RESUMO
BACKGROUND AND AIMS: Living root tissues significantly constrain plant water uptake under drought, but we lack functional traits to feasibly screen diverse plants for variation in the drought responses of these tissues. Water stress causes roots to lose volume and turgor, which are crucial to root structure, hydraulics and growth. Thus, we hypothesized that root pressure-volume (p-v) curve traits, which quantify the effects of water potential on bulk root turgor and volume, would capture differences in rootstock drought tolerance. METHODS: We used a greenhouse experiment to evaluate relationships between root p-v curve traits and gas exchange, whole-plant hydraulic conductance and biomass under drought for eight grapevine rootstocks that varied widely in drought performance in field trials (101-14, 110R, 420A, 5C, 140-Ru, 1103P, Ramsey and Riparia Gloire), grafted to the same scion variety (Vitis vinifera 'Chardonnay'). KEY RESULTS: The traits varied significantly across rootstocks, and droughted vines significantly reduced root turgor loss point (πtlp), osmotic potential at full hydration (πo) and capacitance (C), indicating that roots became less susceptible to turgor loss and volumetric shrinkage. Rootstocks that retained a greater root volume (i.e. a lower C) also maintained more gas exchange under drought. The rootstocks that previous field trials have classified as drought tolerant exhibited significantly lower πtlp, πo and C values in well-watered conditions, but significantly higher πo and πtlp values under water stress, than the varieties classified as drought sensitive. CONCLUSIONS: These findings suggest that acclimation in root p-v curve traits improves gas exchange in persistently dry conditions, potentially through impacts on root hydraulics or root to shoot chemical signalling. However, retaining turgor and volume in previously unstressed roots, as these roots deplete wet soil to moderately negative water potentials, could be more important to drought performance in the deep, highly heterogenous rooting zones which grapevines develop under field conditions.
Assuntos
Secas , Vitis , Desidratação , Folhas de Planta/fisiologia , Raízes de Plantas , Solo , Vitis/fisiologiaRESUMO
INTRODUCTION: The effects of single-fraction gamma knife radiosurgery (sf-GKRS) on patients with renal cell carcinoma (RCC) brain metastases (BM) in the era of targeted agents (TA) and immune checkpoint inhibitors (ICI) are insufficiently studied. METHODS AND MATERIALS: Clear cell metastatic RCC patients treated with sf-GKRS due to BM in 2005-2014 at three European centres were retrospectively analysed (n = 43). Median follow-up was 56 months. Ninety-five percent had prior nephrectomy, 53% synchronous metastasis and 86% extracranial disease at first sf-GKRS. Karnofsky performance status (KPS) ranged from 60 to 100%. Outcome measures were overall survival (OS), local control (LC) and adverse radiation effects (ARE). RESULTS: One hundred and ninety-four targets were irradiated. The median number of targets at first sf-GKRS was two. The median prescription dose was 22.0 Gy. Thirty-seven percent had repeated sf-GKRS. Eighty-eight percent received TA. LC rates at 12 and 18 months were 97% and 90%. Median OS from the first sf-GKRS was 15.7 months. Low serum albumin (HR for death 5.3), corticosteroid use pre-sf-GKRS (HR for death 5.8) and KPS < 80 (HR for death 9.1) were independently associated with worse OS. No further prognostic information was gleaned from MSKCC risk group, synchronous metastasis, age, number of BM or extracranial metastases. Other prognostic scores for BM radiosurgery, including DS-GPA, renal-GPA, LLV-SIR and CITV-SIR, again, did not add further prognostic value. ARE were seldom symptomatic and were associated with tumour volume, 10-Gy volume and pre-treatment perifocal oedema. ARE were less common among patients treated with TA within 1 month of sf-GKRS. CONCLUSIONS: We identified albumin, corticosteroid use and KPS as independent prognostic factors for sf-GKRS of clear cell RCC BM. Studies focusing on the prognostic significance of albumin in sf-GKRS are rare. Further studies with a larger number of patients are warranted to confirm the above analytical outcome. Also, in keeping with previous studies, our data showed optimal rates of local tumour control and limited toxicity post radiosurgery, rendering GKRS the tool of choice in the management of RCC BM.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Seleção de Pacientes , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Carga TumoralRESUMO
Confusion remains as to what is meant by Denonvilliers' fascia. This review searched the literature on pelvic surgical anatomy to determine whether there is agreement with Denonvilliers' original description and its implication in defining the correct anterior plane of dissection when mobilizing the rectum. The original French description of the fascia was translated into English and then compared both with French and with English studies identified by searching PubMed, Medline and Scopus from 1836 to June 2015. Special emphasis was given to the years between 1980 and 2015 in order to capture the literature pertinent to, and following on from, the description of total mesorectal excision for rectal cancer. The final literature search revealed 16 studies from the original 2150 citations. Much of the debate was concerned with the origin and development of the fascia, arising from either the 'fusion' or the 'condensation' of local primitive tissue into a mature 'multilayered' structure. Controversy regarding the correct plane of rectal mobilization occurs as a result of different interpretations by surgeons, anatomists and radiologists and bears little resemblance to Denonvilliers' original description. This may reflect wide anatomical variability in the adult pelvis or a form of dissection artefact. Further study is required to investigate this. Logically, for both men and women, the plane of rectal mobilization should be behind Denonvilliers' fascia and between it and the fascia propria of the rectum.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Dissecação/métodos , Fáscia/anatomia & histologia , Pelve/anatomia & histologia , Reto/anatomia & histologia , Adulto , Feminino , Humanos , Masculino , Pelve/cirurgia , Neoplasias Retais/cirurgia , Reto/cirurgiaRESUMO
We report the second family with AIMP1 deficiency, due to a homozygous truncating AIMP1 (g.107248613 C > T) mutation. This female showed early-onset developmental arrest, intractable epileptic spasms, microcephaly, and a rapid clinical course leading to premature death, associated with cerebral atrophy and myelin deficiency on brain MRI. Clinical and neuroimaging findings are consistent with a primary neuronal degenerative disorder, rather than with the previously reported Perlizaeus-Merzbacher-like phenotype. Given its critical role in neurofilament assembly 16, impaired myelin formation is due to neuronal/axonal dysfunction. We propose that AIMP1 deficiency be added to the differential diagnosis of infantile onset, progressive neurodegenerative disease.
Assuntos
Citocinas/deficiência , Citocinas/genética , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/genética , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/genética , Proteínas de Ligação a RNA/genética , Fatores Etários , Encéfalo/patologia , Feminino , Humanos , Recém-Nascido , Mutação , Substância Branca/patologiaRESUMO
The metabolic control of phenylalanine levels is a challenge during illness. We present the metabolic management of a 6 year old boy with classical PKU who was diagnosed with stage III intraabdominal Burkit's lymphoma and underwent surgical resection and chemotherapy. The metabolic control during chemotherapy was achieved by the use of parenteral custom made amino acid solution and pro-active adjustment of intake. From the 94 obtained plasma phenylalanine (Phe) levels, 18.4% were above our clinic's recommended upper limit (360 µmol/L, 6 mg/dL) while 52.7% of Phe levels were below the recommended lower limit (120 µmol/L, 2 mg/dL). Phe levels above recommended range were associated with low caloric/protein intake, while levels below recommended range reflected the difficulty in achieving the full prescribed Phe intake. We recommend early institution of custom made amino acid solution with maximum amino acid content and caloric intake to provide optimal phenylalanine control. Administration of phenylalanine via regular intravenous amino acid solution may assist in avoiding low Phe levels when prescribed intake is compromised due to vomiting and other disease related illnesses. Use of custom made, phenylalanine free amino acid solution proved beneficial in the management of blood phenylalanine levels in a PKU patient during chemotherapy for Burkitt lymphoma.
Assuntos
Linfoma/tratamento farmacológico , Nutrição Parenteral , Fenilalanina/sangue , Fenilcetonúrias/terapia , Antineoplásicos/efeitos adversos , Criança , Gerenciamento Clínico , Hospitalização , Humanos , Masculino , Fenilcetonúrias/sangue , Fenilcetonúrias/induzido quimicamenteRESUMO
BACKGROUND: GAMT deficiency is an autosomal recessive disorder of creatine biosynthesis resulting in severe neurological complications in untreated patients. Currently available treatment is only successful to stop disease progression, but is not sufficient to reverse neurological complications occurring prior to diagnosis. Normal neurodevelopmental outcome in a patient, treated in the newborn period, highlights the importance of early diagnosis. METHODS: Targeted mutation analysis (c.59G>C and c.327G>A) in the GAMT gene by the QIAxcel system and GAA measurement by a novel two-tier method were performed in 3000 anonymized newborn blood dot spot cards. RESULTS: None of the targeted mutations were detected in any newborn. Two novel heterozygous variants (c.283_285dupGTC; p.Val95dup and c.278_283delinsCTCGATGCAC; p.Asp93AlafsX35) were identified by coincidence. Carrier frequency for these insertion/deletion types of GAMT mutations was 1/1475 in this small cohort of newborns. GAA levels were at or above the 99th percentile (3.12 µmol/l) in 4 newborns. Second-tier testing showed normal results for 4 newborns revealing 0.1% false positive rate. No GAMT mutations were identified in 4 of the newborns with elevated GAA levels in the first tier testing. CONCLUSION: This is the first two-tier study to investigate carrier frequency of GAMT deficiency in the small cohort of newborn population to establish evidence base for the first steps toward newborn screening for this treatable neurometabolic disorder.
Assuntos
Guanidinoacetato N-Metiltransferase/genética , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos dos Movimentos/congênito , Adulto , Alelos , Sequência de Bases , Creatina/sangue , Análise Mutacional de DNA , Diagnóstico Precoce , Feminino , Frequência do Gene , Guanidinoacetato N-Metiltransferase/sangue , Guanidinoacetato N-Metiltransferase/deficiência , Heterozigoto , Humanos , Recém-Nascido , Transtornos do Desenvolvimento da Linguagem/sangue , Masculino , Dados de Sequência Molecular , Transtornos dos Movimentos/sangue , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/genética , Mutagênese Insercional , Triagem Neonatal , Deleção de SequênciaRESUMO
OBJECTIVE: This paper reviews the literature on the pathways of lymphatic drainage of the rectum and their significance in radical cancer surgery. METHOD: This paper reviews some of the seminal works on the lymphatic drainage of the rectum and its surgical implications when operating on patients with rectal cancer. Publications were searched via Medline, sourced from reference lists and by cross referencing with the most widely cited papers. RESULTS: The classical European description of the anatomy of the lymphatic drainage of the rectum is presented. Early lymphatic mapping techniques and the role of newer technologies in lymphatic mapping, including sentinel lymph node mapping are discussed. The differing philosophies between Western practice, of dissection in the plane of the fascia propria and the Japanese wider pelvic lymphadenectomy are discussed. CONCLUSIONS: A clear understanding of the regional lymphatic drainage of the rectum and precise anatomical mobilisation of the rectum is the surgical cornerstone to excellent locoregional control of rectal cancer. The success of the differing Western and Japanese philosophies on the degree of pelvic lymphadenectomy suggests a possible role for 'selective wide pelvic lymphadectomy'. Mapping lateral lymphatic drainage pathways could augment the selection process for radiotherapy.
Assuntos
Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias Retais/cirurgia , Corantes , Europa (Continente) , Humanos , Japão , Linfonodos/cirurgia , Neoplasias Retais/patologia , Azul TripanoRESUMO
OBJECTIVE: The aim of this study was to determine the demand for hospital resources generated by anastomotic leakage, including surgical, medical, imaging, pathology, and other allied health consultations or services and length of postoperative hospital stay. METHOD: Data were obtained from a comprehensive, prospective hospital registry of all resections for colorectal cancer from January 1995 to December 2004 and from retrospective review of patients' notes. RESULTS: Forty-one patients with a leak spent 92 days in intensive care, required 129 days of total parenteral nutrition, 69 days of enteric feeding and 41 days on ventilation and had a median postoperative hospital stay of 28 days (range 11-104). These patients required 24 re-operations and 2273 separate medical consultations or allied services. CONCLUSION: Anastomotic leakage generates a very considerable demand for hospital resources and diverts these resources from the hospital population at large.
Assuntos
Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/economia , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/economia , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva/economia , Tempo de Internação/economia , Masculino , Encaminhamento e Consulta/economia , Sistema de Registros , Estudos RetrospectivosRESUMO
BACKGROUND: Approximately 20-30% of all intracranial metastases are located in the posterior fossa. The clinical evolution hinges on factors such as tumor growth dynamics, local topographic conditions, performance status, and prompt intervention. Fourth ventricle (V4) compression with secondary life-threatening obstructive hydrocephalus remains a major concern, often requiring acute surgical intervention. We have previously reported on the application of adaptive hypofractionated Gamma Knife Radiosurgery in the acute management of critically located metastases, a technique known to us as rapid rescue radiosurgery (3R). We report the results of 3R in the management of posterior fossa lesions and ensuing V4 decompression. CASE DESCRIPTIONS: Four patients with V4 compression due to posterior fossa metastases were treated with 3R by three separate gamma knife radiosurgical sessions (GKRS) over a period of seven days. Mean V4 volume was 1.02 cm3 at GKRS 1, 1.13 cm3 at GKRS 2, and 1.12 cm3 at GKRS 3. Mean tumor volume during the week of treatment was 10 cm3 at both GKRS 1 and 2 and 9 cm3 at GKRS 3. On average, we achieved a tumor volume reduction of 52% and a V4 size increase of 64% at the first follow-up (4 weeks after GKRS 3). Long-term follow-up showed continued local tumor control, stable V4 volume, and absence of hydrocephalus. CONCLUSION: For this series, 3R was effective in terms of rapid tumor ablation, V4 decompression, and limited radiation-induced toxicity. This surgical procedure may become an additional tool in the management of intractable posterior fossa metastasis with V4 compression.
RESUMO
BACKGROUND AND PURPOSE: Investigate effects of stereotactic radiotherapy (SRT) or surgical metastasectomy (SM) on overall survival (OS) in metastatic renal cell carcinoma (mRCC) in the era of targeted agents (TA). MATERIAL AND METHODS: mRCC patients (nâ¯=â¯117) treated with SRT (nâ¯=â¯57), SM (nâ¯=â¯30) or both modalities sequentially (nâ¯=â¯30) at two oncological centres in Sweden in 2005-2014 were retrospectively included. Median follow-up (mFU) was 63â¯months. RESULTS: A majority had clear cell histology, 1-3 metastases, and ECOG performance status of 0 or 1. Two thirds had intermediate or poor risk and 44% synchronous metastases. 65% received TA. SRT patients were more likely to have adverse risk profiles. Median OS was 51â¯months without significant differences between SRT and SM. ECOG 1 vs 0 (HR 2.9; CI 1.6-5.2; pâ¯<â¯0.001), intracranial targets (HR 1.8; CI 1.1-3.2; pâ¯=â¯0.03) and watchful waiting >18â¯months prior to treatment (HR 0.3; CI 0.2-0.6; pâ¯=â¯0.001) were independently associated with OS. 15% of curatively treated patients (nâ¯=â¯60) were relapse-free with mFU of 87â¯months. CONCLUSIONS: OS after SRT was comparable to SM and longer than expected considering patients with adverse risk profiles were common. Fit patients with non-brain metastases treated after an initial period of watchful waiting had the best prognosis.
Assuntos
Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Radiocirurgia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Terapia Combinada , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Metastasectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Suécia/epidemiologia , Resultado do TratamentoRESUMO
The immunosuppressive drug, mizoribine, has been used to prevent rejection of organ allografts in humans and in animal models. Based on studies in cell lines, mizoribine has been postulated to be an inhibitor of inosine monophosphate (IMP) dehydrogenase (EC1.2.1.14), a pivotal enzyme in the formation of guanine ribonucleotides from IMP. To further characterize the mechanism of action of this drug, we studied the effect of mizoribine on human peripheral blood T cells stimulated with alloantigen, anti-CD3 MAb, or pharmacologic mitogens. Mizoribine (1-50 micrograms/ml) was able to inhibit T cell proliferation by 10-100% in a dose-dependent fashion to all stimuli tested. Measurements of purine ribonucleotide pools by HPLC showed that mizoribine led to a decrease in intracellular GTP levels, and that repletion of GTP reversed its antiproliferative effects. We also examined sequential events occurring after T cell stimulation. Early events in T cell activation, as assessed by steady-state mRNA levels of c-myc, IL-2, c-myb, histone, and cdc2 kinase, as well as surface IL-2 receptor expression, were unaffected. However, cell cycle analysis revealed decreased numbers of cells in S, G2, and M phases, and showed that the G1/S block was reversed with GTP repletion. These data indicate that mizoribine has an effect on T cell proliferation by a mechanism distinct from that of cyclosporine or corticosteroids, and therefore may be useful in combination immunosuppressive regimens.
Assuntos
Nucleotídeos de Guanina/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ribonucleosídeos/farmacologia , Linfócitos T/fisiologia , Trifosfato de Adenosina/metabolismo , Northern Blotting , Proteína Quinase CDC2/genética , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Ciclosporinas/farmacologia , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Interleucina-2/metabolismo , Receptores de Interleucina-2/metabolismo , Linfócitos T/efeitos dos fármacosRESUMO
Factor XIII A subunit (FXIIIA) is found in plasma, platelets, and monocytes. The hemopoietic contributions to FXIIIA in these components were studied in patients transplanted with marrows from donors with different FXIIIA phenotypes. In three patients with successful engraftment (by DNA genotyping, red cell phenotyping, and cytogenetic studies) platelet and monocyte FXIIIA changed to donor phenotypes with hematologic recovery. Thus, FXIIIA in platelets and monocytes is synthesized de novo and/or from their progenitor cells. Plasma FXIIIA phenotype change after transplantation was more complex. Patient I changed from phenotype 1-1 (one electrophoretically fast band) to 1-2 (three bands) in 115 d; patients 2 and 3 did not change completely from phenotype 1-2 to 1-1 in up to 458 d, but did show enrichment of the fastest band. Thus, while there is a definite contribution of donor hemopoiesis to plasma FXIIIA, another source of recipient FXIIIA appears to be present to delay or prevent the phenotype change.
Assuntos
Transplante de Medula Óssea , Fator XIII/sangue , Hematopoese , Adulto , Plaquetas/análise , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/cirurgia , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/cirurgia , Masculino , Pessoa de Meia-Idade , Monócitos/análise , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/cirurgia , Fenótipo , Plasma/análise , TransglutaminasesRESUMO
Transient events that occur during plasma instabilities in fusion reactors impart large heat fluxes onto the surrounding plasma-facing components (PFCs). Erosion and splashing of PFCs can contaminate the plasma and shorten material lifetime. Although tungsten is currently considered the most promising candidate material for future PFCs, concerns over the thermal shock performance during type-I ELMs (transient events expected in fusion devices) necessitate the study of other comparable materials. ELM-like heat loading was applied via a pulsed Nd:YAG millisecond laser on a pristine molybdenum (Mo) surface to measure surface melting and mass loss. One potential advantage of Mo is its higher specific heat of vaporization, which could lead to reduced particle emission. Imaging of the surface after loading revealed that complete surface melting began at 1.0 MJ m-2 (heat load parameter of 31.62 MJ m-2 s-1/2). Photon excitation also increased significantly above 1.0 MJ m-2, indicating possible phase change. At 1.4 MJ m-2 (44.27 MJ m-2 s-1/2), in situ mass loss measurements found an exponential increase in particle emission, indicating the presence of droplet formation and boiling. Direct comparisons of erosion during pulsed heat loading between PFC candidate materials will ensure that future fusion devices design components with optimal thermal strength.
RESUMO
This study aims to provide evidence of biomedical scientists' competence in blood film cytomorphology and to improve continuing assessment and training. Twenty photomicrographs are prepared from historical teaching slides, and a slide projector timer is designed and built to trigger slide advance automatically every 30 sec. Haematology staff in local district general hospitals take part in the study. During each visit, the test is explained and participants mark their observations on individual results sheets. Two sets (accepted and rejected) of observations are generated, which are validated by peer review. The accepted set is scored. No evidence is found to prove that members of each department were drawn from separate groups (P=0.36). Seniors and routine cytomorphologists are compared for each department and a non-zero difference in score was found (P=0.00). A comparison is made between the number of times a scored or non-scored observation is recorded, resulting in a probability that approaches zero. Thus, it is highly unlikely that the observations are drawn from one pool, and the test score and ability in cytomorphology would appear to be directly related. This study challenges the notion that unrestricted time, clinical data and a microscope are required for haematology blood film cytomorphology tests. Introduction of this type of test would provide biomedical science with a valuable assessment tool.
Assuntos
Células Sanguíneas/patologia , Competência Clínica/normas , Testes Hematológicos/métodos , Pessoal de Saúde , Humanos , Variações Dependentes do Observador , Controle de Qualidade , Reprodutibilidade dos TestesRESUMO
We describe a novel hemi-nested, allele specific whole blood PCR assay for detection of the factor V Leiden mutation associated with the plasma defect, activated protein C resistance. This assay utilizes 5 microliters of whole blood without prior DNA extraction. The hemi-nested design, employing an outer primer pair in combination with nested, allele specific primers obviates the need for restriction enzyme digestion. PCR reactions are analysed directly on agarose or polyacrylamide minigels. The assay confirmed the genotypes of 50 individuals previously categorized by PCR and Mn11 digestion, and has been subsequently utilized in the genotyping of 445 individuals referred for thrombosis studies.
Assuntos
Alelos , Fator V/análise , Mutação , Reação em Cadeia da Polimerase/métodos , HumanosRESUMO
To determine whether the factor V Leiden mutation is associated with decreased bleeding in individuals with severe hemophilia A, factor concentrate utilization, maximum annual number of bleeding episodes, and the prevalence of hemophilic arthropathy between carriers and non-carriers of the factor V Leiden mutation were compared. Heterozygosity for the factor V Leiden mutation was found in 6 of 137 subjects (4.4%). Carriers of the factor V Leiden mutation utilized less factor concentrate (geometric mean: 310 vs. 1185 units/kg/year) and had fewer bleeding episodes than non-carriers (proportion with 10 or fewer bleeding episodes in their worst year: 50 vs. 11%). However, the factor V Leiden mutation was not associated with the absence of arthropathy. The intron 22 inversion mutation of the factor VIII gene was tested for in a subgroup of 80 subjects, but it was not found to be a significant variable for any of the bleeding endpoints. The results of this small study are consistent with the hypothesis that the factor V Leiden mutation imparts a protective effect; however, a larger confirmatory study in which the factor VIII molecular defects can be controlled for is needed. Furthermore, most severe hemophiliacs who used fewer than 200 units/kg/year of factor concentrate or who had experienced 10 or fewer bleeding episodes per year did not carry the factor V Leiden mutation, suggesting that the proportion of severe hemophiliacs whose mild clinical course can be attributed to the factor V Leiden mutation is small.
Assuntos
Fator V/genética , Hemofilia A/genética , Mutação Puntual , Adolescente , Adulto , Criança , Pré-Escolar , Fator VIII/genética , Fator VIII/uso terapêutico , Hemofilia A/sangue , Hemofilia A/tratamento farmacológico , Heterozigoto , Humanos , Masculino , FenótipoRESUMO
We seek to develop a clinically useful measure of antiretroviral medication adherence. Because there is no gold standard for adherence, we will assess the clinical validity of patient- and provider-reported adherence by the strength of their expected associations with current viral load, depressive symptoms, alcohol and illicit drug use, and homelessness. The Veterans Aging Cohort 3 Site Study (VACS 3) is a multisite study of 881 patients at Cleveland, Houston, and Manhattan Veterans Affairs health care systems. Data was collected on adherence using patient report and provider assessment; depressive symptoms using the Center for Epidemiological Studies Depression (CESD) and provider assessment; alcohol use using the Alcohol Use Disorders Identification Test (AUDIT) and provider assessment; and homelessness using patient report only. Viral load was collected from electronic laboratory data. Although agreement between providers and patients about the patient's adherence was not better than chance (61%; weighted kappa =.07), both patient and provider-reported adherence were related to viral load (P <.001), current alcohol use (P <.01), current drug use (P <.01), and depressive symptoms (P <.001). Patient-reported adherence was also associated with homelessness (P <.05). In multivariate regression models, provider assessment of adherence demonstrated independent associations with viral load (P <.001), current alcohol use (P <.001), current drug use (P <.001), and depressive symptoms (P <.001) after adjustment for the patient's report of adherence (also significantly associated). The consistent and largely independent association between patient and provider reported adherence and a range of variables previously shown to be associated with adherence suggests that patient- and provider-reported adherence independently measure actual adherence. Future work will explore how patient- and provider-reported adherence might best be combined, and whether the measure may be further enhanced with pharmacy refill data.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV-1 , Cooperação do Paciente/psicologia , Padrões de Prática Médica , Autoavaliação (Psicologia) , Veteranos , Doença Crônica , Infecções por HIV/psicologia , Humanos , Estudos Longitudinais , Análise de Regressão , Estatísticas não Paramétricas , Inquéritos e Questionários , Estados Unidos , Carga ViralRESUMO
Traditional, open-ended provider questions regarding patient symptoms are insensitive. Better methods are needed to measure symptoms for clinical management, patient-oriented research, and adverse drug-event reporting. Our objective was to develop and initially validate a brief, self-reported HIV symptom index tailored to patients exposed to multidrug antiretroviral therapies and protease inhibitors, and to compare the new index to existing symptom measures. The research design was a multistage design including quantitative review of existing literature, qualitative and quantitative analyses of pilot data, and quantitative analyses of a prospective sample. Statistical analyses include frequencies, chi-square tests for significance, linear and logistic regression. The subjects were from a multisite convenience sample (n = 73) within the AIDS Clinical Trials Group and a prospective sample from the Cleveland Veterans Affairs Medical Center (n = 115). Measures were patient-reported symptoms and health-related quality of life, physician-assessed disease severity, CD4 cell count, and HIV-1 RNA viral quantification. A 20-item, self-completed HIV symptom index was developed based upon prior reports of symptom frequency and bother and expert opinion. When compared with prior measures the index included more frequent and bothersome symptoms, yet was easier to use (self-report rather than provider interview). The index required less than 5 minutes to complete, achieved excellent completion rates, and was thought comprehensive and comprehensible in a convenience sample. It was further tested in a prospective sample of patients and demonstrated strong associations with physical and mental health summary scores and with disease severity. These associations were independent of CD4 cell count and HIV-1 RNA viral quantification. This 20-item HIV symptom index has demonstrated construct validity, and offers a simple and rational approach to measuring HIV symptoms for clinical management, patient-oriented research, and adverse drug reporting.
Assuntos
Infecções por HIV/fisiopatologia , Autoavaliação (Psicologia) , Índice de Gravidade de Doença , Terapia Antirretroviral de Alta Atividade , Distribuição de Qui-Quadrado , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Humanos , Estudos Prospectivos , Qualidade de Vida , Análise de Regressão , Reprodutibilidade dos TestesRESUMO
We have evaluated radiosensitivity parameters for cellular transformation from published experimental data on neoplastic transformations induced in C3H10T1/2 cells by BEVALAC ions. The measured RBE values are well reproduced by a track theory calculation using sets of m-target parameters with either m = 2 or m = 3, suggesting a quadratic or cubic extrapolation to low doses of gamma rays. Using track theory one is thus able to predict transformation frequencies in those cells after an arbitrary radiation field, under known or assumed conditions of exposure, in a manner shown earlier for cellular survival. Extension of these calculations to interpret cancer incidence in vivo is also discussed.
Assuntos
Transformação Celular Neoplásica/efeitos da radiação , Animais , Linhagem Celular Transformada , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta à Radiação , Transferência de Energia , Íons , Metais , Camundongos , Modelos Teóricos , Aceleradores de Partículas , Raios XRESUMO
Lux-marked bacterial biosensors and a commercial toxicity testing bacterial strain (Microtox) were exposed to 2,4-dichlorophenol (DCP) and the light output response measured. Increasing DCP concentrations caused a decrease in light output in all three biosensors with an order of sensitivity (in terms of luminescence decrease over the DCP concentration range) of Pseudomonas fluorescens < Escherichia coli < Microtox. Adsorption of DCP to E. coli was measured using uniformly ring labelled [14C]DCP and found to be very rapid. The effect of pH on toxicity and adsorption was also investigated. Low pH values increased the amount of DCP adsorbed to the cell and increased the toxicity of DCP.