RESUMEN
AdipoRon is an adiponectin receptor 1, 2 (ADIPOR1 and ADIPOR2) agonist with potential antifibrotic effects. Whether AdipoRon can mitigate joint stiffness in a rabbit model of arthrofibrosis is unknown. We examined the efficacy of intravenous (IV) AdipoRon at mitigating contracture in a rabbit model of knee arthrofibrosis. Fifty-six female New Zealand White rabbits were divided into three dosing groups: vehicle (dimethyl sulfoxide, DMSO), 2.5 mg/kg AdipoRon, and 5 mg/kg AdipoRon. AdipoRon, in DMSO, was administered IV preoperatively and for 5 days postoperatively (30 rabbits, Aim 1). AdipoRon was again dosed similarly after Kirschner wire (K-wire) removal at 8 weeks (26 rabbits; Aim 2). The primary outcome of joint passive extension angle (PEA,°) was measured at 8, 10, 12, 16, and 24 weeks following index surgery. At 24 weeks, rabbits were euthanized and limbs were harvested to measure posterior capsular stiffness (N cm/°). In Aim 1, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 16-week (p < 0.05). In Aim 2, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 10-week (p < 0.05). In both aims, no significant differences were observed at later time points. Capsular stiffness was no different in any group. We are the first to report the efficacy of IV AdipoRon in a rabbit model of arthrofibrosis. We identified a significant dose-dependent decrease in joint PEA at early time points; however, no differences were observed between groups at later time points. Clinical Significance: The present investigation provided the first assessment of AdipoRon's efficacy in mitigating knee stiffness in the current gold standard rabbit model of arthrofibrosis. Results of this investigation provided further evidence as to the potential role of AdipoRon as a preventative for arthrofibrosis in large mammals.
Asunto(s)
Fibrosis , Receptores de Adiponectina , Animales , Conejos , Femenino , Receptores de Adiponectina/agonistas , Contractura/prevención & control , Contractura/etiología , Contractura/tratamiento farmacológico , Modelos Animales de Enfermedad , Piperidinas/uso terapéutico , Piperidinas/farmacologíaRESUMEN
During the 1970s, scientists first used botulinum toxin to treat strabismus. While testing on monkeys, they noticed that the toxin could also reduce wrinkles in the glabella area. This led to its widespread use in both medical and cosmetic fields. The objective of the study was to evaluate the potential use of Botox in managing post-operative contracture after below-knee amputation. We conducted a systematic review In Pubmed, Cochrane Library, Embase, and Google Scholar using the MESH terms Botox, botulinum toxin, post-operative contracture, amputation, and below knee amputation. Our goal was to evaluate the potential use of Botox to manage post-operative contracture in patients who have undergone below-knee amputation. Our findings show evidence in the literature that Botox can effectively manage stump hyperhidrosis, phantom pain, and jumping stump, but no clinical trial has been found that discusses the use of Botox for post-operative contracture. Botox has been used in different ways to manage spasticity. Further studies and clinical trials are needed to support the use of Botox to manage this complication.
Asunto(s)
Amputación Quirúrgica , Toxinas Botulínicas Tipo A , Contractura , Fármacos Neuromusculares , Complicaciones Posoperatorias , Humanos , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/farmacología , Complicaciones Posoperatorias/tratamiento farmacológico , Contractura/cirugía , Contractura/tratamiento farmacológico , Contractura/etiología , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/farmacología , Muñones de AmputaciónRESUMEN
Winchester syndrome (WS) is a rare genetic disorder with a handful of cases reported to date. We report a 14-year-old male who presented with growth retardation, contracture of left lower limb due to thick indurated skin, hypertrichosis, and bilateral corneal opacity. There was complete improvement in joint contracture with oral betamethasone pulse and weekly oral methotrexate.
Asunto(s)
Betametasona , Metotrexato , Humanos , Masculino , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Betametasona/uso terapéutico , Betametasona/administración & dosificación , Adolescente , Administración Oral , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificación , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Anomalías Múltiples/tratamiento farmacológico , Síndrome , Contractura/tratamiento farmacológico , Quimioterapia CombinadaRESUMEN
The purpose of this study was to observe the therapeutic effect of extracorporeal shock wave (ESW) on extensional joint contracture of knee joint in rats and its mechanism on articular capsule fibrosis. Thirty-two SD rats were randomly divided into blank control, immobilization, natural recovery, and ESW intervention groups. Except for the control group, the left knee joints of other rats were fixed with external fixation brace for 4 weeks when they were fully extended to form joint contracture. The effect of intervention was assessed by evaluating joint contracture, total cell count and collagen deposition in joint capsule, and protein expression levels of TGF-ß1, p-Smad2/3, Smad2/3, p-JNK, JNK, I and III collagen in joint capsule. ESW can effectively reduce arthrogenic contracture, improve the histopathological changes of anterior joint capsule, inhibit the high expression of target protein and the excessive activation of TGF-ß1/Smad2/3/JNK signal pathway. Inhibition of excessive activation of TGF-ß1/Smad2/3/JNK pathway may be one of the potential molecular mechanisms by which extracorporeal shock wave can play a role.
Asunto(s)
Contractura , Factor de Crecimiento Transformador beta1 , Ratas , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Rango del Movimiento Articular , Ratas Sprague-Dawley , Articulación de la Rodilla/patología , Cápsula Articular/patología , Contractura/tratamiento farmacológico , Colágeno/metabolismo , FibrosisRESUMEN
Joint contracture causes distressing permanent mobility disorder due to trauma, arthritis, and aging, with no effective treatment available. A principal and irreversible cause of joint contracture has been regarded as the development of joint capsule fibrosis. However, the molecular mechanisms underlying contracture remain unclear. We established a mouse model of knee joint contracture, revealing that fibrosis in joint capsules causes irreversible contracture. RNA-sequencing of contracture capsules demonstrated a marked enrichment of the genes involved in the extracellular region, particularly periostin (Postn). Three-dimensional magnetic resonance imaging and immunohistological analysis of contracture patients revealed posterior joint capsule thickening with abundant type I collagen (Col1a2) and POSTN in humans. Col1a2-GFPTG ; Postn-/- mice and chimeric mice with Col1a2-GFPTG ; tdTomatoTG bone marrow showed fibrosis in joint capsules caused by bone marrow-derived fibroblasts, and POSTN promoted the migration of bone marrow-derived fibroblasts, contributing to fibrosis and contracture. Conversely, POSTN-neutralizing antibody attenuated contracture exacerbation. Our findings identified POSTN as a key inducer of fibroblast migration that exacerbates capsule fibrosis, providing a potential therapeutic strategy for joint contracture.
Asunto(s)
Médula Ósea , Contractura , Humanos , Ratones , Animales , Médula Ósea/patología , Rango del Movimiento Articular , Contractura/genética , Contractura/tratamiento farmacológico , Fibrosis , Fibroblastos/patologíaRESUMEN
Segmental stiff skin syndrome is a rare fibrosing scleroderma-like disorder characterized by progressive indurations of the skin leading to joint contractures, decreased mobility, and pain. Treatment options are limited; we report a patient that showed improvement with anti-IL17 biologic therapy.
Asunto(s)
Contractura , Enfermedades Cutáneas Genéticas , Humanos , Piel , Enfermedades Cutáneas Genéticas/tratamiento farmacológico , Contractura/tratamiento farmacológicoRESUMEN
Rehabilitation protocols to treat joint contracture and muscle atrophy following anterior cruciate ligament (ACL) reconstruction have not been established. In this study, we examined the combined effects of exercise therapy and steroid administration on joint contracture and muscle atrophy following ACL reconstruction. Rats received ACL transection and reconstructive surgery in one knee. After surgery, they were divided into four groups: no intervention, treadmill exercise (started from day three post-surgery, 12 m/min, 60 min/d, 6 d/week), treatment with the steroidal drug dexamethasone (250 µg/kg on days 0-5, 7, and 9 post-surgery), and dexamethasone treatment plus treadmill exercise. Age-matched untreated rats were used as controls. At day 10 or 30 post-surgery, we assessed ACL-reconstruction-induced joint contracture, joint capsule fibrosis, osteophyte formation, and muscle atrophy of the rectus femoris and gastrocnemius. Treadmill exercise after ACL reconstruction improved several indicators of muscle atrophy in both muscles, but it did not have positive effects on joint contracture. Dexamethasone treatment after ACL reconstruction improved joint contracture and joint capsule fibrosis at both timepoints and partially attenuated osteophyte formation at day 10 post-surgery, but delayed recovery from atrophy of the rectus femoris at day 30 post-surgery. The two treatments combined improved both joint contracture and atrophy of the rectus femoris and gastrocnemius. Exercise therapy combined with steroid administration may therefore be a novel therapeutic strategy for joint contracture and muscle atrophy following ACL reconstruction.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Contractura , Osteofito , Ratas , Animales , Lesiones del Ligamento Cruzado Anterior/patología , Lesiones del Ligamento Cruzado Anterior/cirugía , Osteofito/patología , Osteofito/cirugía , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/etiología , Atrofia Muscular/patología , Músculo Cuádriceps/patología , Músculo Cuádriceps/cirugía , Reconstrucción del Ligamento Cruzado Anterior/métodos , Reconstrucción del Ligamento Cruzado Anterior/rehabilitación , Fibrosis , Dexametasona/farmacología , Dexametasona/uso terapéutico , Contractura/tratamiento farmacológico , Contractura/etiología , Contractura/patologíaRESUMEN
Dear Editor, Scurvy is a nutritional disorder which can develop after prolonged (>1-3 months) severe vitamin C deficiency. Vitamin C is a cofactor in several enzyme reactions involved in collagen synthesis. The defect in collagen causes blood vessel fragility, poor wound healing, mucocutaneous bleedings, hair abnormalities, bone pains, and joint contractures due to periosteal and intraarticular bleeding (1,2). Risk factors for scurvy development are undernutrition, low socioeconomic status, older age, male sex, alcoholism, tobacco smoking, and severe psychiatric illnesses (1-3). The required daily intake for vitamin C is ~60 mg, and this amount of vitamin C can be found in only one medium-sized orange. For this reason, the disease is rarely encountered in developed countries and is often underrecognized by healthcare personnel. Herein, we present an illustrative case of scurvy in order to raise the awareness of this disorder. A 61-year-old Caucasian man was admitted to hospital due to fatigue, hypotension (80/50 mmHg), severe normocytic anemia (hemoglobin 76 g/L), kidney failure (estimated glomerular filtration rate of 6 mL/min/1.73m2) and mild elevation in C-reactive protein (30.9 mg/L). Prior medical history included radical cystoprostatectomy with an ileal conduit performed eight years ago due to a bladder tumor and moderate chronic kidney disease with recurrent urinary tract infections. The patient was also an alcoholic and tobacco smoker, with a very low-income and a poor diet. He did not use any medications. Heteroanamnestically, the current clinical state had developed slowly over several weeks. At admission, the patient was afebrile, lethargic, malnourished, and immobile due to generalized weakness, bone pains, and hip and knee contractures. He had generalized edema, mostly related to kidney failure, as well as severe hypoalbuminemia (serum albumin 19 g/L). There were multiple ecchymoses (Figure 1, a) and perifollicular bleedings (Figure 1, b) in the skin. The teeth were defective, and the patient's facial hair had a "corkscrew" appearance (Figure 1, c). The platelet count was normal, as was the serum fibrinogen level and the prothrombin- and activated partial thromboplastin times. Vancomycin-resistant Enterococcus faecium and multi-drug-resistant Acinetobacter baumanii were isolated from the urine. Therefore, hemodialysis, linezolid, and colistin were started. However, the patient continued to be lethargic, immobile, and with prominent skin bleeding. Medical workup excluded the possibility of an underlying malignancy or an autoimmune disorder. Finally, scurvy was suspected and 500 mg daily of oral vitamin C was introduced into therapy. In the following two weeks, the general condition of the patient significantly improved and he was discharged from the hospital in good condition - mobile and with complete resolution of skin lesions (Figure 1, d and e). Three months later, the patient was still under maintenance hemodialysis and had mild anemia (hemoglobin 123 g/L). Interestingly, scurvy was the first disease in the history of medicine for which a randomized trial found a cure (4). The differential diagnosis of scurvy includes skin infections, hematologic disorders, collagen vascular disorders, and anticoagulant/antiplatelet side-effects (1). Pathognomonic skin findings which may help raise suspicion of scurvy are perifollicular bleedings and "corkscrew" hair. Notably, laboratory testing for vitamin C concentration is not necessary to confirm scurvy as it tends to reflect recent dietary intake of vitamin C (2). Nevertheless, it may be useful to identify less typical cases (2). In our case, rapid clinical improvement with the resolution of skin lesions and joint contractures after the introduction of vitamin C confirmed the clinical diagnosis of scurvy. Additionally, vitamin C deficiency could be, at least partly (besides kidney failure and acute infection), responsible for severe anemia at disease presentation (5). This case serves to remind clinicians not to forget scurvy when treating patients at risk for vitamin C deficiency who present with fatigue, anemia, bone pains, and unexplained mucocutaneous bleedings. In suspected cases, vitamin C should be administered without hesitation.
Asunto(s)
Anemia , Deficiencia de Ácido Ascórbico , Contractura , Insuficiencia Renal , Escorbuto , Anemia/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Deficiencia de Ácido Ascórbico/complicaciones , Deficiencia de Ácido Ascórbico/diagnóstico , Deficiencia de Ácido Ascórbico/terapia , Proteína C-Reactiva/uso terapéutico , Colistina/uso terapéutico , Contractura/tratamiento farmacológico , Fatiga , Fibrinógeno/uso terapéutico , Humanos , Linezolid/uso terapéutico , Masculino , Persona de Mediana Edad , Protrombina/uso terapéutico , Insuficiencia Renal/tratamiento farmacológico , Escorbuto/complicaciones , Escorbuto/diagnóstico , Albúmina Sérica/uso terapéutico , Tromboplastina/uso terapéutico , Vancomicina/uso terapéutico , VitaminasRESUMEN
Joint immobilization is frequently administered after fractures and ligament injuries and can cause joint contracture as a side effect. The structures responsible for immobilization-induced joint contracture can be roughly divided into muscular and articular. During remobilization, although myogenic contracture recovers spontaneously, arthrogenic contracture is irreversible or deteriorates further. Immediately after remobilization, an inflammatory response is observed, characterized by joint swelling, deposit formation in the joint space, edema, inflammatory cell infiltration, and the upregulation of genes encoding proinflammatory cytokines in the joint capsule. Subsequently, fibrosis in the joint capsule develops, in parallel with progressing arthrogenic contracture. The triggers of remobilization-induced joint inflammation are not fully understood, but two potential mechanisms are proposed: 1) micro-damage induced by mechanical stress in the joint capsule, and 2) nitric oxide (NO) production via NO synthase 2. Some interventions can modulate remobilization-induced inflammatory and subsequent fibrotic reactions. Anti-inflammatory treatments, such as steroidal anti-inflammatory drugs and low-level laser therapy, can attenuate joint capsule fibrosis and the progression of arthrogenic contracture in remobilized joints. Antiproliferative treatment using the cell-proliferation inhibitor mitomycin C can also attenuate joint capsule fibrosis by inhibiting fibroblast proliferation without suppressing inflammation. Conversely, aggressive exercise during the early remobilization phases is counterproductive, because it facilitates inflammatory and then fibrotic reactions in the joint. However, the adverse effects of aggressive exercise on remobilization-induced inflammation and fibrosis are offset by anti-inflammatory treatment. To prevent the progression of arthrogenic contracture during remobilization, therefore, care should be taken to control inflammatory and fibrotic reactions in the joints.
Asunto(s)
Contractura , Antiinflamatorios/farmacología , Contractura/tratamiento farmacológico , Fibrosis , Humanos , Inflamación/patología , Articulación de la Rodilla , Rango del Movimiento ArticularRESUMEN
Bladder neck contracture (BNC), one of the most challenging complications after transurethral resection of the prostate (TURP) and photoselective vaporization of the prostate (PVP), lacks effective treatment. In the present study, our experience in treating BNC using GreenLight laser vaporization with triamcinolone acetonide (TA) injections was shared. This is a retrospective cohort study that included 46 patients with BNC after TURP and PVP in our center. GreenLight laser surgeries (180 W) were carried out and TA was administrated simultaneously. TA injections were repeated every week for three times after surgeries. The perioperative and postoperative parameters were reviewed and compared. Bladder neck tissues were examined by immunohistochemical staining to explore the expressions of collagen I, matrix metalloproteinase-3 (MMP-3), and transforming growth factor-ß (TGF-ß) after treatments. The chief complaint symptoms of all patients were significantly relieved after our treatments. None of them showed BNC recurrence during the follow-up. Complications were rare and mild. Postoperative assessments including maximal urinary flow rate (P < 0.01), International Prostate Symptom Score (P < 0.01), quality of life index (P < 0.01), and post-void residual volume (P < 0.001) were significantly better than baseline values, respectively. Immunohistochemical staining showed significantly lower expressions of collagen I (P < 0.001), MMP-3 (P < 0.001), and TGF-ß (P < 0.001) after treatments. In conclusion, 180-W GreenLight laser with repeated TA injections demonstrated the safety and long-term efficacy in treating BNC, by inhibiting the expressions of fibrotic factors. Our procedure was a promising treatment for BNC after PVP and TURP.
Asunto(s)
Contractura , Terapia por Láser , Hiperplasia Prostática , Resección Transuretral de la Próstata , Colágeno , Contractura/tratamiento farmacológico , Contractura/etiología , Humanos , Terapia por Láser/métodos , Rayos Láser , Masculino , Metaloproteinasa 3 de la Matriz , Hiperplasia Prostática/cirugía , Calidad de Vida , Estudios Retrospectivos , Factor de Crecimiento Transformador beta , Factores de Crecimiento Transformadores , Resección Transuretral de la Próstata/efectos adversos , Resultado del Tratamiento , Triamcinolona Acetonida/uso terapéutico , Vejiga Urinaria/cirugía , VolatilizaciónRESUMEN
BACKGROUND: Breast cancer is the most common malignancy among women worldwide. As survival rates increase, breast reconstruction and quality of life gain importance. Of all women undergoing breast reconstruction, approximately, 70% opt for silicone implants and 50% of those develop capsular contracture, the most prevalent long-term complication. The collagenase of the bacterium Clostridium histolyticum (CCH) showed promising results in the therapy of capsule contracture; however, its influence on residual cancer cells is unknown. The aim of this study was to investigate whether CCH-treatment negatively impacts breast cancer cells in vitro and in vivo. METHODS: MDA-MB-231 and MCF-7 cells were used in this study. In vitro, we tested the influence of CCH on proliferation, wound healing, migration and cell cycle by MTT-assay, scratch-assay, transwell-migration-assay, and flow cytometry. In vivo, solid tumors were induced in immune-deficient mice. CCH was injected into the tumors and tumor growth and metastasis formation was monitored by caliper measurement, in vivo bioluminescence imaging and histology. Gene expression analysis was performed by microarray including 27,190 genes. RESULTS: CCH-incubation led to a dose-dependent reduction in proliferation for both cell lines, while wound healing was reduced only in MDA-MB-231 cells. No morphological alterations were monitored in cell cycle or apoptosis. In vivo, bioluminescence imaging and histology did not show any evidence of metastasis. Although CCH led to changes in gene expression of breast cancer cells, no relevant alterations in metastasis-related genes were monitored. CONCLUSION: CCH has no impact on tumor growth or metastasis formation in vitro and in vivo. This paves the way for first clinical trials.
Asunto(s)
Neoplasias de la Mama , Contractura , Colagenasa Microbiana , Animales , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Clostridium histolyticum , Colagenasas/efectos adversos , Colagenasas/uso terapéutico , Contractura/tratamiento farmacológico , Contractura/metabolismo , Contractura/prevención & control , Femenino , Ratones , Colagenasa Microbiana/efectos adversos , Colagenasa Microbiana/uso terapéutico , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND: Capsular contracture (CC) is the most common long-term complication of breast surgery with prosthesis. Leukotriene receptor antagonists (LRAs) have been tested as a potential treatment; however, mixed results have been observed. OBJECTIVES: The aim of this study was to undertake a meta-analysis to clarify the treatment and prophylactic capabilities of LRAs in the management of CC. METHODS: A systematic literature search of the most popular English-language databases was performed to identify relevant primary publications. We included all studies that used the Baker scale to evaluate the treatment and preventive capabilities of LRAs. RESULTS: Six eligible studies were included based on predefined inclusion and exclusion criteria, totalling 2276 breasts, of which 775 did not receive LRAs and 1501 did. Final pooled results showed that LRAs could help manage CC with a risk difference (RD) of -0.38 with a corresponding 95% CI of -0.69 to -0.08, showing statistical significance at a Z value of 2.48, Pâ =â 0.01. Subgroup analysis based on the type of drug showed that only montelukast yielded statistical significance (RDâ =â -0.27, 95% CI = -0.51 to -0.03, Zâ =â 2.20, Pâ =â 0.03). Zafirlukast did not seem to influence CC. Further subgroup analysis based on treatment timing showed that prophylaxis was ineffective and only treatment for ongoing CC yielded statistically significant improvements. CONCLUSIONS: The current meta-analysis proved that LRAs could be used in the management of CC. Only treatment for ongoing CC showed statistically significant improvements. Montelukast seemed to be more efficient with a safer profile for adverse effects, whereas zafirlukast yielded no statistically significant results.
Asunto(s)
Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Contractura , Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Neoplasias de la Mama/etiología , Contractura/inducido químicamente , Contractura/tratamiento farmacológico , Femenino , Humanos , Contractura Capsular en Implantes/etiología , Contractura Capsular en Implantes/prevención & control , Antagonistas de Leucotrieno/uso terapéuticoRESUMEN
We present a case of a 53-year-old female patient who was treated with 5-Fluorouracil (5-FU) after postsurgical contracture. A review of the literature regarding the use of 5-FU injections as a minimally invasive way to treat contracture was performed. We describe that the use of 5-FU injections is the preferred method for the effective treatment of contracture with minimal risk to the patient.
Asunto(s)
Contractura/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Fluorouracilo/uso terapéutico , Procedimientos de Cirugía Plástica/efectos adversos , Absceso/etiología , Absceso/terapia , Antibacterianos/uso terapéutico , Contractura/etiología , Contractura/patología , Drenaje , Eritema , Cara/cirugía , Femenino , Humanos , Persona de Mediana Edad , Cuello/patología , Complicaciones Posoperatorias/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Systemic sclerosis (SSc; scleroderma) is an autoimmune connective tissue disease that affects the skin and subcutaneous tissue, in addition to the internal organs of the whole body. Onset in childhood is uncommon; however, both patients with childhood-onset and adult-onset SSc are positive for anti-nuclear antibodies (ANAs).Detection of SSc-related anti-nuclear antibodies is often useful for predicting clinical features, disease course, and outcomes. CASE PRESENTATION: A 5-year-old Japanese female manifested gradually progressive abnormal gait disturbance, regression of motor development, Raynaud's phenomenon, and the shiny appearance of the skin of the face and extremities at age 2. On admission, she presented a mask-like appearance, loss of wrinkles and skin folds, puffy fingers, moderate diffuse scleroderma (18/51 of the modified Rodnan total skin thickness score), and contracture in the ankle and proximal interphalangeal joints. Grossly visible capillary hemorrhage on nail fold and severe abnormal capillaroscopy findings including bleeding, giant loop and disappearance of capillaryconsistent with the late phase in SSc. A skin biopsy showed fibrous thickening of the dermis, entrapment of an eccrine sweat glands, and thickened fiber. Chest high-resolution computed tomographic scanning demonstrated patchy areas of ill-defined air-space opacity and consolidation predominantly involving the posterior basilar aspects of the lower lobes presenting withinterstitial lung disease. Positive ANA (1:160 nucleolar and homogeneous nuclear staining by indirect fluorescent antibody technique) and double-seropositive for anti-Th/To and anti-PM-Scl antibodies were identified. She was diagnosed with diffuse cutaneous SSc based on the Pediatric Rheumatology European Society/American College of Rheumatology/European League Against Rheumatism Provisional Classification Criteria for Juvenile Systemic Sclerosis and was successfully treated with immunosuppressive agents, including methylprednisolone pulses and intravenous cyclophosphamide. CONCLUSIONS: We experienced the first case of juvenile SSc with anti-PM-Scl and anti-Th/To antibodies. ILD was identified as a typical feature of patients with these autoantibodies; however, diffuse cutaneous SSc and joint contraction were uncharacteristically associated. The case showed unexpected clinical findings though the existence of SSc-related autoantibodies aids in determining possible organ involvement and to estimate the children's outcome.
Asunto(s)
Autoanticuerpos/sangre , Nucléolo Celular/inmunología , Contractura/sangre , Contractura/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Esclerodermia Sistémica/sangre , Preescolar , Contractura/etiología , Femenino , Humanos , Esclerodermia Sistémica/complicaciones , Resultado del TratamientoRESUMEN
PURPOSE: To present our preliminary experience in managing patients with highly recurrent bladder neck contractures (BNCs) after transurethral resection of the prostate (TURP). METHODS: Between February 2015 and March 2018, 28 patients with highly recurrent BNCs who had failed multiple prior to endoscopic treatments were managed with transurethral resection and intra- and post-operative triamcinolone acetonide injections. The scar tissue was resected to the circular fiber at the bladder neck, and triamcinolone acetonide (2 mL, 40 mg/mL) was injected at the incision sites (8 points) using a cystoscopic injection needle. The cystoscopy-guided injections were repeated every four weeks for total three times after surgery. The patients were followed up at 3, 6, 12 months after surgery, and in July-August 2019. RESULTS: The recurrent interval before the treatments was 2.2 ± 1.2 months, without any BNC recurrence in the first 12 weeks after transurethral resection. The urinary flow rate increased significantly and was maintained during the follow-up period. Adequate voiding function was reported in 25 of 28 patients at a median follow-up of 2.8 (1.7, 3.9) years. One of the three patients with decreased urinary flow rate had underactive detrusor and no BNC recurrence. The complications were mild and tolerable. CONCLUSION: Transurethral resection of the scar tissue combined with intra- and post-operative triamcinolone acetonide injections resulted in a success rate of 92.9% in patients with highly recurrent BNC following TURP. It is a simple, safe, and effective treatment for highly recurrent BNCs.
Asunto(s)
Contractura/tratamiento farmacológico , Contractura/cirugía , Glucocorticoides/administración & dosificación , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/cirugía , Resección Transuretral de la Próstata , Triamcinolona Acetonida/administración & dosificación , Enfermedades de la Vejiga Urinaria/tratamiento farmacológico , Enfermedades de la Vejiga Urinaria/cirugía , Anciano , Terapia Combinada , Humanos , Inyecciones Intralesiones , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Recurrencia , Procedimientos Quirúrgicos Urológicos Masculinos/métodosRESUMEN
Neonatal brachial plexus injury (NBPI) causes disabling and incurable contractures, or limb stiffness, which result from proteasome-mediated protein degradation impairing the longitudinal growth of neonatally denervated muscles. We recently showed in a mouse model that the 20S proteasome inhibitor, bortezomib, prevents contractures after NBPI. Given that contractures uniquely follow neonatal denervation, the current study tests the hypothesis that proteasome inhibition during a finite window of neonatal development can prevent long-term contracture development. Following neonatal forelimb denervation in P5 mice, we first outlined the minimum period for proteasome inhibition to prevent contractures 4 weeks post-NBPI by treating mice with saline or bortezomib for varying durations between P8 and P32. We then compared the ability of varying durations of longer-term proteasome inhibition to prevent contractures at 8 and 12 weeks post-NBPI. Our findings revealed that proteasome inhibition can be delayed 3-4 days after denervation but is required throughout skeletal growth to prevent contractures long term. Furthermore, proteasome inhibition becomes less effective in preventing contractures beyond the neonatal period. These therapeutic effects are primarily associated with bortezomib-induced attenuation of 20S proteasome ß1 subunit activity. Our collective results, therefore, demonstrate that temporary neonatal proteasome inhibition is not a viable strategy for preventing contractures long term. Instead, neonatal denervation causes a permanent longitudinal growth deficiency that must be continuously ameliorated during skeletal growth. Additional mechanisms must be explored to minimize the necessary period of proteasome inhibition and reduce the risk of toxicity from long-term treatment.
Asunto(s)
Bortezomib/uso terapéutico , Contractura/prevención & control , Parálisis Neonatal del Plexo Braquial/tratamiento farmacológico , Inhibidores de Proteasoma/uso terapéutico , Animales , Bortezomib/administración & dosificación , Bortezomib/farmacología , Contractura/tratamiento farmacológico , Ratones , Parálisis Neonatal del Plexo Braquial/prevención & control , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteasoma/administración & dosificación , Inhibidores de Proteasoma/farmacología , Sarcómeros/efectos de los fármacos , Sarcómeros/metabolismoRESUMEN
PURPOSE: Shoulder internal rotation contractures (IRC) are common sequela of brachial plexus birth injuries (BPBI). Botulinum toxin A (BTX-A) injection into targeted muscles has been described to facilitate functional improvement at the shoulder joint and prevent glenohumeral dysplasia. The purpose of this study was to assess the outcomes of BTX-A injections on shoulder IRC in children with BPBI. METHODS: We conducted a retrospective analysis of 47 children with shoulder IRC due to BPBI, who were treated with BTX-A. Shoulder passive external rotation in adduction and Active Movement Scale external rotation scores were recorded before and after BTX-A injection. We also recorded the number of children who underwent secondary surgical balancing procedures to improve shoulder motion after BTX-A injection. RESULTS: Mean age at the time of injection was 12 months (range, 5-23 months). Subjects demonstrated a significant increase in passive external rotation of 46° (range, 10° to 90) at 4 months; an average improvement of 18° (range, -30° to 80°) persisted at 11 months after injection. A total of 28 patients (60%) underwent subsequent external rotation tendon transfer. At 5-year follow-up, 7 patients (15%) had adequate functional shoulder range of motion and did not undergo external rotation tendon transfer. CONCLUSIONS: Botulinum toxin A injections result in improvement in IRC due to BPBI, which is sustained beyond the expected half-life of 3 months. As many as 15% of patients who have this treatment avoid external rotation tendon transfer. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.
Asunto(s)
Traumatismos del Nacimiento , Toxinas Botulínicas , Neuropatías del Plexo Braquial , Plexo Braquial , Contractura , Articulación del Hombro , Traumatismos del Nacimiento/complicaciones , Traumatismos del Nacimiento/tratamiento farmacológico , Toxinas Botulínicas/uso terapéutico , Plexo Braquial/lesiones , Neuropatías del Plexo Braquial/tratamiento farmacológico , Contractura/tratamiento farmacológico , Contractura/etiología , Humanos , Lactante , Rango del Movimiento Articular , Estudios Retrospectivos , Rotación , HombroRESUMEN
INTRODUCTION: H Syndrome is an autosomal recessive (AR) disease caused by defects in SLCA29A3 gene. This gene encodes the equilibrative nucleoside transporter, the protein which is highly expressed in spleen, lymph node and bone marrow. Autoinflammation and autoimmunity accompanies H Syndrome (HS). AIM: The aim was to further elucidate the mechanisms of disease by molecular studies in a patient with SLC29A3 gene defect. PATIENT AND METHODS: Mitochondrial dysfunction, lysosomal integrity, cytokine response in response to stimulation with different pattern recognition receptor ligands, and circulating cell-free mitochondrial-DNA(ccf-mtDNA) level in plasma were analyzed compared to controls to understand the cellular triggers of autoinflammation. RNA sequencing (RS) analyses were also performed in monocytes before/after culture with lipopolysaccharide. RESULTS: Patient had progressive destructive arthropathy in addition to clinical findings due to combined immunodeficiency. Pure red cell aplasia (PRCA), vitiligo, diabetes, multiple autoantibody positivity, lymphopenia, increased acute phase reactants were present. Recent thymic emigrants (RTE), naïve T cells were decreased, effector memory CD4 + T cells, nonclassical inflammatory monocytes were increased. Patient's peripheral blood mononuclear cells secreted more IL-1ß and IL-6, showed lysosomal disruption and significant mitochondrial dysfunction compared to healthy controls. Plasma ccf-mtDNA level was significantly elevated compared to age-matched controls (p < 0.05). RNA sequencing studies revealed decreased expression of NLR Family Caspase Recrument-Domain Containing 4(NLRC4), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4(PFKFB4), serine dehydratase(SDS), heparan sulfate(Glucosamine) 3-O-sulfotransferase 1(HS3ST1), neutral cholesterol ester hydrolase 1 (NCEH1), and interleukin-8 (IL-8) in patient's monocytes compared to controls. Longstanding PRCA, which is possibly autoimmune, resolved after initiating monthly intravenous immunoglobulins (IVIG) and low dose steroids to the patient. CONCLUSION: Although autoinflammation and autoimmunity are reported in HS, by functional analyses we here show in the present patient that over-active inflammasome pathway in HS might be related with mitochondrial and lysosomal dysfunction. Increased plasma ccf-mtDNA may be used as a biomarker of inflammasomopathy in HS. HS should be included in the classification of primary immunodeficiency diseases.
Asunto(s)
Autoinmunidad/genética , Contractura/genética , Pérdida Auditiva Sensorineural/genética , Histiocitosis/genética , Síndromes de Inmunodeficiencia/genética , Proteínas de Transporte de Nucleósidos/genética , Adolescente , Contractura/tratamiento farmacológico , Contractura/inmunología , Contractura/patología , Glucocorticoides/uso terapéutico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Sensorineural/inmunología , Pérdida Auditiva Sensorineural/patología , Histiocitosis/tratamiento farmacológico , Histiocitosis/inmunología , Histiocitosis/patología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/patología , Inflamasomas/inmunología , Lisosomas/inmunología , Lisosomas/patología , Masculino , Mitocondrias/inmunología , Mitocondrias/patología , Resultado del TratamientoAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Contractura/tratamiento farmacológico , Interleucina-17/genética , Mutación , Enfermedades Cutáneas Genéticas/tratamiento farmacológico , Piel/patología , Adolescente , Contractura/genética , Contractura/patología , Femenino , Humanos , Interleucina-17/antagonistas & inhibidores , Enfermedades Cutáneas Genéticas/genética , Enfermedades Cutáneas Genéticas/patología , Secuenciación del ExomaRESUMEN
Eosinophilic fasciitis (EF) is a rare form of fibrosing disorder associated with peripheral eosinophilia with scleroderma-like skin induration and fasciitis in the extremities resulting in painful swelling, erythema and progressive contracture. We present a case report of EF and a literature review to raise awareness of this unusual condition and also highlight key features in its management.