Performance, intestinal permeability, and gene expression of selected tight junction proteins in broiler chickens fed reduced protein diets supplemented with arginine, glutamine, and glycine subjected to a leaky gut model.

Changing dietary protein and amino acids may impact intestinal barrier function. Experiments were conducted in broiler chickens to evaluate supplementation of L-glutamine, glycine, and L-arginine in a reduced protein (RP) diet. Experiment 1 examined the growth performance of broilers fed 5 dietary treatments: 1) a standard diet; 2) an RP diet (193.9 g/kg CP in grower and 176.9 g/kg CP in finisher); 3) RP diet supplemented with 10 g/kg L-Gln; 4) RP diet supplemented with 10 g/kg Gly; 5) RP diet supplemented with 5 g/kg L-Arg. Each experimental diet was replicated 6 times with 10 birds per replicate. In a subset of 96 birds, experiment 2 tested the 4 RP diets with and without dexamethasone (DEX) to induce leaky gut. Each diet was replicated 24 times. Fluorescein isothiocyanate dextran (FITC-d) was used to test intestinal permeability (IP). Gene expression of selected tight junction proteins in ileal and jejunal tissues was assayed by quantitative PCR. From day 7 to 35, the RP diet increased feed intake (FI) (P < 0.05) and body weight gain (BWG) compared with the standard diet while Gln reduced FI and BWG (P < 0.05) compared with RP. Gly had no effect on BWG or FCR. Supplementation of Arg improved FCR from day 21 to 35 and day 7 to 35. In experiment 2, Arg tended to lower FITC-d (P = 0.086). DEX increased passage of FITC-d into the serum (P < 0.001). The villi surface area was increased in birds fed higher Arg (P < 0.05). DEX and diet interacted (P < 0.01) for jejunal claudin-3 mRNA level where DEX upregulated claudin-3 for all diets except the Arg diet. In summary, with a moderate reduction of protein, satisfactory performance can be obtained. Although Gln and Gly had no demonstrable positive effect on IP and performance of broilers, increasing the dietary Arg by approximately 140% improved FCR and showed indications of improved intestinal barrier function of birds fed an RP diet under a stress model.

Reduced protein diet and amino acid concentration alter intestinal barrier function and performance of broiler chickens with or without synthetic glucocorticoid.

Little is known about the effect of low-protein (LP) diets on intestinal barrier function and permeability. In the first part of this study, starting on day 9 of age, the growth performance of the birds fed 3 experimental diets in each phase of feeding (G/F: grower/finisher) was investigated. Three experimental diets were as follows: LP (170/150 g/kg CP) fortified with essential amino acids (EAA), standard protein (SP), (202/190 g/kg), and high protein (HP) (220/210 g/kg). LP and SP diets contained a similar level of EAA concentration, while the HP diet contained 10% above the Ross 308 specifications. Each diet was replicated 6 times (10 male birds per replicate). The second part investigated intestinal permeability (IP) and function on additional 72 birds. On days 14, 16, and 20, a total of 36 birds (12 birds per diet) were injected with dexamethasone (DEX) to induce leaky gut. Birds fed LP diets had lower body weight gain (BWG) and higher feed conversion ratio (FCR) compared with SP and HP diets in both grower and finisher phases of feeding. For the challenge part, DEX increased the FCR independent of diets. Diet and DEX interacted for BWG, whereby the effect of diets was only evident in sham-injected birds. Birds fed LP had a higher fluorescein isothiocyanate dextran (FITC-d) concentration indicating a more permeable intestine compared to HP, but similar to SP. DEX increased FITC-d concentration in all dietary treatments. Birds fed LP had less ileal zonula occludens-2 (ZO-2) expression in comparison with SP, but not HP. DEX increased the expression of Claudin3 and ZO-2 and reduced Claudin1 (P < 0.05) and junctional adhesion molecule 2 in the ileum. Expression of ileal Na+-dependent glucose transporter 1 (SGLT1) was upregulated in LP fed group. It is concluded that compared with SP, IP can be maintained in LP by supplementing EAA. However, when compared with HP, feeding birds with LP may lead to a higher IP. DEX had a profound independent effect on intestinal barrier function.

Gene expression and morphological changes in the intestinal mucosa associated with increased permeability induced by short-term fasting in chickens.

Short-term fasting for 4.5 and 9 hr has been demonstrated to increase intestinal permeability (IP) in chickens. This study aimed to investigate the effects of 0, 4.5, 9 and 19.5 hr fasting on intestinal gene expression and villus-crypt architecture of enterocytes in jejunal and ileal samples. On day 38, Ross-308 male birds were fasted according to their group and then euthanised. Two separate intestinal sections (each 2 cm long, jejunum and ileum) were collected. One section was utilised for villus height and crypt depth measurements. The second section was snap-frozen in liquid nitrogen for quantitative polymerase chain reaction (qPCR) analysis of tight junction proteins (TJP) including claudin-1, claudin-3, occludin, zonula occludens (ZO-1, ZO-2), junctional adhesion molecules (JAM) and E-cadherin. Additionally genes involved in enterocyte protection including glucagon-like peptide (GLP-2), heat-shock protein (HSP-70), intestinal alkaline phosphatase (IAP), mammalian target of rapamycin (mTOR), toll-like receptors (TLR-4), mucin (MUC-2), cluster differentiation (CD-36) and fatty acid-binding protein (FABP-6) were also analysed. Normally distributed data were analysed using one-way analysis of variance ANOVA. Other data were analysed by non-parametric one-way ANOVA. Villus height and crypt depth were increased (p < .05) only in the ileum after fasting for 4.5 and 9 hr compared with non-fasting group. mRNA expression of claudin-3 was significantly reduced in the ileum of birds fasted for 9 and 19.5 hr, suggesting a role in IP modulation. However, all other TJP genes examined were not statistically different from control. Nevertheless, ileal FABP-6 of all fasted groups was significantly reduced, which could possibly be due to reduced bile acid production during fasting.

A post-transcriptional mechanism regulates calpastatin expression in bovine skeletal muscle.

The objective of this study was to investigate whether single nucleotide polymorphisms (SNP) in the calpain 1 (CAPN1), calpain 3 (CAPN3) and calpastatin (CAST) genes, which have been shown to be associated with shear force and tenderness differences in the skeletal muscle of cattle, contribute to phenotypic variation in muscle tenderness by modulating the transcriptional activity of their respective gene. The mRNA expression of the calpain and CAST genes was assessed in the longissimus lumborum muscle (LLM) of cattle from two herds located in distinct production zones on the east (New South Wales, NSW) and west (Western Australia, WA) of Australia. The cattle in the herds were mainly Brahman cattle (Bos indicus) with smaller populations of Angus cattle (Bos taurus). There were 191 steers in the WA herd and 107 steers and 106 heifers in the NSW herd. These herds were established by choosing cattle from the diverse population which had different single nucleotide polymorphism (SNP) genotypes at the CAPN1, CAPN3 and CAST loci. Using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the transcriptional activities of the CAPN1 and the CAST genes, but not the CAPN3 gene, were found to differ between favorable, positively associated with tenderness, and unfavorable, negatively associated with tenderness, allelic variants of these genes. These findings suggest that the muscle shear force and consumer taste panel differences in tenderness explained by the CAPN1 and CAST gene markers are a consequence of alterations in their mRNA levels, which may ultimately influence the protein activity of these genes, thereby altering the rate and(or) the extent of postmortem proteolysis in skeletal muscle. Of particular importance were the significantly lower type II and type III CAST 5' splice variant mRNA levels that were detected in the LLM muscle of Brahman and Angus cattle with 2 favourable alleles of the CAST:c.2832A > G polymorphism. Moreover, a reduction in the abundance of an alternative polyadenylated variant of the CAST transcript, terminated at the proximal polyadenylation site, provides a unique insight into the potential involvement of a post-transcriptional regulatory mechanism which may influence protein expression levels in bovine skeletal muscle.

Quantitative analyses of genes associated with mucin synthesis of broiler chickens with induced necrotic enteritis.

Clostridial infection of the intestine can result in necrotic enteritis (NE), compromising production and health of poultry. Mucins play a major role in protecting the intestinal epithelium from infection. The relative roles of different mucins in gut pathology following bacterial challenge are unclear. This study was designed to quantify the expression of mucin and mucin-related genes, using intestinal samples from an NE challenge trial where birds were fed diets with or without in-feed antimicrobials. A method for quantifying mucin gene expression was established using a suite of reference genes to normalize expression data. This method was then used to quantify the expression of 11 candidate genes involved in mucin, inflammatory cytokine, or growth factor biosynthesis (IL-18, KGF, TLR4, TFF2, TNF-α, MUC2, MUC4, MUC5ac, MUC5b, MUC13, and MUC16). The only genes that were differentially expressed in the intestine among treatment groups were MUC2, MUC13, and MUC5ac. Expression of MUC2 and MUC13 was depressed by co-challenge with Eimeria spp. and Clostridium perfringens. Antimicrobial treatment prevented an NE-induced decrease in MUC2 expression but did not affect MUC13. The expression of MUC5ac was elevated in birds challenged with Eimeria spp./C. perfringens compared with unchallenged controls and antimicrobial treatment. Changes to MUC gene expression in challenged birds is most likely a consequence of severe necrosis of the jejunal mucosa.

Effect of variable long-term maternal feed allowance on the development of the ovine placenta and fetus.

Maternal feed allowance during pregnancy can affect the development of the ovine placenta and fetus. The impact of variations in feed allowance prior to as well as throughout pregnancy has received less attention. Ewes were offered 0.6 (R), 1.2 (C) or 1.8 (AL) maintenance requirements from 89 days before conception until day 133 of pregnancy. Ewes were euthanised on days 50, 92 and 133 of pregnancy. Ewe live weight and body condition score, maternal and fetal metabolic and hormonal profiles, fetal body dimensions and organ weights, and the number, weight and morphology of placentomes were measured. Maternal live weight and condition score were lower in R compared to AL ewes at all stages of pregnancy (P<0.05). Plasma glucose and albumin concentrations of R ewes were significantly reduced (P<0.05) at mid and late gestation, respectively. Placental components were generally unresponsive to long term variations in maternal feed allowance. However, placental weight was significantly (P<0.05) correlated with fetal weight at days 50 (r=0.59) and 133 (r=0.69) of gestation. By late gestation growth-retarded singleton fetuses from R ewes were 19% lighter (P<0.05), with reduced abdominal (9%) and thoracic (10%) girths (P<0.05) but of similar crown-rump length compared with fetuses from AL ewes. These differences were associated with significantly reduced IGF-I concentrations in fetal plasma (P<0.05). In conclusion, maternal, placental and fetal adaptations to long established planes of variable maternal feed allowance were able to maintain fetal growth during early and mid-pregnancy while fetal growth restriction, associated with reduced fetal IGF-I levels, became apparent in late pregnancy.

Characterization of transport systems for cysteine, lysine, alanine, and leucine in wool follicles of sheep.

Aspects of the uptake of the AA Cys, Leu, Ala, and Lys into wool follicles were investigated using short-term culture of thin strips of sheep skin. Following verification of the reliability of the model system, the sites of uptake of the radiolabeled AA were shown to differ and to be consistent with their different roles in fiber production. Cysteine appeared in the zone of keratinization immediately distal to the follicle bulb. Lysine was incorporated into the germinative cells of the follicle bulb and the cells of the inner root sheath. Leucine and Ala were incorporated into the follicle bulb, inner root sheath, and keratinizing fiber. The incorporation of all AA into the dermal papilla was low. The relative rates of uptake of the AA into the wool follicle were as follows: L-Cys (100), L-Leu (5.5), L-Ala (2.5), and L-Lys (0.8). Uptake of Cys was saturable and followed Michaelis-Menten kinetics, suggesting a carrier-mediated system, with little or no diffusion. The majority (70%) of Cys uptake into follicles was via a Na-independent system that was not inhibited by alpha-(methyl-amino)isobutyric acid or 2-amino-2-norbonanecarboxylic acid and therefore is not via the normal Cys transport systems A, ASC, or L. Uptake of Cys appeared to be via a low-affinity, high-capacity transport system, which may be unique to the fiber-producing follicle. The majority of Ala transport had characteristics consistent with the functioning of system A (Na-dependent, inhibited by alpha-(methylamino)isobutyric acid, and low substrate affinity). Leucine uptake was inhibited by 2-amino-2-norbonanecarboxylic acid but was Na-dependent, suggesting that a variant of system L operates in the follicle to transport Leu. Lysine uptake was consistent with the operation of the usual Lys transporter system y+. Diets designed to maximize wool growth should provide AA profiles reflecting the relative rates of uptake demonstrated in this study. Investigations of possible polymorphisms in genes encoding AA transport proteins in follicles may reveal a source of genetic differences in wool growth potential among genotypes.

Correction of severe crouch gait in patients with spastic diplegia with use of multilevel orthopaedic surgery.

BACKGROUND: Severe crouch gait in patients with spastic diplegia causes excessive loading of the patellofemoral joint and may result in anterior knee pain, gait deterioration, and progressive loss of function. Multilevel orthopaedic surgery has been used to correct severe crouch gait, but no cohort studies or long-term results have been reported, to our knowledge. METHODS: In order to be eligible for the present retrospective cohort study, a patient had to have a severe crouch gait, as defined by sagittal plane kinematic data, that had been treated with multilevel orthopaedic surgery as well as a complete clinical, radiographic, and instrumented gait analysis assessment. The surgical intervention consisted of lengthening of contracted muscle-tendon units and correction of osseous deformities, followed by the use of ground-reaction ankle-foot orthoses until stable biomechanical realignment of the lower limbs during gait was achieved. Outcome at one and five years after surgery was determined with use of selected sagittal plane kinematic and kinetic parameters and valid and reliable scales of functional mobility. Knee pain was recorded with use of a Likert scale, and all patients had radiographic examination of the knees. RESULTS: Ten subjects with severe crouch gait and a mean age of 12.0 years at the time of surgery were studied. After surgery, the patients walked in a more extended posture, with increased extension at the hip and knee and reduced dorsiflexion at the ankle. Pelvic tilt increased, and normalized walking speed was unaltered. Knee pain was diminished, and patellar fractures and avulsion injuries healed. Improvements in functional mobility were found, and, at the time of the five-year follow-up, fewer patients required the use of wheelchairs or crutches in the community than had been the case prior to intervention. CONCLUSIONS: Multilevel orthopaedic surgery for older children and adolescents with severe crouch gait is effective for relieving stress on the knee extensor mechanism, reducing knee pain, and improving function and independence.

Gene expression profiling of bovine skeletal muscle in response to and during recovery from chronic and severe undernutrition.

Gene expression profiles of LM from beef cattle that underwent significant postweaning undernutrition were studied using complementary DNA (cDNA) microarrays. After 114 d of undernutrition, the RNA from LM showed 2- to 6-fold less expression of many genes from the classes of muscle structural proteins, muscle metabolic enzymes, and extracellular matrix compared with animals on a rapid growth diet. The expression levels of these genes had mostly returned to pretreatment levels after 84 d of realimentation. The gene expression changes associated with undernutrition and BW loss showed an emphasis on downregulation of gene expression specific to fast-twitch fibers, typical of starving mammals, with a preferential atrophy of glycolytic fast-twitch fibers. We also identified a small group of genes that showed 2- to 5-fold elevated expression in LM after 114 d of undernutrition. Putative roles for these genes in atrophying skeletal muscle are regulation of myogenic differentiation (CSRP3), maintenance of mesenchymal stem cells (CYR61), modulation of membrane function (TM4SF2), prevention of oxidative damage (SESN1), and regulation of muscle protein degradation (SQSTM1). A significant increase in stearoyl-CoA desaturase (SCD) gene expression was observed in atrophying muscle, suggesting either that increased fatty acid synthesis is part of the tissue response to caloric restriction, or that SCD plays another role in energy metabolism in the mixed cellular environment of bovine skeletal muscle.

Lengthening and transfer of hamstrings for a flexion deformity of the knee in children with bilateral cerebral palsy: technique and preliminary results.

Between July 2000 and April 2004, 19 patients with bilateral spastic cerebral palsy who required an assistive device to walk had combined lengthening-transfer of the medial hamstrings as part of multilevel surgery. A standardised physical examination, measurement of the Functional Mobility Scale score and video or instrumented gait analysis were performed pre- and post-operatively. Static parameters (popliteal angle, flexion deformity of the knee) and sagittal knee kinematic parameters (knee flexion at initial contact, minimum knee flexion during stance, mean knee flexion during stance) were recorded. The mean length of follow-up was 25 months (14 to 45). Statistically significant improvements in static and dynamic outcome parameters were found, corresponding to improvements in gait and functional mobility as determined by the Functional Mobility Scale. Mild hyperextension of the knee during gait developed in two patients and was controlled by adjustment of their ankle-foot orthosis. Residual flexion deformity > 10 degrees occurred in both knees of one patient and was treated by anterior distal femoral physeal stapling. Two children also showed an improvement of one level in the Gross Motor Function Classification System.

Myogenesis in sheep is altered by maternal feed intake during the peri-conception period.

The effect of varying short-term maternal feed intake during the peri-conception period on the development of ovine fetal muscle at mid-gestation was investigated. Superovulated donor Merino ewes (n = 24) were fed a roughage/grain pelleted diet (10.1 MJME/kg dry matter) at either 1.5x maintenance (H; high) or 0.5x maintenance (L; low) from 18 days before until 6 days after ovulation. Embryos were transferred to recipient ewes (n = 60) on day 6. Singleton fetuses were collected on day 75 of gestation and placental weights, fetal body dimensions and fetal organ and muscle weights recorded. The number, type and size of muscle fibres and the dry matter, RNA, DNA and protein content in the semitendinosus muscle were determined. Maternal feed intake did not influence body dimensions, organ development or muscle weights in the fetus. However, L feed intake decreased total muscle fibre number in the fetus by approximately 20% (P = 0.06) compared to H feed intake. This resulted from a reduced secondary to primary fibre ratio (P < 0.05) and indicated that secondary fibre formation occurred at a reduced rate in L fetuses. In addition, protein:DNA ratio tended to be lower in muscles of L fetuses (P < 0.1). It is concluded that restricting feed intake over the peri-conception period reduces or delays myogenesis in fetal sheep. The potential mechanisms by which nutritional availability during this period may influence subsequent myogenic development are discussed.

Supramalleolar derotation osteotomy of the tibia, with T plate fixation. Technique and results in patients with neuromuscular disease.

Torsional deformities of the tibia are common in children, but in the majority both the torsion and the associated disturbance of gait resolve without intervention. There are, however, a significant number of children and adults with neuromuscular disease who present with pathological tibial torsion, which may require surgical correction. We conducted a prospective study in two centres, to investigate the outcome of supramalleolar derotation osteotomy of the tibia, using internal fixation with the AO-ASIF T plate. A range of outcome variables was collected, prospectively, for 57 patients (91 osteotomies), including thigh foot angle, foot progression angle, post-operative complications and serial radiographs. Correction of thigh foot angle and foot progression angle was satisfactory in all patients. Three major complications were recorded; one aseptic nonunion, one fracture through the osteotomy site after removal of the plate and one distal tibial growth arrest. We found that supramalleolar derotation osteotomy of the tibia, with AO-ASIF T plate fixation is an effective method for the correction of torsional deformities of the tibia and the associated disturbances of gait in children and adults with neuromuscular disease, with a 5.3% risk of major complications.

Walking speed in children and young adults with neuromuscular disease: comparison between two assessment methods.

Self-selected walking speed is being increasingly used as a primary outcome measure in the management of neuromuscular disease. It would be useful if the speed recorded in the gait laboratory represented the child's walking speed in the community. This study investigated the difference in self-selected walking speeds between a 10-meter walk, as measured during instrumented gait analysis, and a 10-minute walk. The authors found that self-selected walking speed during the 10-minute walk was slower than the self-selected walking speed recorded during the 10-meter walk. The former may be more representative of walking speed in the community setting. Walking speed measured during walks of 10 minutes or more should become an integral part of gait laboratory evaluation.

Femoral derotation osteotomy in spastic diplegia. Proximal or distal?

We describe the results of a prospective study of 28 children with spastic diplegia and in-toed gait, who had bilateral femoral derotation osteotomies undertaken at either the proximal intertrochanteric or the distal supracondylar level of the femur. Preoperative clinical evaluation and three-dimensional movement analysis determined any additional soft-tissue surgery. Distal osteotomy was faster with significantly lower blood loss than proximal osteotomy. The children in the distal group achieved independent walking earlier than those in the proximal group (6.9 +/- 1.3 v 10.7 +/- 1.7 weeks; p < 0.001). Transverse plane kinematics demonstrated clinically significant improvements in rotation of the hip and the foot progression angle in both groups. Correction of rotation of the hip was from 17 +/- 11 degrees internal to 3 +/- 9.5 degrees external in the proximal group and from 9 +/- 14 degrees internal to 4 +/- 12.4 degrees external in the distal group. Correction of the foot progression angle was from a mean of 10.0 +/- 17.3 degrees internal to 13.0 +/- 11.8 degrees external in the proximal group (p < 0.001) compared with a mean of 7.0 +/- 19.4 degrees internal to 10.0 +/- 12.2 degrees external in the distal group (p < 0.001). Femoral derotation osteotomy at both levels gives comparable excellent correction of rotation of the hip and foot progression angles in children with spastic diplegia.

Hip surveillance in children with cerebral palsy. Impact on the surgical management of spastic hip disease.

We studied prospectively the impact of a hip surveillance clinic on the management of spastic hip disease in children with cerebral palsy in a tertiary referral centre. Using a combination of primary clinical and secondary radiological screening we were able to detect spastic hip disease at an early stage in most children and to offer early surgical intervention. The principal effect on surgical practice was that more preventive surgery was carried out at a younger age and at a more appropriate stage of the disease. The need for reconstructive surgery has decreased and that for salvage surgery has been eliminated. Displacement of the hip in children with cerebral palsy meets specific criteria for a screening programme. We recommend that hip surveillance should become part of the routine management of children with cerebral palsy. The hips should be examined radiologically at 18 months of age in all children with bilateral cerebral palsy and at six- to 12-monthly intervals thereafter. A co-ordinated approach by orthopaedic surgeons and physiotherapists may be the key to successful implementation of this screening programme.

Modified technique for varus derotation osteotomy of the proximal femur in children.

BACKGROUND: The results of a study in which the Richards' intermediate hip screw and the AO (Association for the Study of Internal Fixation (ASIF)) 908 fixed-angle blade plate were compared for use in proximal femoral osteotomy in children have previously been reported. In that study loss of position at the osteotomy site was reported as a specific complication associated with the use of the Richards' intermediate hip screw. METHODS: The authors devised a simple modification of surgical technique using the Richards' intermediate hip screw to enhance the stability of the fixation. In the present article the results of a prospective study of that modified technique are reported and compared with the results of the previous study. RESULTS: During a 2-year period 24 proximal femoral osteotomies were performed on 12 children with cerebral palsy, using the modified technique by two surgeons. Only two of the 12 patients (16%) required postoperative immobilization in a hip spica cast. This represents a significant reduction in the level of spica casting when compared with the previous cohort study (61%). CONCLUSION: A simple modification of surgical technique improves the stability of fixation in proximal femoral osteotomy in children who have cerebral palsy. This resulted in a decreased need for supplementary hip spica casting and may reduce morbidity.

Isolated calf lengthening in cerebral palsy. Outcome analysis of risk factors.

We assessed the medium-term outcome of three methods of isolated calf lengthening in cerebral palsy by clinical examination, observational gait analysis and, where appropriate, instrumented gait analysis. The procedures used were percutaneous lengthening of tendo Achillis, open Z-lengthening of tendo Achillis and lengthening of the gastrosoleus aponeurosis (Baker's procedure). We reviewed 195 procedures in 134 children; 45 had hemiplegia, 65 diplegia and 24 quadriplegia. We established the incidence of calcaneus and recurrent equinus and identified 'at-risk' groups for each. At follow-up, 42% had satisfactory calf length, 22% had recurrent equinus and 36% calcaneus. The incidence of calcaneus in girls at follow-up was significantly higher (p = 0.002) while boys had an increased rate of recurrent equinus (p = 0.012). Children with diplegia who had surgery when aged eight years or younger had a 44% risk of calcaneus, while those over eight years had a 19% risk (p = 0.046). Percutaneous lengthening of tendo Achillis in diplegia was the least predictable, only 38% having a satisfactory outcome compared with 50% in the other procedures. The incidence of recurrent equinus in hemiplegic patients was 38%. Only 4% developed calcaneus. The type of surgery did not influence the outcome in patients with hemiplegia or quadriplegia. Severity of involvement, female gender, age at operation of less than eight years and percutaneous lengthening of tendo Achillis were 'risk factors' for calcaneus. Hemiplegia, male gender, and an aponeurosis muscle lengthening increased the risk of recurrent equinus.

The effect of botulinum toxin type A and a variable hip abduction orthosis on gross motor function: a randomized controlled trial.

Hip displacement is the second most common deformity after equinus in children with cerebral palsy (CP), and may result in dislocation, pain, fixed deformity and loss of function. We studied the combined effects of intramuscular injections of botulinum toxin type A (BTX-A) to the adductors and hamstrings and a variable hip abduction orthosis (SWASH), on gross motor function, hip displacement and progression to surgery, in a randomized clinical trial. Thirty-nine children, with bilateral spastic cerebral palsy, and mean age 3 years + 2 months (range 1 year+7 months--4 years +10 months) entered the trial. Gross Motor Function Classification System (GMFCS) levels were as follows: one child was level II, 11 were level III, 13 were level IV and 14 were level V. After concealed randomization, 20 were allocated to the control group and 19 to the intervention group. Thirty-five children completed the follow up at 1 year. The novel intervention group received up to 4.0 U BOTOX/kg/muscle, 16 U/kg/body weight every 6 months plus the use of a SWASH brace. The control group received clinical best practice comprising physiotherapy but no hip abduction bracing. Both groups showed improvements in total Gross Motor Function Measure (GMFM) score [mean 6.0% BTX-A group; 6.1% Control; 95% CI -- 6.7, 6.5 (NS)], however, there was no additional treatment effect for the study group. There were similar improvements on GMFM goal scores and GMFM-66 scores, but again no additional treatment effect was observed. Multiple regression of change in total GMFM by GMFCS classification for each group showed greater improvement in the total scores from baseline in the BTX-A/SWASH treated group than the control group. In the first year, nine children (two in the intervention group and seven in the control group) required soft tissue surgery because of progressive hip migration in excess of 40%. A longer-term follow up of a larger cohort may be required to determine the effect of the combined treatment on hip displacement.

Which implant for proximal femoral osteotomy in children? A comparison of the AO (ASIF) 90 degree fixed-angle blade plate and the Richards intermediate hip screw.

We reviewed the clinical and radiologic results of 164 proximal femoral osteotomies in 132 children using the AO (ASIF) 90 degree fixed-angle blade plate and the Richards intermediate hip screw to establish the clinical and radiologic outcomes, establish the incidence of complications, and determine the relative indications and contraindications for the two implants. The incidence of complication in this series was 9% (15 complications in 14 osteotomies in 13 patients) including one bursitis, one wound breakdown with exposure of the underlying plate, five infections, two peroneal nerve palsies, one fractured shaft of femur, one fractured neck of femur, two technical errors, one painful nonunion, and one loss of fixation. There were five (3%) revisions in total. Fifty-six osteotomies in 44 patients were performed using the Richards intermediate hip screw, and 108 osteotomies were performed in 88 patients using the AO 90 degree fixed-angle blade plate. We found that both implants were effective with an acceptable rate of complications and revision surgery.

Analgesic effects of botulinum toxin A: a randomized, placebo-controlled clinical trial.

Postoperative pain in children with spastic cerebral palsy (CP) is often attributed to muscle spasm and is difficult to manage using opiates and benzodiazepines. Adductor-release surgery to treat or prevent hip dislocation in children with spastic CP is frequently performed and is often accompanied by severe postoperative pain and spasm. A double-blinded, randomized, placebo-controlled clinical trial of 16 patients (mean age 4.7 years) with a mainly spastic type of CP (either diplegic or quadriplegic in distribution) was used to test the hypothesis that a significant proportion of postoperative pain is secondary to muscle spasm and, therefore, might be reduced by a preoperative chemodenervation of the target surgical muscle by intramuscular injection of botulinum toxin A (BTX/A). Compared with the placebo, BTX/A was found to be associated with a reduction in mean pain scores of 74% (P<0.003), a reduction in mean analgesic requirements of approximately 50% (P<0.005), and a reduction in mean length of hospital admission of 33% (P<0.003). It was concluded that an important component of postoperative pain in the patient population is due to muscle spasm and this can be managed effectively by preoperative injection with BTX/A. These findings may have implications for the management of pain secondary to muscle spasm in other clinical settings.