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1.
Ir J Psychol Med ; 39(1): 8-19, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35236522

RESUMO

OBJECTIVE: To assess community mental health in suburban Dublin in 2018, 5 years after Ireland's economic recession ended. METHODS: A cross-sectional, face-to-face, household survey was conducted in a random cluster sample of 351 households in Tallaght, a deprived suburb of Dublin. RESULTS: A majority of respondents (61.3%) reported stress over the previous 12 months, with a higher rate in areas of high (66.9%) compared to lower deprivation (55.5%). Deprivation was not related to rates of loneliness (20.2%), feeling depressed (20.2%), loss of interest (19.7%) or anxiety (22.5%). Mean score for positive mental health (59.3/100, with a higher score indicating better mental health) was lower than that reported in a national sample in 2007 (68/100); positive mental health was associated with not living with a person with chronic illness, self-identifying as 'non-Irish' and greater age. Mean score for psychological distress (76.7/100, with a higher score indicating less distress) was also lower than that in 2007 (82/100); less psychological distress was associated with not living with a person with chronic illness or disability, greater age and identifying as non-Irish. The rate of 'probable mental illness' over the previous 4 weeks (13.1%) was higher than in 2007 (7%). CONCLUSIONS: Our findings emphasise the high prevalence of stress, especially in deprived suburban areas; the centrality of carer burden in determining mental wellbeing; and associations between positive mental health on the one hand and greater age and identifying as non-Irish on the other.


Assuntos
Recessão Econômica , Saúde Mental , Estudos Transversais , Humanos , Irlanda , Inquéritos e Questionários
2.
QJM ; 111(8): 555-559, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29860494

RESUMO

BACKGROUND: Health has a complex relationship with economic conditions. Ireland's economic recession (2008-13) and sharp recovery (from 2014 onwards) offer a valuable opportunity to study self-reported health and its correlates in the context of rapid economic change. AIM: To assess the correlates of self-reported health in Dublin, Ireland after the economic recession of 2008-13. DESIGN: Cross-sectional, face-to-face household survey using random cluster sampling. METHODS: Self-reported health and its correlates were assessed in randomly selected households in Tallaght (a suburb of Dublin) and results were compared with a similar survey in 2014. RESULTS: Five hundred and eighty-three eligible households were invited to participate and interviews were completed in 351 (response rate: 60.2%). The proportion of respondents rating their health as 'very good' or 'good' was 71.8%, essentially unchanged from four years earlier (70.8%). In 2018, better self-reported health was associated with less stress, holding private health insurance, not living with a person with a disability or chronic illness, and greater education; taken together, these factors explained 39.4% of variation in self-reported health. Unlike 2014, self-reported health in 2018 was no longer directly associated with employment status. CONCLUSIONS: Self-reported health has stabilized in Ireland since the end of the economic recession, but its correlates have shifted. Stress and carer burden are now among the strongest correlates of poor self-reported health in Ireland.


Assuntos
Recessão Econômica/estatística & dados numéricos , Saúde Pública , Autorrelato/estatística & dados numéricos , Determinantes Sociais da Saúde/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Características da Família , Feminino , Inquéritos Epidemiológicos , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto Jovem
3.
Surg Oncol ; 21(2): 143-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21440434

RESUMO

The standard of practice in breast cancer surgery is that all patients with a positive sentinel node mandate an axillary lymph node dissection (ALND). Recently, this dogma has been challenged by a trial from ACOSOG (American College Of Surgeons Oncology Group) (Trial Z0011) which demonstrated that patients (without clinically/radiologically apparent axillary metastases) undergoing breast conserving surgery (i.e lumpectomy followed by whole breast radiotherapy) with positive sentinel nodes failed to derive any significant benefit by having an axillary lymph node dissection (ALND) [2]. The logical progression from this study is to question the validity of performing routine axillary lymph node dissections on all patients with positive sentinel lymph nodes (SLN). In addition to the Z0011 trial, there is emerging data that additional patients exist who fail to derive any benefit from axillary surgery. The aim of this article is to discuss the potential subpopulations of patients that may avoid unnecessary ALND in the modern era of breast cancer management.


Assuntos
Neoplasias da Mama/cirurgia , Excisão de Linfonodo/métodos , Axila , Feminino , Humanos , Metástase Linfática , Recidiva Local de Neoplasia , Biópsia de Linfonodo Sentinela , Análise de Sobrevida , Resultado do Tratamento
4.
Eur J Gastroenterol Hepatol ; 23(4): 308-10, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21389860

RESUMO

BACKGROUND: Postinfective bile acid malabsorption comprises a group of patients with a history of an episode of acute gastroenteritis triggering chronic diarrhoea. We identified these patients retrospectively from our medical records and assessed their long-term clinical course. MATERIALS AND METHODS: We examined the records of 135 patients with 75 selenium-homocholic acid taurine results less than 10% (1 week retention). RESULTS: Twenty-five patients (13 female, 12 male) had a diagnosis of postinfective bile acid malabsorption established after extensive investigations. Cholestyramine was used to treat diarrhoea with a mean frequency of diarrhoea decreasing from 7.8 to 1.9 (P=0.001). The mean cholestyramine dose decreased from 8.2 to 5.4 g/day (P=0.005). Eighteen of 25 (72%) patients had a successful resolution of their diarrhoea by cholestyramine and have continued it to date. The median duration of outpatient follow-up was 1.58 years (range: 1-5 years). A further prospective telephone enquiry of these 18 patients revealed that 15 of 18 patients continued to take cholestyramine (median: 6 years, range: 1-15 years). There were no hospital admissions related to diarrhoea and there was no mortality in this group of patients. CONCLUSION: The long-term outlook of this group of patients is excellent. We have shown the chronic nature of this condition as evidenced by the continued requirement of cholestyramine.


Assuntos
Ácidos e Sais Biliares/metabolismo , Infecções por Campylobacter/metabolismo , Diarreia/metabolismo , Disenteria Bacilar/metabolismo , Síndromes de Malabsorção/metabolismo , Shigella sonnei/isolamento & purificação , Doença Aguda , Resinas de Troca Aniônica/uso terapêutico , Infecções por Campylobacter/tratamento farmacológico , Infecções por Campylobacter/microbiologia , Resina de Colestiramina/uso terapêutico , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/microbiologia , Feminino , Seguimentos , Humanos , Síndromes de Malabsorção/tratamento farmacológico , Síndromes de Malabsorção/microbiologia , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
5.
Int Immunol ; 22(5): 359-66, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20190037

RESUMO

Therapeutic effects of green tea involve an inhibitory function of its constituent polyphenol epigallocatechin gallate (EGCG) on cell signaling. The specificity and mechanism(s) by which EGCG inhibits cell signaling have remained unclear. Here, we demonstrate that green tea and EGCG induce suppressor of cytokine signaling 1 (SOCS1) gene expression, a negative regulator of specific cell signaling pathways. In mouse immune cells, EGCG induces SOCS1 expression via an oxidative (superoxide) pathway and activation of the signal transducer and activator of transcription 5 transcription factor. EGCG inhibited SOCS1-regulated cell signaling, but this inhibitory effect was abrogated in cells deficient in SOCS1. These findings identify a mechanism by which EGCG inhibits cell signaling with specificity, mediated by induction of the negative regulator SOCS1.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Proteínas Supressoras da Sinalização de Citocina/genética , Chá/química , Regulação para Cima/efeitos dos fármacos , Animais , Catequina/farmacologia , Células Cultivadas , Perfilação da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/imunologia , Relação Estrutura-Atividade , Superóxidos/imunologia , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/deficiência , Proteínas Supressoras da Sinalização de Citocina/imunologia
7.
Transplant Proc ; 40(5): 1315-8, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18589095

RESUMO

PURPOSE: Although the risk of kidney donation has been determined in many studies to be low with respect to morbidity and mortality, it is important to keep in mind that patients are put at some risk when they donate an organ for transplantation. The reported incidence of end-stage renal disease (ESRD) among kidney donors ranges from 0.2% to 0.5% with varying follow-up times. Herein, we have reported four living kidney donors at our institution who progressed to ESRD. MATERIALS AND METHODS: We reviewed registry data and medical records of patients who underwent donor nephrectomy at our institution between October 1, 1959, and June 30, 2005, particularly cases who developed ESRD. RESULTS: Between October, 1959, and the end of June, 2005, 3591 kidney transplants were performed at our center including 1195 of the organs (33%) from living donors, whose mean age was 41.9 years. Four kidney donors (0.33%) developed ESRD. Their mean age at donation was 31 years; the mean age at ESRD development was 46.5 years. All four patients donated to siblings with renal failure. Two of the four (50%) had another first-degree relative who subsequently developed renal failure. Two of the four (50%) smoked tobacco subsequent to donor surgery, and one (25%) was obese. CONCLUSIONS: Progression to ESRD is rare among living renal donors. Kidney donation is safe when strict eligibility criteria are met. There may be an increased risk for progression to ESRD among donors with a family history of renal disease.


Assuntos
Falência Renal Crônica/etiologia , Doadores Vivos , Nefrectomia/efeitos adversos , Coleta de Tecidos e Órgãos/efeitos adversos , Adulto , Idade de Início , Humanos , Falência Renal Crônica/epidemiologia , Transplante de Rim/fisiologia , Pessoa de Meia-Idade , Núcleo Familiar , Seleção de Pacientes , Estudos Retrospectivos , Segurança
8.
Eur J Gastroenterol Hepatol ; 19(5): 383-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17413288

RESUMO

This article attempts to summarize the ethics of nutritional support at the end of life. Although ethics are timeless, they have to be applied or adapted to new situations arising from our ability to prolong life by the application of relatively new nutritional treatments. The application of the law, and guidance from professional bodies on withholding or withdrawing treatment remains an emotive challenge for all involved in nutritional care and for society as a whole.


Assuntos
Apoio Nutricional/ética , Assistência Terminal/ética , Idoso , Demência/terapia , Ética Clínica , Humanos , Doenças do Sistema Nervoso/terapia , Apoio Nutricional/métodos , Assistência Terminal/métodos
9.
Clin Nutr ; 24(2): 229-35, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15784483

RESUMO

BACKGROUND & AIMS: Home Parenteral Nutrition (HPN) is an accepted treatment of intestinal failure but is mostly restricted to a few large specialist centres in the UK. The provision of high-quality HPN is of paramount importance to patients with intestinal failure, but its restriction to large specialist centres limits the number of patients who can receive it. The study aim was to determine if HPN can be effectively administered in a non-specialist centre. METHODS: Adult HPN patients at a single District General Hospital in the United Kingdom were analysed by indications, complications and outcome. RESULTS: 2310 patient weeks of HPN were provided to 23 patients, aged 18-80 years with intestinal failure. Catheter infection rate was 0.315 per patient year, with one patient excluded due to persistent nasal digitation. Patients spent 89.96% of their time at home and 82.6% achieved a Karnowsky Index of 70 (generally self-caring or greater). CONCLUSIONS: HPN can be practised at non-specialist District General Hospital level achieving complication rates comparable to large specialist centres, and this lends weight to the argument for a network model to widen provision beyond large tertiary referral specialist centres in the United Kingdom.


Assuntos
Cateterismo/efeitos adversos , Acessibilidade aos Serviços de Saúde , Enteropatias/terapia , Nutrição Parenteral no Domicílio/normas , Qualidade da Assistência à Saúde , Sepse/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral no Domicílio/efeitos adversos , Nutrição Parenteral no Domicílio/métodos , Sepse/prevenção & controle , Resultado do Tratamento , Reino Unido
10.
Proc Nutr Soc ; 62(3): 719-25, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14692607

RESUMO

The British Artificial Nutrition Survey 2001 recorded 507 home parenteral nutrition (HPN) patients (Crohn's disease 31.5%, vascular disease 19.7%, cancer 6.9%). Parenteral nutrition was administered via tunnelled central line (92%) and supplied by a commercial homecare company in 89% of cases. The majority of HPN patients live at home (95.5%) with an independent life (74%), normal activity (59.2%) and 92% survive 1 year. However, there is good evidence that the geographical distribution of HPN patients is uneven (prevalence no patients to thirty-six patients per million of the population) suggesting inequity of access. Patients are increasingly concerned about the distances travelled to main centres and variable standards of more local support. Funding issues continue to cause difficulties as commissioning of health care transfers from Health Authorities to Primary Care Trusts. The two nationally-funded intestinal failure units provide HPN services to 220 HPN patients. HPN-related readmissions have displaced those awaiting admission for intestinal failure treatment, for which the waiting list mortality in one unit has risen to 14%. The government has now recognised HPN as a specialised service distinct from intestinal failure and that existing medium-sized HPN units should be encouraged to take on HPN patients from intestinal failure units and smaller units. In Scotland a Managed Clinical HPN Network supported by the Scottish administration now cares for seventy-two patients under common protocols. The challenge for the future is how to provide high-quality care to all who need it in the rest of the UK.


Assuntos
Acessibilidade aos Serviços de Saúde , Serviços de Assistência Domiciliar/organização & administração , Enteropatias/terapia , Nutrição Parenteral no Domicílio , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Serviços de Assistência Domiciliar/normas , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Nutrição Parenteral no Domicílio/estatística & dados numéricos , Nutrição Parenteral no Domicílio/tendências , Qualidade da Assistência à Saúde , Reino Unido
11.
Meat Sci ; 60(1): 85-94, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22063109

RESUMO

To investigate effects of pre-slaughter handling on blood and muscle biochemistry and venison quality, paddock-shot (n=8) and commercially slaughtered red deer (n=8) were compared. The deer were kept in two larger groups. One stag per group per day was head-shot, exsanguinated, electrically stimulated then transported 150 m to a deer slaughter premises (DSP) for processing. Prior to each slaughter day one of the groups was mustered into a deer yards and six (including two experimental) deer were selected for commercial handling and processing (including electrical stimulation) at the same DSP. Blood samples taken during exsanguination showed higher levels of cortisol, progesterone, glucose, lactate, albumin, creatine kinase, lactate dehydrogenase, aspartate aminotransferase and packed cell volume in the DSP-killed deer compared with the paddock-shot deer (P<0.05). Interpretation of these values indicated that pre-slaughter handling created moderate stress and high levels of muscular exertion or damage, possibly related to antagonism during lairage. However muscle glycogen, pH and meat quality measurements showed only minor, muscle-specific differences between treatments.

13.
J Urol ; 166(5): 1647-50, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11586194

RESUMO

PURPOSE: We review the indication, surgical technique and outcome of orthotopic renal transplantation. MATERIALS AND METHODS: The medical records of 1,000 patients who underwent renal transplantation at our institution between August 24, 1993 and August 1, 2000, as well as orthotopic renal transplantation were reviewed. RESULTS: Orthotopic renal transplantation was performed in 4 males and 1 female with severe iliac atherosclerosis or retained bilateral iliac fossa kidney transplant. Mean patient age was 56 years. There were 2 patients who received kidneys from living related donors, and 3 underwent cadaveric renal transplantation. Left orthotopic renal transplantation was successful in 4 cases, and 1 was converted to iliac fossa renal transplant because of a pulseless splenic artery and renal artery thrombosis after native renal endarterectomy. Orthotopic renal revascularization was done with splenic artery in 2, native renal artery in 2 and left renal vein in all 4 patients. Urinary tract reconstruction was performed with stented (2) or nonstented (2) ureteroureterostomy. Antibody induction, purine antagonists, calcineurin inhibitors and glucocorticoids were used for immunosuppression. Mean preoperative and 1-month postoperative serum creatinine was 7.9 and 1.3 mg./dl., respectively. Patient and graft survival was 100% during followup, which ranged from 6 months to 5 years. CONCLUSIONS: Despite the technical challenges, orthotopic renal transplantation in patients with unsuitable pelvic vessels can result in excellent patient and graft survival.


Assuntos
Nefropatias/cirurgia , Transplante de Rim , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Eur J Public Health ; 11(2): 198-200, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11420811

RESUMO

BACKGROUND: To date there have been no studies estimating the hidden prevalence of opiate use in Dublin. METHODS: A multisource enumeration followed by the application of the capture-recapture method with log-linear modelling including age and gender stratification to remove heterogeneity was implemented to provide an estimate of the unknown size of the opiate-using population. Two medical and one legal data sources were used. RESULTS: It was found that the ratio of known to unknown opiate users was 1:1.15 with a total of 13,460 (95% CI: 12,037-15,306) users estimated in Dublin in 1996. CONCLUSION: The findings of this study have important ramifications for service delivery.


Assuntos
Transtornos Relacionados ao Uso de Opioides/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Direito Penal/estatística & dados numéricos , Feminino , Humanos , Irlanda/epidemiologia , Modelos Lineares , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Prevalência , Distribuição por Sexo
15.
J Urol ; 165(6 Pt 2): 2265-8, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11371960

RESUMO

PURPOSE: Urinary tract anomalies or dysfunction leaves the bladder unsuitable for urine drainage in a significant proportion of children presenting for kidney transplantation. We reviewed a multi-institutional experience to determine the ramifications of kidney transplantation in children with bladder augmentation or urinary diversion. MATERIALS AND METHODS: During a 28-year period 18 boys and 12 girls 1.7 to 18 years old (mean age 12.1) received 31 kidney transplants. Cause of end stage renal disease was renal dysplasia in 8 cases, posterior urethral valves in 5, obstructive uropathy in 5, neurogenic bladder/chronic pyelonephritis in 4, spina bifida/chronic pyelonephritis in 3, prune belly syndrome in 3 and reflux in 2. RESULTS: Of the patients 17 had augmented bladder (ileum 9, ureter 5, sigmoid 2 and stomach 1), 12 had incontinent urinary conduits (8 ileum, 6 colon) and 1 had a continent urinary reservoir. Surgical complications included 1 case each of stomal stenosis, stomal prolapse, renal artery stenosis, urine leak, enterovesical fistula and wound dehiscence. Medical complications included urinary tract infection in 21 cases and metabolic acidosis in 5. A bladder stone developed in 1 patient. There was no correlation between the incidence of symptomatic urinary tract infections and type of urinary drainage. Acidosis was more common in patients with augmented bladder (4 of 17 versus 1 of 14) but there was no correlation between the bowel segment used and the occurrence of acidosis. Graft survival was 90% at 1 year, 78% at 5 years and 60% at 10 years. Etiology of graft loss included chronic rejection in 6 cases, noncompliance in 4 and acute rejection in 1. There were no deaths. CONCLUSIONS: Drainage of transplanted kidneys into an augmented bladder or urinary conduit is an appropriate management strategy when the native bladder is unsuitable or absent. Patients with kidney transplants drained into augmented bladder or urinary conduit are at increased risk for urine infection. Graft survival is not adversely affected compared to historical controls when a kidney transplant is drained into a urinary conduit or augmented bladder.


Assuntos
Transplante de Rim , Procedimentos de Cirurgia Plástica , Bexiga Urinária/cirurgia , Derivação Urinária , Procedimentos Cirúrgicos Urológicos , Adolescente , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Transplante de Rim/imunologia , Masculino , Complicações Pós-Operatórias
16.
Tech Urol ; 7(1): 55-6, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11272680

RESUMO

PURPOSE: To determine the need for postoperative cystography following extravesical ureteroneocystostomy for renal transplantation. MATERIALS AND METHODS: The clinical courses of 200 consecutive kidney transplant recipients who underwent urinary tract reconstruction by parallel incision extravesical ureteroneocystostomy were reviewed. RESULTS: Five of the 200 recipients did not have the study because of early mortality (1) or medical problems (4). Grade I vesicoureteral reflux was present in 5 (3%) of 182 unstented allograft ureters and 5 of 13 stented allograft ureters. Two patients (1%) underwent repeat ureteroneocystostomy, one for obstruction and one for extravasation. The cystograms were normal in both patients. CONCLUSIONS: Routine retrograde cystography is unnecessary following urinary tract reconstruction by parallel incision extravesical ureteroneocystostomy.


Assuntos
Cistostomia/métodos , Transplante de Rim , Cuidados Pós-Operatórios , Ureter/cirurgia , Bexiga Urinária/diagnóstico por imagem , Humanos , Radiografia
17.
Urol Clin North Am ; 28(4): 677-86, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11791486

RESUMO

A systematic team approach to the assessment of renal transplant candidates is one of several factors that have resulted in improved kidney transplant and recipient survival rates, rates that were only imagined 4 decades ago.


Assuntos
Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim , Humanos , Seleção de Pacientes , Taxa de Sobrevida , Resultado do Tratamento
18.
Meat Sci ; 59(2): 211-20, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22062680

RESUMO

A total of 14 female red deer were included in a study on the effects of low voltage carcass electrical stimulation on meat tenderness, colour stability and water-holding capacity. Carcasses were randomly allocated to either electrical stimulation treatment (ES; 90-95 V unipolar pulses, 7.5 ms duration, 15 Hz for a duration of 55 s) or no electrical stimulation (non-ES) (n=7 in each group). Temperature and pH decline was recorded in M.m. triceps brachii, longissimus dorsi et lumborum (at the last rib; LD) and biceps femoris, at intervals from 0.5 to 20 h post-mortem. At 24 h post-mortem, LD from the left side were excised, vacuum packaged and refrigerated at -1.5°C. Glycogen concentrations, measured at 30 min post-mortem, and ultimate pH did not differ between groups. Compared to controls, ES increased the rate of muscle pH decline and produced lower shear forces at 1 day, 1 week and 3 weeks post-mortem, but these differences disappeared by 6 and 12 weeks post-mortem. Sarcomere lengths at 24 h post-mortem were unchanged by ES. After 1 week of refrigerated storage, ES significantly reduced display life (hours of Minolta a* value ⩾ 12), but this difference disappeared at 3, 6 and 12 weeks of ageing. ES did not affect drip at any ageing time point. The present results demonstrate that the benefits of ES on tenderness are not permanent, and the procedure is not necessary for a long-term, chilled product. This study showed no detrimental effects of using electrical stimulation on meat colour stability or drip loss.

20.
Transplantation ; 70(12): 1707-12, 2000 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-11152101

RESUMO

BACKGROUND: HuM291 is a humanized anti-CD3 monoclonal antibody engineered to reduce binding to Fcgamma receptors and complement fixation. HuM291 has a long serum half-life and mediated profound depletion of circulating T cells in chimpanzees; HuM291 also has significantly less mitogenic and cytokine-releasing activity than OKT3 in vitro. METHODS: A phase I dose-escalation study was conducted in 15 end-stage renal disease patients scheduled for renal allografts from living donors. Patients received one i.v. HuM291 injection before transplantation. Five doses were tested: 0.015 microg/kg, 0.15 microg/kg, 0.0015 mg/kg, 0.0045 mg/kg, and 0.015 mg/kg. Patients were followed for adverse events, laboratory abnormalities, serum cytokine levels, pharmacokinetics, and CD2+, CD3+, CD4+, and CD8+ T cell counts. RESULTS: HuM291 was well tolerated; most adverse events were mild to moderate in severity and included headache, nausea, chills, and fever. These occurred within the first few hours after HuM291 administration, resolved within 24 to 48 hr, and were likely related to cytokine release. In general, peak tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 levels were detected 1 to 6 hr postdosing only at the three highest doses and were generally undetectable by 24-hr postdosing. Serious adverse events possibly related to HuM291 included clotting of a fistula (two patients), chemical cellulitis (one patient), and increased serum creatinine/decreased hematocrit (one patient). At doses > or = 0.0015 mg/kg (0.1 mg/70 kg), HuM291 induced rapid, marked depletion of peripheral T cells within 2 hr; duration of T cell depletion was dose dependent. At the two highest dose levels, T cells remained depleted for approximately 1 week. CONCLUSIONS: A single HuM291 dose rapidly depleted circulating T cells in a dose-dependent manner and was associated with only mild to moderate symptoms of cytokine release.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Complexo CD3/imunologia , Transplante de Rim/imunologia , Adulto , Idoso , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Citocinas/sangue , Relação Dose-Resposta Imunológica , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/terapia , Humanos , Falência Renal Crônica/cirurgia , Doadores Vivos , Depleção Linfocítica , Masculino , Camundongos , Pessoa de Meia-Idade , Pan troglodytes , Linfócitos T/imunologia
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