RESUMO
Prisoners are a priority group for hepatitis C (HCV) treatment. Although treatment durations will become shorter using directly acting antivirals (DAAs), nearly half of prison sentences in Scotland are too short to allow completion of DAA therapy prior to release. The purpose of this study was to compare treatment outcomes between prison- and community-based patients and to examine the impact of prison release or transfer during therapy. A national database was used to compare treatment outcomes between prison treatment initiates and a matched community sample. Additional data were collected to investigate the impact of release or transfer on treatment outcomes. Treatment-naïve patients infected with genotype 1/2/3/4 and treated between 2009 and 2012 were eligible for inclusion. 291 prison initiates were matched with 1137 community initiates: SVRs were 61% (95% CI 55%-66%) and 63% (95% CI 60%-66%), respectively. Odds of achieving a SVR were not significantly associated with prisoner status (P=.33). SVRs were 74% (95% CI 65%-81%), 59% (95% CI 42%-75%) and 45% (95% CI 29%-62%) among those not released or transferred, transferred during treatment, or released during treatment, respectively. Odds of achieving a SVR were significantly associated with release (P<.01), but not transfer (P=.18). Prison-based HCV treatment achieves similar outcomes to community-based treatment, with those not released or transferred during treatment doing particularly well. Transfer or release during therapy should be avoided whenever possible, using anticipatory planning and medical holds where appropriate.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Resposta Viral Sustentada , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prisões , Características de Residência , Escócia , Resultado do Tratamento , Adulto JovemRESUMO
High concentrations of acetyl polyamines have been observed in human breast cancer compared with the equivalent normal tissue, however, no explanation as to the reason for the increases has been proposed. In this study, we show that changes in the enzymes responsible for the breakdown of acetyl polyamines occur in breast cancer tissue. Spermidine/spermine N1-acetyltransferase, the first and rate-limiting enzyme in polyamine catabolism, is increased in the tumor tissue whereas polyamine oxidase (PAO) is decreased. The changes in PAO correlate with prognostic factors, and activity decreases as the size and histological grade of tumors increase. The metabolism of polyamines by PAO generates locally high concentrations of hydrogen peroxide, a known inducer of apoptosis; thus, low PAO activity may contribute to the low level of apoptosis seen in tumor cells. Therefore, drugs that induce PAO activity may be a novel means of attacking tumor cells.
Assuntos
Acetiltransferases/metabolismo , Neoplasias da Mama/enzimologia , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Acetilação , Poliaminas Biogênicas/metabolismo , Neoplasias da Mama/patologia , Catálise , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Poliamina OxidaseRESUMO
We have developed a water-sealed infant calorimeter (IC) system which uses the techniques of closed-circuit spirometry to measure oxygen consumption (VO2) in premature and full-term infants. Carbon dioxide production (VCO2) is simultaneously calculated from the effluent mixed expired CO2 and the circulating flowrate. Respiratory Quotient (RQ) and Energy Expenditure (EE) are then calculated from the primary data. Measurement of VO2, VCO2, and calculation of RQ were +/- 5.0% of predicted values determined by burning ethyl alcohol or volume extraction and CO2 infusion in our bench model. Measurement in 11 premature infants produced mean values for VO2 and VCO2 of 8.5 +/- 2.5 ml/min/kg and 8.5 +/- 2.4 ml/min/kg, respectively. This system is noninvasive, does not interfere with infant tube feedings or iv infusions, and permits safe, long-term monitoring of the infant's metabolic activity. It allows a more exact matching or oral or intravenous feedings to the actual energy expenditure of the infants, and offers potential advantages for the nutritional management of sick infants.
Assuntos
Calorimetria Indireta/instrumentação , Calorimetria/instrumentação , Dióxido de Carbono/metabolismo , Metabolismo Energético , Recém-Nascido Prematuro/metabolismo , Consumo de Oxigênio , Humanos , Recém-Nascido , Cinética , Troca Gasosa PulmonarRESUMO
A newly developed closed circuit water-sealed infant calorimeter has been used to measure oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient (RQ) and resting energy expenditure (REE) in 31 infants. There were 17 full-term and 14 premature infants. VO2 was measured volumetrically, keeping the inspired oxygen concentration constant. VCO2 was determined by infrared analysis of the mixed expired gases. Values for REE and RQ were calculated from measurements of VO2 and VCO2. All values were normalized for the infants body weight. Our findings demonstrate significant differences in VO2, VCO2, and REE associated with weight, gestational age, postnatal age, activity, feeding, and sex. In addition, VO2, VCO2, and REE were significantly higher for the premature infants. The water-sealed indirect calorimetry system: (a) is safe and noninvasive, (b) does not interfere with infant tube feeding or IV infusion, (c) permits long-term monitoring of metabolic activity, and (d) allows a more exact matching of oral and intravenous feedings to actual energy expenditure. We are finding that indirect calorimetry removes the guess work from writing daily caloric regimens, with potential advantage for the treatment of sick infants.
Assuntos
Dióxido de Carbono/fisiologia , Metabolismo Energético , Recém-Nascido Prematuro , Consumo de Oxigênio , Respiração , Calorimetria Indireta , Ingestão de Energia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , DescansoRESUMO
The imprinting control region (ICR) located far upstream of the H19 gene, in conjunction with enhancers, modulates the transcription of Igf2 and H19 genes in an allele-specific manner. On paternal inheritance, the methylated ICR silences the H19 gene and indirectly facilitates transcription from the distant Igf2 promoter, whereas on the maternal chromosome the unmethylated ICR, together with enhancers, activates transcription of the H19 gene and thereby contributes to the repression of Igf2. This repression of maternal Igf2 has recently been postulated to be due to a chromatin boundary or insulator function of the unmethylated ICR. Central to the insulator model is the site-specific binding of a ubiquitous nuclear factor CTCF which exhibits remarkable flexibility in functioning as transcriptional activator or silencer. We suggest that the ICR positioned close to the enhancers in an episomal context might function as a transcriptional silencer by virtue of interaction of CTCF with its modifiers such as SIN3A and histone deacetylases. Furthermore, a localised folded chromatin structure resulting from juxtaposition of two disparate regulatory sequences (enhancer ICR) could be the mechanistic basis of ICR-mediated position-dependent (ICR-promoter) transcriptional repression in transgenic Drosophila.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento/genética , Inativação Gênica , Impressão Genômica/genética , Fator de Crescimento Insulin-Like II/genética , Proteínas/genética , RNA não Traduzido/genética , Animais , Humanos , RNA Longo não CodificanteRESUMO
The value of M.R.I. in diagnosing spinal disorders has been tested in a series of 100 patients. C.T., myelography, discography and the operative findings are compared with the M.R.I. findings. The results indicate that M.R.I. is a valuable diagnostic investigation.
Assuntos
Imageamento por Ressonância Magnética , Doenças da Coluna Vertebral/diagnóstico , Traumatismos da Coluna Vertebral/diagnóstico , Acidentes de Trabalho , Acidentes de Trânsito , Austrália , Humanos , Disco Intervertebral/diagnóstico por imagem , Jurisprudência , Mielografia , Doenças da Coluna Vertebral/diagnóstico por imagem , Traumatismos da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Following intracytoplasmic sperm injection (ICSI), approximately 60-70% of oocytes are fertilized and of these embryos, approximately 45% withstand in-vitro culture conditions to produce healthy blastocysts. The efficiency of implantation of 2-4-cell embryos selected at the pronuclear stage and that of blastocysts are comparable. However, prolonged selection of embryos in vitro (4-5 days), has been proposed to eliminate chromosomal abnormalities, more specifically those inherited by defective spermatozoa. This hypothesis is based upon the assumption that the paternal genetic contribution is indispensable for blastocyst development. Here we examine this hypothesis and suggest that phenotypic manifestation of paternal genomic abnormalities might not occur prior to implantation. In addition to the parent-of-origin effect during embryogenesis, blastocyst transfer may not prevent the inheritance of genetic defects involving 'male factor' loci.