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1.
Trials ; 24(1): 229, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36966310

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up. METHODS: This protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0-100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups. DISCUSSION: Persistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI. TRIAL REGISTRATION: Dutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020. CLINICALTRIALS: gov NCT04755127. Registered after the start of inclusion on 15 February 2021.


Assuntos
Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Sinovite , Humanos , Punho , Sinovectomia/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/cirurgia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Sinovite/tratamento farmacológico , Antirreumáticos/efeitos adversos , Injeções Intra-Articulares/efeitos adversos , Dor/tratamento farmacológico , Resultado do Tratamento , Artroscopia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Prenat Diagn ; 42(7): 862-872, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35441720

RESUMO

OBJECTIVE: The diagnostic yield for congenital heart defects (CHD) with routine genetic testing is around 10%-20% when considering pathogenic CNVs or aneuploidies as positive findings. This is a pilot study to investigate the utility of genome sequencing (GS) for prenatal diagnosis of CHD. METHODS: Genome sequencing (GS, 30X) was performed on 13 trios with CHD for which karyotyping and/or chromosomal microarray results were non-diagnostic. RESULTS: Trio GS provided a diagnosis for 4/13 (30.8%) fetuses with complex CHDs and other structural anomalies. Findings included pathogenic or likely pathogenic variants in DNAH5, COL4A1, PTPN11, and KRAS. Of the nine cases without a genetic etiology by GS, we had outcome follow-up data on eight. For five of them (60%), the parents chose to keep the pregnancy. A balanced translocation [46,XX,t(14; 22)(q32.33; q13.31)mat] was detected in a trio with biallelic DNAH5 mutations, which together explained the recurrent fetal situs inversus and dextrocardia that was presumably due to de novo Phelan-McDermid syndrome. A secondary finding of a BRCA2 variant and carrier status of HBB, USH2A, HBA1/HBA2 were detected in the cohort. CONCLUSIONS: GS expands the diagnostic scope of mutation types over conventional testing, revealing the genetic etiology for fetal heart anomalies. Patients without a known genetic abnormality indicated by GS likely opted to keep pregnancy especially if the heart defect could be surgically repaired. We provide evidence to support the application of GS for fetuses with CHD.


Assuntos
Doenças Fetais , Cardiopatias Congênitas , Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Feminino , Coração Fetal , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Humanos , Projetos Piloto , Gravidez , Diagnóstico Pré-Natal/métodos
3.
J Wrist Surg ; 9(3): 190-196, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32509421

RESUMO

Background Septic arthritis is a potentially joint-destructing condition if not treated properly. Septic wrist accounts for ∼5% of all septic arthritis. Arthroscopic lavage is a well-documented treatment for septic arthritis of the knee, hip, or shoulder only. Previous studies on septic wrist were limited to case reports or retrospective studies focusing on open treatment, and functional outcome was seldom documented. Our study aims to evaluate the effectiveness of arthroscopic treatment and to investigate the functional outcome. Materials and Methods Patients were retrospectively reviewed over a period of 10 years. Parameters including age, gender, history of prior injury, duration of symptoms, joint aspirates and intraoperative tissue culture, radiological and arthroscopic findings, antibiotics used, number of operations, and hospital stay were reviewed. Functional outcomes were evaluated with QuickDASH (disabilities of the arm, shoulder, and hand) score. Results From 2007 to 2016, 14 patients (15 septic wrists) underwent arthroscopic surgery. One patient had bilateral involvement. The average age was 63.9 years and the average duration of symptoms was 6.08 days. Average follow-up time was 10 months. All except two patients (85.7%) responded to single arthroscopic treatment. Two required subsequent operations for concomitant tenosynovitis. There were no major complications. The most common isolated organism was Staphylococcus aureus . Only one case had severe joint erosion during follow-up. The average QuickDASH score was 19.7. Duration of symptoms 5 days or more before admission was associated with higher QuickDASH score ( p = 0.04). Conclusion Early arthroscopic treatment should be considered for all patients admitted for septic arthritis of the wrist if not contraindicated. Level of Evidence This is a Level III, retrospective review.

4.
Microbiology (Reading) ; 166(2): 96-119, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31799915

RESUMO

The human gut microbiota controls factors that relate to human metabolism with a reach far greater than originally expected. Microbial communities and human (or animal) hosts entertain reciprocal exchanges between various inputs that are largely controlled by the host via its genetic make-up, nutrition and lifestyle. The composition of these microbial communities is fundamental to supply metabolic capabilities beyond those encoded in the host genome, and contributes to hormone and cellular signalling that support the dynamic adaptation to changes in food availability, environment and organismal development. Poor functional exchange between the microbial communities and their human host is associated with dysbiosis, metabolic dysfunction and disease. This review examines the biology of the dynamic relationship between the reciprocal metabolic state of the microbiota-host entity in balance with its environment (i.e. in healthy states), the enzymatic and metabolic changes associated with its imbalance in three well-studied diseases states such as obesity, diabetes and atherosclerosis, and the effects of bariatric surgery and exercise.


Assuntos
Microbioma Gastrointestinal/fisiologia , Redes e Vias Metabólicas , Animais , Aterosclerose/metabolismo , Aterosclerose/microbiologia , Aterosclerose/terapia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/terapia , Disbiose/metabolismo , Disbiose/microbiologia , Disbiose/terapia , Ácidos Graxos Voláteis/metabolismo , Interações entre Hospedeiro e Microrganismos , Humanos , Obesidade/metabolismo , Obesidade/microbiologia , Obesidade/terapia
5.
7.
Hong Kong Med J ; 21(3): 217-23, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25810024

RESUMO

OBJECTIVE: To evaluate the treatment outcomes of enchondroma of the hand with artificial bone substitute versus autologous (iliac) bone graft. DESIGN: Historical cohort study. SETTING: Tertiary referral centre, Hong Kong. PATIENTS: A total of 24 patients with hand enchondroma from January 2001 to December 2013 who underwent operation at the Prince of Wales Hospital and Alice Ho Miu Ling Nethersole Hospital in Hong Kong were reviewed. Thorough curettage of the tumour was performed in all patients, followed by either autologous bone graft impaction under general anaesthesia in 13 patients, or artificial bone substitute in 11 patients (10 procedures were performed under local or regional anaesthesia and 1 was done under general anaesthesia). The functional outcomes and bone incorporation were measured by QuickDASH (shortened version of the Disabilities of the Arm, Shoulder and Hand questionnaire) scores and radiological appearance, respectively. The mean follow-up period was 59 months. RESULTS: There were eight men and 16 women, with a mean age of 40 years. Overall, 17 cases involved phalangeal bones and seven involved metacarpal bones. Among both groups of patients, most of the affected digits had good range of motion and function after surgery. One patient in each study group had complications of local soft tissue inflammation. One patient in the artificial bone substitute group was suspected to have recurrence 8 years after operation. Among the autologous bone graft group, four patients had persistent donor site morbidity at the last follow-up. In all patients, radiographs showed satisfactory bone incorporation. CONCLUSIONS: Artificial bone substitute is a safe and effective treatment option for hand enchondroma, with satisfactory functional and radiographic outcomes. Artificial bone substitute offers the additional benefits of enabling the procedure to be done under local anaesthesia on a day-case basis with minimal complications.


Assuntos
Neoplasias Ósseas/cirurgia , Substitutos Ósseos/uso terapêutico , Transplante Ósseo , Condroma/cirurgia , Mãos/cirurgia , Recidiva Local de Neoplasia/cirurgia , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Transplante Ósseo/efeitos adversos , Condroma/diagnóstico por imagem , Feminino , Mãos/diagnóstico por imagem , Humanos , Ílio/transplante , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Centros de Atenção Terciária , Sítio Doador de Transplante , Resultado do Tratamento , Adulto Jovem
8.
Fetal Diagn Ther ; 37(2): 141-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25342109

RESUMO

OBJECTIVES: To investigate how the introduction of noninvasive prenatal testing (NIPT) influenced women's testing choices following a positive Down syndrome screening. METHODS: A retrospective study was conducted to compare differences in the uptake rates of invasive prenatal diagnosis (IPD) or no testing in one public hospital 1 year before (pre-NIPT) and 1 and 2 years after the introduction of NIPT in private in August 2011 using descriptive analysis and a χ² test. Conventional screening was funded publicly, but NIPT was not. Multivariable binary logistic regression was used to determine factors affecting choices. RESULTS: In pre-NIPT and in years 1 and 2 after the introduction of NIPT, 306, 362 and 401 women who screened positive were seen, respectively. In year 1 and year 2, 12.6 and 26.7% of them underwent NIPT while IPD was decreased by 16.3 and 25.6%, respectively (p < 0.001). Both chorionic villus sampling and amniocentesis decreased in year 1, but only the former in year 2. However, the rate of declining further testing was similar before and after NIPT (p = 0.213). In multivariable analysis, first trimester screening, nulliparity and working women were significant predictors of accepting NIPT, while only nulliparity was a predictor of declining IPD (OR = 0.61). CONCLUSIONS: Introduction of NIPT resulted in a significant decrease in IPD for 2 consecutive years..


Assuntos
Povo Asiático/etnologia , Síndrome de Down/diagnóstico , Síndrome de Down/etnologia , Diagnóstico Pré-Natal/tendências , Adulto , Amniocentese/métodos , Amniocentese/tendências , Amostra da Vilosidade Coriônica/métodos , Amostra da Vilosidade Coriônica/tendências , Estudos de Coortes , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Retrospectivos , Ultrassonografia Pré-Natal/métodos , Ultrassonografia Pré-Natal/tendências
9.
Hong Kong Med J ; 20(5): 460-3, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25307077

RESUMO

We report a case of digital ischaemia in a 31-year-old man who presented with sudden hand numbness, swelling, and cyanosis 4 days after a jellyfish sting. This is a rare complication of jellyfish sting, characterised by a delayed but rapid downhill course. Despite serial monitoring with prompt fasciotomy and repeated debridement, he developed progressive ischaemia in multiple digits with gangrenous change. He subsequently underwent major reconstructive surgery and aggressive rehabilitation. Although jellyfish stings are not uncommon, no severe jellyfish envenomation has been reported in the past in Hong Kong and there has not been any consensus on the management of such injuries. This is the first local case report of jellyfish sting leading to serious hand complications. This case revealed that patients who sustain a jellyfish sting deserve particular attention to facilitate early detection of complications and implementation of therapy.


Assuntos
Mordeduras e Picadas/complicações , Cnidários , Mãos/irrigação sanguínea , Isquemia/diagnóstico , Adulto , Animais , Diagnóstico Diferencial , Gangrena/complicações , Gangrena/diagnóstico , Gangrena/cirurgia , Mãos/patologia , Mãos/cirurgia , Humanos , Isquemia/complicações , Masculino
10.
Skeletal Radiol ; 42(7): 983-92, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23653220

RESUMO

OBJECTIVE: To assess dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) as a measure of vascularity in scaphoid delayed-union or non-union. MATERIALS AND METHODS: Thirty-five patients (34 male, one female; mean age, 27.4 ± 9.4 years; range, 16-51 years) with scaphoid delayed-union and non-union who underwent DCE MRI of the scaphoid between September 2002 and October 2012 were retrospectively reviewed. Proximal fragment vascularity was classified as good, fair, or poor on unenhanced MRI, contrast-enhanced MRI, and DCE MRI. For DCE MRI, enhancement slope, Eslope comparison of proximal and distal fragments was used to classify the proximal fragment as good, fair, or poor vascularity. Proximal fragment vascularity was similarly graded at surgery in all patients. Paired t test and McNemar test were used for data comparison. Kappa value was used to assess level of agreement between MRI findings and surgical findings. RESULTS: Twenty-five (71 %) of 35 patients had good vascularity, four (11 %) had fair vascularity, and six (17 %) had poor vascularity of the proximal scaphoid fragment at surgery. DCE MRI parameters had the highest correlation with surgical findings (kappa = 0.57). Proximal scaphoid fragments with surgical poor vascularity had a significantly lower Emax and Eslope than those with good vascularity (p = 0.0043 and 0.027). The sensitivity, specificity, positive and negative predictive value and accuracy of DCE MRI in predicting impaired vascularity was 67, 86, 67, 86, and 80 %, respectively, which was better than that seen with unenhanced and post-contrast MRI. Flattened time intensity curves in both proximal and distal fragments were a feature of protracted non-union with a mean time interval of 101.6 ± 95.5 months between injury and MRI. CONCLUSIONS: DCE MRI has a higher diagnostic accuracy than either non-enhanced MRI or contrast enhanced MRI for assessing proximal fragment vascularity in scaphoid delayed-union and non-union. For proper interpretation of contrast-enhanced studies in scaphoid vascularity, one needs to incorporate the time frame between injury and MRI.


Assuntos
Fraturas Ósseas/patologia , Fraturas Mal-Unidas/patologia , Angiografia por Ressonância Magnética/métodos , Meglumina , Compostos Organometálicos , Osso Escafoide/irrigação sanguínea , Osso Escafoide/lesões , Adolescente , Adulto , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Osso Escafoide/patologia , Sensibilidade e Especificidade , Adulto Jovem
11.
J Wrist Surg ; 2(4): 355-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24436842

RESUMO

The dorsal wrist ganglion is the most common wrist mass, and previous studies have shown that it arises from the scapholunate interval in the vast majority of cases. Treatment has traditionally been open excision, and more recently arthroscopic resection has been established as an effective and less invasive treatment method. However, application of this technique to ganglia in atypical locations has not been reported, where open excision is the usual practice. This report describes two cases of atypical dorsal wrist ganglia that arose from the lunotriquetral (LT) joint, demonstrated by arthroscopic visualization and wrist arthrogram in one of them. Arthroscopic resection was performed, and the application of this technique to a dorsal wrist ganglion with an atypical origin and location is described.

12.
Bone Marrow Transplant ; 47(7): 924-33, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22002488

RESUMO

As the threshold nucleated cell dose for one-unit umbilical cord blood (UCB) in adults has not to date been firmly established, we prospectively compared one- vs two-unit UCB transplantation after reduced intensity conditioning (RIC) in adult patients with hematological malignancies. Study design specified one-UCB unit if the cryopreserved total nucleated cell (TNC) dose was 2.5 × 10(7)/kg recipient weight, otherwise two units matched at minima of 4/6 HLA loci to the patient and 3/6 to each other were infused. A total of 27 patients received one unit; 23 patients received two units. Median time to ANC >500/µL was 24 days (95% confidence interval 22-28 days), 25 days for one unit and 23 days for two units (P=0.99). At day 100, ANC >500/µL was 88.4 and 91.3% in the one- and two-unit groups (P=0.99), respectively. Three-year EFS was 28.6% and 39.1% in the one- and two-unit groups (P=0.71), respectively. Infusion of two units was associated with a significantly lower relapse risk, 30.4% vs 59.3% (P=0.045). Infused cell doses (TNC, CD3(+), CD34(+) and CD56(+)CD3(neg)) did not impact on engraftment, OS or EFS. Taken together, one-unit UCB transplantation with a threshold cell dose 2.5 × 10(7)/kg recipient weight after RIC is a viable option for adults, although infusion of two units confers a lower relapse incidence.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Neoplasias Hematológicas/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Estudos Prospectivos , Condicionamento Pré-Transplante/efeitos adversos , Resultado do Tratamento , Adulto Jovem
13.
J Hand Surg Eur Vol ; 37(8): 738-44, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22170244

RESUMO

The treatment of hypoplastic thumb (modified Blauth's type IIIb and IV) by pollicization is culturally unfavourable in the Chinese population and digit preservation is preferred. An innovative reconstruction method using a nonvascularized hemi-longitudinal metatarsal graft was performed in six cases with an average follow-up of 87.7 months. Overall hand function was good, as assessed using the Jebsen hand function test. Grip strength and pinch power were significantly weaker than the normal contralateral hand. There was no neurovascular or wound complication. The only donor site complication was a metatarsal fracture, which healed uneventfully with casting. There had been no permanent morbidity to the donor site, as all donor metatarsals hypertrophied and regained normal growth potentials. Linear growth of the transferred metatarsals was evident radiologically (average 1.5 mm/year). Free hemi-longitudinal metatarsal transfer is a feasible method with good functional outcome in the attainment of a 5-digit hand in patients with type IIIb/IV hypoplastic thumb.


Assuntos
Deformidades da Mão/cirurgia , Ossos do Metatarso/transplante , Procedimentos de Cirurgia Plástica/métodos , Polegar/anormalidades , Feminino , Força da Mão , Humanos , Lactente , Masculino , Recuperação de Função Fisiológica , Resultado do Tratamento
14.
Transpl Immunol ; 25(1): 16-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21624462

RESUMO

BACKGROUND: Reactive oxygen species (ROS) such as superoxide (O(2)(-)) play important roles in inflammatory processes. By altering the redox environment, ROS modulate the activation of transcription factors and cytokine genes involved in acute cellular rejection. The NAD(P)H oxidase is a multi-subunit enzyme present in leucocytes and endothelial cells, and is a key source of O(2)(-). 3 single nucleotide polymorphisms (SNPs) of the p22 phox subunit were investigated in a large cohort of renal allograft recipients. METHODS: The C242T, A640G and A-930G SNPs were studied in 244 Caucasian patients with end stage renal failure (ESRF) (148 renal allograft recipients and 96 dialysis patients) using standard PCR. Acute rejection was diagnosed by renal biopsy in 66 allograft recipients (44.6%). Normal controls were DNA samples extracted from 131 umbilical cord bloods following uncomplicated obstetric delivery. RESULTS: A highly significant increase in the frequency of the T242 allele in patients with ESRF compared to controls (31.3% vs 16.7%, p<0.0001) and in allograft recipients without acute rejection compared to those with rejection (37.8% vs 27.3%, p<0.0001) was demonstrated. CONCLUSION: These results show that the T242 allele may predispose to the development of ESRF, but paradoxically reduce susceptibility to acute rejection through reduced NAD(P)H oxidase activity.


Assuntos
Rejeição de Enxerto/genética , Falência Renal Crônica/genética , Transplante de Rim , NADPH Oxidases/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Feminino , Rejeição de Enxerto/imunologia , Humanos , Falência Renal Crônica/imunologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , NADPH Oxidases/imunologia , Transplante Homólogo , População Branca
15.
Hong Kong Med J ; 16(4): 287-91, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20683072

RESUMO

OBJECTIVE: To review the accuracy of different investigation modalities for upper limb nerve sheath tumours and the resulting surgical outcomes, and propose a standard algorithm to deal with such tumours to minimise complications. DESIGN: Retrospective review. SETTING: Regional hospital, Hong Kong. PATIENTS: All patients with upper limb nerve sheath tumours being excised in our hospital from 1999 to 2008. MAIN OUTCOME MEASURES: The accuracy rate of different investigations, as well as corresponding neurological deficits after excision and recurrence rates. RESULTS: A total of 23 (10 male and 13 female) patients, aged between 28 and 72 (mean, 46) years, underwent excision of 25 lesions during the study period. The mean duration of symptom was 2.5 years and tumour size ranged from 1 to 10.5 cm (mean, 2.6 cm). A majority (80%) presented with a typical triad; only one had a true neurological deficit. Twenty-two ultrasonography and 20 magnetic resonance images were obtained, with a diagnostic accuracy of 77% and 100%, respectively. Eight fine-needle aspiration cytology examinations and two core biopsies were performed, which had respective accuracy rates of 13% and 100%. Fifteen patients experienced neurological deficits after the operation; three showed spontaneous recovery. Among 12 patients with long-term residual neurological sequelae, five had both motor and sensory deficits and four had moderate-to-severe disability. No recurrence was reported. CONCLUSION: Nerve sheath tumours in the hand need to be managed with care. Among the different investigation modalities, magnetic resonance imaging was considered to be the gold standard. Yet ultrasonography is still the most easily accessible and least invasive investigation in public hospital setting. Complications are liable to ensue even if patients are managed by hand specialists. Thus, well-planned operations and detailed discussions with the patient are important prerequisites before operation.


Assuntos
Neoplasias de Bainha Neural/cirurgia , Complicações Pós-Operatórias/etiologia , Extremidade Superior/cirurgia , Adulto , Idoso , Algoritmos , Biópsia por Agulha , Feminino , Hong Kong , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias de Bainha Neural/patologia , Estudos Retrospectivos , Extremidade Superior/patologia
16.
Leukemia ; 24(8): 1397-405, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20535152

RESUMO

Signal transducer and activator of transcription-5 (STAT5) is a critical transcription factor for normal hematopoiesis and its sustained activation is associated with hematologic malignancy. A persistently active mutant of STAT5 (STAT5a(S711F)) associates with Grb2-associated binding protein 2 (Gab2) in myeloid leukemias and promotes growth in vitro through AKT activation. Here we have retrovirally transduced wild-type or Gab2(-/-) mouse bone marrow cells expressing STAT5a(S711F) and transplanted into irradiated recipient mice to test an in vivo myeloproliferative disease model. To target Gab2-independent AKT/mTOR activation, we treated wild-type mice separately with rapamycin. In either case, mice lacking Gab2 or treated with rapamycin showed attenuated myeloid hyperplasia and modestly improved survival, but the effects were not cytotoxic and were reversible. To improve on this approach, we combined in vitro targeting of STAT5-mediated AKT/mTOR using rapamycin with inhibition of the STAT5 direct target genes bcl-2 and bcl-X(L) using ABT-737. Striking synergy with both drugs was observed in mouse BaF3 cells expressing STAT5a(S711F), TEL-JAK2 or BCR-ABL and in the relatively single agent-resistant human BCR-ABL-positive K562 cell line. Therefore, targeting distinct STAT5-mediated survival signals, for example, bcl-2/bcl-X(L) and AKT/mTOR may be an effective therapeutic approach for human myeloproliferative neoplasms.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Compostos de Bifenilo/farmacologia , Transtornos Mieloproliferativos/patologia , Nitrofenóis/farmacologia , Fator de Transcrição STAT5/fisiologia , Sirolimo/farmacologia , Sulfonamidas/farmacologia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Compostos de Bifenilo/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular , Citometria de Fluxo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Mieloproliferativos/fisiopatologia , Nitrofenóis/administração & dosagem , Piperazinas/administração & dosagem , Piperazinas/farmacologia , Fator de Transcrição STAT5/efeitos dos fármacos , Sirolimo/administração & dosagem , Sulfonamidas/administração & dosagem
17.
J Hand Surg Am ; 34(4): 710-4, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19345875

RESUMO

We report a case of intraosseous glomus tumor that developed in the right ring finger distal phalanx of a 19-year-old man. Clinical and radiographic findings were atypical. The tumor was excised en bloc because of the extensive involvement. The left second toe was transferred to the right ring finger to reconstruct the excised finger part. Symptom relief, function, and cosmetic outcome were satisfactory during 2-year follow-up.


Assuntos
Amputação Cirúrgica , Neoplasias Ósseas/cirurgia , Falanges dos Dedos da Mão/cirurgia , Dedos/cirurgia , Tumor Glômico/cirurgia , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Dedos do Pé/transplante , Tomografia Computadorizada por Raios X , Biópsia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Estética , Falanges dos Dedos da Mão/diagnóstico por imagem , Falanges dos Dedos da Mão/patologia , Dedos/diagnóstico por imagem , Dedos/patologia , Seguimentos , Tumor Glômico/diagnóstico por imagem , Tumor Glômico/patologia , Humanos , Microcirurgia , Invasividade Neoplásica , Força de Pinça/fisiologia , Complicações Pós-Operatórias/fisiopatologia , Reoperação
18.
Bone Marrow Transplant ; 44(3): 145-56, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19182832

RESUMO

We studied the pharmacokinetic (PK) profile of single daily dose i.v. BU in children who underwent reduced-intensity conditioning (RIC) transplantation. A cohort of 19 patients < or =4 years of age (group 1) and 33 patients >4 years (group 2) was studied. Patients received a BU test dose for PK studies, followed by two treatment doses adjusted to target an area under the curve (AUC) of 4000 microM min per day. Patients in group 1 attained a lower AUC as compared to group 2 (3568 vs 4035 microM min). In group 1, 67% patients and in group 2, 84% patients achieved AUC within the targeted range. Stable donor chimerism was achieved in 56% patients in group 1 and 79% in group 2. Eight patients required a second transplantation because of graft failure. Because of the concern that a low AUC adversely affected outcomes, a second cohort of 23 patients followed a modified protocol with a targeted AUC of 5000 microM min. A higher AUC was attained (4825 microM min). Stable donor chimerism was achieved in 91% of patients. Our results show that RIC regimens using two single daily doses of i.v. BU are effective in children, but a targeted AUC of 5000 microM min is recommended.


Assuntos
Bussulfano/farmacocinética , Transplante de Células-Tronco Hematopoéticas , Agonistas Mieloablativos/farmacocinética , Neoplasias/metabolismo , Neoplasias/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Fatores Etários , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Criança , Pré-Escolar , Intervalo Livre de Doença , Humanos , Lactente , Masculino , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/efeitos adversos , Taxa de Sobrevida , Quimeras de Transplante , Resultado do Tratamento
19.
J Exp Biol ; 211(Pt 12): 1964-8, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18515727

RESUMO

In the present study, we aimed to clone an osmotic stress transcriptional factor (Ostf) from gill cells of Japanese eels. In addition, we measured its expression in Percoll-gradient-isolated gill chloride (CC) and pavement (PVC) cells and determined the regulation of its expression in primary gill cell culture. Using degenerative primers and RACE techniques, we cloned a cDNA of 615bp, encompassing the coding sequence of Ostf (204 amino acids). The cloned Ostf1 DNA sequence shared 84% DNA homology with the Ostf1 of tilapia. In general, the basal Ostf expression level was found to be significantly higher in CCs than in PVCs. In the direct transfer of fish from freshwater to seawater, a significant but transient induction of Ostf mRNA in CCs and PVCs was measured after 6h of acclimation. Compared with gill CCs, the level of induction measured at PVCs was lower. In the seawater-to-freshwater transfer, no significant change in Ostf transcript levels was detected in either CCs or PVCs. To decipher the regulatory mechanism of Ostf expression, we conducted experiments using primary gill cell culture to specifically address the involvement of two putative osmosensors (i.e. intracellular ion strength/macromolecular crowding and cytoskeleton) in the regulation of Ostf expression. Hypertonic treatment using impermeable solutes (i.e. NaCl, 500 mOsmol l(-1)) induced Ostf mRNA expression in 6h, but no noticeable effect was measured using permeable solute (i.e. urea, 500 mOsmol l(-1)). The induction was transcriptionally regulated and was abolished by the addition of organic osmolytes (i.e. betaine, inositol or taurine) into the culture media. Addition of colchicine (an inhibitor of microtubule polymerization) to hypertonic (with added NaCl, 500 mOsmol l(-1)) cells reduced Ostf mRNA expression, suggesting that an increase in intracellular ionic strength and the integrity of the cytoskeleton are involved in the activation of Ostf mRNA expression in the cells. Collectively, the results of this study reveal, for the first time, the differential expression of Ostf in isolated CCs and PVCs. The resulting knowledge can shed light on how Ostf participates in hyperosmotic adaptation in fish gills.


Assuntos
Enguias/genética , Regulação da Expressão Gênica/fisiologia , Brânquias/metabolismo , Fatores de Transcrição/genética , Equilíbrio Hidroeletrolítico/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Betaína , Células Cultivadas , Clonagem Molecular , Colchicina , Primers do DNA/genética , Enguias/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Dados de Sequência Molecular , Análise de Sequência de DNA , Homologia de Sequência , Cloreto de Sódio , Especificidade da Espécie , Fatores de Transcrição/metabolismo , Ureia
20.
J Orthop Surg (Hong Kong) ; 16(1): 88-90, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18453667

RESUMO

PURPOSE: To review the efficacy and safety of needle aponeurotomy for Dupuytren's contracture in Chinese patients. METHODS: Seven men and one woman aged 50 to 80 (mean, 67) years underwent needle aponeurotomy for Dupuytren's contracture. Five were manual workers and the other 3 were retired. Their chief complaints were difficulty moving the fingers, clumsiness of the hand, and occasional pain in the palm. No patient had any family history of Dupuytren's contracture. RESULTS: 41 points were released in 13 fingers (3 middle, 3 ring, and 7 little). Immediately after release, the respective mean flexion contracture correction of the metacarpophalangeal and proximal interphalangeal joints were 50 (from 50 to 0) and 35 (from 46 to 11) degrees. At 22-month follow-up, the respective mean residual flexion contracture of both joints were 12 and 27 degrees; the corresponding long-term improvements were 70 and 41%. No patient had a wound complication or neurovascular injury. All had a normal score for Disabilities of the Arm, Shoulder, and Hand. CONCLUSION: For Chinese patients with Dupuytren's contracture, needle aponeurotomy is safe and effective. Long-term correction is better maintained in metacarpophalangeal than proximal interphalangeal joints (70 vs 41%).


Assuntos
Contratura de Dupuytren/cirurgia , Fasciotomia , Mãos , Agulhas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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