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1.
Endoscopy ; 56(3): 174-181, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37949103

RESUMO

BACKGROUND: Device-assisted enteroscopy (DAE) has become a well-established diagnostic and therapeutic tool for the management of small-bowel pathology. We aimed to evaluate the performance measures for DAE across the UK against the quality benchmarks proposed by the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We retrospectively collected data on patient demographics and DAE performance measures from electronic endoscopy records of consecutive patients who underwent DAE for diagnostic and therapeutic purposes across 12 enteroscopy centers in the UK between January 2017 and December 2022. RESULTS: A total of 2005 DAE procedures were performed in 1663 patients (median age 60 years; 53% men). Almost all procedures (98.1%) were performed for appropriate indications. Double-balloon enteroscopy was used for most procedures (82.0%), followed by single-balloon enteroscopy (17.2%) and spiral enteroscopy (0.7%). The estimated depth of insertion was documented in 73.4% of procedures. The overall diagnostic yield was 70.0%. Therapeutic interventions were performed in 42.6% of procedures, with a success rate of 96.6%. Overall, 78.0% of detected lesions were marked with a tattoo. Patient comfort was significantly better with the use of deep sedation compared with conscious sedation (99.7% vs. 68.5%; P<0.001). Major adverse events occurred in only 0.6% of procedures. CONCLUSIONS: Performance measures for DAE in the UK meet the ESGE quality benchmarks, with high diagnostic and therapeutic yields, and a low incidence of major adverse events. However, there is room for improvement in optimizing sedation practices, standardizing the depth of insertion documentation, and adopting marking techniques to aid in the follow-up of detected lesions.


Assuntos
Enteropatias , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Enteropatias/diagnóstico , Enteropatias/terapia , Estudos Retrospectivos , Melhoria de Qualidade , Endoscopia Gastrointestinal/métodos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Enteroscopia de Duplo Balão/métodos
2.
Am J Med Genet A ; 176(11): 2404-2418, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30216658

RESUMO

Warsaw breakage syndrome (WBS) is a recently recognized DDX11-related rare cohesinopathy, characterized by severe prenatal and postnatal growth restriction, microcephaly, developmental delay, cochlear anomalies, and sensorineural hearing loss. Only seven cases have been reported in the English literature, and thus the information on the phenotype and genotype of this interesting condition is limited. We provide clinical and molecular information on five additional unrelated patients carrying novel bi-allelic variants in the DDX11 gene, identified via whole exome sequencing. One of the variants was found to be a novel Saudi founder variant. All identified variants were classified as pathogenic or likely pathogenic except for one that was initially classified as a variant of unknown significance (VOUS) (p.Arg378Pro). Functional characterization of this VOUS using heterologous expression of wild type and mutant DDX11 revealed a marked effect on protein stability, thus confirming pathogenicity of this variant. The phenotypic data of the seven WBS reported patients were compared to our patients for further phenotypic delineation. Although all the reported patients had cochlear hypoplasia, one patient also had posterior labyrinthine anomaly. We conclude that while the cardinal clinical features in WBS (microcephaly, growth retardation, and cochlear anomalies) are almost universally present, the breakage phenotype is highly variable and can be absent in some cases. This report further expands the knowledge of the phenotypic and molecular features of WBS.


Assuntos
Anormalidades Múltiplas/genética , Quebra Cromossômica , Sequência de Aminoácidos , Criança , Pré-Escolar , RNA Helicases DEAD-box/química , RNA Helicases DEAD-box/genética , DNA Helicases/química , DNA Helicases/genética , Orelha Interna/diagnóstico por imagem , Fácies , Feminino , Regulação da Expressão Gênica , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Modelos Moleculares , Fenótipo , Inibidores de Proteassoma/farmacologia , Estabilidade Proteica , Síndrome , Tomografia Computadorizada por Raios X
3.
Scand J Gastroenterol ; 53(5): 527-532, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29161901

RESUMO

OBJECTIVE: Photodynamic therapy (PDT) was used as therapy for early neoplasia associated with Barrett's oesophagus (BE). This is 5-year follow-up of patients enrolled into randomised controlled trial of 5-aminolaevulinic acid (ALA) vs. Photofrin PDT. METHODS: Biopsies were taken from original Barrett's segment during endoscopic follow up using Seattle protocol. Endoscopic mucosal resection (EMR) ± radiofrequency ablation (RFA) was preferred therapy in patients who failed PDT and/or had recurrent neoplasia. RESULTS: Fifty eight of 64 patients enrolled in the original trial were followed up including 31 patients treated with ALA PDT (17 patients with ≤6 cm, 14 patients with >6 cm segment of BE) and 27 treated with Photofrin PDT (14 patients with ≤6 cm, 13 patients with >6 cm BE). Initial success was achieved in 65% (20/31) ALA and 48% (13/27) Photofrin patients (p = .289). Thirty five percent patients (7/20) relapsed in ALA group and 54% (7/13) relapsed in Photofrin group (p = .472). At a median follow-up of 67 months, no significant difference was found in long-term complete reversal of intestinal metaplasia (CR-IM) and complete reversal of dysplasia (CR-D) between ALA and Photofrin groups (78% vs. 63%; p = .18; 90% vs. 76%; p = .26). Original length of BE did not alter long-term outcome. Four patients from each group progressed to invasive oesophageal adenocarcinoma. Initial success of ALA PDT was associated with significantly better likelihood of long-term remission (p = .03). CONCLUSIONS: Initial response to PDT plays key role in long term outcome. RFA ± EMR have, however, become preferred minimally invasive ablative therapy for BE-related neoplasia due to poor efficacy of PDT.


Assuntos
Adenocarcinoma/terapia , Ácido Aminolevulínico/uso terapêutico , Esôfago de Barrett/terapia , Éter de Diematoporfirina/uso terapêutico , Neoplasias Esofágicas/terapia , Fotoquimioterapia , Adulto , Idoso , Esôfago de Barrett/complicações , Ablação por Cateter , Progressão da Doença , Ressecção Endoscópica de Mucosa , Feminino , Humanos , Hiperplasia/patologia , Estimativa de Kaplan-Meier , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Indução de Remissão , Resultado do Tratamento
4.
J Clin Gastroenterol ; 50(6): 518-23, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26974762

RESUMO

BACKGROUND AND AIM: Many indirect noninvasive scores to predict liver fibrosis are calculated from routine blood investigations. Only limited studies have compared their efficacy head to head. We aimed to compare these scores with liver biopsy fibrosis stages in patients with chronic hepatitis C. MATERIALS AND METHODS: From blood investigations of 1602 patients with chronic hepatitis C who underwent a liver biopsy before initiation of antiviral treatment, 19 simple noninvasive scores were calculated. The area under the receiver operating characteristic curves and diagnostic accuracy of each of these scores were calculated (with reference to the Scheuer staging) and compared. RESULTS: The mean age of the patients was 41.8±9.6 years (1365 men). The most common genotype was genotype 4 (65.6%). Significant fibrosis, advanced fibrosis, and cirrhosis were seen in 65.1%, 25.6, and 6.6% of patients, respectively. All the scores except the aspartate transaminase (AST) alanine transaminase ratio, Pohl score, mean platelet volume, fibro-alpha, and red cell distribution width to platelet count ratio index showed high predictive accuracy for the stages of fibrosis. King's score (cutoff, 17.5) showed the highest predictive accuracy for significant and advanced fibrosis. King's score, Göteborg university cirrhosis index, APRI (the AST/platelet count ratio index), and Fibrosis-4 (FIB-4) had the highest predictive accuracy for cirrhosis, with the APRI (cutoff, 2) and FIB-4 (cutoff, 3.25) showing the highest diagnostic accuracy.We derived the study score 8.5 - 0.2(albumin, g/dL) +0.01(AST, IU/L) -0.02(platelet count, 10(9)/L), which at a cutoff of >4.7 had a predictive accuracy of 0.868 (95% confidence interval, 0.833-0.904) for cirrhosis. CONCLUSIONS: King's score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico , Adulto , Biópsia , Plaquetas/metabolismo , Índices de Eritrócitos , Feminino , Genótipo , Globulinas/metabolismo , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/virologia , Testes de Função Hepática , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos
5.
Chin J Traumatol ; 19(5): 298-301, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27780513

RESUMO

Nonunion of the humerus in a severely osteoporotic bone is a likely event especially if the fracture is transverse. The management of such a combination is a challenge. Most of the conventional fixation methods are unlikely to succeed as the bone failure precedes implant failure in osteoporosis. The challenge is further compounded in severe osteoporosis when the cortical thickness is affected more severely. We used a combination of an intramedullary fibula with a locking plate in 5 cases. The results show that it may be a good combination in such situations as the bone strength is augmented and the plate pullout is less likely.


Assuntos
Placas Ósseas , Fíbula/transplante , Fixação Intramedular de Fraturas/métodos , Fraturas não Consolidadas/cirurgia , Fraturas do Úmero/cirurgia , Osteoporose/complicações , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Endoscopy ; 47(11): 980-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26126159

RESUMO

BACKGROUND AND STUDY AIM: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01). CONCLUSION: The Registry reports on endoscopic therapy for Barrett's neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.


Assuntos
Adenocarcinoma/cirurgia , Esôfago de Barrett/cirurgia , Ablação por Cateter , Neoplasias Esofágicas/cirurgia , Esôfago/cirurgia , Lesões Pré-Cancerosas/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Esofagoscopia , Esôfago/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/patologia , Mucosa/cirurgia , Lesões Pré-Cancerosas/patologia , Sistema de Registros , Resultado do Tratamento , Reino Unido
7.
Scand J Gastroenterol ; 50(11): 1315-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25956748

RESUMO

OBJECTIVE: Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are effective non-surgical options for the treatment of Barrett's esophagus (BE) associated neoplasia. Development of subsquamous intestinal metaplasia after successful PDT and/or RFA is a recognized phenomenon; however, the occurrence of neoplasia arising from buried glands is a rare complication. METHODS: This is a prospective case series of patients treated with PDT and/or RFA from 1999 to 2014 at University College London Hospital for neoplasia associated with BE, whose outcomes were analyzed retrospectively. Prior to any ablative therapy any visible nodularity was removed with endoscopic mucosal resection (EMR). After successful PDT and/or HALO RFA treatment, defined as a complete reversal of dysplasia and metaplasia, patients underwent endoscopic follow up using the Seattle protocol. RESULTS: A total of 288 patients were treated, 91 with PDT between 1999 and 2010, 173 with RFA between 2007 and 2014, and 24 with both PDT and RFA for neoplasia associated with BE. Subsquamous neoplasia occurred in seven patients (7/288, 2%). The first patient developed subsquamous invasive adenocarcinoma and underwent curative surgery. Another five patients with subsquamous neoplasia (either high-grade dysplasia or intramucosal cancer) were treated successfully with EMR. The final patient developed subsquamous invasive esophagogastric junctional adenocarcinoma with liver metastases. CONCLUSION: Development of subsquamous neoplasia after an apparently successful PDT and/or RFA is a rare but recognized complication. Clinicians should be aware of this phenomenon and have a low threshold for performing an EMR. Thorough surveillance following successful PDT and/or RFA ensuring high-quality endoscopy is required.


Assuntos
Adenocarcinoma/complicações , Esôfago de Barrett/complicações , Neoplasias Esofágicas/complicações , Lesões Pré-Cancerosas/patologia , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter , Esofagoscopia , Feminino , Humanos , Hiperplasia/complicações , Hiperplasia/patologia , Londres , Masculino , Metaplasia/complicações , Metaplasia/patologia , Pessoa de Meia-Idade , Fotoquimioterapia , Resultado do Tratamento
8.
Gastroenterology ; 145(1): 87-95, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23542069

RESUMO

BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or early neoplasia increasingly receive endoscopic mucosal resection and radiofrequency ablation (RFA) therapy. We analyzed data from a UK registry that follows the outcomes of patients with BE who have undergone RFA for neoplasia. METHODS: We collected data on 335 patients with BE and neoplasia (72% with HGD, 24% with intramucosal cancer, 4% with low-grade dysplasia [mean age, 69 years; 81% male]), treated at 19 centers in the United Kingdom from July 2008 through August 2012. Mean length of BE segments was 5.8 cm (range, 1-20 cm). Patients' nodules were removed by endoscopic mucosal resection, and the patients then underwent RFA every 3 months until all areas of BE were ablated or cancer developed. Biopsies were collected 12 months after the first RFA; clearance of HGD, dysplasia, and BE were assessed. RESULTS: HGD was cleared from 86% of patients, all dysplasia from 81%, and BE from 62% at the 12-month time point, after a mean of 2.5 (range, 2-6) RFA procedures. Complete reversal dysplasia was 15% less likely for every 1-cm increment in BE length (odds ratio = 1.156; SE = 0.048; 95% confidence interval: 1.07-1.26; P < .001). Endoscopic mucosal resection before RFA did not provide any benefit. Invasive cancer developed in 10 patients (3%) by the 12-month time point and disease had progressed in 17 patients (5.1%) after a median follow-up time of 19 months. Symptomatic strictures developed in 9% of patients and were treated by endoscopic dilatation. Nineteen months after therapy began, 94% of patients remained clear of dysplasia. CONCLUSIONS: We analyzed data from a large series of patients in the United Kingdom who underwent RFA for BE-related neoplasia and found that by 12 months after treatment, dysplasia was cleared from 81%. Shorter segments of BE respond better to RFA; http://www.controlled-trials.com, number ISRCTN93069556.


Assuntos
Adenocarcinoma/cirurgia , Esôfago de Barrett/cirurgia , Ablação por Cateter , Neoplasias Esofágicas/cirurgia , Esofagoscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/cirurgia , Estadiamento de Neoplasias , Sistema de Registros , Resultado do Tratamento
10.
J Foot Ankle Surg ; 50(4): 490-3, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21397526

RESUMO

Tuberculosis of the talus is a rare condition, and the diagnosis can be difficult to make because of inconclusive laboratory and ancillary testing. In such cases, accurate diagnosis and appropriate treatment may require the use of a transmalleolar osteotomy to gain access to the involved portion of the talar body. In the case described in this article, a transmalleolar approach was used to gain access to a lytic lesion of the talar body so as to obtain microbiological and histopathological specimens for diagnostic purposes, and to thoroughly debride the lesion. After 6 years of postsurgical follow-up, the patient was leading a normal life with a full range of ankle and subtalar motion. The rarity of the diagnosis, and the use of the transmalleolar approach to a lytic and likely infected lesion in the body of the talus, makes this case worthy of public discussion.


Assuntos
Desbridamento/métodos , Osteotomia/métodos , Tálus/cirurgia , Tuberculose Osteoarticular/cirurgia , Adulto , Diagnóstico Diferencial , Seguimentos , Humanos , Masculino , Tuberculose Osteoarticular/diagnóstico
11.
iScience ; 24(9): 102973, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34471865

RESUMO

Regulatory T cells (Treg) prevent the migration of effector T cells toward sites of inflammation, thereby limiting disease progression. We investigated this aspect of Treg function using psoriatic arthritis (PsA) as an exemplar of chronic inflammation. Patients with PsA had an increased Th17:Treg ratio which was reversed by anti-tumor necrosis factor (TNF) therapy. Utilizing an in vitro migration assay, Treg from patients with PsA treated with conventional therapy paradoxically boosted CCR6+ effector T-cell (a surrogate for Th17) migration toward CCL20. In contrast, Treg from patients with PsA treated with anti-TNF suppressed CCL20-driven effector T-cell migration. The boosting effect of TNF blockade upon Treg suppression of migration was accompanied by increased effector T-cell CCL20 production and enhanced interaction between Treg and effector T cells. This study provides mechanistic insight into Treg modulation of effector T-cell migration in patients with chronic inflammation and how this can be targeted by therapy.

12.
Ren Fail ; 31(5): 406-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19839842

RESUMO

Acute renal infarction is an uncommon and under-diagnosed disease. Its clinical presentation is nonspecific and often mimics other more common disease entities. The diagnosis is usually missed or delayed, which frequently results in irreversible renal parenchyma damage. High index of suspicion is required for early diagnosis, as timely intervention may prevent loss of kidney function. We report a case of acute renal infarction following coronary angiography in a patient with paroxysmal atrial fibrillation who initially presented with acute abdominal pain mimicking appendicitis.


Assuntos
Dor Abdominal/etiologia , Infarto/complicações , Rim/irrigação sanguínea , Dor Abdominal/diagnóstico por imagem , Doença Aguda , Idoso , Analgésicos/uso terapêutico , Proteína C-Reativa/análise , Meios de Contraste , Creatinina/sangue , Dalteparina/uso terapêutico , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Infarto/diagnóstico por imagem , Infarto/tratamento farmacológico , Rim/diagnóstico por imagem , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
13.
Ortop Traumatol Rehabil ; 11(3): 264-70, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19620744

RESUMO

BACKGROUND: The distal third of the tibia is unique in the sense that it has a minimal muscle cover and consequently the blood supply is easily compromised after a fracture in this area. Infected non union in this area provides a challenge to the orthopaedic surgeon. These difficulties are especially profound in the geriatric age group. MATERIAL AND METHODS: 12 cases with an infected non union of the distal third of the tibia were managed with acute docking over a distance of up to 2.5 cms. The age of these patients was more than 55 years. RESULTS: The average shortening at final follow up was 1.8 cms. The bone results were assessed according to the protocol laid down by the association for the study and application of the method of Ilizarov. Accordingly we had 3 excellent, 8 good and 1 fair result. The functional result was calculated as per the Ilizarov criteria [1]. On this basis we had 7 excellent, 4 good and 1 fair result. CONCLUSION: The acute docking modality is applicable to the distal tibia in such situations even in the geriatric population with predictable results.


Assuntos
Doenças Ósseas Infecciosas/terapia , Drenagem/métodos , Fraturas não Consolidadas/complicações , Fraturas da Tíbia/complicações , Idoso , Doenças Ósseas Infecciosas/etiologia , Doenças Ósseas Infecciosas/cirurgia , Feminino , Fraturas não Consolidadas/cirurgia , Humanos , Técnica de Ilizarov/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
14.
Ortop Traumatol Rehabil ; 11(1): 55-60, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19259062

RESUMO

BACKGROUND: To assess the pattern of mass casualty incidents managed at our hospital over the last eight years, and evolve a differentiating classification based on this pattern. A combination of retrospective and prospective assessment was made. MATERIAL AND METHODS: All patients receiving injuries in mass casualty incidents and managed at our hospital. Patients with an injury severity score above 9. Management of injuries as per the trauma management protocol. Classification based on the data collected during the study and application of this classification to the subsequent mass casualty incidents to allow comparison between similar incidents in different settings. RESULTS: A classification system that mainly differentiates mass casualty incidents on the hospital basis, the criteria being: the time interval between the first information to first reception, and the percentage of admission above the maximum normal intake. CONCLUSIONS: The Barzullah classification system is the first attempt at developing a hospital based differentiation in mass casualty incidents. It provides a valid and easy method of comparing such incidents between hospitals and perhaps a basis for developing protocol for mass disaster management.


Assuntos
Cuidados Críticos/organização & administração , Planejamento em Desastres/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Incidentes com Feridos em Massa/classificação , Triagem/estatística & dados numéricos , Ferimentos e Lesões/classificação , Diagnóstico Diferencial , Eficiência Organizacional , Feminino , Humanos , Escala de Gravidade do Ferimento , Israel/epidemiologia , Masculino , Incidentes com Feridos em Massa/estatística & dados numéricos , Centro Cirúrgico Hospitalar/estatística & dados numéricos , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/epidemiologia
15.
Trop Doct ; 38(4): 260, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18820209

RESUMO

Every major mass disaster challenges the health care services, especially in the third world. These challenges include the expected situations mainly pertaining to the overload of patients and the stretching of hospital facilities. We report our experiences about several unforseen challenges faced by our hospital in the 2005 earthquake that struck the Kashmir region.


Assuntos
Desastres , Terremotos , Serviços Médicos de Emergência , Família , Humanos , Índia
16.
Oncotarget ; 9(33): 22945-22959, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29796164

RESUMO

Early oesophageal adenocarcinoma (OA) and pre-neoplastic dysplasia may be treated with endoscopic resection and ablative techniques such as photodynamic therapy (PDT). Though effective, discrete areas of disease may be missed leading to recurrence. PDT further suffers from the side effects of off-target photosensitivity. A tumour specific and light targeted therapeutic agent with optimised pharmacokinetics could be used to destroy residual cancerous cells left behind after resection. A small molecule antibody-photosensitizer conjugate was developed targeting human epidermal growth factor receptor 2 (HER2). This was tested in an in vivo mouse model of human OA using a xenograft flank model with clinically relevant low level HER2 expression and heterogeneity. In vitro we demonstrate selective binding of the conjugate to tumour versus normal tissue. Light dependent cytotoxicity of the phototherapy agent in vitro was observed. In an in vivo OA mouse xenograft model the phototherapy agent had desirable pharmacokinetic properties for tumour uptake and blood clearance time. PDT treatment caused tumour growth arrest in all the tumours despite the tumours having a clinically defined low/negative HER2 expression level. This new phototherapy agent shows therapeutic potential for treatment of both HER2 positive and borderline/negative OA.

17.
Acta Orthop Belg ; 73(4): 500-6, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17939481

RESUMO

Pedicle screw instrumentation is an important tool in an orthopaedic surgeon's armamentarium in the management of spinal fractures. Complications with this system have been studied extensively. Due to the exacting technique the possibility of surgical error exists while using this modality. We studied a series of 216 cases where pedicular screws had been used and isolated 34 cases of implant failure. Retrospective analyses of their radiographs showed that surgical error does contribute to the implant failure in a statistically significant manner.


Assuntos
Parafusos Ósseos , Erros Médicos , Fraturas da Coluna Vertebral/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos
18.
Oncotarget ; 8(15): 25080-25096, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28212575

RESUMO

BACKGROUND: Mucin glycoprotein 1 (MUC1) is a glycosylated transmembrane protein on epithelial cells. We investigate MUC1 as a therapeutic target in Barrett's epithelium (BE) and esophageal adenocarcinoma (EA) and provide proof of concept for a light based therapy targeting MUC1. RESULTS: MUC1 was present in 21% and 30% of significantly enriched pathways comparing BE and EA to squamous epithelium respectively. MUC1 gene expression was x2.3 and x2.2 higher in BE (p=<0.001) and EA (p=0.03). MUC1 immunohistochemical expression increased during progression to EA and followed tumor invasion. HuHMFG1 based photosensitive antibody drug conjugates (ADC) showed cell internalization, MUC1 selective and light-dependent cytotoxicity (p=0.0006) and superior toxicity over photosensitizer alone (p=0.0022). METHODS: Gene set enrichment analysis (GSEA) evaluated pathways during BE and EA development and quantified MUC1 gene expression. Immunohistochemistry and flow cytometry evaluated the anti-MUC1 antibody HuHMFG1 in esophageal cells of varying pathological grade. Confocal microscopy examined HuHMFG1 internalization and HuHMFG1 ADCs were created to deliver a MUC1 targeted phototoxic payload. CONCLUSIONS: MUC1 is a promising target in EA. Molecular and light based targeting of MUC1 with a photosensitive ADC is effective in vitro and after development may enable treatment of locoregional tumors endoscopically.


Assuntos
Adenocarcinoma/genética , Antineoplásicos Imunológicos/farmacologia , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Imunoconjugados/farmacologia , Luz , Mucina-1/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Biomarcadores , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Biologia Computacional , Progressão da Doença , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Perfilação da Expressão Gênica , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Imuno-Histoquímica , Mucina-1/metabolismo , Gradação de Tumores , Metástase Neoplásica
19.
Int J Health Sci (Qassim) ; 10(1): 57-68, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27004058

RESUMO

OBJECTIVES: Diabetes mellitus (DM), is affecting an ever increasing number of people worldwide. Diabetes is associated with several musculoskeletal manifestations. These may involve, the upper as well as the lower limb. We conducted this study to find out the prevalence of musculoskeletal problems in type 2 diabetics in the Kashmiri population. METHODOLOGY: The study was conducted on 403 patients with diabetes and 300 controls. All patients underwent screening for any musculoskeletal abnormalities. The patients with musculoskeletal abnormalities were further assessed to find the exact diagnosis according to predefined criteria. RESULTS: The hand was involved in 80 patients [19.8%] in the diabetic group and 15 (5%) patients of the control group. The elbow was affected in 56 patients [14%] in the diabetic group and 24 patients [5.9%] in the non-diabetic group. The shoulder involvement was diagnosed in 61 patients [15%] on the diabetic cohort and 15 patients in the non-diabetic cohort. All the upper limb figures showed a statistically significant difference i.e. P value <0.05. CONCLUSION: The prevalence of musculoskeletal complications in type 2 diabetics in Kashmir is quite high.

20.
Saudi Med J ; 26(11): 1796-9, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16311668

RESUMO

OBJECTIVE: To assess the clinical characteristics of Crohn's disease (CD) in Qatar. METHODS: This is a retrospective descriptive study. We studied 50 CD patients admitted to Hamad General Hospital over a period of 8 years from January 1995 to December 2002. We retrospectively collected and analyzed the demographic and clinical data. We made the diagnostic classification of definite CD in accordance with the criteria based on the International Classification of Disease ninth revision [ICD-9]. We based the obtained information on the following parameters: the age at the time of admission, gender and Crohn's risk factor profiles. RESULTS: Of the studied population, 60% were males and 40% females. Sixty-two percent were Qataris and 38% expatriates. Most of the subjects were <40 years of age (80%). Fifty-two percent had ileo-colonic disease, 24% colonic and 24% ileal disease. The majority of the Crohn's patients had the symptom of abdominal pain (84%), followed by weight loss (80%) and diarrhea (70%). Pallor sign was most frequent in patients with inflammatory CD (76.9%) and obstructive CD (66.7%), whereas we found the anal signs in patients with fistulas (84.2%). CONCLUSION: The study showed a relatively high frequency of ileo-colonic Crohn's disease compared to colonic and ileal diseases. We observed that the most frequent symptom is abdominal pain.


Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Obstrução Intestinal/diagnóstico , Adolescente , Adulto , Distribuição por Idade , Biópsia por Agulha , Colo/fisiopatologia , Países em Desenvolvimento , Feminino , Hospitais Gerais , Humanos , Íleo/fisiopatologia , Imuno-Histoquímica , Incidência , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Obstrução Intestinal/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Catar/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Distribuição por Sexo
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