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This review discusses the general principles underlying responsible antibiotic usage in reptiles. Very little evidence underlies antibiotic usage in reptiles, and there are no published guidelines for responsible antibiotic usage. A literature search was performed to review the evidence for bacterial involvement in the pathology of selected common diseases of reptiles, allowing the development of recommendations for responsible antibiotic treatment of those diseases.
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Gestão de Antimicrobianos , Animais , Antibacterianos/uso terapêutico , RépteisRESUMO
PURPOSE: Perthes' disease (PD) results from loss of blood supply to the hip and can progress to femoral head deformity. MRI in the early course of the disease can provide data on the initial extent of infarct. Vascularity of the femoral head is assessed by gadolinium-enhanced MRI (contrast MRI), which may be improved by the digital subtraction technique (subtraction MRI). We hypothesized that gadolinium-enhanced MRI without subtraction was comparable with subtraction MRI in depicting the femoral head perfusion. METHODS: In all, 34 patients (34 hips) with unilateral PD had gadolinium-enhanced MRI as part of a prospectively randomized study. Nine patients had three MRIs, 15 had two and ten had a single MRI. Measurement of perfusion of the femoral head (MRI perfusion index) was obtained using digital image analysis on all the MRIs, including both before and after subtraction. A paired sample t-test was performed to compare the measurements. RESULTS: The mean age of the patients was 8.9 years (sd 1.6). At the time of diagnosis, the subtraction MRI did not elicit a statistically significant difference in MRI perfusion index measurements when compared with the contrast MRI (p = 0.19). The same findings were found when including all patients at various stages of the disease (p = 0.30). Qualitatively, although some subtraction MRI images showed superior delineation of epiphysis, there are no significant differences throughout the whole series. CONCLUSION: Although the current literature supports the increasing role of the subtraction MRI for PD management, our study proposed that the contrast MRI without subtraction technique appears adequate in assessing femoral head perfusion. LEVEL OF EVIDENCE: Level I - Diagnostic study.
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Objective: The central role of vitamin D in bone health is well recognized. However, controversies regarding its clinical application remain. We therefore aimed to review the definition of hypovitaminosis D, the skeletal and extra-skeletal effects of vitamin D and the available therapeutic modalities. Design: Narrative and systematic literature review. Methods: An international working group that reviewed the current evidence linking bone and extra-skeletal health and vitamin D therapy to identify knowledge gaps for future research. Results: Findings from observational studies and randomized controlled trials (RCTs) in vitamin D deficiency are discordant, with findings of RCTs being largely negative. This may be due to reverse causality with the illness itself contributing to low vitamin D levels. The results of many RCTs have also been inconsistent. However, overall evidence from RCTs shows vitamin D reduces fractures (when administered with calcium) in the institutionalized elderly. Although controversial, vitamin D reduces acute respiratory tract infections (if not given as bolus monthly or annual doses) and may reduce falls in those with the lowest serum 25-hydroxyvitamin D (25OHD) levels. However, despite large ongoing RCTs with 21 00026 000 participants not recruiting based on baseline 25OHD levels, they will contain a large subset of participants with vitamin D deficiency and are adequately powered to meet their primary end-points. Conclusions: The effects of long-term vitamin D supplementation on non-skeletal outcomes, such as type 2 diabetes mellitus (T2DM), cancer and cardiovascular disease (CVD) and the optimal dose and serum 25OHD level that balances extra-skeletal benefits (T2DM) vs risks (e.g. CVD), may soon be determined by data from large RCTs.
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Suplementos Nutricionais , Terapia de Reposição Hormonal , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/uso terapêutico , Humanos , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
Significant fracture history in children is defined as having at least one vertebral fracture, at least 2 fractures by age 10, or at least 3 fractures by age 19. Between September 2011 and December 2014, clinical data were collected on children with a significant fracture history that attended a major Australian children's hospital. Fifty-six patients were identified as having 305 fractures in total, including 44 vertebral fractures. 18% of patients (10/56) were diagnosed with osteogenesis imperfecta (OI) by a bone health expert, molecular testing or both, and they sustained 23% of all fractures (71/305). Analysis of serum bone biochemistry showed all median values to be within a normal range and no clinically significant differences between patients with and without OI. The DXA and pQCT derived bone mineral density (BMD) and bone mineral content (BMC) Z scores were reduced overall. DXA derived total body and lumbar spine areal BMD-for-age and BMC-for-age Z scores were significantly lower in children who had vertebral fractures or who were later diagnosed with OI. Similarly, pQCT performed on radii and tibiae showed Z scores significantly less than zero. pQCT-derived limb muscle cross sectional area Z scores were significantly lower in the OI subgroup. In conclusion, this study describes the bone phenotype of children referred to a tertiary hospital clinic for recurrent fractures and highlights a subset of children with previously undiagnosed OI, but a larger cohort without classic OI. Thus it can be clinically challenging to differentiate between children with OI type 1 (mild phenotype) and non-OI children without bone densitometry and genetic testing. We conclude that recurrent fractures in children should prompt a comprehensive bone and systemic health assessment to eliminate an underlying pathology.
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Fraturas Ósseas/diagnóstico , Fraturas Ósseas/etiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Osteogênese Imperfeita/complicações , RecidivaRESUMO
PURPOSE OF REVIEW: Osteogenesis imperfecta (OI) is a genetic bone disorder resulting in bone fragility. It has a heterogeneous phenotype which typically includes reduced bone mass, multiple fractures, deformity, and chronic disability. Bisphosphonate treatment remains the first-line medical management, but there is still debate on aspects of its effectiveness. This review summarizes current knowledge about long-term bisphosphonate use in OI with recommendations on clinical application. RECENT FINDINGS: Bisphosphonates increase bone mineral density, most notably of the vertebrae, and reduce fracture risk in the pediatric OI population. Gains in strength and mobility, together with the permissive effect on orthopedic surgery (e.g., in combination with intramedullary rodding) and physiotherapy, have resulted in improved quality of life for those with OI. As experience in its use continues, the risks and benefits of long-term bisphosphonate treatment in OI are slowly emerging. Patient registries containing data on genotype, phenotype, fractures, bisphosphonate treatment, orthopedic intervention, and functional outcomes are essential for systematic evaluation given the lack of large multi-centered randomized control trials.
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Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas Espontâneas/prevenção & controle , Osteogênese Imperfeita/tratamento farmacológico , Densidade Óssea , Humanos , Imidazóis/uso terapêutico , Procedimentos Ortopédicos , Pamidronato , Modalidades de Fisioterapia , Qualidade de Vida , Ácido ZoledrônicoRESUMO
Vitamin D and calcium are important nutrients for skeletal growth and bone health. Children and pregnant women are particularly vulnerable to 25-hydroxy vitamin D deficiency (VDD). VDD, with or without dietary calcium deficiency, can lead to nutritional rickets (NR), osteomalacia, and disturbances in calcium homeostasis. Multiple studies have linked VDD to adverse health outcomes in both children and pregnant women that extend beyond bone health. VDD remains an important global public health concern, and an important differentiation must be made between the impact of VDD on children and adults. Reports of increased incidence of NR continue to emerge. NR is an entirely preventable condition, which could be eradicated in infants and children worldwide with adequate vitamin D and calcium supplementation. The desire and necessity to put in place systems for preventing this potentially devastating pediatric disease should not elicit dispute. VDD and NR are global public health issues that require a collaborative, multi-level approach for the implementation of feasible preventative strategies. This review highlights the history, risk factors, and controversies related to VDD during pregnancy and childhood with a particular focus on global NR prevention.
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Osteogenesis imperfecta (OI) is a genetic bone fragility disorder characterized by low bone mass, skeletal deformity, and variable short stature. OI is predominantly caused by dominant mutations affecting type 1 collagen synthesis, with a number of other genes implicated in OI over recent years. The clinical severity of OI can vary greatly, even within families who share a common mutation. Optimal management of OI requires a multidisciplinary approach involving pediatrician, endocrinologist (bone and mineral physician), rehabilitation specialist, orthopedic surgeon, dentist, geneticist, social worker/psychologist, physiotherapist, and occupational therapist. Bisphosphonate therapy remains the mainstay of medical treatment in OI and has been shown to decrease bone pain, enhance well-being, improve muscle strength and mobility and decrease fracture incidence. Novel therapies are beginning to emerge as more is understood about the signaling pathways involved in bone formation. The following summarizes the diagnosis, genetic heterogeneity and management of OI in pediatric practice.
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Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas Ósseas/prevenção & controle , Osteogênese Imperfeita/terapia , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Fraturas Ósseas/terapia , Humanos , Terapia Ocupacional , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/genética , Equipe de Assistência ao Paciente , Modalidades de FisioterapiaRESUMO
Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long-term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.
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Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteogênese/efeitos dos fármacos , Erupção Dentária/efeitos dos fármacos , Adulto , Fatores Etários , Conservadores da Densidade Óssea/efeitos adversos , Criança , Difosfonatos/efeitos adversos , Humanos , Procedimentos Cirúrgicos Bucais , Técnicas de Movimentação DentáriaRESUMO
OBJECTIVE: Evaluate clinical outcome of early cyclic intravenous pamidronate treatment in children with moderate-to-severe osteogenesis imperfecta (OI), commenced before three years of age. METHODS: A retrospective review of 17 patients with moderate-to-severe OI. Development, anthropometry, fracture history, bone mineral density (BMD) and biochemistry were collected at baseline, 12 and 24 months. RESULTS: Four had OI type I, eleven had type III, one OI-FKBP10 type and one OI type V. Mean age at start of pamidronate was 14 ± 11 months. Pamidronate ranged from 6 to 12 mg/kg/year. No adverse reaction apart from fever and vomiting was noted. Long bone fracture decreased from a mean of 10.4/year to 1.2/year after 12 months and 1.4/year after 24 months (p = 0.02). Lumbar spine age- and height-matched BMD Z-scores increased (p < 0.005). Sixteen with vertebral compression fractures at baseline all showed improved vertebral shape (p < 0.001). Concavity index, likewise, improved (p < 0.005). Motor milestones compared to historical data show earlier attainment in rolling over, crawling, pulling to stand and walking independently but not sitting. CONCLUSION: Cyclic intravenous pamidronate, started under 3 years of age in children with moderate-to-severe OI, was well tolerated and associated with an increase in lumbar spine BMD, reduced fracture frequency, vertebral remodelling and attainment of motor milestones at an earlier age.
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Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Fraturas Ósseas/prevenção & controle , Osteogênese Imperfeita/tratamento farmacológico , Densidade Óssea , Pré-Escolar , Feminino , Humanos , Lactente , Infusões Intravenosas , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/fisiologia , Masculino , Destreza Motora , Pamidronato , Estudos RetrospectivosRESUMO
Complex regional pain syndrome (CRPS) is a disorder that can cause significant functional morbidity. While it usually presents in adulthood, it has also been reported in children. Multiple treatment modalities have been reported with mixed success. Bisphosphonate therapy has been shown to be effective in adult patients, but there are limited data in children. We report the successful use of intravenous pamidronate therapy in diminishing pain, improving function, and restoring bone mass in an 11-year-old girl with CRPS of her left lower limb following a tibial fracture. Previous treatment with intense physiotherapy and regional sympathetic blockade had not improved her symptoms. Pain improved within weeks of the first pamidronate infusion, with subsequent improvement in function. The benefit in pain reduction and function was sustained during the 2-year treatment regime. Improvement in bone mass and density was demonstrated by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerised tomography (pQCT). pQCT scans showed marked improvement in bone size and geometry and muscle bulk on the affected side. No adverse affects were reported. We conclude that intravenous pamidronate was associated with reduced pain, a return of function, and recovery of bone and muscle parameters in a child with CRPS. Before definitive conclusions can be drawn, a randomised controlled trial similar to those undertaken in adults previously is required to fully validate this approach.
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Densidade Óssea/efeitos dos fármacos , Difosfonatos/uso terapêutico , Distrofia Simpática Reflexa/tratamento farmacológico , Tíbia/efeitos dos fármacos , Fraturas da Tíbia/complicações , Absorciometria de Fóton , Anti-Inflamatórios/uso terapêutico , Criança , Feminino , Humanos , Perna (Membro)/fisiopatologia , Pamidronato , Distrofia Simpática Reflexa/etiologia , Distrofia Simpática Reflexa/fisiopatologia , Tíbia/fisiopatologia , Fraturas da Tíbia/fisiopatologia , Resultado do TratamentoRESUMO
Osteoporosis secondary to chronic disease in children has emerged as a major health issue. As the severity of a child's illness increases, so too does the number of factors affecting their bone health. Determinants of bone health in children include level of mobility, exposure to osteotoxic medication, nutritional status, calcium and vitamin D intake, chronic inflammation and pubertal development.
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Densidade Óssea/fisiologia , Osso e Ossos/fisiopatologia , Doença Crônica/reabilitação , Osteoporose/prevenção & controle , Osteoporose/terapia , Adolescente , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Criança , Difosfonatos/uso terapêutico , Glucocorticoides/efeitos adversos , Humanos , Imobilização/fisiologia , Osteonecrose/etiologia , Osteonecrose/fisiopatologia , Osteonecrose/terapia , Osteoporose/etiologia , Puberdade Tardia/complicações , Puberdade Tardia/fisiopatologia , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/fisiopatologia , Deficiência de Vitamina D/prevenção & controleRESUMO
Abnormalities in the growth plate may lead to short stature and skeletal deformity including Leri Weil syndrome, which has been shown to result from deletions or mutations in the SHOX gene, a homeobox gene located at the pseudoautosomal region of the X and Y chromosome. We studied the expression of SHOX protein, by immunohistochemistry, in human fetal and childhood growth plates and mRNA by in situ hybridization in childhood normal and Leri Weil growth plate. SHOX protein was found in reserve, proliferative, and hypertrophic zones of fetal growth plate from 12 wk to term and childhood control and Leri Weil growth plates. The pattern of immunostaining in the proliferative zone of childhood growth plate was patchy, with more intense uniform immunostaining in the hypertrophic zone. In situ hybridization studies of childhood growth plate demonstrated SHOX mRNA expression throughout the growth plate. No difference in the pattern of SHOX protein or mRNA expression was seen between the control and Leri Weil growth plate. These findings suggest that SHOX plays a role in chondrocyte function in the growth plate.
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Lâmina de Crescimento/embriologia , Lâmina de Crescimento/metabolismo , Proteínas de Homeodomínio/metabolismo , Adolescente , Criança , Feminino , Proteínas de Homeodomínio/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Biologia Molecular , RNA Mensageiro/metabolismo , Proteína de Homoeobox de Baixa EstaturaRESUMO
Leri-Weill syndrome (LWS) is a skeletal dysplasia with mesomelic short stature, bilateral Madelung deformity (BMD) and SHOX (short stature homeobox-containing gene) haploinsufficiency. The effect of 24 months of recombinant human growth hormone (rhGH) therapy on the stature and BMD of two females with SHOX haploinsufficiency (demonstrated by fluorescence in situ hybridisation) and LWS was evaluated. Both patients demonstrated an increase in height standard deviation score (SDS) and height velocity SDS over the 24 months of therapy. Patient 1 demonstrated a relative increase in arm-span and upper segment measurements with rhGH while patient 2 demonstrated a relative increase in lower limb length. There was appropriate advancement of bone age, no adverse events and no significant deterioration in BMD. In this study, 24 months of rhGH was a safe and effective therapy for the disproportionate short stature of SHOX haploinsufficiency, with no clinical deterioration of BMD.
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Estatura/efeitos dos fármacos , Estatura/genética , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/genética , Hormônio do Crescimento/uso terapêutico , Proteínas de Homeodomínio/genética , Adolescente , Braço/anatomia & histologia , Braço/crescimento & desenvolvimento , Osso e Ossos/diagnóstico por imagem , Criança , Feminino , Mãos/diagnóstico por imagem , Haplótipos , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Perna (Membro)/anatomia & histologia , Perna (Membro)/crescimento & desenvolvimento , Masculino , Fenótipo , Radiografia , Proteína de Homoeobox de Baixa EstaturaRESUMO
This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on stature, by comparing the growth and phenotype of 26 SHOX haploinsufficient individuals with 45 relatives and population standards. It confirmed that SHOX haploinsufficiency leads to growth restriction from birth to final height. Compared to unaffected siblings, the SHOX haploinsufficient cohort was 2.14 SDS (3.8 cm) shorter at birth and 2.1 SDS shorter through childhood. At final height females were 2.4 SDS (14.4 cm) shorter and males 0.8 SDS (5.3 cm) shorter than normal siblings. The family height analysis suggests that the effect of SHOX haploinsufficiency on growth may have been previously underestimated at birth and overestimated in males at final height. SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54%. Females were more severely affected than males. We conclude that SHOX is a major growth gene and that mutations are associated with a broad range of phenotype.
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Desenvolvimento Ósseo/genética , Transtornos do Crescimento/genética , Crescimento/genética , Proteínas de Homeodomínio/genética , Adolescente , Adulto , Determinação da Idade pelo Esqueleto , Idoso , Braço/anatomia & histologia , Braço/crescimento & desenvolvimento , Estatura/genética , Estatura/fisiologia , Densidade Óssea/genética , Densidade Óssea/fisiologia , Osso e Ossos/diagnóstico por imagem , Criança , Estudos de Coortes , Feminino , Genótipo , Haplótipos , Humanos , Recém-Nascido , Perna (Membro)/anatomia & histologia , Perna (Membro)/crescimento & desenvolvimento , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Proteína de Homoeobox de Baixa Estatura , SíndromeAssuntos
Estatura/genética , Genes Homeobox/genética , Proteínas de Homeodomínio/genética , Mutação/genética , Osteocondrodisplasias/genética , Estudos de Coortes , Feminino , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/genética , Humanos , Masculino , Osteocondrodisplasias/epidemiologia , Linhagem , Prevalência , Proteína de Homoeobox de Baixa Estatura , SíndromeRESUMO
Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short stature and bilateral Madelung deformity, due to dyschondrosteosis of the distal radius. It results from the loss of one copy of the Short Stature Homeobox Gene (SHOX) from the tip of the short arm of the X or Y chromosome. SHOX molecular testing enabled us to evaluate the histopathology of the radial physis in LWS patients with a documented SHOX abnormality. A widespread disorganisation of physeal anatomy was revealed with disruption of the normal parallel columnar arrangement of chondrocytes. Tandem stacking of maturing chondrocytes within columns was replaced by a side-by-side arrangement. The presence of hypertrophic osteoid with micro-enchondromata in the radial metaphysis suggests abnormal endochondral ossification. The Vickers' ligament was confirmed to blend with the triangular fibrocartilage complex (TFCC). This histopathological study demonstrates that the zone of dyschondrosteosis in LWS is characterised by marked disruption of normal physeal chondrocyte processes and that a generalised physeal abnormality is present.
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Lâmina de Crescimento/patologia , Proteínas de Homeodomínio/genética , Osteocondrodisplasias/patologia , Osteocondrodisplasias/cirurgia , Rádio (Anatomia)/anormalidades , Adolescente , Estatura , Criança , Aberrações Cromossômicas , Feminino , Seguimentos , Humanos , Mutação , Osteocondrodisplasias/genética , Rádio (Anatomia)/cirurgia , Amplitude de Movimento Articular , Proteína de Homoeobox de Baixa Estatura , Resultado do Tratamento , Articulação do Punho/fisiopatologiaRESUMO
We tested the hypothesis that X-linked genes determining stature which are subject to skewed or non-random X-inactivation can account for discordance in height in monozygotic female twins. Height discordant female monozygotic adult twins (20 pairs) were identified from the Australian Twin Registry, employing the selection criteria of proven monozygosity and a measured height discordance of at least 5 cm. Differential X-inactivation was examined in genomic DNA extracted from peripheral lymphocytes by estimating differential methylation of alleles at the polymorphic CAG triplet repeat of the Androgen receptor gene (XAR). There were 17/20 MZ pairs heterozygous at this locus and informative for analysis. Of these, 10/17 both had random X-inactivation, 5/17 showed identical X-inactivation patterns of non random inactivation and 2/17 (12%) showed discordant X-inactivation. There was no relationship between inactivation patterns and self-report chorionicity. We conclude that non-random X-inactivation does not appear to be a major contributor to intra-pair height discordance in female MZ twins.
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Estatura/genética , Mecanismo Genético de Compensação de Dose , Ligação Genética/genética , Sistema de Registros , Gêmeos Monozigóticos/genética , Adulto , Estudos de Coortes , Desoxirribonuclease HpaII , Feminino , Humanos , Reação em Cadeia da Polimerase , Fatores Sexuais , Repetições de Trinucleotídeos/genética , Estudos em Gêmeos como AssuntoAssuntos
Síndrome de Beckwith-Wiedemann/complicações , Hiperinsulinismo/etiologia , Hipoglicemia/etiologia , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/metabolismo , Pré-Escolar , Aberrações Cromossômicas , Deficiências do Desenvolvimento/etiologia , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperinsulinismo/metabolismo , Hiperinsulinismo/terapia , Hipoglicemia/metabolismo , Hipoglicemia/terapia , Lactente , Recém-Nascido , MasculinoRESUMO
OBJECTIVE: To describe the aetiology, clinical features and appropriate treatment for hepatic glycogenosis in poorly controlled type 1 diabetes. METHODS: A review of three adolescents with poor diabetes control, hepatomegaly and elevated serum liver transaminase concentrations. RESULTS: Symptoms included abdominal pain, anorexia, nausea and vomiting. All had tender hepatomegaly; two had splenomegaly. Liver biopsy was performed on two patients. Histology revealed hepatic glycogenosis in both; one also demonstrated macrovesicular steatosis. With improved glycaemic control, all three showed resolution of their symptoms, organomegaly and elevated serum liver transaminase concentrations. CONCLUSIONS: Insulin-reversible hepatic glycogenosis is the most common cause of hepatomegaly and raised serum liver transaminase concentrations in children and adolescents with type 1 diabetes. Having excluded other causes of hepatic dysfunction, a 4 week therapeutic trial of improved glycaemic control is recommended prior to more invasive investigations.