RESUMEN
BACKGROUND: To evaluate the feasibility of a protocol using combined magnetic resonance imaging (MRI), clinical data, and electroencephalogram (EEG) to identify neonates with mild neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH) who are eligible for "early exit". METHODS: Retrospective chart review of TH cases at a single Level III NICU over a 5-year period was used to describe the demographic, clinical, and outcome data in neonates that received early exit in contrast to 72 hour TH treatment. RESULTS: Two hundred and eight TH cases, including 18 early exit cases (9%) and 9 cases (4%) evaluated for early exit with MRI but continued on 72 hours of TH, were identified. Early exit and 72 hour treatment groups did not differ in demographics or cord gas measures, although early exit neonates had a shorter length of stay (pâ<â0.05). Consistent with the early exit protocol, no early exit infants had evidence of moderate or severe encephalopathy on EEG or evidence of hypoxic ischemic injury on MRI at 24 hours of life. Neurology follow up between age 1 and 18 months was available for 10 early exit infants, 8 of whom had a normal examination. CONCLUSIONS: Early MRI at 24 hours of age, alongside clinical and EEG criteria, is feasible as part of a protocol to identify neonates eligible for early exit from therapeutic hypothermia.
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Duración de la Terapia , Electroencefalografía/métodos , Hipotermia Inducida/métodos , Hipoxia-Isquemia Encefálica , Imagen por Resonancia Magnética/métodos , Toma de Decisiones Clínicas , Protocolos Clínicos , Femenino , Humanos , Hipoxia-Isquemia Encefálica/diagnóstico , Hipoxia-Isquemia Encefálica/terapia , Lactante , Recién Nacido , Tiempo de Internación , Masculino , Examen Neurológico/métodos , Evaluación de Resultado en la Atención de Salud , Índice de Severidad de la EnfermedadRESUMEN
Adult T-cell leukemia/lymphoma (ATLL) develops after infection with human T-cell leukemia virus-1 (HTLV-1) after a long latency period. The negative regulatory programmed death-1/programmed death-1 ligand 1 (PD-1/PD-L1) pathway has been implicated in the induction of cytotoxic T-lymphocyte (CTL) exhaustion during chronic viral infection along with tumor escape from host immunity. To determine whether the PD-1/PD-L1 pathway could be involved in the establishment of persistent HTLV-1 infections and immune evasion of ATLL cells in patients, we examined PD-1/PD-L1 expression on cells from 27 asymptomatic HTLV-1 carriers (ACs) and 27 ATLL patients in comparison with cells from 18 healthy donors. PD-1 expression on HTLV-1-specific CTLs from ACs and ATLL patients was dramatically elevated. In addition, PD-1 expression was significantly higher on CD8+ T cells along with cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-specific CTLs in ATLL patients compared with ACs and control individuals. Primary ATLL cells in 21.7% of ATLL patients expressed PD-L1, whereas elevated expression was not observed in cells from ACs. Finally, in functional studies, we observed that an anti-PD-L1 antagonistic antibody upregulated HTLV-1-specific CD8+T-cell response. These observations suggest that the PD-1/PD-L1 pathway plays a role in fostering persistent HTLV-1 infections, which may further ATLL development and facilitate immune evasion by ATLL cells.
Asunto(s)
Antígenos CD/análisis , Proteínas Reguladoras de la Apoptosis/análisis , Leucemia-Linfoma de Células T del Adulto/inmunología , Antígenos CD/inmunología , Proteínas Reguladoras de la Apoptosis/inmunología , Antígeno B7-H1 , Linfocitos T CD8-positivos/química , Linfocitos T CD8-positivos/inmunología , Estudios de Casos y Controles , Progresión de la Enfermedad , Virus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T del Adulto/etiología , Leucemia-Linfoma de Células T del Adulto/patología , Receptor de Muerte Celular Programada 1 , Linfocitos T Citotóxicos/inmunologíaRESUMEN
OBJECTIVE: We aimed to describe the adherence patterns to antiretroviral therapy (ART) in a cohort of HIV-infected children. METHODS: Between the periods May to October 2005, 63 HIV-infected children and their caregivers recruited consecutively at four Paediatric Infectious Disease Clinics in Greater Kingston and St. Catherine, Jamaica, were interviewed. Adherence was defined as no missed doses in the last four days. Biomedical markers and factors associated with adherence were explored. RESULTS: Global adherence level was 85.7% (54/63) and was significantly higher for children in residential care (approaching 100%) compared to 76.3% for children in family care (p = 0.008). Children had median age 7.9 years (range 0.8 - 19.4 years) and 57% were male. Median duration on ART was 18.3 months (range 0.1 - 123.8 months). Median CD4 count and per cent available for 95.2% (60/63) and 92.1% (58/63) children were 440 cells per microL (IQR 268-897 cells/pL) and 24.9% (IQR 15.6 - 42.7%), respectively. Median viral load was 9.60 x 103 copies/ml (IQR 0.05 x 10(3) - 52.50 x 10(3)) with 16% (10/63) having viral loads < or = 50 copies/ml. Children in residential care (n=26), receiving directly observed therapy had higher CD4 counts (p = 0.006) and CD4 per cent (p < or = 0.001). Factors associated with non-adherence were primarily caregiver related, especially long work hours (p = 0.002) and nausea as a side effect of ART (p = 0.007). Non-adherence was positively correlated with missing clinic appointments (r = 0.342, p = 0.009) and increasing age of child (r = 0.310, p = 0.013). CONCLUSION: In resource-limited settings, psychosocial factors contribute significantly to nonadherence and should complement biomedical markers in predicting adherence to antiretroviral therapy in children.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Adolescente , Antirretrovirales/uso terapéutico , Biomarcadores , Recuento de Linfocito CD4/estadística & datos numéricos , Niño , Preescolar , Estudios Transversales , Femenino , Infecciones por VIH/inmunología , Humanos , Lactante , Jamaica , Lamivudine/uso terapéutico , Masculino , Nevirapina/uso terapéutico , Encuestas y Cuestionarios , Adulto Joven , Zidovudina/uso terapéuticoRESUMEN
There are over 7,000 people on dialysis in Australia and this is predicted to increase due to the ageing population and the high incidence of diabetes mellitus. Discontinuation of dialysis is the second most frequent cause of death in dialysis patients in Australia. Risk factors for the discontinuation of dialysis include: co-morbidities (especially diabetes mellitus) and being older. Because the decision to discontinue dialysis is a major life choice, collaborative decision making should be encouraged, and the patient needs assurances of the continuation of care and kindness, a palliative care plan, and the alleviation of suffering. Patients decide to discontinue dialysis because of an unacceptable quality of life, depression and a chronic failure to thrive. Health professionals need to support end of life decision making using an ethical decision framework. A review of current literature was undertaken and revealed a paucity of information in regard to palliation in those with end stage renal disease who had discontinued dialysis. The fear of dying, pain, suffering, and abandonment that a patient and/or their family may perceive as being associated with death may create barriers to decisions to discontinue with dialysis treatments. Therefore health care personnel should provide information with honesty to allow patients to predict their quality of life and death. Support for the patient and family during the dying period should be multi-disciplinary, with clear and timely communication between all members of the team.
Asunto(s)
Actitud Frente a la Salud , Toma de Decisiones/ética , Fallo Renal Crónico/psicología , Diálisis Renal , Cuidado Terminal , Privación de Tratamiento , Planificación Anticipada de Atención/ética , Planificación Anticipada de Atención/legislación & jurisprudencia , Factores de Edad , Actitud Frente a la Muerte , Australia/epidemiología , Comorbilidad , Conducta Cooperativa , Familia/psicología , Miedo , Conducta de Ayuda , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Inutilidad Médica/ética , Inutilidad Médica/legislación & jurisprudencia , Inutilidad Médica/psicología , Participación del Paciente/legislación & jurisprudencia , Participación del Paciente/psicología , Rol Profesional , Relaciones Profesional-Paciente , Calidad de Vida/legislación & jurisprudencia , Calidad de Vida/psicología , Diálisis Renal/ética , Diálisis Renal/psicología , Apoyo Social , Cuidado Terminal/ética , Cuidado Terminal/organización & administración , Cuidado Terminal/psicología , Privación de Tratamiento/ética , Privación de Tratamiento/legislación & jurisprudenciaRESUMEN
This phenomenological study was conducted to investigate the biopsychosocial impact of end-stage renal disease on dialysis patients and their partners. Forty-four participants were interviewed separately (22 patients and their partners) by way of two open-ended questions, and multiple themes were identified from verbatim transcripts. Both the patients and partners viewed their relationship very positively, and both were overwhelmed by the impact of dialysis on their lives. Anger, depression and hopelessness were evident in the patients, whilst a pervasive sadness, resentment, guilt and loss were prevalent in the partners. This study gives a unique perspective on the negative impact which dialysis can have on couples, yet it also suggests that some are able to cope in a positive way despite the many life-style adjustments required by dialysis. The results of this study indicate that nurses need to recognize and respond to the tremendous emotional impact that chronic illness and its treatment can have on families in an era where it is possible to sustain life for years with the use of life support technology.
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Actitud Frente a la Salud , Fallo Renal Crónico/psicología , Fallo Renal Crónico/terapia , Diálisis Peritoneal Ambulatoria Continua/psicología , Diálisis Renal/psicología , Esposos/psicología , Adaptación Psicológica , Adulto , Anciano , Actitud Frente a la Muerte , Femenino , Pesar , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Investigación Metodológica en Enfermería , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/enfermería , Calidad de Vida , Diálisis Renal/efectos adversos , Diálisis Renal/enfermería , Encuestas y CuestionariosRESUMEN
Acid extracts of the intermediate pituitaries of the gars, L. spatula and L. osseus, were fractionated by Sephadex G-50 column chromatography and analyzed by radioimmunoassay. This procedure revealed that immunoreactive forms of N-acetylated beta-endorphin- and alpha-MSH-sized material were present in equimolar amounts and represented the major end products of the POMC biosynthetic pathway in these species. Cation-exchange chromatography indicated that multiple N-acetylated forms of beta-endorphin were present in the intermediate pituitaries of the two species of gar, and that these forms differed in their net positive charge and in their apparent molecular weight. Reversed-phase HPLC analysis of the alpha-MSH-related material indicated that up to 90% of the total MSH in the pituitary of the gar was N-acetylated. Furthermore, the predominant form of alpha-MSH in both species of gar was N,O-diacetyl-ACTH(1-13)-NH2. Nearly identical results were obtained following the analysis of alpha-MSH-related peptides in the intermediate pituitary of the bowfin, A. calva. The pattern of posttranslational processing of POMC observed in the intermediate pituitaries of holostean fishes is very similar to the processing events observed in lungfishes, turtles, and mammals; hence, the processing of POMC has been remarkably conserved during vertebrate evolution.
Asunto(s)
Peces/metabolismo , Hipófisis/química , Proopiomelanocortina/metabolismo , alfa-MSH/análisis , betaendorfina/análisis , Acetilación , Animales , Femenino , Inmunohistoquímica , MasculinoRESUMEN
PURPOSE: The purpose of this study was to determine the clinical outcome for pediatric patients with peripheral neuroepithelioma treated with combined modality therapy and followed long enough to account for late relapses. PATIENTS AND METHODS: Fifteen patients, ages 3 3/12 to 19 10/12 years, with peripheral neuroepithelioma (median follow-up 91 months) were diagnosed at The Children's Hospital, Denver, Colorado over the period 1980-1989. All of these malignancies originated in the soft tissues. A critical review of these cases was performed with particular consideration given to the site and stage of the tumor and to the radiographic findings at presentation. Thirteen patients had bulk (> 5 cm in the greatest dimension) or metastatic disease. Four patients had primary tumors involving the chest wall. All patients received chemotherapy, which included at least doxorubicin, vincristine, and cyclophosphamide. Definitive surgical resections were performed on 13 of 15 patients. RESULTS: Five patients relapsed. Three were late relapses 24-44 months after diagnosis. Three of the five patients who relapsed had chest wall primaries. There were three deaths in this series due to peripheral neuroepithelioma and one due to sepsis. The overall survival was 68.5%, and the recurrence-free, survival 55.2%. Two patients with pulmonary relapses were treated with surgery and intensive chemotherapy and remain free of disease > 51 months following recurrence. CONCLUSIONS: Combined treatment modalities appear to be important for optimal outcome. This series represents the first report of favorable outcome of peripheral neuroepithelioma using a series with follow-up that is long enough to account for late relapses.
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Tumores Neuroectodérmicos Periféricos Primitivos/terapia , Neoplasias de los Tejidos Blandos/terapia , Adolescente , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Masculino , Tumores Neuroectodérmicos Periféricos Primitivos/mortalidad , Tumores Neuroectodérmicos Periféricos Primitivos/patología , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
The frequency of asymptomatic carriage of the hepatitis virus types B and C in an inner city area (South London) was assessed in a survey of 1002 subjects attending their General Practitioner for minor, non-hepatic complaints. Ten subjects were seropositive for hepatitis B surface antigen (HBsAg) (1 per cent), but only one, who declined liver biopsy, had any clinical laboratory evidence of hepatitis B virus-related chronic liver disease. Carriage of, and exposure to, hepatitis B virus was significantly more frequent among people born outside the UK/Eire and those with a history of jaundice. Among people of Caribbean origin the frequency of hepatitis B virus markers fell from 31 per cent among those born in the Caribbean to 11 per cent amongst second generation subjects born in this country. Despite careful counselling, offers of further investigation and treatment of those affected, and vaccination of vulnerable children or partners, were often declined. Four percent of the same population had antibodies to the hepatitis C virus using the Ortho anti-hepatitis C virus enzyme-linked immunosorbent assay but this figure fell to 0.9 per cent when a second test, based on synthetic peptides rather than a recombinant antigen, was used. None had any abnormality of standard liver function tests. Chronic asymptomatic carriage of hepatitis, particularly in inner city areas, may be more common than previously recognized. Effective use of antiviral agents and vaccination will be limited until appropriate health education dispels the widespread misconceptions and fears associated with a diagnosis of chronic viral hepatitis.
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Portador Sano/epidemiología , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Población Urbana , Adulto , Enfermedad Crónica , Femenino , Hepatitis B/etnología , Hepatitis C/etnología , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma.
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Carcinoma Hepatocelular/metabolismo , Hepatopatías/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Unión a Tiroxina/metabolismo , Adulto , Enfermedad Crónica , Citosol/metabolismo , Humanos , Persona de Mediana Edad , Tiroxina/metabolismoRESUMEN
As part of a larger study designed to investigate the interaction of factors such as cirrhosis and hepatitis B virus infection as aetiological agents in the development of hepatocellular carcinoma, we investigated the status of hepatic HBV-DNA sequences in 156 cirrhotic patients. Forty-one were HBsAg seropositive and 18 (44%) of these had HBV-DNA sequences detectable in their livers. There are also 26 subjects who showed markers of a previous HBV infection (anti-HBs/anti-HBc), only one (4%) of whom had demonstrable hepatic HBV-DNA sequences. No sequences were found in any of the remaining 89 patients who were seronegative for all markers. Thus, liver HBV-DNA was only detected in the presence of a serum marker, usually HBsAg.
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Carcinoma Hepatocelular/análisis , ADN Viral/análisis , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Cirrosis Hepática/microbiología , Neoplasias Hepáticas/análisis , Hígado/análisis , Biopsia , Carcinoma Hepatocelular/sangre , Humanos , Hígado/patología , Cirrosis Hepática/sangre , Neoplasias Hepáticas/sangreRESUMEN
To determine whether previous observations suggesting reduced ability of thyroxine-binding globulin (TBG) to bind exogenous thyroid hormones in hepatocellular carcinoma (HCC) might form the basis of a useful clinical test, we have investigated a larger series involving 49 patients and 10 healthy subjects. The binding ratio (mol hormone bound/mol TBG at a given hormone concentration) for both T4 and T3 was significantly reduced when compared to both cirrhotic and normal subjects. No overlap in T4 binding occurred between HCC patients and the control groups. Serial measurements on serum samples obtained from five cirrhotic patients who ultimately developed HCC revealed significant reductions in binding for both hormones up to 60 months prior to the clinical diagnosis of HCC. A reduced ability to bind thyroid hormones appears to be a specific feature of serum TBG from HCC patients and is one of the earliest alterations seen among cirrhotic subjects who ultimately develop the disease.
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Carcinoma Hepatocelular/metabolismo , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Unión a Tiroxina/metabolismo , Adulto , Anciano , Humanos , Persona de Mediana Edad , Hormonas Tiroideas/metabolismoRESUMEN
The haematological variables, haematinic state, and placental function of more than 2000 pregnant women, heterozygous for either alpha- or beta-thalassaemia genes, were examined during pregnancy. Four features emerged. Firstly, it was possible by discriminant function analysis of haematological variables to distinguish in pregnant patients between the anaemia caused by thalassaemia trait and that caused by iron deficiency. Secondly, patients with thalassaemia become significantly more anaemic in pregnancy, beta more than alpha, but this was mainly due to plasma dilution. From the data percentile curves were drawn for each type of thalassaemia which predicted the patients' expected "normal" haemoglobin throughout gestation. Thirdly, patients with alpha-thalassaemia had the same incidence of iron deficiency as normal pregnant patients, whereas in those with beta-thalassaemia it was four times less common. The incidence of folic acid and vitamin B12 deficiency was the same in all groups. Finally, as assessed by serum oestriol concentration, there did not appear to be any abnormality of placental function or fetal development associated with maternal thalassaemia, and, also, there seemed to be no increase in maternal or fetal morbidity in pregnancy.
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Complicaciones Hematológicas del Embarazo/sangre , Talasemia/sangre , Adulto , Anemia Hipocrómica/diagnóstico , Diagnóstico Diferencial , Recuento de Eritrocitos , Índices de Eritrocitos , Estriol/sangre , Femenino , Ferritinas/sangre , Ácido Fólico/sangre , Hemoglobina A2/análisis , Humanos , Embarazo , Talasemia/diagnóstico , Factores de Tiempo , Vitamina B 12/sangreRESUMEN
The haematological indices of Peninsular Arabs (United Arab Emirate Nationals, Yemeni and Omani) have been examined. The most outstanding feature, seen in 40-50% of all subjects, was one of hypochromia, microcytosis associated with erythrocytosis. In approximately 5% the hypochromia was severe (MCH 19-22 pg) and 20% of these were found to have beta thalassaemia trait. In 10% of subjects the hypochromia was moderate (MCH 23-24 pg) and beta thalassaemia was confirmed in only 10%. The remaining 25% had a mild hypochromia (MCH 25-27 pg) and no beta thalassaemia was detected. The cause of the hypochromia in subjects with a normal Hb A2 (30% of the total population) is probably alpha thalassaemia, firstly because in those patients with an MCH of 19-24 pg the other haematological parameters are statistically the same as those with proven beta thalassaemia and, secondly, in those with an MCH of 25-27 pg iron deficiency is not common (6% of the population). The degree and pattern of the distribution of hypochromia of the three major ethnic groups of the Peninsular Arabs could be explained either by different alpha and beta thalassaemia genes being operative or by different degrees of inbreeding of the same genes.
Asunto(s)
Genes , Talasemia/genética , Adolescente , Adulto , Índices de Eritrocitos , Femenino , Ferritinas/sangre , Sangre Fetal/análisis , Hemoglobina A2/análisis , Hemoglobinas Anormales/análisis , Humanos , Masculino , Persona de Mediana Edad , Omán , Embarazo , Complicaciones Hematológicas del Embarazo , Arabia Saudita , Talasemia/sangre , Talasemia/epidemiología , Emiratos Árabes Unidos , YemenRESUMEN
The titre of HBsAg in the serum of patients with HBsAg seropositive hepatocellular carcinoma rose in 12 (80%) of 15 cases during chemotherapy with either adriamycin or etoposide and in five cases there was at least a four-fold rise in titre. Anti-HBs and anti-HBc status did not change and serum markers of HBV infection did not become apparent in the 32 patients who were seronegative at presentation. The chemotherapy-related rise in HBsAg titre did not appear to be responsible for deterioration in hepatocellular function and it was not associated with any change in HBeAg/anti-HBe status.
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Antineoplásicos/farmacología , Carcinoma Hepatocelular/inmunología , Anticuerpos contra la Hepatitis B/análisis , Antígenos de Superficie de la Hepatitis B/análisis , Neoplasias Hepáticas/inmunología , Adolescente , Adulto , Anciano , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Femenino , Antígenos e de la Hepatitis B/análisis , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
In 73 patients with fulminant viral hepatitis, non-A non-B hepatitis (NANB) was most common (43.8%), with hepatitis type A (HAV) diagnosed in 31.5% and hepatitis type B (HBV) in 24.7%. The non-A non-B group had a significantly longer duration from the onset of symptoms to the appearance of encephalopathy (median 21 days) compared with the HAV and HBV groups (medians 10 and seven days, p less than 0.01 and p less than 0.005 respectively). In the HAV group the severity of liver damage, judged by the maximum prolongation of the prothrombin time, was significantly less than in the HBV group (58 and 150 seconds prolonged respectively, p less than 0.005), and cerebral oedema was significantly less frequent (39% and 72% respectively, p less than 0.05). Consistent with this, the survival rate was higher in the HAV group (43.4%) compared with the HBV group (16.6%) and NANB group (9.3%) (p less than 0.005). These variations in presentation and clinical course may be a consequence of differences in the pathogenesis of the hepatic necrosis.