Does idiopathic congenital talipes equinovarus have an impact on attainment of developmental milestones? A multicentre international study.

Purpose: The Ponseti method is a well-established approach to treating clubfoot. Potentially, both the underlying pathology and adherence to post-correction bracing can affect lower limb function and age of independent standing and walking. This cohort study investigates the age at which infants with idiopathic clubfoot treated using the Ponseti method achieved three selected developmental milestones and whether or not this correlated with treatment compliance. Methods: A prospectively collected database from four centres was visited. Inclusion criteria were patients with idiopathic clubfoot with no comorbidities or prior treatment. Age at attainment of independent standing, walking, nocturnal continence was compared across three groups: I) congenital talipes equinovarus (CTEV) children compliant with treatment; II) CTEV children non-compliant with treatment; and III) typically-developed siblings. Minimum follow-up was five years. Results: In all, 130 patients (198 feet) fitted the inclusion criteria: 43:87 (F:M). Standing was achieved by a mean 12.0 months in group I (sd 2.50); 12.0 months (sd 2.0) in II and ten months (sd 3.0) in III. Walking was achieved by a mean 15 months (sd 4.0) in group I, 14 months (sd 1.75) in II and 12 months (sd 3) in III, respectively. Both the compliant and non-compliant CTEV children were significantly slower at achieving standing and walking compared to sibling controls (p < 0.0001). There was no significant difference between age of nocturnal continence between the three groups. Conclusion: Infants with idiopathic clubfoot treated according to the Ponseti method achieve independent standing and walking approximately two months later than their typically-developed siblings. The delay is not related to the use of the foot abduction brace. Level of evidence: III

Dynamic splinting home therapy for toe walking: a case report

Serial casting is frequently prescribed for toe-walking but that does not allow continued physical therapy (PT). This report described a child and family who chose dynamic splinting (DS) with concurrent PT for treatment. The patient presented with right hemiparesis; below average motor skills and a gait pattern of toe contact (without ankle foot orthosis). Four months of PT plus 6 hours/night of DS as home therapy, the patient's passive dorsiflexion increased 14° and she gained the ability to walk in "flat foot" contact without the Ankle Foot Orthosis. This concurrent treatment achieved improved gait pattern and strength training not possible with casting

Idiopathic toe-walking in children, adolescents and young adults: a matter of local or generalised stiffness?

<p>Abstract</p> <p>Background</p> <p>Idiopathic Toe Walking (ITW) is present in children older than 3 years of age still walking on their toes without signs of neurological, orthopaedic or psychiatric diseases. ITW has been estimated to occur in 7% to 24% of the childhood population. To study associations between Idiopathic Toe Walking (ITW) and decrease in range of joint motion of the ankle joint. To study associations between ITW (with stiff ankles) and stiffness in other joints, muscle strength and bone density.</p> <p>Methods</p> <p>In a cross-sectional study, 362 healthy children, adolescents and young adults (mean age (sd): 14.2 (3.9) years) participated. Range of joint motion (ROM), muscle strength, anthropometrics sport activities and bone density were measured.</p> <p>Results</p> <p>A prevalence of 12% of ITW was found. Nine percent had ITW and severely restricted ROM of the ankle joint. Children with ITW had three times higher chance of severe ROM restriction of the ankle joint. Participants with ITW and stiff ankle joints had a decreased ROM in other joints, whereas bone density and muscle strength were comparable.</p> <p>Conclusion</p> <p>ITW and a decrease in ankle joint ROM might be due to local stiffness. Differential etiological diagnosis should be considered.</p

‘Multi-Epitope-Targeted’ Immune-Specific Therapy for a Multiple Sclerosis-Like Disease via Engineered Multi-Epitope Protein Is Superior to Peptides

Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS) yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and “epitope spread”, have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such “multi-epitope-targeting” approach in murine experimental autoimmune encephalomyelitis (EAE) associated with a single (“classical”) or multiple (“complex”) anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc) encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as “multi-epitope-targeting” agents. Y-MSPc was superior to peptide(s) in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells). Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of “classical” or “complex EAE” or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a “multi-epitope-targeting” strategy is required for effective immune-specific therapy of organ-specific autoimmune diseases associated with complex and dynamic pathogenic autoimmunity, such as MS; our data further demonstrate that the “multi-epitope-targeting” approach to therapy is optimized through specifically designed multi-epitope-proteins, rather than myelin peptide cocktails, as “multi-epitope-targeting” agents. Such artificial multi-epitope proteins can be tailored to other organ-specific autoimmune diseases

Idiopathic toe walking and sensory processing dysfunction

<p>Abstract</p> <p>Background</p> <p>It is generally understood that toe walking involves the absence or limitation of heel strike in the contact phase of the gait cycle. Toe walking has been identified as a symptom of disease processes, trauma and/or neurogenic influences. When there is no obvious cause of the gait pattern, a diagnosis of idiopathic toe walking (ITW) is made. Although there has been limited research into the pathophysiology of ITW, there has been an increasing number of contemporary texts and practitioner debates proposing that this gait pattern is linked to a sensory processing dysfunction (SPD). The purpose of this paper is to examine the literature and provide a summary of what is known about the relationship between toe walking and SPD.</p> <p>Method</p> <p>Forty-nine articles were reviewed, predominantly sourced from peer reviewed journals. Five contemporary texts were also reviewed. The literature styles consisted of author opinion pieces, letters to the editor, clinical trials, case studies, classification studies, poster/conference abstracts and narrative literature reviews. Literature was assessed and graded according to level of evidence.</p> <p>Results</p> <p>Only one small prospective, descriptive study without control has been conducted in relation to idiopathic toe walking and sensory processing. A cross-sectional study into the prevalence of idiopathic toe walking proposed sensory processing as being a reason for the difference. A proposed link between ITW and sensory processing was found within four contemporary texts and one conference abstract.</p> <p>Conclusion</p> <p>Based on the limited conclusive evidence available, the relationship between ITW and sensory processing has not been confirmed. Given the limited number and types of studies together with the growing body of anecdotal evidence it is proposed that further investigation of this relationship would be advantageous.</p

Gene transfer by viral vectors into blood vessels in a rat model of retinopathy of prematurity

AIMS—To test the feasibility of gene transfer into hyaloid blood vessels and into preretinal neovascularisation in a rat model of retinopathy of prematurity (ROP), using different viral vectors.
METHODS—Newborn rats were exposed to alternating hypoxic and hyperoxic conditions in order to induce ocular neovascularisation (ROP rats). Adenovirus, herpes simplex, vaccinia, and retroviral (MuLV based) vectors, all carrying the β galactosidase (β-gal) gene, were injected intravitreally on postnatal day 18 (P18). Two sets of controls were also examined: P18 ROP rats injected with saline and P18 rats that were raised in room air before the viral vectors or saline were injected. Two days after injection, the rats were killed, eyes enucleated, and β-gal expression was examined by X-gal staining in whole mounts and in histological sections.
RESULTS—Intravitreal injection of the adenovirus and vaccinia vectors yielded marked β-gal expression in hyaloid blood vessels in the rat ROP model. Retinal expression of β-gal with these vectors was limited almost exclusively to the vicinity of the injection site. Injection of herpes simplex yielded a punctuate pattern of β-gal expression in the retina but not in blood vessels. No significant β-gal expression occurred in rat eyes injected with the retroviral vector.
CONCLUSIONS—Adenovirus is an efficient vector for gene transfer into blood vessels in an animal model of ROP. This may be a first step towards utilising gene transfer as a tool for modulating ocular neovascularisation for experimental and therapeutic purposes.


Development of a practical guide for the early recognition for malignant melanoma of the foot and nail unit

Background: malignant melanoma is a rare but potentially lethal form of cancer which may arise on the foot. Evidence suggests that due to misdiagnosis and later recognition, foot melanoma has a poorer prognosis than cutaneous melanoma elsewhere.Methods: a panel of experts representing podiatry and dermatologists with a special interest in skin oncology was assembled to review the literature and clinical evidence to develop a clinical guide for the early recognition of plantar and nail unit melanoma.Results: a systematic review of the literature revealed little high quality data to inform the guide. However a significant number of case reports and series were available for analysis. From these, the salient features were collated and summarised into the guide. Based on these features a new acronym "CUBED" for foot melanoma was drafted and incorporated in the guide.Conclusions: the use of this guide may help clinicians in their assessment of suspicious lesions on the foot (including the nail unit). Earlier detection of suspicious pedal lesions may facilitate earlier referral for expert assessment and definitive diagnosis. The guide is currently being field tested amongst practitioner