RESUMO
OBJECTIVES: People with HIV (PWHIV) are likely to need therapies for comorbidities as they age. We assessed risk of drug-drug interactions (DDIs) in PWHIV. METHODS: The Climate-HIV electronic recording system was used to cross-sectionally analyse records from PWHIV aged ≥ 18 years attending four UK HIV units with a current antiretroviral (ARV) prescription in February 2018. Antiretroviral and non-ARV medications were categorized by clinical significance of DDIs (University of Liverpool DDI tool). Potential DDIs were predicted using treatment guidelines for commonly recorded comorbidities. RESULTS: Among 4630 PWHIV (44% female), 41% were ≥ 50 years old. The average number of non-ARV comedications increased from < 1 for patients aged ≤ 24 years to > 5 for patients aged ≥ 75 years; 65% were taking one or more non-ARV comedications. The median (interquartile range) number of non-ARVs was 1 (0-2) and 2 (1-5) for those aged < 50 and ≥ 50 years, respectively. Common comorbidities/concurrent health conditions occurred more frequently in patients aged ≥ 50 years vs. < 50 (53% vs. 34%). Boosted protease inhibitors were associated with the highest proportion of contraindicated comedications; dolutegravir and raltegravir had the fewest. For non-ARVs, sildenafil and quetiapine were most likely to result in DDIs. Guideline-recommended treatments for hepatitis C, hepatitis B, and tuberculosis had the highest proportions of contraindications when combined with ARV regimens, while treatments for hepatitis C, malignancy, and mental health conditions had the highest proportion of combinations potentially causing DDIs requiring dose monitoring or adjustment. CONCLUSIONS: Non-ARV use by PWHIV is high and increases with age. Treatment decisions for ageing PWHIV should consider guideline recommendations for comorbidities.
Assuntos
Fármacos Anti-HIV/classificação , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Tomada de Decisão Clínica , Comorbidade , Contraindicações de Medicamentos , Estudos Transversais , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimedicação , Guias de Prática Clínica como Assunto , Reino Unido , Adulto JovemRESUMO
This case demonstrates that laparoscopic-assisted enteroscopy (LAE) is a safe and effective technique to aid diagnosis and treatment of small bowel lesions that are difficult to identify with traditional and advanced imaging and interventional techniques. In patients where definite bowel lesions are identified on small bowel capsule endoscopy or small bowel enteroscopy, LAE can be extremely valuable in pinpointing the lesion intra-operatively. This technique may have certain merit for laparoscopic Crohn's stricturoplasty.
Assuntos
Endoscopia Gastrointestinal/métodos , Hemorragia Gastrointestinal/cirurgia , Doenças do Íleo/diagnóstico , Adulto , Humanos , Doenças do Íleo/cirurgia , Laparoscopia/métodos , MasculinoRESUMO
This article reports an unusual case of delayed presentation of a tension faecopneumothorax after traumatic injury to the diaphragm 5 years previously. Three important clinical lessons are highlighted: (a) for suspected tension pneumothorax, if a considerable quantity of serous fluid is drained in addition to air, a communication with the peritoneal cavity should be considered; (b) spontaneous tension pneumothorax is an extremely rare condition and other causes should be kept in mind; and (c) in the presence of a tension pneumothorax and diaphragmatic hernia, the contents of the visceral sac may be completely reduced and the hernia may be masked.
Assuntos
Colo/lesões , Hérnia Diafragmática Traumática/complicações , Perfuração Intestinal/etiologia , Pneumotórax/etiologia , Adulto , Fezes , Humanos , Masculino , Fatores de Tempo , Ferimentos Perfurantes/complicaçõesRESUMO
BACKGROUND: Full thickness rectal prolapse may be difficult to view in the outpatient setting. We present a novel method to demonstrate it using equipment commonly found in the Urology clinic.
Assuntos
Prolapso Retal/diagnóstico , Urologia/instrumentação , Desenho de Equipamento , Humanos , BanheirosRESUMO
The pathogenic mechanisms responsible for the deleterious changes in ethanol-exposed skeletal muscle are unknown, although apoptosis may be a causal process. We therefore investigated the responses of skeletal muscle to acute or chronic ethanol exposure in male Wistar rats. In acute studies, rats were dosed with ethanol (75 mmol (3.46 g)/kg BW) and killed after either 2.5 or 6 hours. In chronic studies, rats were fed ethanol as 35% of total dietary energy for 6 weeks. Apoptosis was determined by either DNA fragmentation or TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick end labelling) assays. The results showed that apoptosis was not increased in the ethanol-exposed muscle in both acute and chronic studies compared to appropriate controls.
Assuntos
Apoptose/efeitos dos fármacos , Etanol/toxicidade , Músculo Esquelético/efeitos dos fármacos , Animais , Fragmentação do DNA/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Masculino , Ratos , Ratos WistarRESUMO
The pathogenic mechanisms responsible for alcohol-induced muscle disease are unknown, although it is possible that increased proto-oncogene expression may be the causative process. Therefore, we investigated the responses of skeletal muscle c-myc protein and mRNA to a standard acute ethanol dosage regimen (75 mmol/kg/body weight [BW]) for 2.5 to 24 hours. Comparative studies were made on the heart. Acute ethanol administration in vivo led to an increase in c-myc proto-oncogene mRNA in rat skeletal and cardiac muscle. The changes in c-myc mRNA were mirrored by increases in the c-myc protein as demonstrated by immunohistochemistry. The changes in the c-myc protein were localized to the myonuclei, with no corresponding changes seen in the interstitial cell nuclei. This is the first report of altered proto-oncogene expression in muscle in response to ethanol. Increased c-myc mRNA and protein may reflect adaptive changes, a stress response, or another uncharacterized cellular adaptation.
Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Genes myc/genética , Proteínas Musculares/biossíntese , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-myc/biossíntese , RNA Mensageiro/biossíntese , Animais , Autorradiografia , Northern Blotting , Imuno-Histoquímica , Masculino , Proteínas Proto-Oncogênicas c-myc/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Ratos , Inanição/metabolismo , Estimulação Química , Regulação para Cima/efeitos dos fármacosRESUMO
Between one- and two-thirds of all alcohol abusers have impairment of muscle function that may be accompanied by biochemical lesions and/or the presence of a defined myopathy characterised by selective atrophy of Type II fibres. Perturbations in protein metabolism are central to the effects on muscle and account for the reductions in muscle mass and fibre diameter. Ethanol abuse is also associated with abnormalities in carbohydrate (as well as lipid) metabolism in skeletal muscle. Ethanol-mediated insulin resistance is allied with the inhibitory effects of ethanol on insulin-stimulated carbohydrate metabolism. It acutely impairs insulin-stimulated glucose and lipid metabolism, although it is not known whether it has an analogous effect on insulin-stimulated protein synthesis. In alcoholic cirrhosis, insulin resistance occurs with respect to carbohydrate metabolism, although the actions of insulin to suppress protein degradation and stimulate amino acid uptake are unimpaired. In acute alcohol-dosing studies defective rates of protein synthesis occur, particularly in Type II fibre-predominant muscles. The relative amounts of mRNA-encoding contractile proteins do not appear to be adversely affected by chronic alcohol feeding, although subtle changes in muscle protein isoforms may occur. There are also rapid and sustained reductions in total (largely ribosomal) RNA in chronic studies. Loss of RNA appears to be related to increases in the activities of specific muscle RNases in these long-term studies. However, in acute dosing studies (less than 1 day), the reductions in muscle protein synthesis are not due to overt loss of total RNA. These data implicate a role for translational modifications in the initial stages of the myopathy, although changes in transcription and/or protein degradation may also be superimposed. These events have important implications for whole-body metabolism.
Assuntos
Alcoolismo/metabolismo , Etanol/metabolismo , Doenças Musculares/metabolismo , Metabolismo dos Carboidratos , Humanos , Proteínas Musculares/metabolismoRESUMO
This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Carol C. Cunningham and Victor R. Preedy. The presentations were (1) Ribosomal content, ribosomal localization and the levels of ribosomal protein mRNA and rRNA in rat skeletal muscle exposed to ethanol, by Alistair G. Paice, John E. Hesketh, Timothy J. Peters, and Victor R. Preedy; (2) Altered hepatic mitochondrial ribosome structure after chronic ethanol administration, by Vinood B. Patel and Carol C. Cunningham; (3) Clinical aspects of hepatic protein metabolism and alcohol, by Elena Volpi; and (4) Effects of oral intake of alanine plus glutamine on ethanol metabolism and ethanol-related depression in motor activity, by Kazunori Mawatari, H. Masaki, M. Mori, and Kunio Torii.
Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Fígado/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , RNA Ribossômico 18S/efeitos dos fármacos , Proteínas Ribossômicas/efeitos dos fármacos , Alanina/farmacologia , Animais , Glutamina/farmacologia , Humanos , Fígado/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Músculo Esquelético/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , RNA Ribossômico 18S/metabolismo , Proteínas Ribossômicas/metabolismoAssuntos
Músculo Esquelético/patologia , Doenças Musculares/induzido quimicamente , Penicilamina/toxicidade , Análise de Variância , Animais , Cobre/metabolismo , Relação Dose-Resposta a Droga , Hormônios/sangue , Ferro/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Fibras Musculares de Contração Rápida/efeitos dos fármacos , Fibras Musculares de Contração Rápida/patologia , Fibras Musculares de Contração Lenta/efeitos dos fármacos , Fibras Musculares de Contração Lenta/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Doenças Musculares/patologia , RNA/metabolismo , Ratos , Ratos Wistar , Zinco/metabolismoAssuntos
Etanol/farmacologia , Genes myc , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-myc/biossíntese , RNA Mensageiro/biossíntese , Transcrição Gênica , Animais , Ingestão de Alimentos , Jejum , Coração/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Inanição , Transcrição Gênica/efeitos dos fármacosAssuntos
Anlodipino/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Anlodipino/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , DNA/metabolismo , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Proteínas/metabolismo , RNA/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fatores de TempoAssuntos
Endotoxinas/toxicidade , Etanol/toxicidade , RNA/metabolismo , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/metabolismo , Inanição/metabolismo , Distribuição TecidualRESUMO
Changes in cardiac protein composition occur in a variety of patho-physiological situations and are usually accompanied by modifications in protein synthesis. Although adjustments in protein synthesis during starvation may be adaptive, the alterations in protein synthesis seen in response to ethanol ingestion may be pathological and an important step in the genesis of alcoholic heart muscle disease. The alterations in heart muscle in hypertension are initially adaptive but in the long term they are deleterious, and involve both transcription and translation. While adequate methods exist for quantifying the amount of mRNA for contractile and non-contractile proteins, such studies of gene-expression provide no dynamic information on the rate at which tissue proteins are lost or accrued. This can only be determined by measuring the rate of protein turnover, i.e. either protein synthesis or protein breakdown. Techniques for directly determining the rates of protein breakdown are limited or involve surgical procedures. Methods for measuring the rate of protein synthesis are described, and are illustrated by their application to the investigation of starvation and ethanol toxicity. In particular, attention is focused on the fact that reliable rates of protein synthesis are obtained only if the specific radioactivity of the precursor at the site of protein synthesis (aminoacyl-tRNA) is assessed.