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BACKGROUND: Autologous haematopoietic stem cell transplantation (AHSCT) is an effective treatment for patients with multiple sclerosis (MS) who have highly active disease, despite the use of standard disease-modifying therapies (DMTs). However, the optimal time for offering AHSCT to patients with 'aggressive' MS is yet to be established. OBJECTIVES: The objective was to explore the safety and efficacy of AHSCT as a first-line DMT in patients with 'aggressive' MS. METHODS: All patients with 'aggressive' MS who received AHSCT as a first-line DMT in five European and North American centres were retrospectively evaluated. RESULTS: Twenty patients were identified. The median interval between diagnosis and AHSCT was 5 (1-20) months. All had multiple poor prognostic markers with a median pre-transplant Expanded Disability Status Scale (EDSS) score of 5.0 (1.5-9.5). After a median follow-up of 30 (12-118) months, the median EDSS score improved to 2.0 (0-6.5, p < 0.0001). No patient had further relapses. Three had residual magnetic resonance imaging (MRI) disease activities in the first 6 months post-transplant, but no further new or enhancing lesions were observed in subsequent scans. CONCLUSION: AHSCT is safe and effective as a first-line DMT in inducing rapid and sustained remission in patients with 'aggressive' MS.
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Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla , Humanos , Esclerose Múltipla/terapia , Estudos Retrospectivos , Transplante Autólogo , Resultado do TratamentoRESUMO
OBJECTIVES: Although presbycusis typically becomes symptomatic only in older age, slight and mild hearing loss may be detectable well before this. We studied current prevalence and characteristics of hearing loss in Australian mid-life adults. STUDY DESIGN: This was a population-derived national cross-sectional study nested within the Longitudinal Study of Australian Children. METHODS: A total of 1485 parents/guardians (87.3% female) aged 30-59 years underwent air-conduction audiometry. Hearing loss was defined in three ways to maximize cross-study comparability: high Fletcher index (mean of 1, 2 and 4 kHz; primary outcome relevant to speech perception), lower frequency (mean of 1 and 2 kHz) and higher frequency (mean of 4 and 8 kHz). Multivariable logistic regression examined how losses vary by age, sex and neighbourhood disadvantage. RESULTS: On high Fletcher index, 27.3% had bilateral and 23.8% unilateral thresholds >15 dB hearing level (HL) (slight or worse), and 4.9% had bilateral and 6.3% unilateral thresholds >25 dB HL (mild or worse). Bilateral higher frequency losses were more common than lower frequency losses for thresholds >15 dB HL (30.9% vs. 26.4%) and >25 dB HL (11.0% vs. 4.6%). Age increased the risk of bilateral speech and higher frequency losses (all P for trend < 0.05), but not lower frequency losses >25 dB HL. Although sex was not associated with speech and lower frequency losses, men were more likely to have bilateral higher frequency losses (e.g. >15 dB HL: odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.5-3.2, P < 0.001). CONCLUSIONS: Both slight and mild hearing loss show high and rising prevalence across mid-life. This offers opportunities to prevent progression to reduce the profound later burden of age-related hearing loss.
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Perda Auditiva/epidemiologia , Adulto , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de DoençaRESUMO
Systemic sclerosis (SSc) is a rare disabling autoimmune disease with a similar mortality to many cancers. Two randomized controlled trials of autologous hematopoietic stem cell transplantation (AHSCT) for SSc have shown significant improvement in organ function, quality of life and long-term survival compared to standard therapy. However, transplant-related mortality (TRM) ranged from 3-10% in patients undergoing HSCT. In SSc, the main cause of non-transplant and TRM is cardiac related. We therefore updated the previously published guidelines for cardiac evaluation, which should be performed in dedicated centers with expertize in HSCT for SSc. The current recommendations are based on pre-transplant cardiopulmonary evaluations combining pulmonary function tests, echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic testing, initiated at Northwestern University (Chicago) and subsequently discussed and endorsed within the EBMT ADWP in 2016.
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Cardiopatias/diagnóstico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Escleroderma Sistêmico/terapia , Cardiopatias/complicações , Cardiopatias/diagnóstico por imagem , Humanos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/mortalidadeRESUMO
ICON Far UltraViolet (FUV) imager contributes to the ICON science objectives by providing remote sensing measurements of the daytime and nighttime atmosphere/ionosphere. During sunlit atmospheric conditions, ICON FUV images the limb altitude profile in the shortwave (SW) band at 135.6 nm and the longwave (LW) band at 157 nm perpendicular to the satellite motion to retrieve the atmospheric O/N2 ratio. In conditions of atmospheric darkness, ICON FUV measures the 135.6 nm recombination emission of O+ ions used to compute the nighttime ionospheric altitude distribution. ICON Far UltraViolet (FUV) imager is a CzernyTurner design Spectrographic Imager with two exit slits and corresponding back imager cameras that produce two independent images in separate wavelength bands on two detectors. All observations will be processed as limb altitude profiles. In addition, the ionospheric 135.6 nm data will be processed as longitude and latitude spatial maps to obtain images of ion distributions around regions of equatorial spread F. The ICON FUV optic axis is pointed 20 degrees below local horizontal and has a steering mirror that allows the field of view to be steered up to 30 degrees forward and aft, to keep the local magnetic meridian in the field of view. The detectors are micro channel plate (MCP) intensified FUV tubes with the phosphor fiber-optically coupled to Charge Coupled Devices (CCDs). The dual stack MCP-s amplify the photoelectron signals to dominate the CCD noise and the rapidly scanned frames are co-added to digitally create 12-second integrated images. Digital on-board signal processing is used to compensate for geometric distortion and satellite motion and to achieve data compression. The instrument was originally aligned in visible light by using a special grating and visible cameras. Final alignment, functional and environmental testing and calibration were performed in a large vacuum chamber with a UV source. The test and calibration program showed that ICON FUV meets its design requirements and is ready to be launched on the ICON spacecraft.
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OBJECTIVE: Honey is recognised to be a good topical wound care agent owing to a broad-spectrum of antimicrobial activity combined with healing properties. Surgihoney RO (SH1) is a product based on honey that is engineered to produce enhanced reactive oxygen species (ROS) and has been reported to be highly antimicrobial. The objective was to investigate the ability of the engineered honey and its comparators to prevent biofilm formation in vitro. METHOD: We tested the ability of three medical-grade honeys SH1, Activon manuka honey (MH) and Medihoney manuka honey (Med), alongside five antimicrobial dressings (AMDs) to prevent the formation of biofilms by 16 isolates. Honeys were serially double diluted from 1:3 down to 1:6144 and the lowest dilution achieving a statistically significant reduction in biomass of at least 50%, compared with untreated controls, was recorded. RESULTS: Although all the honeys were antibacterial and were able to prevent the formation of biofilms, SH1 was the most potent, with efficacy at lower dilutions than the medical honeys for five isolates, and equivalent dilutions for a further six. Additionally, SH1 was superior in antibacterial potency to three commercially available AMDs that contain honey. CONCLUSION: SH1 is effective at preventing bioflms from forming and is superior to medical honeys and AMDs in in vitro tests. DECLARATION OF INTEREST: Surgihoney RO was provided free of charge for testing by Matoke Holdings, UK and the hospital pharmacy provided the other honeys and dressings. This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
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Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Mel , Acinetobacter baumannii/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
BACKGROUND: Familial occurrence is common in colorectal cancer (CRC), but whether this increased familial risk differs by colonic subsite of the index patients CRC is not well understood. AIM: To quantify the risk of CRC in first-degree (FDR), second-degree (SDR) and first cousin (FC) relatives of individuals with CRC, stratified by subsite in the colorectum and age at diagnosis. METHODS: Colorectal cancers diagnosed between 1980 and 2010 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age and gender-matched CRC-free controls were selected to form the comparison group for determining CRC risk in relatives using Cox regression analysis. RESULTS: Of the 18,208 index patients diagnosed with CRC, 6584 (36.2%) were located in the proximal colon, 5986 (32.9%) in the distal colon and 5638 (31%) in the rectum. The elevated risk of CRC in relatives was similar in analysis stratified for CRC colorectal subsites in the index cases. FDR had similarly elevated risk of all site CRC, whether the index patient had cancer in the proximal colon [hazards ratio (HR): 1.85; 95% CI: 1.70-2.02], distal colon (HR: 1.90; 95% CI: 1.73-2.08) or rectum (HR: 1.83; 95% CI: 1.66-2.02) compared to relatives of controls. This risk was consistently greater for FDR when cases developed CRC below the age of 60 years. CONCLUSIONS: Relatives of CRC patients have a similarly elevated risk of CRC regardless of colonic tumour subsite in the index patient, and it is greatest for relatives of younger age index cases.
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Neoplasias do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Saúde da Família , Reto/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Utah/epidemiologia , Adulto JovemRESUMO
Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome caused by mutations in the adenomatous polyposis coli (APC) gene. Clinical genetic testing fails to identify disease causing mutations in up to 20% of clinically apparent FAP cases. Following the inclusion of multiplex ligation-dependent probe amplification (MLPA) probes specific for APC promoter 1B, seven probands were identified with a deletion of promoter 1B. Using haplotype analysis spanning the APC locus, the seven families appear to be identical by descent from a common founder. The clinical phenotype of 19 mutation carriers is classical FAP with colectomy at an average age of 24. The majority of cases had a large number of duodenal and gastric polyps. Measurements of allele-specific expression of APC mRNA using TaqMan assay confirmed that relative expression in the allele containing the promoter 1B deletion was reduced 42-98%, depending on tissue type. This study confirms the importance of APC promoter deletions as a cause of FAP and identifies a founder mutation in FAP patients from the United States.
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Proteína da Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/genética , Regiões Promotoras Genéticas , Deleção de Sequência , Polipose Adenomatosa do Colo/patologia , Proteína da Polipose Adenomatosa do Colo/química , Adulto , América , Efeito Fundador , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/química , RNA Mensageiro/metabolismoRESUMO
A long history of urbanization and industrialization has affected trace elements in New York City (NYC) soils. Selected NYC pedons were analyzed by aqua regia microwave digestion and sequential chemical extraction as follows: water soluble (WS); exchangeable (EX); specifically sorbed/carbonate bound (SS/CAR); oxide-bound (OX); organic/sulfide bound (OM/S). Soils showed a range in properties (e.g., pH 3.9 to 7.4). Sum of total extractable (SUMTE) trace elements was higher in NYC parks compared to Bronx River watershed sites. NYC surface horizons showed higher total extractable (TE) levels compared to US non-anthropogenic soils. TE levels increased over 10 year in some of the relatively undisturbed and mostly wooded park sites. Surface horizons of park sites with long-term anthropogenic inputs showed elevated TE levels vs. subsurface horizons. Conversely, some Bronx River watershed soils showed increased concentrations with depth, reflective of their formation in a thick mantle of construction debris increasing with depth and intermingled with anthrotransported soil materials. Short-range variability was evident in primary pedons and satellite samples (e.g., Pb 253 ± 143 mg/kg). Long-range variability was indicated by PbTE (348 versus 156 mg/kg) and HgTE (1 versus 0.3 mg/kg) concentrations varying several-fold in the same soil but in different geographic locations. Relative predominance of fractions: RES (37 %) > SS/CAR (22 %) > OX (20 %) > OM/S (10 %) > EX (7 %) > WS (4 %). WS and EX fractions were greatest for Hg (7 %) and Cd (14 %), respectively. RES was predominant fraction for Co, Cr, Ni, and Zn (41 to 51 %); SS/CAR for Cd and Pb (40 and 63 %); OM/S for Cu and Hg (36 and 37 %); and OX for As (59 %).
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Monitoramento Ambiental , Poluentes do Solo/análise , Solo/química , Oligoelementos/análise , Metais Pesados/análise , Cidade de Nova IorqueAssuntos
Doença de Crohn/terapia , Síndrome da Aderência Leucocítica Deficitária/terapia , Adulto , Aloenxertos , Antígenos CD18/genética , Antígenos CD18/imunologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença de Crohn/complicações , Doença de Crohn/genética , Doença de Crohn/imunologia , Humanos , Síndrome da Aderência Leucocítica Deficitária/complicações , Síndrome da Aderência Leucocítica Deficitária/genética , Síndrome da Aderência Leucocítica Deficitária/imunologia , Masculino , Indução de RemissãoRESUMO
The 50th annual National Scientific Conference of the Australian Society for Medical Research was held in Cairns, Queensland, 13-16 November 2011. The theme, 'Indigenous Health: ACTION on Prevention' highlighted the direct action being undertaken by health and medical researchers, as well as allied health professionals, to improve long-term health outcomes for Indigenous Australians.
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Ocupações Relacionadas com Saúde , Serviços de Saúde do Indígena , Garantia da Qualidade dos Cuidados de Saúde , Sociedades Médicas , Pesquisa sobre Serviços de Saúde , Humanos , Queensland , PesquisadoresRESUMO
In this paper we describe novel and specific roles for the apoptotic regulators Bcl2 and Bim in hearing and stapes development. Bcl2 is anti-apoptotic while Bim is pro-apoptotic. Characterization of the auditory systems of mice deficient for these molecules revealed that Bcl2â»/â» mice suffered severe hearing loss. This was conductive in nature and did not affect sensory cells of the inner ear, with cochlear hair cells and neurons present and functional. Bcl2â»/â» mice were found to have a malformed, often monocrural, porous stapes (the small stirrup-shaped bone of the middle ear), but a normally shaped malleus and incus. The deformed stapes was discontinuous with the incus and sometimes fused to the temporal bones. The defect was completely rescued in Bcl2â»/â»Bimâ»/â» mice and partially rescued in Bcl2â»/â»Bimâº/â» mice, which displayed high-frequency hearing loss and thickening of the stapes anterior crus. The Bcl2â»/â» defect arose in utero before or during the cartilage stage of stapes development. These results implicate Bcl2 and Bim in regulating survival of second pharyngeal arch or neural crest cells that give rise to the stapes during embryonic development.
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Perda Auditiva Condutiva/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Estribo/crescimento & desenvolvimento , Animais , Proteínas Reguladoras de Apoptose/deficiência , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 11 Semelhante a Bcl-2 , Orelha Média/diagnóstico por imagem , Orelha Média/patologia , Desenvolvimento Embrionário , Genótipo , Perda Auditiva Condutiva/patologia , Perda Auditiva de Alta Frequência/metabolismo , Perda Auditiva de Alta Frequência/patologia , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/deficiência , Proteínas Proto-Oncogênicas c-bcl-2/genética , Radiografia , Estribo/metabolismo , Estribo/fisiopatologiaRESUMO
BACKGROUND: Paracentesis for malignant ascites is usually performed as an in-patient procedure, with a median length of stay (LoS) of 3-5 days, with intermittent clamping of the drain due to a perceived risk of hypotension. In this study, we assessed the safety of free drainage and the feasibility and cost-effectiveness of daycase paracentesis. METHOD: Ovarian cancer admissions at Hammersmith Hospital between July and October 2009 were audited (Stage 1). A total of 21 patients (Stage 2) subsequently underwent paracentesis with free drainage of ascites without intermittent clamping (October 2010-January 2011). Finally, 13 patients (19 paracenteses, Stage 3), were drained as a daycase (May-December 2011). RESULTS: Of 67 patients (Stage 1), 22% of admissions and 18% of bed-days were for paracentesis, with a median LoS of 4 days. In all, 81% of patients (Stage 2) drained completely without hypotension. Of four patients with hypotension, none was tachycardic or symptomatic. Daycase paracentesis achieved complete ascites drainage without complications, or the need for in-patient admission in 94.7% of cases (Stage 3), and cost £954 compared with £1473 for in-patient drainage. CONCLUSIONS: Free drainage of malignant ascites is safe. Daycase paracentesis is feasible, cost-effective and reduces hospital admissions, and potentially represents the standard of care for patients with malignant ascites.
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Procedimentos Cirúrgicos Ambulatórios , Ascite/cirurgia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/economia , Paracentese/efeitos adversos , Paracentese/economia , Adulto , Idoso , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Procedimentos Cirúrgicos Ambulatórios/economia , Ascite/diagnóstico por imagem , Ascite/economia , Ascite/etiologia , Análise Custo-Benefício , Gerenciamento Clínico , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Londres , Prontuários Médicos , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Paracentese/métodos , Segurança do Paciente , Radiografia , Estudos Retrospectivos , Resultado do Tratamento , Reino UnidoRESUMO
Despite recent tissue-engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunofluorescence targeted at immunologically relevant molecules, we have studied the early (48 h and 1 week) immunological responses within larynxes transplantated between seven pairs of National Institutes of Health (NIH) minipigs fully homozygous at the major histocompatibility complex (MHC) locus. There were only small changes in expression of some molecules (relative to interindividual variation) and these were clearest in samples from the subglottic region, where the areas of co-expression of CD25(+) CD45RC(-) CD8(-) and of CD163(+) CD172(+) MHC-II(-) increased at 1 week after transplant. In one case, infiltration by recipient T cells was analysed by T cell receptor (TCR) Vß spectratype analysis; this suggested that changes in the T cell repertoire occur in the donor subglottis mucosal tissues from day 0 to day 7, but that the donor and recipient mucosal Vß repertoires remain distinct. The observed lack of strong immunological responses to the trauma of surgery and ischaemia provides encouraging evidence to support clinical trials of laryngeal transplantation, and a basis on which to interpret future studies involving mismatches.
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Laringe/transplante , Porco Miniatura/imunologia , Porco Miniatura/cirurgia , Animais , Antígenos CD/metabolismo , Feminino , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T , Laringe/imunologia , Laringe/patologia , Complexo Principal de Histocompatibilidade , Masculino , Modelos Animais , Suínos , Porco Miniatura/genética , Fatores de Tempo , Imunologia de Transplantes , Transplante HomólogoRESUMO
Staphylococcus aureus is a bacterial pathogen that causes severe infections among humans. The increasing emergence of antibiotic resistance necessitates the development of new strategies to combat the spread of disease. One approach is photodynamic inactivation using porphyrin photosensitizers, which generate superoxide and other radicals in the presence of light, causing cell death via the oxidation of proteins and lipids. In this study, we analyzed a novel library of meso-substituted and metallated porphyrins for activity against multidrug-resistant S. aureus. From a library of 251 compounds, 51 showed antimicrobial activity, in three discrete classes of activity: those that functioned only in light, those that had toxicity only in darkness, and those that displayed activity regardless of illumination. We further demonstrated the broad-spectrum activity of these compounds against a variety of pathogens, including Bacillus anthracis, Enterococcus faecalis, and Escherichia coli. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) analyses of lead compounds (XPZ-263 and XPZ-271) revealed strong activity and killing towards methicillin-resistant S. aureus (MRSA) strains. An analysis of mutation frequencies revealed low incidences of resistance to lead compounds by E. coli and MRSA. Finally, an exploration of the underlying mechanism of action suggests that these compounds do not depend solely upon light-induced radical generation for toxicity, highlighting their potential for clinical applications.
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Antibacterianos/farmacologia , Metaloporfirinas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Bacillus anthracis/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Fotoquimioterapia , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidadeRESUMO
There is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. Regenerative medicine offers promise, but cannot presently deliver implants with functioning neuromuscular units. A single well-documented laryngeal transplant in man was a qualified success, but more information is required before clinical trials may be proposed. We studied the early response of the larynx to laryngeal transplantation between 17 pairs of NIH minipigs full matched at the MHC2 locus. Following iterative technical improvements, pigs had good swallowing and a patent airway at 1 week. No significant changes in mucosal blood flux were observed compared with pre-operative measurements. Changes in muscle morphology and fibre phenotype were observed in transplant muscles retrieved after 7 days: the levels of fast and slow myosin heavy chain (MyHC) protein were reduced and embryonic MyHC was up regulated consistent with denervation induced atrophy. At 1 week laryngeal transplantation can result in good swallowing, and is not associated with clinical evidence of ischemia-reperfusion injury in MHC-matched pigs.
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Deglutição/fisiologia , Doenças da Laringe/cirurgia , Músculos Laríngeos/fisiopatologia , Laringe/transplante , Cadeias Pesadas de Miosina/metabolismo , Traumatismo por Reperfusão/cirurgia , Animais , Modelos Animais de Doenças , Feminino , Doenças da Laringe/fisiopatologia , Músculos Laríngeos/metabolismo , Masculino , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Suínos , Porco MiniaturaRESUMO
Constitutional mismatch repair-deficiency (CMMR-D) syndrome is an autosomal recessive condition characterized by hematologic malignancies, brain tumors, Lynch syndrome-associated cancers and skin manifestations reminiscent of neurofibromatosis type 1 (NF1). In contrast to Lynch syndrome, CMMR-D syndrome is exceptionally rare, onset typically occurs in infancy or early childhood and, as described in this report, may also present with colonic polyposis suggestive of attenuated familial adenomatous polyposis (AFAP) or MUTYH associated polyposis (MAP). Here we describe two sisters with CMMR-D syndrome due to germline bi-allelic MSH6 mutations. Both sisters are without cancer, are older than typical for this condition, have NF1 associated features and a colonic phenotype suspicious for an attenuated polyposis syndrome. This report highlights the role of skin examinations in leading to an underlying genetic diagnosis in individuals with colonic adenomatous polyposis, but without mutations associated with AFAP or MAP.
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Polipose Adenomatosa do Colo/diagnóstico , Neoplasias Encefálicas/diagnóstico , Neoplasias Colorretais/diagnóstico , Síndromes Neoplásicas Hereditárias/diagnóstico , Polipose Adenomatosa do Colo/genética , Neoplasias Encefálicas/genética , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Feminino , Instabilidade Genômica , Genótipo , Humanos , Repetições de Microssatélites , Mutação , Síndromes Neoplásicas Hereditárias/genética , Linhagem , Pele/patologia , Adulto JovemRESUMO
Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intra-transplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P=0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for all patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P=0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term follow-up would be required to fully assess the differences in therapeutic effectiveness between the two regimens.
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Transplante de Células-Tronco Hematopoéticas/métodos , Esclerose Múltipla/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Animais , Soro Antilinfocitário/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carmustina/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Rejeição de Enxerto/prevenção & controle , Mobilização de Células-Tronco Hematopoéticas , Cavalos , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Qualidade de Vida , CoelhosRESUMO
We report the safety and feasibility of autologous CD133+ cell implantation into the lower extremity muscles of patients with critical limb ischemia, whose only other option was limb amputation. Nine patients participated in the study: seven patients suffering from arteriosclerosis obliterans, one with thromboangiitis obliterans (Buerger's disease) and one with thromboembolic disorder. Autologous PBSC were collected after the administration of G-CSF (10 mcg/kg/day). CD133+ cells were selected using the CLINIMACS cell separation device and were injected i.m. without earlier cryopreservation using a 22-gauge needle into multiple sites 3 cm apart in the gastrocnemius/soleus muscle, or depending on clinical circumstances, in the foot or quadriceps muscle, or both, of the involved leg. There were no complications from either leukapheresis or injection. Stem cell injection prevented leg amputation in seven of the nine patients. In this small cohort of patients with end-stage critical limb ischemia, quality of life (Short Form-36) physical component score improved significantly at 3 (P=0.02) and 6 (P=0.01) months, but not at 1 year (P=0.08). There was a trend towards the improvement in pain-free treadmill walking time (P=0.13) and exercise capacity (P=0.16) at 1 year. Lower extremity limb salvage was achieved for seven of the nine treated patients.