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1.
J Biol Chem ; 299(6): 104727, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37080390

RESUMO

Human cytomegalovirus (HCMV) latency in CD34+ progenitor cells is the outcome of a complex and continued interaction of virus and host that is initiated during very early stages of infection and reflects pro- and anti-viral activity. We hypothesized that a key event during early infection could involve changes to host miRNAs, allowing for rapid modulation of the host proteome. Here, we identify 72 significantly upregulated miRNAs and three that were downregulated by 6hpi of infection of CD34+ cells which were then subject to multiple in silico analyses to identify potential genes and pathways important for viral infection. The analyses focused on the upregulated miRNAs and were used to predict potential gene hubs or common mRNA targets of multiple miRNAs. Constitutive deletion of one target, the transcriptional regulator JDP2, resulted in a defect in latent infection of myeloid cells; interestingly, transient knockdown in differentiated dendritic cells resulted in increased viral lytic IE gene expression, arguing for subtle differences in the role of JDP2 during latency establishment and reactivation of HCMV. Finally, in silico predictions identified clusters of genes with related functions (such as calcium signaling, ubiquitination, and chromatin modification), suggesting potential importance in latency and reactivation. Consistent with this hypothesis, we demonstrate that viral IE gene expression is sensitive to calcium channel inhibition in reactivating dendritic cells. In conclusion, we demonstrate HCMV alters the miRNAome rapidly upon infection and that in silico interrogation of these changes reveals new insight into mechanisms controlling viral gene expression during HCMV latency and, intriguingly, reactivation.


Assuntos
Infecções por Citomegalovirus , Infecção Latente , MicroRNAs , Humanos , Citomegalovirus/genética , Latência Viral , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/metabolismo , MicroRNAs/genética
2.
Nat Commun ; 14(1): 1041, 2023 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823200

RESUMO

Vaccination against human cytomegalovirus (CMV) infection remains high priority. A recombinant form of a protein essential for CMV entry, glycoprotein B (gB), demonstrated partial protection in a clinical trial (NCT00299260) when delivered with the MF59 adjuvant. Although the antibody titre against gB correlated with protection poor neutralising responses against the 5 known antigenic domains (AD) of gB were evident. Here, we show that vaccination of CMV seronegative patients induces an antibody response against a region of gB we term AD-6. Responses to the polypeptide AD-6 are detected in >70% of vaccine recipients yet in <5% of naturally infected people. An AD-6 antibody binds to gB and to infected cells but not the virion directly. Consistent with this, the AD-6 antibody is non-neutralising but, instead, prevents cell-cell spread of CMV in vitro. The discovery of AD-6 responses has the potential to explain part of the protection mediated by gB vaccines against CMV following transplantation.


Assuntos
Infecções por Citomegalovirus , Vacinas contra Citomegalovirus , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Citomegalovirus , Infecções por Citomegalovirus/prevenção & controle , Vacinas contra Citomegalovirus/imunologia , Proteínas do Envelope Viral
3.
Pathology ; 54(1): 49-54, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34955242

RESUMO

Previous reports have shown that quantification of high tumour grade is of prognostic significance for patients with prostate cancer. In particular, percent Gleason pattern 4 (GP4) has been shown to predict outcome in several studies, although conflicting results have also been reported. A major issue with these studies is that they rely on surrogate markers of outcome rather than patient survival. We have investigated the prognostic predictive value of quantifying GP4 in a series of prostatic biopsies containing Gleason score 3+4=7 and 4+3=7 tumours. It was found that the length of GP4 tumour determined from the measurement of all biopsy cores from a single patient, percent GP4 present and absolute GP4 were all significantly associated with distant progression of tumour, all-cause mortality and cancer-specific mortality over a 10-year follow-up period. Assessment of the relative prognostic significance showed that these parameters outperformed division of cases according to Gleason score (3+4=7 versus 4+3=7). International Society of Urological Pathology (ISUP) Grade Groups currently divide these tumours, according to Gleason grading guidelines, into grade 2 (3+4=7) and grade 3 (4+3=7). Our results indicate that this simple classification results in the loss of important prognostic information. In view of this we would recommend that ISUP Grade Groups 2 and 3 be amalgamated as grade 2 tumour with the percentage of GP4 carcinoma being appended to the final grade, e.g., 3+4=7 carcinoma with 40% pattern 4 tumour would be classified as ISUP Grade Group 2 (40%).


Assuntos
Adenocarcinoma/patologia , Prognóstico , Neoplasias da Próstata/patologia , Biópsia com Agulha de Grande Calibre , Humanos , Masculino , Gradação de Tumores/métodos , Próstata/patologia , Prostatectomia , Estudos Retrospectivos
4.
Colorectal Dis ; 22(12): 2222-2231, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32668070

RESUMO

AIM: The aim was to explore whether people with an ileostomy in the UK and Ireland receive the dietary advice they require. METHOD: An online survey with multiple-choice questions asked people with an ileostomy about the dietary advice they received and would have preferred to receive. Participants were recruited via websites of the Ileostomy and Internal Pouch Association and Crohn's and Colitis UK and via social media. People with a current ileostomy, age 16 years or over, and living in the UK or Ireland were eligible for inclusion. Responses were analysed using descriptive statistics. RESULTS: In all, 291 eligible responses were received and included in the analysis; 201 (69%) received advice on diet for their ileostomy from a healthcare professional or the internet. Of the 90 who did not receive dietary advice, 82 (91%) would have liked advice. Stoma nurses were the most common source of dietary advice (55%), but many other sources were frequently reported. Most (62%) felt that at least some dietary advice they received was conflicting. Over half (55%) felt anxious about managing their diet with a new ileostomy, 39% were confused, and 31% frustrated. Of 291 respondents, 29% received advice from a dietitian compared to 60% who would have preferred advice from a dietitian. CONCLUSION: Many people undergoing ileostomy surgery do not receive the dietary advice and support they require. Healthcare professionals working with people with an ileostomy should be mindful they are often anxious about their diet and require clear and consistent dietary advice and support.


Assuntos
Ileostomia , Estomas Cirúrgicos , Humanos , Recém-Nascido , Irlanda , Inquéritos e Questionários , Reino Unido
5.
Gen Comp Endocrinol ; 287: 113350, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794732

RESUMO

Since its discovery in birds, gonadotropin-inhibitory hormone (GnIH) has triggered investigation in the other groups of vertebrates. In the present study, we have identified a single gnih gene in the European eel (Anguilla anguilla), a representative species of a basal group of teleosts (Elopomorphs). We have also retrieved a single gnih gene in Osteoglossomorphs, as well as in more recently emerged teleosts, Clupeocephala. Phylogeny and synteny analyses allowed us to infer that one of the two gnih paralogs emerged from the teleost-specific whole genome duplication (TWGD or 3R), would have been lost shortly after the 3R, before the emergence of the basal groups of teleosts. This led to the presence of a single gnih in extant teleosts as in other vertebrates. Two gnih paralogs were still found in some teleost species, such as in salmonids, but resulting from the additional whole genome duplication that specifically occurred in this lineage (4R). Eel gnih was mostly expressed in the diencephalon part of the brain, as analyzed by quantitative real-time PCR. Cloning of eel gnih cDNA confirmed that the sequence of the GnIH precursor encoded three putative mature GnIH peptides (aaGnIH-1, aaGnIH-2 and aaGnIH-3), which were synthesized and tested for their direct effects on eel pituitary cells in vitro. Eel GnIH peptides inhibited the expression of gonadotropin subunits (lhß, fshß, and common a-subunit) as well as of GnRH receptor (gnrh-r2), with no effect on tshß and gh expression. The inhibitory effect of GnIH peptides on gonadotropic function in a basal teleost is in agreement with an ancestral inhibitory role of GnIH in the neuroendocrine control of reproduction in vertebrates.


Assuntos
Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hipófise/metabolismo , Animais , Enguias , Feminino , Filogenia , Sintenia
6.
Br J Surg ; 103(8): 962-70, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27146793

RESUMO

BACKGROUND: Chewing gum may stimulate gastrointestinal motility, with beneficial effects on postoperative ileus suggested in small studies. The primary aim of this trial was to determine whether chewing gum reduces length of hospital stay (LOS) after colorectal resection. Secondary aims included examining bowel habit symptoms, complications and healthcare costs. METHODS: This clinical trial allocated patients randomly to standard postoperative care with or without chewing gum (sugar-free gum for at least 10 min, four times per day on days 1-5) in five UK hospitals. The primary outcome was LOS. Cox regression was used to calculate hazard ratios for LOS. RESULTS: Data from 402 of 412 patients, of whom 199 (49·5 per cent) were allocated to chewing gum, were available for analysis. Some 40 per cent of patients in both groups had laparoscopic surgery, and all study sites used enhanced recovery programmes. Median (i.q.r.) LOS was 7 (5-11) days in both groups (P = 0·962); the hazard ratio for use of gum was 0·94 (95 per cent c.i. 0·77 to 1·15; P = 0·557). Participants allocated to gum had worse quality of life, measured using the EuroQoL 5D-3L, than controls at 6 and 12 weeks after operation (but not on day 4). They also had more complications graded III or above according to the Dindo-Demartines-Clavien classification (16 versus 6 in the group that received standard care) and deaths (11 versus 0), but none was classed as related to gum. No other differences were observed. CONCLUSION: Chewing gum did not alter the return of bowel function or LOS after colorectal resection. REGISTRATION NUMBER: ISRCTN55784442 (http://www.controlled-trials.com).


Assuntos
Goma de Mascar , Colectomia , Íleus/prevenção & controle , Tempo de Internação/estatística & dados numéricos , Cuidados Pós-Operatórios , Idoso , Defecação , Feminino , Flatulência , Motilidade Gastrointestinal , Humanos , Masculino , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Método Simples-Cego , Reino Unido/epidemiologia
8.
Colorectal Dis ; 18(2): O74-80, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26682875

RESUMO

AIM: Nutrition is an important element of the Enhanced Recovery After Surgery (ERAS) programme. Patients have previously indicated that nutrition is a key component of ERAS that requires improvement. Our aim was to explore the perioperative nutrition experiences of colorectal surgical patients to identify barriers and facilitators to the integration of nutrition within ERAS. METHOD: Sixteen individuals undergoing colorectal surgery participated in a semi-structured interview between postoperative day three and hospital discharge. The topic guide was developed iteratively throughout the study; topics included preoperative counselling, carbohydrate loading, fasting and postoperative nutrition. A constant comparison technique was employed during coding, and an inductive thematic analysis was used. Validity was ensured by double coding a sample of transcripts. RESULTS: Findings are presented in the context of the following clinical themes: preoperative information, preoperative fasting, carbohydrate loading and nutritional drinks, postoperative diet and discharge. Individuals received too much general information which was repetitive, contradictory and not disease specific; this formed a key barrier affecting nutrition. Other barriers were negative experiences of nutritional drinks, stoma management, nausea and vomiting, and challenges from the hospital environment. Facilitators included interactions with staff, food accessibility and choice, and motivation for discharge. CONCLUSION: The key barrier to adherence of perioperative nutrition protocols was poor provision of information. Targeted information regarding postoperative diet, stoma management and coping with nausea and vomiting would be beneficial for colorectal surgical patients. Easily accessible food provided by ward staff was considered a facilitator.


Assuntos
Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório/reabilitação , Terapia Nutricional/psicologia , Assistência Perioperatória/psicologia , Período Perioperatório/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Digestório/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Nutricional/métodos , Alta do Paciente , Assistência Perioperatória/métodos , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/psicologia , Pesquisa Qualitativa
9.
Pathology ; 47(6): 520-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26325671

RESUMO

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.


Assuntos
Adenocarcinoma/patologia , Gradação de Tumores , Neoplasias da Próstata/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos/administração & dosagem , Biópsia com Agulha de Grande Calibre , Quimiorradioterapia/métodos , Conferências de Consenso como Assunto , Difosfonatos/administração & dosagem , Humanos , Imidazóis/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Gradação de Tumores/normas , Patologia Cirúrgica/normas , Modelos de Riscos Proporcionais , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Sociedades Médicas , Urologia/normas , Ácido Zoledrônico
10.
Allergy ; 67(12): 1601-4, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23004679

RESUMO

BACKGROUND: Caveolin-1 has emerged as a critical regulator of signaling pathways involved in lung fibrosis and inflammation. METHODS: Therefore, we investigated whether caveolin-1 is deficient in asthmatic patients and in a murine model of asthma. RESULTS: Immunohistochemical analyses of endobronchial biopsies showed a remarkable loss of caveolin-1 in the lungs of asthmatic patients compared with controls. This loss was most evident in bronchial epithelial cells and associated with an increase in the expression of extracellular matrix proteins: collagen I, tenascin, and periostin. Cultured primary bronchial epithelial cells of asthmatics had lower caveolin-1 expression compared with control cells. In addition, caveolin-1 expression was significantly decreased in peripheral blood monocytes from asthma patients. The loss of caveolin-1 was also observed in a mouse model for asthma (mice sensitized and challenged with aspergillus fumigatus). CONCLUSIONS: To our knowledge, this is the first demonstration that the regulatory protein caveolin-1 is reduced in patients with asthma.


Assuntos
Asma/metabolismo , Brônquios/metabolismo , Caveolina 1/metabolismo , Células Epiteliais/metabolismo , Monócitos/metabolismo , Animais , Caveolina 1/deficiência , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/metabolismo , Feminino , Humanos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Transdução de Sinais
11.
Saudi J Kidney Dis Transpl ; 22(1): 107-11, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21196623

RESUMO

Fulminant hepatic failure (FHF) is a rare but well-recognized complication of primary herpes simplex virus (HSV) infection in immunocompromised patients. Here, we report two cases of acute hepatitis and FHF secondary to primary HSV type 1 infection following renal transplantation in the absence of any mucocutaneous manifestation. High levels of HSV type-1 DNA were detected in the blood. Both patients were seronegative for HSV 1 and HSV 2 immunoglobulin G (IgG) before transplantation, whereas the donor of patient 1 was HSV 1 IgG-positive but had no viremia and the donor of patient 2 was HSV-seronegative. Patient 1 recovered with acyclovir and immunoglobulin whereas patient 2 did not respond and succumbed to death. HSV-seronegative patients are potentially at risk of developing severe primary HSV disease following transplantation, particularly in the absence of routine anti-viral prophylaxis. HSV infection should always be excluded in transplant patients with hepatic dysfunction.


Assuntos
Hepatite Viral Humana/virologia , Herpes Simples/virologia , Herpesvirus Humano 1/patogenicidade , Transplante de Rim/efeitos adversos , Falência Hepática Aguda/virologia , Aciclovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Biópsia , Evolução Fatal , Feminino , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/tratamento farmacológico , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/genética , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
J Med Imaging Radiat Oncol ; 54(3): 224-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20598010

RESUMO

Erectile dysfunction (ED) commonly affects the quality of life of men after treatment of prostate cancer. We conducted a placebo-controlled, crossover randomised trial to assess the efficacy and tolerability of sildenafil citrate in the treatment of ED developing after external beam radiation treatment (EBRT) of localized prostate cancer. Sixty-six patients who had developed ED following radiation treatment agreed to participate and were allocated to sildenafil or placebo to be taken prior to four sexual attempts. In the crossover period, subjects received the alternative tablet for a further four attempts. Allocation was centrally randomized, and researchers and patients were both blinded to the trial arm. Efficacy was assessed using the International Index of Erectile Function (IIEF) questionnaire and with a separate global efficacy question. Forty-three subjects completed the study. There was a significant increase in mean scores from baseline for all domains of the IIEF with sildenafil compared with placebo (P < 0.001). Affirmative response to the global efficacy question was more common after taking sildenafil compared with placebo. In approximately half of the patients, the improvement in the erectile function domain score corresponded to a moderate improvement in ED (e.g. success 'sometimes' to 'most times'). Sildenafil was associated with mild flushing, nasal stuffiness or indigestion in 8-10% patients and moderate flushing in 10%. The current study adds to the evidence that phosphodiesterase inhibitors are an effective and well-tolerated treatment for ED after EBRT for prostate cancer.


Assuntos
Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Piperazinas/administração & dosagem , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional/efeitos adversos , Sulfonas/administração & dosagem , Idoso , Terapia Combinada , Estudos Cross-Over , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Neoplasias da Próstata/complicações , Purinas/administração & dosagem , Citrato de Sildenafila , Resultado do Tratamento , Vasodilatadores/administração & dosagem
13.
J Med Imaging Radiat Oncol ; 54(3): 287-97, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20598017

RESUMO

AIM: In this study we estimated (a) the number of linear accelerators required in Australia and New Zealand to achieve a 52.3% treatment rate; (b) the 'GAP' between the actual and required number of linear accelerators; c) the number of persons not treated (PNT), premature deaths (PD) and years of life lost (YLL) as a result of the 'GAP'; and (d) to review the actions being taken by health jurisdictions in Australia and in New Zealand to address the 'GAP' and reach the 52.3% treatment rate. MATERIAL AND METHODS: The actual number of fully staffed and operating linear accelerators (A) in Australian and New Zealand was obtained from a survey of radiotherapy facilities in December 2009. The required number of linear accelerators (R) was calculated from the projected cancer incidence figures for 2009 and was based on 1.6 linear accelerators being required per 1000 new cancer patients. The 'GAP' in Radiotherapy services (G) was R minus A. The maximum treatment capacity (MTC) was the ratio of A over R multiplied by 52.3%, assuming that all linear accelerators were operating at 100% capacity. As each linear accelerator can treat 331 new patients each year, the number of new cancer PNT is G x 331. The estimated 5-year survival benefit from radiotherapy is 16%, and the average survival for all patients receiving radiotherapy (radical and palliative) is 0.76 year. Hence, the number of PD attributed to the 'GAP' is PNT x 16%, and the YLL to cancer is PNT x 0.76. A literature search and local knowledge of health department Radiotherapy Plans in all jurisdictions were used to determine the action being taken to achieve a 52.3% treatment rate. RESULTS: In 2009, the 'GAP' was 50 linear accelerators in Australia and the MTC was 38%, the same as it was in 1999, but there has been an increase in PNT each year from 7419 in 1999 to 16,550 in 2009, and PD each year increased from 1187 in 1999 to 2649 in 2009, and YLL each year increased from 5638 in 1999 to 12,585 in 2009. In New Zealand in 2009, the 'GAP' was nine linear accelerators and the MTC was 38%. An estimated 3310 persons did not receive radiotherapy in 2009 in New Zealand, and as a result, there were 523 PD and 2266 YLL. The review showed that new and replacement machines were being installed in all jurisdictions in Australia and in New Zealand. Only Victoria and Queensland have a Radiotherapy Plan beyond 2010, but both have underestimated the projected cancer incidence. CONCLUSION: Urgent action is needed by health departments and governments on both sides of the Tasman to improve access and equity to this essential cancer treatment. There is merit in the Baume Report recommendation of establishing a national body to oversee radiotherapy services in all jurisdictions in Australia. A similar central body should also be considered for New Zealand.


Assuntos
Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Aceleradores de Partículas/provisão & distribuição , Radioterapia Conformacional/estatística & dados numéricos , Austrália/epidemiologia , Nova Zelândia/epidemiologia
14.
J AAPOS ; 12(5): 445-50, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18595756

RESUMO

PURPOSE: To report the outcome of nasolacrimal duct intubation as the primary treatment of congenital nasolacrimal duct obstruction (NLDO) in children younger than 4 years of age. METHODS: A total of 182 eyes of 139 children receiving intubation with planned tube retention for 2 to 5 months were enrolled in a prospective, nonrandomized observational multicenter study (19 sites). Children were ages 6 months to <45 months at the time of surgery, with no previous nasolacrimal surgical procedures and had at least one of the following clinical signs of NLDO: epiphora, mucous discharge, and/or increased tear lake. RESULTS: Treatment success was defined as absence of epiphora, mucous discharge, and increased tear lake at the outcome visit, 1 month after tube removal. The surgical outcome was assessed in 150 eyes (82% of cohort). The proportion of eyes treated successfully was 91% (95% CI: 86%-95%). The outcome dye disappearance test was normal in 125 (86%) eyes, indeterminate in 13 (9%), and abnormal in 7 (5%) of the 145 eyes tested. Monocanalicular tubes were used in 74% of cases. The tube was removed before the planned minimum retention time of 2 months in 61 eyes (41%). For 23 eyes, the early removal was attributed to inadvertent displacement by the patient. CONCLUSIONS: In children 6 months to <45 months of age, nasolacrimal duct intubation in a nonrandomized and noncomparative trial was a successful primary treatment of NLDO in about 90% of cases not lost to follow-up.


Assuntos
Intubação , Obstrução dos Ductos Lacrimais/terapia , Ducto Nasolacrimal , Pré-Escolar , Estudos de Coortes , Remoção de Dispositivo , Feminino , Fluoresceína/farmacocinética , Corantes Fluorescentes/farmacocinética , Humanos , Lactente , Intubação/efeitos adversos , Doenças do Aparelho Lacrimal/etiologia , Obstrução dos Ductos Lacrimais/complicações , Obstrução dos Ductos Lacrimais/congênito , Obstrução dos Ductos Lacrimais/fisiopatologia , Masculino , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Lágrimas/metabolismo , Resultado do Tratamento
15.
J Pathol ; 214(1): 85-95, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17992660

RESUMO

The bone morphogenetic protein (BMP) type II receptor (BMPR-II) is predominantly expressed on the vascular endothelium in the adult lung. Although mutations in BMPR-II are known to underlie many cases of familial pulmonary arterial hypertension (FPAH), little is known regarding the expression of BMPs and their signalling pathways during normal lung development or the impact of BMPR-II mutations on endothelial cell function. We determined the cellular localization and expression levels of BMP4, BMP receptors, and activation of downstream signalling via phospho-Smad1 in a developmental series of human embryonic and fetal lungs by immunohistochemistry. The expression of BMP4 and BMP receptors was temporally and spatially regulated during lung development. BMPR-II expression correlated with phosphorylation of tissue Smad1 and was highest during the late pseudoglandular and early canalicular stage of lung development, when vasculogenesis is intense. Phospho-Smad1 expression was associated with markers of proliferation in endothelial cells. In vitro studies confirmed that BMPs 2 and 4 induced phosphorylation of Smad1/5 and pulmonary artery endothelial cell (PAEC) migration and proliferation. Adenoviral transfection of PAECs with mutant kinase-deficient BMPR-II, or siRNA knockdown of BMPR-II, inhibited Smad signalling and the proliferative response to BMP4. Our findings support a critical role for BMPs in lung vasculogenesis. Dysfunctional BMP signalling in PAECs during development may lead to abnormal pulmonary vascular development and contribute to the pathogenesis of FPAH.


Assuntos
Proteínas Morfogenéticas Ósseas/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Pulmão/embriologia , Proteína Morfogenética Óssea 4 , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Movimento Celular/fisiologia , Proliferação de Células , Sobrevivência Celular/fisiologia , Células Cultivadas , Endotélio Vascular/metabolismo , Desenvolvimento Fetal/fisiologia , Inativação Gênica , Humanos , Técnicas Imunoenzimáticas , Alvéolos Pulmonares/embriologia , Artéria Pulmonar/metabolismo , Circulação Pulmonar/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transdução de Sinais
16.
Eur J Vasc Endovasc Surg ; 34(3): 274-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17587613

RESUMO

OBJECTIVE: Open aortic aneurysm repair is traditionally associated with an extended hospital stay. The aim of this study was to examine the feasibility of reducing post-operative stay through the implementation of a fast-track, goal directed, clinical pathway for elective open aortic surgery. METHODS: A fast-track clinical pathway for aortic surgery was introduced in a regional vascular unit in September 2005. The pathway has daily goals and targets discharge for all patients on the 3rd post operative day. This study compares thirty consecutive discharges of unselected patients undergoing elective infra-renal aortic surgery following introduction of the pathway to the thirty consecutive cases preceding its introduction. Reasons for prolonged hospital stay were recorded. RESULTS: Six of thirty patients achieved discharge by Day 3. The median hospital stay reduced from 9 (range 4 to 17 days) to 5 days (range 2 to 12 days) following introduction of the pathway. There was one readmission within 30 days and no complications attributable to the pathway implementation. Cardiac complications and home planning were the most common causes of delayed discharge. CONCLUSION: Post-operative stay in patients undergoing standard elective open infra-renal aortic surgery can be safely reduced with the introduction of a goal directed pathway.


Assuntos
Aneurisma Aórtico/cirurgia , Procedimentos Clínicos/estatística & dados numéricos , Deambulação Precoce/estatística & dados numéricos , Objetivos , Tempo de Internação/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricos , Procedimentos Cirúrgicos Vasculares/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Aneurisma Aórtico/epidemiologia , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Inglaterra/epidemiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Ann Bot ; 97(3): 429-41, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16423867

RESUMO

BACKGROUND AND AIMS: A number of strawberry varieties were surveyed for their total ellagic acid concentration, and attempts were made to determine if ellagic acid and ascorbic acid concentrations of two strawberry cultivars could be increased by polythene reflective mulches. METHODS: After adjusting crop yields and cultivation using polythene mulches with two different PAR reflective capacities, field- and polytunnel-grown strawberries were analysed for ellagic acid and ascorbic acid concentrations by HPLC. Comparative measurements of yield and fruit quality were determined along with plant developmental changes. KEY RESULTS: Ellagic acid concentration varied widely with strawberry cultivar (60-341 microg g(-1) frozen weight), as did the ratio of conjugated ellagic acid : free ellagic acid. Also, there was significant year-to-year variation in total ellagic acid concentration with some cultivars. Mulches with different reflective capacities impacted on strawberry production; highly reflective mulches significantly increased growth and yield, the latter due to increases in fruit size and number. CONCLUSIONS: Highly reflective mulches significantly increased total concentrations of ellagic acid and ascorbic acid relative to control in fruit of different cultivars. The potential of agronomic practices to enhance the concentration and amounts of these important dietary bioactive compounds is discussed.


Assuntos
Ácido Ascórbico/análise , Ácido Elágico/análise , Fragaria/fisiologia , Fragaria/efeitos da radiação , Frutas/fisiologia , Frutas/efeitos da radiação , Fotossíntese/efeitos da radiação , Produtos Agrícolas/fisiologia , Ácido Elágico/química , Fragaria/classificação , Frutas/classificação , Variação Genética , Taninos Hidrolisáveis/química , Folhas de Planta/anatomia & histologia , Estações do Ano , Análise Espectral
19.
Exp Biol Med (Maywood) ; 229(9): 902-13, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15388885

RESUMO

Particular intestinal bacteria metabolize the soy isoflavone daidzein to equol and O-desmethylangolensin (O-DMA), metabolites that can be identified in urine. Individuals that harbor bacteria capable of producing equol or O-DMA are known as equol producers (approximately 30%-50% of the population) and O-DMA producers (approximately 80%-90% of the population), respectively. The equol-producer phenotype has been associated with sex hormone-related outcomes in several studies. However, the bacteria responsible for these phenotypes have not yet been identified and factors that influence the manifestation of these phenotypes are not well understood. To evaluate familial clustering of and nongenetic factors associated with these phenotypes, 410 individuals from 112 families participated in phenotyping (3-day soy challenge and Day 4 spot urine collection). In segregation analyses of the equol-producer phenotype, the Mendelian dominant model provided the most parsimonious fit to the data, suggesting that the pattern of inheritance of the equol-producer phenotype is consistent with an autosomal dominant trait. This phenotype was positively associated with education (p trend = 0.01), but not with sex, smoking, or several dietary factors. Results of the segregation analyses of the O-DMA-producer phenotype were inconclusive; no other models provided a more parsimonious fit to the data than the general model. This phenotype was inversely associated with age in a nonlinear model (p = 0.01), positively associated with age- and sex-adjusted height (odds ratio [OR] 10-cm increase = 0.38, 95% confidence interval [CI] = 0.15, 0.95) and body mass index (kg/m(2)) (OR = 0.91, 95% CI = 0.85, 0.96), but not with sex, education, smoking, or several dietary factors. These results suggest the equol-producer phenotype may be under some degree of genetic control and that there are likely other environmental factors not evaluated in the present analysis that contribute to both of these phenotypes. These results provide a foundation for further work to refine our understanding of heritable and environmental determinants of daidzein-metabolizing phenotypes.


Assuntos
Isoflavonas/farmacocinética , Feminino , Humanos , Masculino , Fenótipo , Inquéritos e Questionários
20.
J Clin Pathol ; 57(7): 778-9, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15220378

RESUMO

Bronchial carcinoids are low grade malignancies with an excellent prognosis and a low incidence of metastases. This report describes a case of a typical carcinoid tumour with metastases to the spine after four years and to the heart after eight years. Carcinoid tumours rarely metastasise to the heart and previous reports have identified gastrointestinal primaries as the source in most cases. This is the first published case of typical carcinoid tumour that metastasised to the heart from a bronchial primary.


Assuntos
Neoplasias Brônquicas/patologia , Tumor Carcinoide/secundário , Neoplasias Cardíacas/secundário , Tumor Carcinoide/patologia , Neoplasias Cardíacas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Coluna Vertebral/secundário , Vértebras Torácicas
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