Cognitive dysfunction and quality of life during pollen season in children with seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis often gives rise to impaired quality of life and is believed to also affect cognitive function. We aimed to examine whether cognitive functions were impaired during grass pollen season in symptomatic allergic children and to relate the degree of impairment to quality of life and biomarkers related to stress and inflammation. METHODS: Forty-three grass pollen-allergic children (age 8-17 years) with non-satisfactory effect of medication (antihistamines and nasal steroids daily) during previous seasons were included. In addition, 26 matched non-allergic children were included as controls. Both groups performed cognitive tests (CANTAB) and completed Quality of Life questionnaires outside and during the pollen season. Blood samples were collected and analyzed for stress and inflammatory biomarkers. Pollen level was measured daily. RESULTS: Impaired cognitive function was found in spatial working memory, where the allergic group made more errors compared to the non-allergic group during pollen season, but not off-season. No significant differences could be seen between the allergic group and the controls in the other tests investigating visual memory or attention. Quality of health questionnaires revealed more symptoms and impaired quality of life in allergic compared to non-allergic children, and increased symptoms in allergic children were associated with longer reaction time for simple movement during pollen season. No differences in stress or inflammatory biomarkers could be found between the groups. CONCLUSION: Cognitive function was affected during pollen season in pollen-allergic children, and the more symptoms the allergic children had, the longer the reaction time in the cognitive tests.

What is the best material for molding casts in children?

BACKGROUND: Casts are used to treat clubfeet, developmental dysplasia of the hip (DDH), forearm fractures, and femur fractures. The ability of a cast to maintain a desired shape is termed moldability. Clinicians use plaster, fiberglass, and soft casts. To our knowledge the biomechanical molding characteristics of these 3 materials have never been reported. We hypothesized that moldability of plaster would be better than fiberglass and fiberglass would be better than soft cast. METHODS: We compared 12.7 cm wide casts of plaster, fiberglass, and soft cast. Casts were 5 layers thick, prepared in 40°C water, and placed over 2 layers of cotton padding on 5.1 cm and 15.2 cm diameter foam cylinders. A loading device simulated loads applied by clinicians when molding casts for 4 conditions: clubfoot (thumb-shaped 50 N load on 5.1 cm model), DDH (thumb-shaped 100 N load on 15.2 cm model), forearm fracture (palm-shaped 50 N load on 5.1 cm model), and femur fracture (palm-shaped 100 N load on 15.2 cm model). The loading device applied molding for 7 minutes. Five casts of each material were made for each model. Casts were removed, photographed, and the area of maximal deformation was compared with an unmolded cast. A large area of maximal deformation meant that the deformation was spread out over a large area, less precise molding. RESULTS: In the clubfoot model, plaster was more precise than fiberglass (P=0.002) and soft cast (P<0.0001). In the DDH model, plaster was more precise than fiberglass (P<0.0001) and soft cast (P<0.0001) and fiberglass was more precise than soft cast (P<0.0001).In the femur fracture model, plaster was more precise than fiberglass (P=0.001) and soft cast (P=0.001). CONCLUSIONS: The moldability of plaster is better than fiberglass and soft cast and fiberglass is better than soft cast. CLINICAL RELEVANCE: If precise molding is required, plaster has the best moldability. In cases not requiring precise molding, fiberglass and soft cast are lightweight, waterproof, and available in child-friendly colors.

Bronchodilator Responsiveness Measured by Spirometry and Impulse Oscillometry in Patients with Asthma After Short Acting Antimuscarinic and/or Beta-2-Agonists Inhalation.

Background: Bronchodilator responsiveness (BDR) in asthma involves both the central and peripheral airways but is primarily relieved with beta-2-agonists and evaluated by spirometry. To date, antimuscarinics can be added as a reliever medication in more severe asthma. We hypothesize that combining both short-acting beta-2 agonist (SABA) and short-acting muscarinic antagonist (SAMA) could also improve the responsiveness in mild-moderate asthma. Therefore, we aimed to compare the direct effects of inhaling SABA alone, SAMA alone or combining both SABA and SAMA on the central and peripheral airways in asthma. Methods: Twenty-three patients with mild-moderate BDR in asthma performed dynamic spirometry and impulse oscillometry before (baseline) and multiple timepoints within an hour after inhalation of SABA (salbutamol), SAMA (ipratropium bromide), or both SABA and SAMA at three different visits. Results: The use of SAMA alone did not show any improvement compared to the use of SABA alone. Inhalation of SABA+SAMA, however, averaged either similar or better BDR than SABA alone in FEV1, MMEF, FVC, R5, R20 and R5-R20. Inhaling SABA+SAMA reached a stable BDR in more patients within 0-10 minutes and also reached the FEV1 (Δ%)>12% faster (3.5 minutes) than inhaling SABA alone (5.1 minutes). Inhaling SABA+SAMA was significantly better than SAMA alone in FEV1 (p = 0.015), MMEF (p = 0.0059) and R20 (p = 0.0049). Using these three variables highlighted a subgroup (30%, including more males) of patients that were more responsive to inhaling SABA+SAMA than SABA alone. Conclusion: Overall, combining SAMA with SABA was faster and more consistent at increasing the lung function than SABA alone or SAMA alone, and the additive effect was best captured by incorporating peripheral-related variables. Therefore, SAMA should be considered as an add-on reliever for mild-moderate patients with BDR in asthma.

Comorbidities in hereditary angioedema-A population-based cohort study.

BACKGROUND: In hereditary angioedema (HAE), low levels (type 1) or defect in function (type 2) of the serine-protease inhibitor C1 Inhibitor protein results in activation of the classical pathway of the complement system as well as the contact system. Here, we investigated the risk of comorbidities in HAE. METHODS: Individuals with HAE (n = 239; identified through a physician made diagnosis) and a control cohort from the general population (n = 2383; matched for age, gender, and county of residence) were compared with the Swedish inpatient, cause of death, cancer, and prescription registers. Conditional logistic regression was used to analyze the data. RESULTS: Increased risk of cardiovascular disease (odds ratio [OR] 1.83; 95% confidence interval [CI] 1.32-2.54), including arterial (OR 6.74; 95% CI 1.89-24.06) and venous thromboembolic disease (OR 4.20; 95% CI 2.42-7.23) as well as hypertension (OR 1.64; 95% CI 1.12-2.39) was seen in HAE. There was also an increased number of individuals diagnosed with hyperlipidemia (OR 2.01; 95% CI 1.16-3.50) among HAE patients. Furthermore, the risk of autoimmune disease was increased (OR 1.65; 95% CI 1.15-2.35) being particularly pronounced for systemic lupus erythematosus (OR 71.87; 95% CI 8.80-586.7). The risk of having two or more autoimmune diseases was also higher among HAE patients (p = 0.017). In contrast, the risk of cancer was not increased. Data from the prescription register revealed higher prescription rates of drugs against hypertension, hypothyroidism, and hyperlipidemia among HAE patients. CONCLUSIONS: The results warrant for awareness and prevention of comorbid conditions, in particular, thromboembolic and autoimmune diseases in HAE. Future prophylactic interventions may modify these risks.

The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good?

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.

Intervertebral disc changes with angulation, compression and reduced mobility simulating altered mechanical environment in scoliosis.

PURPOSE: The intervertebral discs become wedged and narrowed in scoliosis, and this may result from altered biomechanical environment. The effects of four permutations of disc compression, angulation and reduced mobility were studied to identify possible causes of progressive disc deformity in scoliosis. The purpose of this study was to document morphological and biomechanical changes in four different models of altered mechanical environment in intervertebral discs of growing rats and in a sham and control groups. METHODS: External rings were attached by percutaneous pins transfixing adjacent caudal vertebrae of 5-week-old Sprague-Dawley rats. Four experimental Groups of animals underwent permutations of the imposed mechanical conditions (A) 15° disc angulation, (B) angulation with 0.1 MPa compression, (C) 0.1 MPa compression and (R) reduced mobility (N = 20 per group), and they were compared with a sham group (N = 12) and control group (N = 8) (total of 6 groups of animals). The altered mechanical conditions were applied for 5 weeks. Intervertebral disc space was measured from micro-CT images at weeks 1 and 5. Post euthanasia, lateral bending stiffness of experimental and within-animal control discs was measured in a mechanical testing jig and collagen crimp was measured from histological sections. RESULTS: After 5 weeks, micro-CT images showed disc space loss averaging 35, 53, 56 and 35% of the adjacent disc values in the four intervention groups. Lateral bending stiffness was 4.2 times that of within-animal controls in Group B and 2.3 times in Group R. The minimum stiffness occurred at an angle close to the in vivo value, indicating that angulated discs had adapted to the imposed deformity, this is also supported by measurements of collagen crimping at concave and convex sides of the disc annuli. CONCLUSION: Loss of disc space was present in all of the instrumented discs. Thus, reduced mobility, that was common to all interventions, may be a major source of the observed disc changes and may be a factor in disc deformity in scoliosis. Clinically, it is possible that rigid bracing for control of scoliosis progression may have secondary harmful effects by reducing spinal mobility.

Nonfusion treatment of adolescent idiopathic scoliosis by growth modulation and remodeling.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a common disorder in which the spine gradually develops a curvature that is first detected in patients between 11 and 17 years of age. The only accepted treatment methods are bracing and surgery. Whether brace treatment alters the natural history is being questioned, and patient compliance is low. Surgery usually includes a spinal fusion that creates a rigid spine and concentrates stresses at the ends. METHODS: This study focuses on correlating the laboratory results with clinical reports for treating patients with AIS. In the laboratory, scoliosis with vertebral wedging has been created by asymmetric mechanical loading and has been corrected by reversing the loading. In the clinic, bracing and derotational casting have been successful in some reports, but compliance has been a problem with bracing and derotational casts have mainly been used in young children. Operative treatment has been successful, but a nonfusion operation remains elusive. FINDINGS AND RESULTS: In the laboratory, axial loading of growth plates altered growth according to the Hueter-Volkmann law, which states that compression decreases and distraction increases growth. Asymmetric loading of the spine caused asymmetric growth resulting in scoliosis with vertebral wedging. Asymmetric loading of tail vertebrae created vertebral wedging according to Wolff's law, which states that the bone remodels over time in response to prevailing mechanical demands. In the clinic, studies have shown that bracing may work if patients wore the brace as prescribed. Derotational casting in young children has been shown to prevent progression and even correct the scoliosis in some patients. Convex vertebral stapling has been successful in mild curves, but the results in larger curves have been disappointing. Anterolateral tethering has been successful in mild curves in young patients, but there is limited experience with this technique in patients with large curves. CONCLUSIONS: A brace that applies the appropriate loading and is worn as prescribed may dramatically improve the results of brace treatment. A procedure using external fixation or adjustable anterolateral tethering may achieve a nonfusion correction of AIS. LEVEL OF EVIDENCE: Level II.

The role of remodeling and asymmetric growth in vertebral wedging.

BACKGROUND: Scoliosis with vertebral wedging is thought to be caused by asymmetric growth (Hueter-Volkmann law), but vertebral diaphyseal remodeling (Wolff's law) may also contribute to the deformity. We investigated whether vertebral wedging in scoliosis might involve both mechanisms. METHODS: An external fixator was used to impose a 30 degrees scoliosis and compression of 0.1 or 0.2 MPa to the tails of 10 5-week-old and 20 14-week-old Sprague-Dawley rats for 6 weeks. The rats were divided into three groups of 10 animals each: Group 1: 5-week-old animals with 0.1 MPa compression; Group 2: 14-week-old animals with 0.1 MPa compression; Group 3: 14-week-old animals with 0.2 MPa compression. Vertebral wedging and diaphyseal curvature were measured from micro CT scans performed at weeks 1, 3, and 6. Wedging due to asymmetrical growth and remodeling was calculated from a Calcein label administered at week 3 and a Xylenol label at week 6. RESULTS: The growth rate of the loaded vertebrae as a per cent of control vertebrae was 60% in Group 1, 40% in Group 2, and 30% in Group 3. The growth rate of control vertebrae in 14-week-old animals was 16% that of 5-week-old animals. The animals in all 3 groups developed a scoliosis with vertebral wedging that averaged 18.7 degrees in Group 1, 8.2 degrees in Group 2, and 10.1 degrees in Group 3. Asymmetric growth was much greater in Group 1 (5-week-old) animals. The ossified epiphyses became wedged and diaphyseal remodeling occurred in all groups. CONCLUSIONS: The major contribution to the vertebral wedging was asymmetric growth in the 5-week-old animals and diaphyseal remodeling in the 14-week-old animals. The results support the concept that if appropriate loads can be applied to human vertebrae through minimally invasive techniques, scoliosis and vertebral wedging can be corrected without a spinal fusion in both adolescents and adults.

Allergic rhinitis with hyper-responsiveness differ from asthma in degree of peripheral obstruction during metacholine challenge test.

Allergic rhinitis (AR) is a risk factor for developing clinical asthma. Moreover, AR is often associated with bronchial hyper-responsiveness (BHR). The aim of this study was to compare the degree of involvement of the peripheral airways during metacholine (MCh) challenge test in asthmatics and patients with AR with or without BHR by using the impulse oscillometry (IOS) technique. Fifty-three patients with seasonal AR were investigated with MCh challenge test and IOS. Thirteen healthy non-reactive subjects served as controls. MCh challenge test was performed, cut-off value FEV1PD20 2000 microg. Linear regression analysis was used to calculate a MCh/FEV1 slope (Slope-FEV1MCh), which was used as an index of BHR. IOS was performed, measuring respiratory resistance and reactance during the MCh challenge test. Twenty-six subjects had both AR and asthma symptoms, 27 patients reported AR only, without asthma symptoms, 17 (63%) manifested BHR by spirometric criteria. Patients with AR and symptoms of asthma manifested greater peripheral airway obstruction compared to those with AR only with BHR. Increased peripheral obstruction in the asthmatic group compared to patients with AR and BHR may explain previous findings that asthmatics perceive greater airway obstruction during MCh challenge tests.

Slipped capital femoral epiphysis.

Slipped capital femoral epiphysis (SCFE) is a common adolescent hip disorder. The etiology of SCFE includes biomechanical and biochemical factors. SCFEs are classified as stable and unstable and are more common in boys than girls and in certain racial groups; most children with SCFEs are obese. Bilateral SCFEs may have a simultaneous or sequential presentation. Imaging studies show a posterior slip of the epiphysis relative to the metaphysis, seen early on lateral radiographs. The most common and effective initial treatment for stable SCFEs is in situ central single-screw fixation; other options include epiphysiodesis, and osteotomy with or without surgical dislocation of the hip. Later reconstruction options, typically reserved for the child with functional abnormalities, include proximal femoral osteotomy, or surgical dislocation of the hip with removal of metaphyseal prominent bone to remove the source of femoroacetabular impingement. Unstable SCFEs have an increased risk of osteonecrosis; the role of reduction, methods of fixation, and decompression are controversial. The natural history of untreated SCFEs is associated with the risk of progression and later degenerative joint disease. Based on treatment methods of 30 to 40 years ago, in situ fixation provided the best long-term function with the lowest risk of complications and the most effective delay of degenerative arthritis regardless of the severity of the SCFE. Newer technologies and techniques are allowing the reevaluation of the role of either acute or later reconstructive osteotomy. It has not yet been determined if these improved techniques will result in better outcomes than in the past. Surgical dislocation of the hip with epiphyseal orientation is a considered treatment option for those technically adept at the procedure; however, the long-term outcome compared with in situ fixation is still unknown.

Alterations in the growth plate associated with growth modulation by sustained compression or distraction.

Sustained mechanical load is known to modulate endochondral growth in the immature skeleton, but it is not known what causes this mechanical sensitivity. This study aimed to quantify alterations in parameters of growth plate performance associated with mechanically altered growth rate. Vertebral and proximal tibial growth plates of immature rats and cattle, and rabbit (proximal tibia only) were subjected to different magnitudes of sustained loading, which altered growth rates by up to 53%. The numbers of proliferative chondrocytes, their rate of proliferation, and the amount of chondrocytic enlargement occurring in the hypertrophic zone were quantified. It was found that reduced growth rate with compression and increased growth rate with distraction were associated with corresponding changes in the number of proliferative chondrocytes per unit width of growth plate, and in the final (maximum) chondrocytic height in the hypertrophic zone (overall correlation coefficients 0.38 and 0.56 respectively). According to multiple linear regression coefficients for these two variables (0.72 and 1.39 respectively), chondrocytic enlargement made a greater contribution to altered growth rates.

Peripheral nitric oxide is increased in rhinitic patients with asthma compared to bronchial hyperresponsiveness.

Allergic rhinitis is a predisposing factor for developing clinical asthma. Moreover, allergic rhinitis is often associated with bronchial hyperresponsiveness (BHR). We hypothesise that patients with asthma have more small airway involvement than those with allergic rhinitis and BHR alone. The aim of this study was to assess peripheral and proximal NO concentration in rhinitic subjects, and to correlate the peripheral NO concentration to the peripheral obstruction in response to methacholine. Patients with allergic rhinitis with or without BHR, or clinical asthma were investigated in and out of the allergy season. Healthy subjects served as controls. Fractional exhaled NO was performed, and peripheral NO concentration and proximal flux of NO was calculated. Methacholine test was performed including impulse oscillometry. Rhinitic patients with asthma demonstrate an increase in both proximal and peripheral NO compared to those with rhinitis alone or those with BHR. There is a trend of increased peripheral NO from patients with rhinitis only, rhinitis and BHR, to rhinitis with asthma. The increase in peripheral NO correlated with an increased peripheral obstruction in response to methacholine. Patients with seasonal allergic rhinitis demonstrated a decrease in both proximal and peripheral NO in the off-season. The results support our hypothesis that rhinitic patients with asthma have more peripheral lung inflammation and small airway involvement compared to rhinitic patients with BHR alone.

Endochondral growth in growth plates of three species at two anatomical locations modulated by mechanical compression and tension.

Sustained mechanical loading alters longitudinal growth of bones, and this growth sensitivity to load has been implicated in progression of skeletal deformities during growth. The objective of this study was to quantify the relationship between altered growth and different magnitudes of sustained altered stress in a diverse set of nonhuman growth plates. The sensitivity of endochondral growth to differing magnitudes of sustained compression or distraction stress was measured in growth plates of three species of immature animals (rats, rabbits, calves) at two anatomical locations (caudal vertebra and proximal tibia) with two different ages of rats and rabbits. An external loading apparatus was applied for 8 days, and growth was measured as the distance between fluorescent markers administered 24 and 48 h prior to euthanasia. An apparently linear relationship between stress and percentage growth modulation (percent difference between loaded and control growth plates) was found, with distraction accelerating growth and compression slowing growth. The growth-rate sensitivity to stress was between 9.2 and 23.9% per 0.1 MPa for different growth plates and averaged 17.1% per 0.1 MPa. The growth-rate sensitivity to stress differed between vertebrae and the proximal tibia (15 and 18.6% per 0.1 MPa, respectively). The range of control growth rates of different growth plates was large (30 microns/day for rat vertebrae to 366 microns/day for rabbit proximal tibia). The relatively small differences in growth-rate sensitivity to stress for a diverse set of growth plates suggest that these results might be generalized to other growth plates, including human. These data may be applicable to planning the management of progressive deformities in patients having residual growth.

Demographic predictors of severity of stable slipped capital femoral epiphyses.

BACKGROUND: The outcome of stable slipped capital femoral epiphysis is directly related to the severity of the slip. If it is assumed that the slip will be less severe if it is diagnosed early, then early diagnosis should improve the prognosis. It was our purpose to determine demographic predictors of the severity of a slipped capital femoral epiphysis. METHODS: A retrospective study of 243 children with a total of 328 stable slipped capital femoral epiphyses was performed. Gender, race, age, and symptom duration were noted. Slip severity was classified as mild (<30 degrees ), moderate (30 degrees to 50 degrees ), or severe (>50 degrees ). Statistical analyses included bivariate, multivariate, linear correlation, and logistic regression techniques. RESULTS: There were 159 boys and eighty-four girls; 149 children had unilateral and ninety-four had bilateral slipped capital femoral epiphysis. Of the bilateral slips, forty-two were simultaneous and fifty-two were sequential. The mean age (and standard deviation) was 12.6 +/- 1.8 years, the mean duration of the symptoms was 5.2 +/- 7.4 months, and the mean slip angle was 29 degrees +/- 20 degrees . There were 199 mild, sixty-eight moderate, and forty-five severe slips. The mean duration of symptoms was 3.5 +/- 5.0 months for the mild slips, 7.7 +/- 9.0 months for the moderate slips, and 8.8 +/- 10.6 months for the severe slips (p < 0.0001). Older children had more severe slips: the average age was 12.3 +/- 1.8 years for the children with a mild slip, 13.0 +/- 1.6 years for those with a moderate slip, and 13.8 +/- 1.8 years for those with a severe slip (p < 0.0001). Multivariate analyses demonstrated that, among the factors studied, only the age of the patient and the duration of the symptoms were associated with the slip severity. Symptom duration and patient age were used as predictors of slip severity in a logistic regression analysis, with > or =30 degrees and <30 degrees used as the categories for slip severity, older than 12.5 years old compared with 12.5 years old or younger used as the categories for age, and more than 2.0 months compared with 2.0 months or less used as the categories for symptom duration. This model predicted the probability of a slip with confidence (p < 0.0001). The odds ratios (with 95% confidence intervals) for age and symptom duration were 2.0 (1.15 to 3.53) and 4.1 (2.34 to 7.12), respectively. Thus, a child with a stable slipped capital femoral epiphysis is 2.0 times more likely to have a moderate or severe slip if he or she is older than 12.5 years of age at the time of the diagnosis and 4.1 times more likely to have a moderate or severe slip if the duration of symptoms was longer than two months. CONCLUSIONS: The only two known significant predictors of the severity of a slipped capital femoral epiphysis are age at diagnosis and symptom duration. For any individual child, slip severity and symptom duration are unique; in a large population, there is a general correlation between slip severity and increases in patient age and increases in the duration of symptoms.

Slipped capital femoral epiphysis: current concepts.

Slipped capital femoral epiphysis is a common hip disorder in adolescents, with an incidence of 0.2 (Japan) to 10 (United States) per 100,000. The etiology is unknown, but biomechanical and biochemical factors play an important role. Symptoms at presentation include pain in the groin, thigh, or knee. Ambulatory patients also may present with a limp. Nonambulatory patients present with excruciating pain. The slipped capital femoral epiphysis is classified as stable when the patient can walk and unstable when the patient cannot walk, even with the aid of crutches. Because the epiphysis slips posteriorly, it is best seen on lateral radiographs. The treatment of choice for stable slipped capital femoral epiphysis is single-screw fixation in situ. This method has a high probability of long-term success, with minimal risk of complications. In the patient with unstable slipped capital femoral epiphysis, urgent hip joint aspiration followed by closed reduction and single- or double-screw fixation provides the best environment for a satisfactory result, while minimizing the risk of complications.

Intervertebral disc adaptation to wedging deformation.

UNLABELLED: Although scoliosis includes wedge deformities of both vertebrae and discs, little is known about the causes of the discal changes, and whether they result from mechanical influences on growth and/or remodelling. METHODS AND MATERIALS: An external apparatus attached to transvertebral pins applied compression and 15 degrees of angulation to each of two adjacent young rat caudal intervertebral discs for 5 weeks (four animals), or for 10 weeks (four animals). Each week, micro-CT scanning documented the in vivo discal wedging. After euthanasia, tail segments (three vertebrae and the 2 angulated discs) were excised and their flexibility was measured over a range of lateral bending. The angle of maximum flexibility was recorded. Then discs were fixed in situ (with the external apparatus in place) and sectioned for polarized light microscopy. RESULTS: The disc-wedging deformity averaged 15 degrees initially, it averaged 20 degrees after 5 weeks, and then reduced to 10 degrees (in 10 week animals). The lateral bending flexibility showed a distinct maximum at an average of 1.1 degrees from the in vivo position in the 5-week animals, indicating structural remodeling of the discs almost to the deformed geometry. The 10-week animals had maximum flexibility at 1.4 degrees from the in vivo position (no significant difference between 5 and 10-week animals.) Collagen crimp angles [Cassidy et al., Conn Tiss Res 1989, 23:75-88] were not significantly different between convex and concave sides, again suggesting that remodeling had occurred. CONCLUSIONS: In a mechanically induced scoliosis deformity in skeletally immature rats, the intervertebral discs underwent remodeling within 5 weeks. This indicates that this animal model is suitable for studying adaptive wedging changes in human scoliosis.

Modulation of vertebral and tibial growth by compression loading: diurnal versus full-time loading.

PURPOSE: This study was designed to determine whether the amount of endochondral growth response to mechanical compression and the underlying growth mechanism differed with night-time or day-time loading, relative to full-time loading. METHODS: Mechanical compression (nominally 0.1 MPa stress) was applied across tibial and tail vertebral growth plates of growing Sprague-Dawley rats. Four groups of animals (five per group) were used: 24/24 h (full-time loading); 12/24 h (day-loading); 12/24 h (night-loading); and 0/24 h (sham instrumented). Contralateral tibiae and adjacent vertebrae served as within-animal controls. The animals were euthanized after eight days. Growth plates were processed for quantitative histology to measure 24-h growth, total and BrdU-positive proliferative zone chondrocyte counts, and hypertrophic chondrocytic enlargement in the growth direction. RESULTS: Growth as a percentage of within-animal control averaged 82% (full-time); 93% (day-loading); 90% (night-loading); 100% (sham) for vertebrae. For proximal tibiae it averaged 70% (full-time); 84% (day-loading); 86% (night-loading); 89% (sham). Reduced amount of hypertrophic chondrocytic enlargement explained about half of this effect in full-time loaded growth plates, but was not significantly altered in half-time loaded growth plates. The remaining variation in growth was apparently explained by reduced total numbers of proliferative zone chondrocytes. These findings indicate that sustained compression loading suppressed growth more than intermittent loading at both anatomical locations.

Percutaneous epiphysiodesis using transphyseal screws for limb-length discrepancies: high variability among growth predictor models.

PURPOSE: Percutaneous epiphysiodesis using transphyseal screws (PETS) was developed as a minimally invasive outpatient procedure to address limb-length discrepancy (LLD) that allowed immediate postoperative weight bearing and was potentially reversible by removing the screws. The aims of our study were to report our results using PETS for LLD and evaluate the accuracy of three growth predictor models. METHODS: Sixteen patients with an average age of 14 years were treated for LLD using PETS. Thirteen patients had screws inserted in a parallel fashion and 3 had crossed screws. We compared the predicted LLD at skeletal maturity using the three growth predictor methods with the actual LLD at skeletal maturity and preoperative LLD with the final LLD at skeletal maturity. RESULTS: The mean LLD at skeletal maturity between the predicted and final measurements was 0.2 cm using the Green-Anderson method, 1.4 cm using the Moseley method, and -0.1 cm using the Paley method. The mean preoperative LLD of 3.1 cm was corrected to 1.7 cm at skeletal maturity (p < 0.001). Six patients complained of pain over the screw heads; however, no patient developed an infection or angular deformity. CONCLUSIONS: The three growth predictor methods predicted the final LLD within an average of 1.4 cm, but there was high variability. Although PETS improved the LLD by a mean of 1.4 cm, we believe the results would have been better if PETS was performed at an earlier skeletal age.

Airway resistance and reactance are affected in systemic sclerosis.

BACKGROUND: Interstitial lung disease often occurs as an early complication of systemic sclerosis (SSc). The aim was to investigate whether impulse oscillometry (IOS) could be used to evaluate lung impairment in SSc. METHODS: Seventy-eight SSc patients, of which 65 had limited cutaneous SSc (lcSSc) and 13 had diffuse cutaneous SSc (dcSSc), were subjected to high-resolution computed tomography (HRCT) and pulmonary function tests (spirometry, IOS, and single breath CO diffusion capacity test). Twenty-six healthy individuals served as controls. RESULTS: Patients with lcSSc had higher levels of peripheral airway resistance, that is, R5-R20 (difference between resistance at 5 Hz and resistance at 20 Hz) showed a median (and interquartile range) of 0.05 (0.02-0.09) in lcSSc, 0.01 (0.00-0.04) in dcSSc and 0.04 (0.01-0.06) in healthy controls. They also had higher levels of reactance: reactance area was 0.26 (0.15-0.56) in lcSSc, 0.20 (0.11-0.29) in dcSSc and 0.18 (0.08-0.30) in healthy controls, and resonant frequency was 10.9 (8.8-14.8) in lcSSc, 9.0 (8.3-11.6) in dcSSc and 9.1 (8.0-13.1) in healthy controls. Airway reactance correlated to fibrotic findings on HRCT, such as ground glass opacities and reticulations. DISCUSSION: This implies that IOS parameters to some extent are related to fibrosis in patients with SSc.

Enlargement of growth plate chondrocytes modulated by sustained mechanical loading.

BACKGROUND: Mechanical compression and distraction forces are known to modulate growth in vertebral growth plates, and they have been implicated in the progression of scoliosis. This study was performed to test the hypothesis that growth differences produced by sustained compression or distraction loading of vertebrae are associated with alterations in the amount of increase in the height of growth plate chondrocytes in the growth direction. METHODS: Compression or distraction force of nominally 60% of body weight was maintained for four weeks on a caudad vertebra of growing rats by an external apparatus attached, by means of transcutaneous pins, to the two vertebrae cephalad and caudad to it. Growth of the loaded and control vertebrae was measured radiographically. After four weeks, the animals were killed and histological sections of the loaded and control vertebrae were prepared to measure the height of the hypertrophic zone (average separation between zonal boundaries), the mean height of hypertrophic chondrocytes, and the amount of increase in cell height in the growth direction. RESULTS: Over the four weeks of the experiment, the growth rates of the compressed and distracted vertebrae averaged 52% and 113% of the control rates, respectively. The reduction in the growth rate of the compressed vertebrae was significant (p = 0.002). In the compressed vertebrae, the height of the hypertrophic zone, the mean chondrocyte height, and the amount of increase in cell height averaged 87%, 85%, and 78% of the control values, respectively, and all were significantly less than the corresponding control values. In the distracted vertebrae, these measurements did not differ significantly from the control values. The height of the hypertrophic zone and the mean chondrocyte height correlated with the growth rate (r (2) = 0.29 [p = 0.03] and r (2) = 0.23 [p = 0.06], respectively), when each variable was expressed as a proportion of the control value. The percentage changes in the measurements of the chondrocytic dimensions relative to the control values were smaller than the percentage changes in the growth rates, a finding that suggested that the rate of chondrocytic proliferation was also modulated by the mechanical loading. CONCLUSIONS: Mechanical loading of tail vertebrae in rats modulated their growth rate, which correlated with changes in the height of hypertrophic chondrocytes. The effects of compression were greater than those of distraction. CLINICAL RELEVANCE: Information about the growth rate and chondrocytic response to mechanical loads in rat vertebrae undergoing mechanically modulated growth will be helpful in determining how human vertebral growth might respond to altered loading states during progression or treatment of scoliosis and other growth-related angular skeletal deformities.