employed increased coronary risk. It can be taken as axiomatic that effective preventive antihypertensive therapy is more likely with drugs with mechanisms and sites of action that are focused on the underlying pathophysiology than with drugs that lower blood pressure by means unrelated to the hypertensive process. Adrenergic predominance plays a major role in the initiation and maintenance of essential hypertension and, consequently, the alpha-adrenergic receptor inhibitors were among the first substances to receive serious consideration as antihypertensive agents. However, since these drugs are nonselective, feedback control of transmitter norepinephrine was lost and, consequently, the clinical expectations of the early alpha-adrenergic receptor inhibitors in the treatment of high blood pressure were not fulfilled. The discovery of selective postjunctional alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, which preserve feedback control of transmitter norepinephrine release, was the crucially important step in the development of specific drugs to combat the hyperactivity of adrenergic vasoconstrictor nerves in hypertension. These drugs have been shown to normalize hemodynamics in hypertensive patients. They lower blood pressure through a reduction in peripheral resistance at rest and during exercise, independent of changes in heart rate and blood pressure, with minimal reflex activation or tolerance development. Alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, represent an attractive choice for initial therapy in all grades of hypertension and are especially appropriate in hypertensive patients with congestive heart failure, asthma and chronic obstructive airways disease, renal impairment, diabetes mellitus, hyperlipidemia, benign prostatic hyperplasia, or gout, and in those involved in vigorous work, sports, or exercise. There are no known contraindications to these drugs, except in patients who are sensitive to quinazolines.