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1.
J Neurochem ; 168(9): 2495-2514, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38515326

RESUMEN

As persistent elevation of transforming growth factor-ß (TGF-ß) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF-ß would be effective against both exacerbations. The effects of TGF-ß and its inhibitor on myoblasts and fibroblasts were tested in vitro and confirmed in vivo, and the dual action of a TGF-ß inhibitor in ameliorating the pathogenic role of TGF-ß in ALS mice was identified. In the peripheral neuromuscular system, fibrosis in the muscles and joint cavities induced by excessive TGF-ß causes joint contracture and muscular degeneration, which leads to motor dysfunction. In an ALS mouse model, an increase in TGF-ß in the central nervous system (CNS), consistent with astrocyte activity, was associated with M1 microglial activity and pro-inflammatory conditions, as well as with neuronal cell death. Treatment with the TGF-ß inhibitor halofuginone could prevent musculoskeletal fibrosis, resulting in the alleviation of joint contracture and delay of motor deterioration in ALS mice. Halofuginone could also reduce glial cell-induced neuroinflammation and neuronal apoptosis. These dual therapeutic effects on both the neuromuscular system and the CNS were observed from the beginning to the end stages of ALS; as a result, treatment with a TGF-ß inhibitor from the early stage of disease delayed the time of symptom exacerbation in ALS mice, which led to prolonged survival.


Asunto(s)
Esclerosis Amiotrófica Lateral , Contractura , Factor de Crecimiento Transformador beta , Animales , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/metabolismo , Ratones , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Contractura/tratamiento farmacológico , Contractura/prevención & control , Ratones Transgénicos , Masculino , Ratones Endogámicos C57BL , Piperidinas/farmacología , Piperidinas/uso terapéutico , Humanos
2.
Clin Genet ; 105(3): 283-293, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38009810

RESUMEN

The Erb-B2 receptor tyrosine kinase 3 (ERBB3) gene was first identified as a cause of lethal congenital contracture syndrome (OMIM 607598), while a recent study reported six additional patients carrying ERBB3 variants which exhibited distinct clinical features with evident intestinal dysmotility (OMIM 243180). The potential connection between these phenotypes remains unknown, and the ERBB3-related phenotype spectrum needs to be better characterized. Here, we described a patient presenting with a multisystemic syndrome including skip segment Hirschsprung disease, bilateral clubfoot deformity, and cardiac defect. Trio-whole exome sequencing revealed a novel compound heterozygous variant (c.1914-7C>G; c.2942_2945del) in the patient's ERBB3 gene. RT-PCR and in vitro minigene analysis demonstrated that variant c.1914-7C>G caused aberrant mRNA splicing. Both variants resulted in premature termination codon and complete loss of ERBB3 function. erbb3b knockdown in zebrafish simultaneously caused a reduction in enteric neurons in the distal intestine, craniofacial cartilage defects, and micrognathia, which phenotypically mimics ERBB3-related intestinal dysmotility and some features of lethal congenital contracture syndrome in human patients. These findings provide further patient and animal evidence supporting that ERBB3 deficiency causes a complex syndrome involving multiple systems with phenotypic variability among distinct individuals.


Asunto(s)
Contractura , Enfermedad de Hirschsprung , Animales , Humanos , Enfermedad de Hirschsprung/genética , Fenotipo , Receptor ErbB-3/genética , Síndrome , Pez Cebra/genética
3.
FASEB J ; 37(5): e22842, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37000501

RESUMEN

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/patología
4.
Am J Med Genet A ; 194(11): e63713, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38924631

RESUMEN

Haploinsufficiency of FOXP1 gene is responsible for a neurodevelopmental disorder presenting with intellectual disability (ID), autism spectrum disorder (ASD), hypotonia, mild dysmorphic features, and multiple congenital anomalies. Joint contractures are not listed as a major feature of FOXP1-related disorder. We report five unrelated individuals, each harboring likely gene disruptive de novo FOXP1 variants or whole gene microdeletion, who showed multiple joint contractures affecting at least two proximal and/or distal joints. Consistent with the phenotype of FOXP1-related disorder, all five patients showed developmental delay with moderate-to-severe speech delay, ID, ASD, and facial dysmorphic features. FOXP1 is implicated in neuronal differentiation and in organizing motor axon projections, thus providing a potential developmental basis for the joint contractures. The combination of joint contractures and neurodevelopmental disorders supports the clinical suspicion of FOXP1-related phenotype.


Asunto(s)
Contractura , Factores de Transcripción Forkhead , Trastornos del Neurodesarrollo , Fenotipo , Proteínas Represoras , Humanos , Factores de Transcripción Forkhead/genética , Masculino , Femenino , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/patología , Niño , Contractura/genética , Contractura/patología , Contractura/diagnóstico , Preescolar , Proteínas Represoras/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Trastorno del Espectro Autista/fisiopatología , Haploinsuficiencia/genética , Adolescente
5.
Connect Tissue Res ; 65(3): 187-201, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38517297

RESUMEN

PURPOSE: Non-weight bearing improves and immobilization worsens contracture induced by anterior cruciate ligament reconstruction (ACLR), but effect persistence after reloading and remobilization remains unclear, and the combined effects of these factors on ACLR-induced contracture are unknown. We aimed to determine 1) whether the effects of short-term (2-week) non-weight bearing or immobilization after ACLR on contracture would be sustained by reloading or remobilization during a 10-week observation period, and 2) how the combination of both interventions compared to the outcome of either alone. METHODS: We divided 88 ACL-reconstructed male rats into four groups: non-intervention, non-weight bearing, joint immobilization, and both interventions. Interventions were performed for 2 weeks, followed by rearing without intervention. Twelve untreated rats were used as controls. At 2, 4, and 12 weeks post-surgery, we assessed range of motion (ROM) and histological changes. RESULTS: ACLR resulted in persistent loss of ROM, accompanied by synovial shortening, capsule thickening, and osteophyte formation. Two weeks of non-weight bearing increased ROM and reduced osteophyte size, but the beneficial effects disappeared within 10 weeks after reloading. Two-week immobilization decreased ROM and facilitated synovial shortening. After remobilization, ROM partially recovered but remained below non-intervention levels at 12 weeks. When both interventions were combined, ROM was similar to immobilization alone. CONCLUSIONS: The beneficial effects of 2-week non-weight bearing on contracture diminished within 10 weeks after reloading. The adverse effects of 2-week immobilization on contracture persisted after 10 weeks of remobilization. The effects of the combined use of both interventions on contracture were primarily determined by immobilization.


Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior , Contractura , Inmovilización , Rango del Movimiento Articular , Animales , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Contractura/patología , Contractura/etiología , Contractura/fisiopatología , Masculino , Inmovilización/efectos adversos , Ratas , Ratas Sprague-Dawley , Soporte de Peso
6.
Connect Tissue Res ; : 1-10, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140391

RESUMEN

PURPOSE: Joint contracture is a common disease in clinical practice, joint bleeding is an important factor affecting the progression of joint contracture. This study aimed to explore the effect of extracorporeal shock wave on alleviating joint capsule fibrosis caused by intra-articular hemorrhage in rats. METHODS: Forty two SD rats were randomly divided into seven groups. Perform simple fixation and fixation after blood injection separately. Measure the range of motion of each group's knee joints and calculate the corresponding degree of contraction. Use HE staining and Masson staining to detect the number of anterior joint capsule cells and collagen deposition. Detection of changes in Wnt1, ß-catenin protein expression in joint capsule using Western blotting. RESULTS: Compared to group C, the degree of knee joint contracture in M1 and M2 groups of rats increased, and collagen deposition, cell number and Wnt1, ß-catenin protein expression also increased accordingly. Compared to M1 and M2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, ß-catenin protein expression were decreased, and the degree of joint contracture in NR1 and NR2 groups showed no significant improvement. Compared to NR1 and NR2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, ß-catenin protein expression were decreased. CONCLUSIONS: Both rat models of knee joint contracture were successful, and joint bleeding can exacerbate joint contracture. Extracorporeal shock waves alleviate joint capsule fibrosis caused by intra-articular bleeding in rats.

7.
World J Urol ; 42(1): 195, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38530433

RESUMEN

PURPOSE: Bladder neck stricture (BNS) is a bothersome disease which may affect patients after trauma or prostatic surgery. It is frustrating due to the low durable success rate of currently available surgical techniques. The aim of the study is to explore the efficacy of a novel technique. MATERIALS & METHODS: The surgical protocol was developed by two high case-volume surgeons. The technique consists of Holmium laser incisions at 3-6-9-12 o'clock. Subsequently, triamcinolone acetonide 40 mg is injected. Two months later, the BNS is endoscopically checked in operatory room and re-procedure take place, if necessary (max 3 times). Failure was defined as the need of definitive urinary diversion. Subjective satisfaction was measured through PGI-I Questionnaire. RESULTS: A total of 45 patients were enrolled. Median age was 63 (IQR 59-69) years and BNS developed by different causes. Naïve BNS procedure patients were 12 (26.7%), others 33 (73.3%) underwent median 2 (IQR 1-4) previous urethrotomies, including 16 other surgeries. Suprapubic bladder catheter was present in 34 patients (75.6%). No complications were registered. Re-procedure at control was necessary in 24 patients (53.3%) for a median of 1 (IQR 1-3) procedures. At median follow-up of 18 months, failures were 4 (8.9%) and urinary incontinence was reported in 2 patients (4.5%) who required incontinence surgery. Median PGI-I was 2. CONCLUSIONS: Our technique of BNS treatment allows good outcomes and high rate of subjective improvement amongst patients. Moreover, naïve patients seem to have better results. However, longer follow-up and higher sample size are mandatory to further assess these data.


Asunto(s)
Contractura , Obstrucción del Cuello de la Vejiga Urinaria , Incontinencia Urinaria , Humanos , Persona de Mediana Edad , Vejiga Urinaria/cirugía , Resultado del Tratamiento , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Incontinencia Urinaria/etiología , Enfermedad Iatrogénica
8.
World J Urol ; 42(1): 172, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38506927

RESUMEN

PURPOSE: To compare the outcomes of patients undergoing robotic YV plasty for bladder neck contracture (BNC) vs. vesico-urethral anastomotic stricture (VUAS). METHODS: A retrospective study included male patients who underwent robotic YV plasty for BNC after endoscopic treatment of BPH or VUAS between August 2019 and March 2023 at a single academic center. The primary assessed was the patency rate at 1 month post-YV plasty and during the last follow-up visit. RESULTS: A total of 21 patients were analyzed, comprising 6 in the VUAS group and 15 in the BNC group. Patients with VUAS had significantly longer operative times (277.5 vs. 146.7 min; p = 0.008) and hospital stay (3.2 vs. 1.7 days; p = 0.03). Postoperative complications were more common in the VUAS group (66.7% vs. 26.7%; p = 0.14). All patients resumed spontaneous voiding postoperatively. Five patients (23.8%) who developed de novo stress urinary incontinence had already an AUS (n = 1) or required concomitant AUS implantation (n = 3), all of whom were in the VUAS group (83.3% vs. 0%; p < 0.0001). The proportion of patients improved was similar in both groups (PGII = 1 or 2: 83.3% vs. 80%; p = 0.31). Stricture recurrence occurred in 9.5% of patients in the whole cohort, with no significant difference between the groups (p = 0.50). Long-term reoperation was required in three VUAS patients, showing a statistically significant difference between the groups (p = 0.05). CONCLUSION: Robotic YV plasty is feasible for both VUAS and BNC. While functional outcomes and stricture-free survival may be similar for both conditions, the perioperative outcomes were less favorable for VUAS patients.


Asunto(s)
Contractura , Procedimientos Quirúrgicos Robotizados , Estrechez Uretral , Obstrucción del Cuello de la Vejiga Urinaria , Humanos , Masculino , Vejiga Urinaria/cirugía , Constricción Patológica/etiología , Constricción Patológica/cirugía , Procedimientos Quirúrgicos Robotizados/efectos adversos , Estudios Retrospectivos , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Obstrucción del Cuello de la Vejiga Urinaria/complicaciones , Contractura/cirugía , Estrechez Uretral/etiología , Estrechez Uretral/cirugía , Prostatectomía/efectos adversos
9.
World J Urol ; 42(1): 14, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38189837

RESUMEN

PURPOSE: Bladder neck contracture (BNC) is a rare but intolerant complication after transurethral surgery of prostate. The present study aims to investigate the incidence and risk factors of BNC in patients diagnosed benign prostate hyperplasia (BPH) and following transurethral resection or enucleation of the prostate (TURP/TUEP). METHODS: This retrospective study included 1008 BPH individuals who underwent transurethral surgery of the prostate between January 2017 and January 2022. Patients' demographics, medical comorbidities, urologic characteristics, perioperative parameters, and the presence of BNC were documented. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: A total of 2% (20/1008) BPH patients developed BNC postoperatively and the median occurring time was 5.8 months. Particularly, the incidences of BNC were 4.7% and 1.3% in patients underwent Bipolar-TURP and TUEP respectively. Preoperative urinary tract infection (UTI), elevated PSA, smaller prostate volume (PV), bladder diverticulum (BD), and B-TURP were significantly associated with BNC in the univariate analysis. Further multivariate logistic regression demonstrated preoperative UTI (OR 4.04, 95% CI 2.25 to 17.42, p < 0.001), BD (OR 7.40, 95% CI 1.83 to 31.66, p < 0.001), and B-TURP (OR 3.97, 95% CI 1.55 to 10.18, p = 0.004) as independent risk factors. All BNC patients were treated with transurethral incision of the bladder neck (TUIBN) combined with local multisite injection of betamethasone. During a median follow-up of 35.8 months, 35% (7/20) of BNC patients recurred at a median time of 1.8 months. CONCLUSION: BNC was a low-frequency complication following transurethral surgery of prostate. Preoperative UTI, BD, and B-TURP were likely independent risk factors of BNC. TUIBN combined with local multisite injection of betamethasone may be promising choice for BNC treatment.


Asunto(s)
Contractura , Hiperplasia Prostática , Masculino , Humanos , Vejiga Urinaria , Próstata , Estudios Retrospectivos , Hiperplasia Prostática/cirugía , Contractura/epidemiología , Contractura/etiología , Betametasona
10.
Int J Hyperthermia ; 41(1): 2350759, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38719202

RESUMEN

INTRODUCTION: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thermal ablation is an effective noninvasive ultrasonic therapy to disrupt in vivo porcine tendon but is prone to inducing skin burns. We evaluated the safety profile of a novel hybrid protocol that minimizes thermal spread by combining long-pulse focused ultrasound followed by thermal ablation. METHODS: In-vivo Achilles tendons (hybrid N = 15, thermal ablation alone N = 21) from 15 to 20 kg Yorkshire pigs were randomly assigned to 6 treatment groups in two studies. The first (N = 21) was ablation (600, 900, or 1200 J). The second (N = 15) was hybrid: pulsed FUS (13.5 MPa peak negative pressure) followed by ablation (600, 900, or 1200 J). Measurements of ankle range of motion, tendon temperature, thermal dose (240 CEM43), and assessment of skin burn were performed in both groups. RESULTS: Rupture was comparable between the two protocols: 1/5 (20%), 5/5 (100%) and 5/5 (100%) for hybrid protocol, compared to 2/7 (29%), 6/7 (86%) and 7/7 (100%) for the ablation-only protocol with energies of 600, 900, and 1200 J, respectively. The hybrid protocol produced lower maximum temperatures, smaller areas of thermal dose, fewer thermal injuries to the skin, and fewer full-thickness skin burns. The standard deviation for the area of thermal injury was also smaller for the hybrid protocol, suggesting greater predictability. CONCLUSION: This study demonstrated a hybrid MRgFUS protocol combining long-pulse FUS followed by thermal ablation to be noninferior and safer than an ablation-only protocol for extracorporeal in-vivo tendon rupture for future clinical application for noninvasive release of contracted tendon.


Asunto(s)
Imagen por Resonancia Magnética , Animales , Porcinos , Imagen por Resonancia Magnética/métodos , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Tendones/diagnóstico por imagen , Terapia por Ultrasonido/métodos
11.
Arch Phys Med Rehabil ; 105(10): 1985-1992, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38866227

RESUMEN

OBJECTIVE: To systematically evaluate the effects of extracorporeal shockwave therapy (ESWT) on pain, clinical and functional outcomes, and satisfaction of patients with Dupuytren disease. DATA SOURCES: A thorough search for all the study types published in English was conducted in PubMed, Scopus, Web of Science, and Embase from inception to August 31, 2022. STUDY SELECTION: Title and abstract and then full-text screening against eligibility criteria was performed independently by 2 reviewers, and a third reviewer achieved consensus. DATA EXTRACTION: Reviewers identified 26 studies, of which 6 were included in the analysis (145 cases). The methodological quality was assessed using the National Heart, Lung, and Blood Institute and the Joanna Briggs Institute checklists. The certainty of evidence was evaluated using the Grading of Recommendation Assessment, Development, and Evaluation. DATA SYNTHESIS: Assessments represented a remarkable improvement in the pain and function through the measurements including the visual analog scale, the Disabilities of Arm Shoulder and Hand Questionnaire, the Michigan Hand Outcome Questionnaire, and Mayo Wrist Score. Patients' satisfaction was also favorable using the Roles and Maudsley score. The hand grip strength improvement was noted in one study measured via a Jamar dynamometer. In addition, the ultrasonographic assessment of the nodules revealed a decrease in the size of the nodules in a patient with multiple bilateral nodules after the treatment. The quality of the included studies was good for all studies except for one that was fair. The certainty of evidence was moderate for pain and function and was low for patients' satisfaction and ultrasonographic findings. CONCLUSIONS: ESWT can lead to significant pain improvement, functional rehabilitation, and patient satisfaction with no adverse effect in the management of Dupuytren disease. Pain may return over time, but not to that severity before the intervention. ESWT-related characteristics and the need for continuation of treatment remain to be fully elucidated in future large clinical trials.


Asunto(s)
Contractura de Dupuytren , Tratamiento con Ondas de Choque Extracorpóreas , Humanos , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Contractura de Dupuytren/rehabilitación , Contractura de Dupuytren/terapia , Contractura de Dupuytren/fisiopatología , Satisfacción del Paciente , Fuerza de la Mano , Dimensión del Dolor , Evaluación de la Discapacidad
12.
BMC Urol ; 24(1): 118, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858691

RESUMEN

PURPOSE: To present the experience of ileal ureter with ileocystoplasty (IUC), and compare the outcomes of IUC in minimally invasive procedures to open procedures. PATIENTS AND METHODS: From December 2017 to April 2023, twenty patients underwent IUC in open or minimally invasive (including laparoscopic and robotic) procedures. The baseline characteristics, perioperative data and follow-up outcomes were collected. Success was defined as relief of clinical symptoms, stable postoperative serum creatine and absence of radiographic obstruction. The perioperative and follow-up outcomes of open procedures and minimally invasive procedures were compared. RESULTS: The etiology included pelvic irradiation (14/20), urinary tuberculosis (3/20) and surgical injury (3/20). Bilateral ureter strictures were repaired in 15 cases. The surgeries conducted consisted of open procedures in 9 patients and minimally invasive procedures in 11 patients. Compared to open procedures, minimally invasive surgeries had less median estimated blood loss (EBL) (100 ml vs. 300 min, p = 0.010) and shorter postoperative hospitalization (27 d vs. 13 d, p = 0.004). Two patients in the open group experienced grade 3 complications (sigmoid fistula and acute cholecystitis in one patient, and pulmonary embolism in another patient). Over a median follow-up period of 20.1 months, the median bladder functional capacity was 300 ml, with a 100% success rate of IUC. CONCLUSION: IUC is feasible in both open and minimally invasive procedures, with acceptable complications and a high success rate. Minimally invasive procedures can have less EBL and shorter postoperative hospitalization than open procedure. However, prospective studies with larger groups and longer follow-up are needed.


Asunto(s)
Íleon , Procedimientos Quirúrgicos Mínimamente Invasivos , Uréter , Vejiga Urinaria , Procedimientos Quirúrgicos Urológicos , Humanos , Masculino , Femenino , Íleon/cirugía , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Vejiga Urinaria/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Uréter/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estudios Retrospectivos , Factores de Tiempo , Laparoscopía/métodos , Anciano , Procedimientos Quirúrgicos Robotizados
13.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-34161280

RESUMEN

Osteogenesis imperfecta (OI) is a genetic disorder that features wide-ranging defects in both skeletal and nonskeletal tissues. Previously, we and others reported that loss-of-function mutations in FK506 Binding Protein 10 (FKBP10) lead to skeletal deformities in conjunction with joint contractures. However, the pathogenic mechanisms underlying joint dysfunction in OI are poorly understood. In this study, we have generated a mouse model in which Fkbp10 is conditionally deleted in tendons and ligaments. Fkbp10 removal substantially reduced telopeptide lysyl hydroxylation of type I procollagen and collagen cross-linking in tendons. These biochemical alterations resulting from Fkbp10 ablation were associated with a site-specific induction of fibrosis, inflammation, and ectopic chondrogenesis followed by joint deformities in postnatal mice. We found that the ectopic chondrogenesis coincided with enhanced Gli1 expression, indicating dysregulated Hedgehog (Hh) signaling. Importantly, genetic inhibition of the Hh pathway attenuated ectopic chondrogenesis and joint deformities in Fkbp10 mutants. Furthermore, Hh inhibition restored alterations in gait parameters caused by Fkbp10 loss. Taken together, we identified a previously unappreciated role of Fkbp10 in tendons and ligaments and pathogenic mechanisms driving OI joint dysfunction.


Asunto(s)
Condrocitos/patología , Articulaciones/fisiopatología , Actividad Motora , Osteogénesis Imperfecta/fisiopatología , Osteogénesis , Proteínas de Unión a Tacrolimus/metabolismo , Animales , Animales Recién Nacidos , Condrogénesis/genética , Colágeno Tipo I/metabolismo , Modelos Animales de Enfermedad , Fibrosis , Marcha , Eliminación de Gen , Regulación de la Expresión Génica , Proteínas Hedgehog/metabolismo , Hidroxilación , Inflamación/genética , Inflamación/patología , Articulaciones/patología , Ligamentos/patología , Lisina/metabolismo , Ratones , Modelos Biológicos , Osificación Heterotópica/complicaciones , Osificación Heterotópica/genética , Osificación Heterotópica/patología , Osificación Heterotópica/fisiopatología , Osteogénesis/genética , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patología , Péptidos/metabolismo , Análisis de Secuencia de ARN , Transducción de Señal , Proteínas de Unión a Tacrolimus/genética , Tendones/patología
14.
Pediatr Dermatol ; 41(4): 688-691, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38291559

RESUMEN

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 Combinada
15.
Urol Int ; 108(5): 442-448, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38740009

RESUMEN

INTRODUCTION: Benign prostatic enlargement (BPE) and lower urinary tract symptoms present challenges in aging men, often addressed through transurethral resection of the prostate (TURP). Despite technological advancements, bladder neck contracture (BNC) remains a concern. This study explores predictors, including comorbidities, influencing BNC after TURP. METHODS: A retrospective cohort study at Changhua Christian Hospital analyzed 2041 BPE patients undergoing bipolar TURP. Preoperative urinary catheterization and resection speed were categorized. Patient data included demographics, comorbidities, operative details, and outcomes. Statistical analyses utilized χ2, Kruskal-Wallis tests, and Cox regression models. RESULTS: Within 3 years, 306 (15%) patients developed BNC. Univariate Cox regression identified chronic heart failure (p = 0.033), chronic obstructive pulmonary disease (COPD; p = 0.002), preoperative urinary catheterization (p < 0.001), and low resection speed (p = 0.045) as significant BNC risk factors. Notably, COPD (p = 0.011) and preoperative urinary catheterization (p < 0.001) emerged as independent risk factors for BNC development in multivariate Cox regression analysis. CONCLUSIONS: Preoperative urinary catheterization and COPD were significant predictors of BNC post-TURP, while resection speed showed no significant influence. These findings offer clinicians insights for risk assessment, enhancing patient outcomes, and optimizing resources post-TURP.


Asunto(s)
Hiperplasia Prostática , Resección Transuretral de la Próstata , Humanos , Masculino , Estudios Retrospectivos , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/complicaciones , Anciano , Factores de Riesgo , Resección Transuretral de la Próstata/efectos adversos , Persona de Mediana Edad , Contractura/etiología , Contractura/cirugía , Complicaciones Posoperatorias/etiología , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Cateterismo Urinario , Vejiga Urinaria/cirugía , Anciano de 80 o más Años , Enfermedad Pulmonar Obstructiva Crónica/complicaciones
16.
BMC Musculoskelet Disord ; 25(1): 803, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39394126

RESUMEN

BACKGROUND: Musculoskeletal alterations causing reduced range of motion of the ankle joint are common in children with cerebral palsy (CP). Objective measurements of passive joint resistance and three-dimensional skeletal muscle volume and muscle architecture can lead to a comprehensive understanding of which factors influence joint range of motion. RESEARCH QUESTION: To investigate the relation between the passive dorsiflexion of the ankle joint, biomechanical contributing factors to the passive joint resistance, and muscular architectural properties of the triceps surae muscle in children with CP. METHODS: In this cross-sectional observational study, 14 children with spastic CP (bilateral: 5, unilateral: 9, Gross Motor Function Classification System (GMFCS) level I:11, II:3) naïve to intramuscular tone reducing treatment, and 14 TD children were included. The passive dorsiflexion of the ankle was measured with a goniometer. Passive joint resistance and related parameters were estimated based on a biomechanical model and measurements using a motorized device, the Neuroflexor. Three-dimensional muscle architecture was quantified with diffusion tensor magnetic resonance imaging (DT-MRI). RESULTS: In the CP group, the median [min, max] passive dorsiflexion was decreased in the most affected leg (MAL) compared to the less affected leg (LAL) (2.5° [-25°, 20°] vs. 12.5° [5°, 30°], p = 0.001). The stiffness coefficient (Nm/rad) in the MAL was significantly higher in children with CP compared to TD children (7.10 [3.39, 62.00] vs. 2.82 [1.24, 10.46], p = 0.015). Muscle architecture properties did not differ between CP and TD, except for pennation angle in the medial gastrocnemius (MG) of the MAL (CP 17.64° (2.29) vs. TD 21.46° (3.20), p = 0.017). The stiffness coefficient, in the MAL, correlated negatively to passive dorsiflexion (rs=-0.638) and pennation angle in medial gastrocnemius (rs=-0.964), and the non-linear coefficient (Non-linear 1) correlated negatively to the fascicle length of the medial gastrocnemius (rs=-0.857). CONCLUSION: This study shows that stiffness of the plantarflexors is related to decreased passive dorsiflexion of the ankle and muscle structure of the MG in high-functioning children with spastic CP. Assessments of how dynamic components as well as microscopic muscle alterations contribute to joint stiffness in the plantarflexors in individuals with CP are warranted. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov, NCT05447299. Observational study. Study start: 2019-01-15, register date: 2022-07-01.


Asunto(s)
Articulación del Tobillo , Parálisis Cerebral , Imagen de Difusión Tensora , Músculo Esquelético , Rango del Movimiento Articular , Humanos , Parálisis Cerebral/fisiopatología , Parálisis Cerebral/diagnóstico por imagen , Parálisis Cerebral/patología , Niño , Masculino , Estudios Transversales , Femenino , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiopatología , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/fisiopatología , Adolescente , Fenómenos Biomecánicos/fisiología
17.
J Hand Surg Am ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38703146

RESUMEN

PURPOSE: Multiple procedures have been described for wrist and finger flexion contractures and spasticity. Fractional lengthening of forearm flexor tendons involves making parallel transverse tenotomies at the musculotendinous junction to elongate the muscle. Currently, there is limited literature to define the biomechanical consequences of this lengthening technique. METHODS: Forty-eight flexor tendons were harvested from eight paired upper limbs including flexor carpi radialis, flexor carpi ulnaris, flexor pollicis longus, and flexor digitorum superficialis tendons. Each tendon that was lengthened was paired with the contralateral tendon as a control. A pair of transverse tenotomies were completed for the fractional lengthening. The first tenotomy was performed at the musculotendinous junction where the tendon narrowed to 75% of its maximal width. The second tenotomy was made 1 cm distal to the first. Tendon length was measured before and after fractional lengthening at a constant resting tension of 1 N. The maximum load at failure of each tendon and the mechanism of failure were each measured and compared with the contralateral side. RESULTS: After fractional lengthening, the mean increase in resting tendon length was 4 mm. When loaded to failure, the mean maximum load of fractionally lengthened tendons was 42% of the mean maximum load of intact tendons. All lengthened tendons failed at the distal tenotomy site. CONCLUSIONS: Fractional lengthening resulted in an increase of 3-6 mm (mean: 4 mm) in tendon length at resting tension. There was a significant loss in tensile strength and load to failure following fractional lengthening compared with an intact musculotendinous unit. CLINICAL RELEVANCE: The reduction in tensile strength following fractional lengthening results in loads at failure that are, in some cases, lower than the estimated forces required to perform basic tasks. Caution during the healing and rehabilitation period is warranted.

18.
J Hand Surg Am ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39352349

RESUMEN

PURPOSE: Flexion contracture of the elbow is a common deformity associated with brachial plexus birth palsy and is often managed with preventive night orthoses. For severe cases, however, surgical interventions may become necessary. This study evaluated the effectiveness of surgically releasing elbow flexion contractures exceeding 30° through partial tenotomy of the brachialis and biceps brachii muscles, along with a division of the lacertus fibrosus. METHODS: We performed 36 anterior elbow releases on patients with injury to the upper trunk (C5-C6) of the brachial plexus and elbow flexion contractures between 30° and 80°. All releases involved lacertus fibrosus section and partial lengthening of the distal portion of the brachialis tendon. In severe cases, biceps brachii tenotomy was also performed. All participants had a minimum follow-up of 12 months and preoperative elbow flexion strength of at least grade 4 on the British Medical Research Council scale, with no deformities in the shape of the ulnohumeral joint or radial head subluxation. RESULTS: Following a mean follow-up of 41 months, the average extension gain was 31° (range, 10°-50°). All patients maintained their flexion strength. Except for two participants with weaker triceps, the mean elbow extension gain was sustained throughout the follow-up period. There were no major or minor complications or reinterventions in the study. CONCLUSIONS: Partial tenotomy of the brachialis and biceps brachii muscles, coupled with lacertus fibrosus section, is an effective treatment for elbow contractures exceeding 30° flexion. This method is successful in individuals with a functioning triceps brachii and elbow extension strength of at least grade 3 on the British Medical Research Council scale. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

19.
J Hand Surg Am ; 49(10): 1044.e1-1044.e11, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39023500

RESUMEN

Spastic elbow deformity in patients with upper motor neuron injuries results from an imbalance of flexor and extensor forces across the ulnohumeral joint. Although not all deformities reflect the same underlying imbalances, the elbow most commonly rests in a flexed position. Patients may present with a combination of muscle spasticity, myostatic contracture, and/or joint contracture. A focused history and physical examination are essential for developing individualized surgical plans that account for variations in deformity severity and patient goals. Patients may present with or without volitional control; goals and treatment options differ depending on the degree of control present. Techniques include hyperselective neurectomy, tendon lengthening, muscle origin release, myotomy, tenotomy, periarticular soft tissue release, and skin rearrangement. This article presents a comprehensive review of the surgical approach to the volitional and nonvolitional spastic elbow deformities.


Asunto(s)
Articulación del Codo , Enfermedad de la Neurona Motora , Espasticidad Muscular , Humanos , Espasticidad Muscular/cirugía , Articulación del Codo/cirugía , Enfermedad de la Neurona Motora/cirugía , Enfermedad de la Neurona Motora/complicaciones , Adulto , Deformidades Adquiridas de la Articulación/cirugía , Deformidades Adquiridas de la Articulación/etiología
20.
J Hand Surg Am ; 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38416094

RESUMEN

PURPOSE: Post-traumatic elbow stiffness is a common occurrence resulting in potentially substantial functional limitations in both daily activities and recreational endeavors. In children, this can be particularly difficult given the early stages of childhood and development and the challenges of rehabilitation. Several studies have reported favorable results of elbow contracture releases in children, resulting in improvements in outcomes. This meta-analysis aimed to determine the efficacy and safety of elbow contracture releases in the pediatric population (<18 years), along with subgroup analyses comparing age groups, operative approach, and post-traumatic versus nontraumatic etiologies. METHODS: Meta-analysis was performed with a multidatabase search (PubMed, OVID, EMBASE, and Medline) according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines on September 25, 2020. Data from all published literature meeting inclusion criteria were extracted and analyzed. RESULTS: Seven studies were included, comprising 114 post-traumatic elbow contractures. Mean age was 13.7 years. Contracture releases of the elbow led to improvements in flexion-extension arc of motion by 48º, and pronosupination arc of motion by 22º. Subgroup analysis comparing age groups of <10, 10-14 and 15-18 years showed greater improvements in flexion-extension arc in the older age group, whereas subgroup analysis comparing injury patterns revealed a larger improvement in pronosupination motion for radial head fractures. Comparing open and arthroscopic procedures, open releases had greater improvement in both flexion-extension and pronosupination motion by 18º and 21º, respectively, although there were limited patients in the arthroscopy group. CONCLUSION: Operative management of pediatric elbow contractures is effective. Older children, children with radial head fractures, and those receiving open contracture releases may be more likely to have greater improvements. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

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