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1.
Clin Otolaryngol ; 42(1): 104-114, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27185184

RESUMEN

BACKGROUND: Head and neck cancers [HNCs] are biologically heterogeneous tumours. The objectives of this study were to describe trends in incidence of HNCs amongst London residents by sex, age, anatomical site, deprivation and ethnicity. METHODS: Annual age-standardised incidence rates [ASRs] were calculated on HNC registration data, overall and for specific cancer sites, by sex and morphology (1985-2010) and area-based socio-economic deprivation score (2006-2010). Age-standardised incidence rate ratios [IRRs] for the main ethnic groups were calculated by cancer site, using White males and females as the reference groups (1998-2009). RESULTS: The ASR of HNC in males increased by 40% from 17.3 [95% CI: 15.8-18.6] to 24.2 [95% CI: 22.5-25.8] per 100 000 and in females by 87% from 7.0 [95% CI: 6.2-7.8] to 13.1 [95% CI: 11.9-14.2] per 100 000. Seventy-three per cent of cases spanned four cancer sites: larynx, thyroid, oral and oropharynx. Larynx was most common (23%), and had the highest male: female ratio (6 : 1); ASRs decreased significantly over time, most notably in males [P < 0.001]. Oral cavity was the second most common (21%), with a male: female ratio of 2 : 1, and increasing ASRs in both sexes [P < 0.001]. The majority of cases were male (64%) and from deprived areas (59%). Deprivation was associated with a significantly higher incidence for larynx (males), oropharynx (males and females) and oral cavity (females) [P < 0.05]. The age-specific rate for middle-aged adults (45-64 years) was high for oropharyngeal cancer. The incidence of thyroid cancers increased significantly in both sexes [P < 0.001], and this was the only site more common in females. One in five cases with known ethnicity was from a non-White group (20%). Compared with their White counterparts, Bangladeshi females had a higher incidence of oral, laryngeal and thyroid cancers; Chinese males and females had a higher incidence of nasopharyngeal cancer; and Pakistani and Indian females and Indian males also had higher incidence of oral cancer. CONCLUSIONS: HNCs are increasing in London males and females with significant variation by cancer site over time; oral and oropharyngeal cancers show the most significant rise, with implications for public health action and service provision.


Asunto(s)
Carcinoma/epidemiología , Carcinoma/patología , Etnicidad/estadística & datos numéricos , Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias de Cabeza y Cuello/patología , Población Blanca/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Londres , Masculino , Persona de Mediana Edad , Distribución por Sexo , Factores Socioeconómicos , Adulto Joven
2.
Psychooncology ; 25(1): 19-27, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26619290

RESUMEN

BACKGROUND: Data linkage studies find that depression before or after a breast cancer diagnosis predicts reduced survival. This study aimed to determine whether depression or bipolar recorded in routine hospital admission data independently predicts survival in English breast cancer patients and whether onset in relation to cancer diagnosis is significant. METHODS: Data on 77,173 women diagnosed with breast cancer (ICD-10 C50) in South East England, 2000-2009, were included. Of these, 131 women had a diagnosis of bipolar affective disorder (ICD-10 F31) and 955 of depression (either depressive episodes (ICD-10 F32) or depressive disorder (ICD-10 F33)) recorded in Hospital Episode Statistics between 3 years before and a year following cancer diagnosis. Kaplan-Meier plots were used to examine overall survival. Cox regression analyses were carried out overall and separately for mood disorder diagnoses before and after the cancer diagnosis and adjusted for confounding variables. RESULTS: A record of depression was a predictor of worse overall survival in breast cancer patients (adjusted HR = 1.33, 95% CI: 1.20-1.48, p < 0.001), while the effect of bipolar was not statistically significant (adjusted HR = 1.33, 95% CI: 0.97-1.82, p = 0.079). New recordings of depression and bipolar diagnoses following a cancer diagnosis appeared better predictors of overall survival than a prior history of either. CONCLUSIONS: There is evidence that English breast cancer patients with depression and bipolar recorded in routine hospital data have worse overall survival than those without these mood disorders. Further work exploring the concordance of records within administrative health data with clinical diagnosis and cause-specific death within these patient groups is needed.


Asunto(s)
Trastorno Bipolar/diagnóstico , Neoplasias de la Mama/psicología , Depresión/diagnóstico , Sobrevivientes/psicología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Inglaterra/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Clasificación Internacional de Enfermedades , Persona de Mediana Edad , Sistema de Registros , Análisis de Supervivencia , Sobrevivientes/estadística & datos numéricos
3.
Br J Clin Pharmacol ; 80(4): 796-807, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25619317

RESUMEN

The International Conference on Harmonization considers older people a 'special population', as they differ from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions (ADRs). Medical practice is often based on single disease guidelines derived from clinical trials that have not included frail older people or those with multiple morbidities. This presents a challenge caring for older people, as drug doses in trials may not be achievable in real world patients and risks of ADRs are underestimated in clinical trial populations. The majority of ADRs in older people are Type A, potentially avoidable and associated with commonly prescribed medications. Several ADRs are particularly associated with major adverse consequences in the elderly and their reduction is therefore a clinical priority. Falls are strongly associated with benzodiazepines, neuroleptics, antidepressants and antihypertensives. There is good evidence for medication review as part of a multifactorial intervention to reduce falls risk in community dwelling elderly. Multiple medications also contribute to delirium, another multifactorial syndrome resulting in excess mortality particularly in frail older people. Clostridium difficile associated with use of broad spectrum antibiotics mainly affects frail older people and results in prolonged hospital stay with substantial morbidity and mortality. Antipsychotics increase the risk of stroke by more than three-fold in patients with dementia. Inappropriate prescribing can be reduced by adherence to prescribing guidelines, suitable monitoring and regular medication review. Given the heterogeneity within the older population, providing individualized care is pivotal to preventing ADRs.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Anciano Frágil/estadística & datos numéricos , Accidentes por Caídas , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Comorbilidad , Delirio , Interacciones Farmacológicas , Enterocolitis Seudomembranosa/inducido químicamente , Enterocolitis Seudomembranosa/epidemiología , Humanos , Prescripción Inadecuada , Conciliación de Medicamentos , Polifarmacia , Factores de Riesgo
4.
J Neurooncol ; 120(3): 531-6, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25154322

RESUMEN

Studies in the United States (US) have reported varying treatment and survival for patients with high grade glioma from different ethnic groups. This study investigates for the first time whether differences also exist in the United Kingdom (UK). This population-based cohort study used cancer registration data for 4,845 patients diagnosed in South East England between 2000 and 2009. Linked self-assigned ethnicity data within Hospital Episode Statistics were used to define White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African, Other and Not known groups. Logistic regression was used to generate odds ratios for a record of receipt of treatment (surgery, radiotherapy and chemotherapy), adjusting for sex, age, morphology, socioeconomic deprivation and comorbidity in each ethnic group. Hazard ratios were generated using Cox regression, adjusting for sex, age, morphology, socioeconomic deprivation, comorbidity and treatment. The overall one-year survival was 28.4 %. Ethnicity data was available for 3,793 (78 %) patients. Receipt of treatment was generally similar between different ethnic groups after adjustment for sex, age, morphology, socioeconomic deprivation and comorbidity. After adjustment for potential confounders, the Indian (HR 0.72, p = 0.037) and Other groups (HR 0.76, p = 0.003) had better survival, while the Not known group (HR 1.34, p < 0.0001) had worse survival than the White group. Patients from UK Indian groups have better survival than White patients while those from Black ethnic groups appear to have similar survival to White patients. These findings suggest the need to investigate possible contributing factors including the completeness of follow-up, clinical performance status and tumour biology.


Asunto(s)
Neoplasias Encefálicas/etnología , Neoplasias Encefálicas/mortalidad , Glioma/etnología , Glioma/mortalidad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Inglaterra/epidemiología , Glioma/patología , Glioma/terapia , Humanos , Clasificación del Tumor , Modelos de Riesgos Proporcionales , Sistema de Registros , Análisis de Supervivencia
6.
Public Health ; 126(1): 57-63, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22153886

RESUMEN

BACKGROUND: English cancer policy has encouraged primary care trusts (PCTs) to consider their 1-year cancer survival estimates. This study quantifies variation in these estimates across 39 PCTs in the London and South East Coast strategic health authorities, and explores their precision, possible confounding by age and bias due to death certificate only (DCO) registrations. STUDY DESIGN: Retrospective observational study. METHODS: One-year relative survival estimates and data on DCO registrations for patients diagnosed with lung, colorectal, breast and prostate cancers between 2002 and 2006 were extracted from the UK Cancer Information Service. Direct age standardization was performed with weightings derived from the standard cancer patient population for Europe. Pearson correlation coefficients between survival estimates and DCO proportions were calculated. RESULTS: Mean 1-year PCT survival estimates ranged from 6.9 to 19.4 percentage points, and the precision of individual estimates ranged from ±0.9 to ±6.5 percentage points (at 95% confidence level). Age standardization significantly changed the estimates of nine PCTs for breast cancer, five PCTs for lung cancer and three PCTs for colorectal cancer. None of the prostate cancer estimates were affected significantly. DCO proportions were positively associated with lung cancer survival and negatively associated with colorectal and breast cancer survival. CONCLUSIONS: PCT 1-year cancer survival estimates may be informative, but caveats relating to data quality and hence the validity of the estimates means that they require careful investigation before naïve use, as random variation, confounding due to age and bias due to DCO registrations may be significant.


Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias del Colon/mortalidad , Neoplasias Pulmonares/mortalidad , Atención Primaria de Salud/estadística & datos numéricos , Neoplasias de la Próstata/mortalidad , Adolescente , Adulto , Anciano , Estudios de Cohortes , Certificado de Defunción , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Sistema de Registros , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
7.
Br J Cancer ; 105(7): 1049-53, 2011 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-21863024

RESUMEN

BACKGROUND: This study aimed to examine the incidence and survival of lung cancer patients from several different ethnic groups in a large ethnically diverse population in the United Kingdom. METHODS: Data on residents of South East England diagnosed with lung cancer between 1998 and 2003 were extracted from the Thames Cancer Registry database. Age- and socioeconomic deprivation-standardised incidence rate ratios were calculated for males and females in each ethnic group. Overall survival was examined using Cox regression, adjusted for age, socioeconomic deprivation, stage of disease and treatment. Results are presented for White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African and Chinese patients, apart from female survival results where only the White, South Asian and Black ethnic groups were analysed. RESULTS: Compared with other ethnic groups of the same sex, Bangladeshi men, White men and White women had the highest incidence rates. Bangladeshi men had consistently higher survival estimates compared with White men (fully adjusted hazard ratio 0.46; P<0.001). Indian (0.84; P=0.048), Black Caribbean (0.87; P=0.47) and Black African (0.68; P=0.007) men also had higher survival estimates. South Asian (0.73; P=0.006) and Black (0.74; P=0.004) women had higher survival than White women. CONCLUSION: Smoking prevention messages need to be targeted for different ethnic groups to ensure no groups are excluded. The apparent better survival of South Asian and Black patients is surprising, and more detailed follow-up studies are needed to verify these results.


Asunto(s)
Etnicidad/estadística & datos numéricos , Neoplasias Pulmonares/etnología , Neoplasias Pulmonares/mortalidad , Anciano , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Reino Unido/epidemiología
8.
Anaesth Rep ; 9(1): 110-113, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34095852

RESUMEN

Complications of transoesophageal echocardiography are numerous and may have serious consequences. We present the case of a 31-year-old woman with postoperative airway obstruction secondary to a transesophageal echocardiography probe. The patient had been admitted with acute myocarditis and required temporary mechanical support with a biventricular assist device. She deteriorated on the intensive care unit several hours later with hypoxaemia, high airway pressures and reduced tidal volumes. Sedation was adequate and no external obstruction in the breathing circuit was observed. The tracheal tube was noted to be permanently deformed in the oropharynx, causing airway obstruction. Tracheal tube exchange was required, and the patient recovered from the event. We suspect that the position of the transoesophageal echocardiography probe in the operating theatre had contributed to the deformity, and the presence of airway obstruction was masked by the reduced ventilatory parameters instituted while on mechanical circulatory support. The biventricular assistance devices were explanted subsequently, and the patient was discharged home on day 31. This is the first reported case of a kinked tracheal tube where transoesophageal echocardiography probe placement was suspected to have contributed. A high index of suspicion is required for this complication on the intensive care unit.

9.
J Exp Med ; 190(1): 31-41, 1999 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-10429668

RESUMEN

The T cell antigen receptor (TCR) and its ligand peptide-major histocompatibility complex (MHC) are small (approximately 7 nm) compared with other abundant cell surface molecules such as integrins, CD43, and CD45 (23-50 nm). We have proposed that molecules at the T cell/antigen-presenting cell (APC) interface segregate according to size, with small "accessory" molecules (e.g., CD2, CD4, CD8, CD28, and CD154) contributing to the formation of a close-contact zone, within which the TCR engages peptide-MHC, and from which large molecules are excluded (Davis, S.J., and P.A. van der Merwe. 1996. Immunol. Today. 17:177-187). One prediction of this model is that increasing the size of these small accessory molecules will disrupt their function. Here, we test this prediction by varying the dimensions of the CD2 ligand, CD48, and examining how this affects T cell antigen recognition. Although the interaction of CD2 on T cells with wild-type or shortened forms of CD48 on APCs enhances T cell antigen recognition, the interaction of CD2 with elongated forms of CD48 is strongly inhibitory. Further experiments indicated that elongation of the CD2/CD48 complex inhibited TCR engagement of peptide-MHC, presumably by preventing the formation of sufficiently intimate contacts at the T cell/APC interface. These findings demonstrate the importance of small size in CD2/CD48 function, and support the hypothesis that T cell antigen recognition requires segregation of cell surface molecules according to size.


Asunto(s)
Antígenos CD/inmunología , Antígenos CD2/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Animales , Células Presentadoras de Antígenos/inmunología , Western Blotting , Antígeno CD48 , Células CHO , Cricetinae , Regulación hacia Abajo , Citometría de Flujo , Ligandos , Sustancias Macromoleculares , Ratones , Unión Proteica , Ratas
10.
Br J Cancer ; 103(7): 1076-80, 2010 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-20736945

RESUMEN

BACKGROUND: Breast cancer 5-year relative survival is low in the North East London Cancer Network (NELCN). METHODS: We compared breast cancer that was diagnosed during 2001-2005 with that in the rest of London. RESULTS: North East London Cancer Network women more often lived in socioeconomic quintile 5 (42 vs 21%) and presented with advanced disease (11 vs 7%). Cox regression analysis showed the survival difference (hazard ratio: 1.27, 95% confidence interval (CI): 1.15-1.41) reduced to 1.00 (95% CI: 0.89-1.11) after adjustment for age, stage, socioeconomic deprivation, ethnicity and treatment. Major drivers were stage and deprivation. Excess mortality was in the first year. CONCLUSION: Late diagnosis occurs in NELCN.


Asunto(s)
Neoplasias de la Mama/mortalidad , Factores Socioeconómicos , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Tardío , Femenino , Humanos , Londres , Persona de Mediana Edad , Análisis de Supervivencia
11.
Palliat Med ; 24(8): 807-11, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20709712

RESUMEN

Population-based studies investigating access to palliative care often use death in a hospice as a proxy for service use. We linked data from a large South London hospice to Thames Cancer Registry (TCR) data to determine whether patients who received hospice services differed from those who did not. We matched hospice data for 2474 cancer patients dying between 2000 and 2006, while resident within a restricted catchment area, to TCR data for residents in this area. During matching 14.2% (n = 352) of hospice patients were excluded due to differing key dates or addresses. In addition, 5.6% (n= 175) of residents initially defined as not receiving hospice services were recorded as dying in a hospice in the TCR dataset. The problems of overlapping catchment areas and of defining patients receiving services meant we could not adequately determine use of hospice services. This method might be applied more successfully to non-urban hospices, primary care trusts or larger regions.


Asunto(s)
Cuidados Paliativos al Final de la Vida/estadística & datos numéricos , Neoplasias/epidemiología , Cuidados Paliativos/estadística & datos numéricos , Investigación sobre Servicios de Salud/métodos , Humanos , Londres/epidemiología , Registro Médico Coordinado , Sistema de Registros
12.
Br J Cancer ; 100(3): 545-50, 2009 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-19127253

RESUMEN

Studies from the US have shown variations in breast cancer incidence, stage distribution, treatment and survival between ethnic groups. Data on 35 631 women diagnosed with breast cancer in South East England between 1998 and 2003 with self-assigned ethnicity information available were analysed. Results are reported for White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African and Chinese women. Age-standardised breast cancer incidence rate ratios, patterns of stage of disease at diagnosis, treatment, overall and breast cancer-specific survival were examined. All ethnic groups studied had lower age-standardised breast cancer incidence rates than White women, with Bangladeshi women having the lowest rate ratio (0.23, 95% CI: 0.20-0.26). White women were the most likely to have a stage recorded at diagnosis (adjusted proportion 75%), and least likely to be diagnosed with metastatic disease (7%). Black African women were the least likely to have a record of cancer surgery (63%) or hormone therapy (32%), and most likely to receive chemotherapy (38%). After fully adjusting for age, socioeconomic deprivation, stage of disease and treatment received, there was no significant variation in breast cancer-specific survival. However, Black African women had significantly worse overall survival (hazard ratio 1.24, P=0.025). These findings suggest that a strategy of earlier detection should be pursued in Black and South Asian women.


Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/etnología , Inglaterra/epidemiología , Etnicidad , Femenino , Humanos , Incidencia , Análisis de Supervivencia
13.
Br J Cancer ; 101(1): 198-201, 2009 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-19471277

RESUMEN

BACKGROUND: Studies from around the world have shown that suicide risk is increased in cancer patients, but no previous detailed analysis has been carried out in England. METHODS: We calculated standardised mortality ratios (SMRs) for suicide in 206,129 men and 211,443 women diagnosed with cancer in South East England between 1996 and 2005, relative to suicide rates in the general population. RESULTS: We found a significantly increased risk of suicide in men (SMR 1.45, 95% confidence interval (CI) 1.20-1.73) and a moderately increased risk in women (SMR 1.19, 95% CI 0.88-1.57). In both sexes, relative risk of suicide was greatest in the first year after cancer diagnosis (SMR for men 2.42, 95% CI 1.84-3.13; SMR for women 1.44, 95% CI 0.82-2.33), and was also greater in individuals diagnosed with types of cancer with high fatality (SMR for men 2.67, 95% CI 1.71-3.97; SMR for women 2.17, 95% CI 0.80-4.73). CONCLUSION: There is a critical period immediately after the diagnosis of cancer during which the excess risk of suicide is particularly high. Carers need to be aware of the importance of attending to both the physical and emotional needs of cancer patients and cancer survivors.


Asunto(s)
Neoplasias/epidemiología , Suicidio/estadística & datos numéricos , Anciano , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/psicología , Factores de Riesgo , Factores Sexuales , Suicidio/psicología
14.
Br J Cancer ; 100(1): 167-9, 2009 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-19018256

RESUMEN

We analysed data on 8987 larynx and 174060 lung cancer patients diagnosed between 1985 and 2004, of which 17.3% of larynx and 35.5% of lung cancers were in females. The age-standardised rates for each cancer declined in both sexes, but since the 1990s, the rates in females over 70 years of age have been diverging.


Asunto(s)
Neoplasias Laríngeas/epidemiología , Neoplasias Pulmonares/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Inglaterra/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores de Tiempo
15.
Clin Oncol (R Coll Radiol) ; 21(5): 417-24, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19375901

RESUMEN

AIMS: This study aimed to describe trends in the incidence and survival of cancer in teenagers and young adults in South East England between 1960 and 2002, and the influence of socioeconomic status upon survival. MATERIALS AND METHODS: Data on 1788 patients aged 15-24 years were extracted from the Thames Cancer Registry, assigning each to a diagnostic group using the Birch and Marsden classification. Age-specific incidence rates in 5-year periods for the age groups 15-19 and 20-24 years were calculated for each diagnosis. Five-year relative survival estimates by diagnostic group were calculated for both age groups using 5-year periods of follow-up and non-overlapping years of diagnosis. To calculate overall survival estimates by socioeconomic group, the 10-year follow-up period 1993-2002 was used. RESULTS: Overall incidence rates were 162 per million person-years in 15-19 year olds and 261 in 20-24 year olds. We found a higher overall incidence in males, in 20-24 year olds and an increasing incidence over the last four decades, particularly in this age group. In both the 15-19 and 20-24 years age groups lymphomas were most common. The 5-year relative survival improved for all diagnostic groups, except bone tumours in the older age group, particularly for leukaemia and slightly more for the 20-24 than 15-19 years age group. Teenagers aged 15-19 years and living in more deprived areas had a significantly lower survival than those in more affluent areas. CONCLUSIONS: These findings confirm the increased incidence and improved outcome of cancer in teenagers and young adults. Future analyses should investigate trends in bone tumour survival across regions, survival by socioeconomic status and the influence of specialised care on further improvements in survival.


Asunto(s)
Neoplasias/epidemiología , Adolescente , Adulto , Distribución por Edad , Inglaterra/epidemiología , Femenino , Humanos , Incidencia , Masculino , Neoplasias/mortalidad , Neoplasias/patología , Factores de Riesgo , Distribución por Sexo , Factores Socioeconómicos , Tasa de Supervivencia/tendencias
16.
Curr Biol ; 5(1): 74-84, 1995 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-7697352

RESUMEN

BACKGROUND: The T-lymphocyte cell-surface molecule, CD2, was the first heterophilic cell-adhesion molecule to be discovered and has become an important paradigm for understanding the structural basis of cell adhesion. Interaction of CD2 with its ligands. CD58 (in humans) and CD48 (in mice and rats), contributes to antigen recognition by T cells. CD2, CD48 and CD58 are closely related members of the immunoglobulin superfamily and their extracellular regions are predicted to have very similar structures. The three-dimensional crystal structure of this region of CD2 has been determined, revealing two immunoglobulin domains with the ligand-binding site situated on an exposed beta sheet in the membrane-distal domain. This GFCC'C" beta sheet is also involved in a homophilic 'head-to-head' interaction in the CD2 crystal lattice, which has been proposed to be a model for the interactions of CD2 with its ligands. RESULTS: We show that the CD2-binding site on rat CD48 lies on the equivalent beta-sheet of its membrane-distal immunoglobulin domain. By making complementary mutations, we have shown that two charged residues in the CD48 ligand-binding site interact directly with two oppositely charged residues in CD2's ligand-binding site. These results indicate that the amino-terminal immunoglobulin domains of CD2 and CD48 bind each other in the same orientation as the CD2-CD2 crystal lattice interaction, strongly supporting the suggestion that CD2 interacts head-to-head with its ligand. Modelling CD48 onto the CD2 structure reveals that the CD2-CD48 complex spans approximately the same distance (134 A) as predicted for the complex between the T-cell receptor and the peptide-bound major histocompatibility complex (MHC) molecule. CONCLUSIONS: Our results, together with recent structural studies of CD2, provide the first indication of the specific topology of a cell-adhesion molecule complex. The similar dimensions predicted for the CD2-CD48 complex and the complex between the T-cell receptor and the peptide-bound MHC molecule suggest that one of the functions of CD2 may be to position the plasma membranes of the T cell and the antigen-presenting (or target) cell at the optimal distance for the low-affinity interaction between the T-cell receptor and the peptide-bound MHC molecule.


Asunto(s)
Antígenos CD/química , Antígenos CD2/química , Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Antígenos CD/genética , Antígenos CD/inmunología , Sitios de Unión , Antígenos CD2/inmunología , Antígeno CD48 , Gráficos por Computador , Cristalografía por Rayos X , Humanos , Datos de Secuencia Molecular , Mutagénesis , Conformación Proteica , Estructura Secundaria de Proteína , Ratas , Proteínas Recombinantes/química , Proteínas Recombinantes/inmunología , Homología de Secuencia de Aminoácido , Linfocitos T/química
17.
Transplantation ; 58(4): 424-30, 1994 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-8073510

RESUMEN

The recipients of combined kidney-pancreas transplants (SPK) are unique because they routinely receive two allografts from the same donor. In a previous study, we found that the long-term graft survival of the two allografts was different, with better graft survival seen in the pancreas allograft. In an attempt to understand the reason for the different graft survival in the recipients of organs from the same donor, we have reviewed the incidence and timing of rejection episodes in 160 consecutive technically successful whole-organ bladder-drained SPK performed at a single institution using a uniform immunosuppressive regimen. Rejection episodes were common. A total of 53% of the recipients had at least one episode of rejection in one of the organs. Multiple rejection episodes requiring hospitalization occurred in 23% of the recipients. The kidney allograft had more frequent rejection episodes than the pancreas allograft: 78 patients had 130 renal rejection episodes while only 50 patients had 65 episodes of pancreas rejection. No rejection episodes occurred in 111 pancreas and 82 kidney grafts (P = 0.0014). Multiple rejection episodes were three times as common in the kidney grafts (20%) than in the pancreas grafts (6%; P = 0.0001). The timing of the first rejection episode was also different. The median time to the first kidney rejection episode was 29 days compared with 39 days to the first pancreas rejection episode (P = 0.0191). Graft survival in the organs was equal when stratified by the number of rejection episodes (none, one, > one) per organ (P = 0.9378). These data suggest that the worse long-term kidney graft survival seen in SPK recipients is due to the greater risk of rejection (relative risk: 2.04; [95% conf. interval: 1.29-3.23]) and a greater frequency of rejection episodes of rejection episodes in the kidney (0.81/patient) compared with the pancreas (0.41/patient). The implications for patient management and the possible reasons for the different rates of rejection are discussed.


Asunto(s)
Rechazo de Injerto/diagnóstico , Supervivencia de Injerto , Trasplante de Riñón/fisiología , Trasplante de Páncreas/fisiología , Adulto , Diabetes Mellitus Tipo 1/cirugía , Femenino , Humanos , Incidencia , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Factores de Tiempo , Trasplante Homólogo
18.
Transplantation ; 63(11): 1611-5, 1997 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-9197355

RESUMEN

Both acute rejection and the function of a renal allograft early after transplantation correlate with long-term graft survival. In this study we assessed the relationship between these two factors in 843 adult recipients of first cadaveric renal grafts, transplanted at a single institution and followed for a minimum of 3.5 years. Patients were divided into four groups according to (1) history of acute rejection (AR) during the first 6 months after transplantation, and (2) concentration of serum creatinine at 6 months after transplantation (SCr(6mo) < or > or = 2 mg/dl). Death censored allograft survival was not significantly different among patients without AR and with low SCr(6mo) (group 1, n=376), patients without AR but with an elevated SCr(6mo) (group 2, n=117), and patients with AR but low SCr(6mo) (group 3, n=185). In contrast, graft survival was significantly worse in patients with AR and an elevated SCr(6mo) (group 4, n=165) compared with patients in the other three groups (Cox, P<0.0001). The elevated SCr(6mo) in group 4 patients was not necessarily the consequence of AR, as 32% of patients in group 4 had a SCr at 10 days after transplantation (SCr(10d)), before they had AR, that was equal to or higher than the SCr(6mo). Based on this observation we investigated the implications of the SCr(10d) concentration for graft prognosis. The SCr(10d) correlated weakly with graft survival (Cox, P=0.05). However, an elevated SCr(10d) correlated with other potential risk factors for graft survival including: Older donors (P<0.0001), male recipients (P<0.0001), and heavier recipients (P<0.0001, all by multivariate regression); and posttransplant factors such as, increasing numbers of AR (P<0.0001), higher posttransplant blood pressure (P<0.0001), and lower doses of cyclosporine (P<0.0001, all by multivariate regression). In conclusion, graft dysfunction predicts poor graft survival only when associated with AR. Similarly, AR predicts a poor renal allograft survival only when associated with graft dysfunction. The SCr(10d) is an indicator of risk factors from both the donor and recipient, and an elevated SCr(10d) predicts a higher risk of acquiring additional risk factors early after transplantation.


Asunto(s)
Rechazo de Injerto/fisiopatología , Trasplante de Riñón/inmunología , Enfermedad Aguda , Adolescente , Adulto , Presión Sanguínea , Creatinina/sangre , Femenino , Supervivencia de Injerto/fisiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Factores de Tiempo , Trasplante Homólogo/inmunología , Trasplante Homólogo/fisiología
19.
Transplantation ; 63(11): 1639-45, 1997 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-9197360

RESUMEN

We retrospectively compared the clinical and financial impact of a final cross-match by T cell flow cytometry (FXM) versus conventional complement-dependent cytotoxicity (CXM) in consecutive primary cadaveric kidney (K) and primary simultaneous cadaveric pancreas-kidney (SPK) transplant recipients. Mean follow-up was 14 months for both the K (range, 5-22 months) and SPK (range, 5-22 months) recipients. There were no instances of a positive CXM result if the FXM result was negative. However, 18 of the 102 (18%) K recipients and 11 of the 66 (17%) SPK recipients were FXM positive, CXM negative, but no grafts lost to hyperacute rejection in this group. In addition, patient survival, graft survival, incidence of acute rejection, and kidney and pancreas function (immediate and late) were not different in the FXM-positive versus the FXM-negative groups. Charges for the CXM and FXM methods were compared over a 6-month period. During that period, the FXM charges averaged $583 less per recipient than the CXM charges (58% reduction in charges), and the time required to perform the FXM method was 50% of that required for the CXM method. These results demonstrate that a clinical pathway for primary transplantation that utilizes the FXM rather than the CXM final cross-match is clinically safe, with no adverse effect on posttransplant outcome, reduces organ preservation time by shortening the waiting period for the final cross-match results, and significantly reduces the tissue typing charges. However, about 9% of all primary K and SPK recipients will be FXM positive, CXM negative on final cross-match and will be unnecessarily denied a transplant. In this study, we describe a method to identify these patients so that they can be tested by traditional CXM to avoid being denied access to donor organs.


Asunto(s)
Prueba de Histocompatibilidad/economía , Prueba de Histocompatibilidad/métodos , Trasplante de Riñón/fisiología , Trasplante de Páncreas/fisiología , Adulto , Cadáver , Costos y Análisis de Costo , Citotoxicidad Inmunológica , Femenino , Citometría de Flujo , Rechazo de Injerto/fisiopatología , Supervivencia de Injerto/fisiología , Humanos , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana Edad , Trasplante de Páncreas/inmunología , Linfocitos T/citología
20.
Transplantation ; 60(12): 1418-21, 1995 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-8545867

RESUMEN

The results after primary cadaveric renal transplantation in 665 consecutive patients were reviewed with respect to posttransplant serum lipids. Data were available for 182 of 665 patients on serum total cholesterol and triglycerides at 1 year posttransplant. Hypercholesterolemia (cholesterol > 200 mg/dl) developed in 141 of 182 patients (77%) and hypertriglyceridemia developed in 73 of 166 patients (44%). At 1 year posttransplant, hypercholesterolemia and hypertriglyceridemia both correlated with age at transplant (P = 0.0001, P = 0.01). Hypercholesterolemia and hypertriglyceridemia were also correlated with obesity as determined by body mass index (kg/m2) (P = 0.006, P = 0.01). Hypertriglyceridemia at 1 year posttransplant correlated with pretransplant triglyceride level (P = 0.006), but hypercholesterolemia did not correlate with pretransplant cholesterol level (P = 0.53). Hyperlipidemia was not correlated with cyclosporine (CsA) or prednisone dose (mg/kg), CsA trough levels, number of rejection episodes, or serum creatinine at 1 year. Despite significant differences in serum cholesterol and triglycerides, actuarial graft and patient survival were similar between the normolipidemic and hyperlipidemic groups.


Asunto(s)
Supervivencia de Injerto , Trasplante de Riñón , Lípidos/sangre , Adulto , Femenino , Humanos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Factores de Riesgo , Análisis de Supervivencia
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