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Biomedical subjects

Andrew Wragg

Publications and source records attributed to Andrew Wragg.

5 recordsLinked to original sources

p53 regulates mitochondrial respiration.

The energy that sustains cancer cells is derived preferentially from glycolysis. This metabolic change, the Warburg effect, was one of the first alterations in cancer cells recognized as conferring a survival advantage. Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory and glycolytic pathways. We identify Synthesis of Cytochrome c Oxidase 2 (SCO2) as the downstream mediator of this effect in mice and human cancer cell lines. SCO2 is critical for regulating the cytochrome c oxidase (COX) complex, the major site of oxygen utilization in the eukaryotic cell. Disruption of the SCO2 gene in human cancer cells with wild-type p53 recapitulated the metabolic switch toward glycolysis that is exhibited by p53-deficient cells. That SCO2 couples p53 to mitochondrial respiration provides a possible explanation for the Warburg effect and offers new clues as to how p53 might affect aging and metabolism.

Adenosine Triphosphate↗

Learning on the Web. Case 5: infective endocarditis.

A 70 year old man presented with microscopic haematuria and proteinuria and a fever five months after having a transurethral resection of the prostate (TURP). Initially urological review was arranged as the family doctor thought that a urinary infection was the most likely diagnosis. The patient was concerned that he was not getting better and he self-referred to a physician. He had continuing fever, weight loss, and malaise. The physician detected a mitral pan-systolic murmur that had not been heard before. On the basis of this finding infective endocarditis was suspected and investigations begun. His subsequent course and its management are discussed in an interactive case presentation.

Aged↗

A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study.

OBJECTIVES: This study was designed to test a rapid protocol of intravenous acetylcysteine for prevention of radiocontrast-induced nephropathy (RCIN). BACKGROUND: Oral acetylcysteine (NAC) may provide better prophylaxis against RCIN than intravenous (i.v.) hydration alone. Current protocols preclude prophylaxis of same-day or emergency patients owing to the need for prolonged pretreatment. METHODS: We prospectively randomized 80 patients with stable renal dysfunction undergoing cardiac catheterization/intervention to a rapid protocol of i.v. NAC (150 mg/kg in 500 ml N/saline over 30 min immediately before contrast followed by 50 mg/kg in 500 ml N/saline over 4 h, n = 41, 67 +/- 10 years, 90% men) or i.v. hydration (1 ml/kg/h N/saline for 12 h pre- and post-contrast, n = 39, 71 +/- 8.8 years, 85% men). RESULTS: Radiocontrast-induced nephropathy occurred in 2 of the 41 patients in the NAC group (5%) and in 8 of the 39 patients in the hydration group (21%; p = 0.045; relative risk: 0.28; 95% confidence interval 0.08 to 0.98). In the NAC group, mean serum creatinine fell from 1.85 +/- 0.59 to 1.77 +/- 0.73 and 1.79 +/- 0.73 mg/dl 48 h and four days post-contrast (p = 0.02 and 0.023 vs. baseline, respectively). In the hydration group, serum creatinine increased from 1.75 +/- 0.41 to 1.81 +/- 0.6 48 h and 1.80 +/- 0.50 mg/dl four days post-contrast (p = 0.99 and 0.23, respectively). NAC infusion was ceased after the bolus in three patients (7%) due to flushing, itching, or a transient rash. CONCLUSIONS: Administration of i.v. NAC should be considered in all patients at risk of RCIN before contrast exposure when time constraints preclude adequate oral prophylaxis, provided the patient is able to tolerate this degree of volume loading.

Acetylcysteine↗

Assessing the performance of specialist registrars.

Assessing the performance of doctors while they are engaged in clinical work is a challenging concept. The introduction of objective-based curricula provides the stimulus and opportunity for the Royal Colleges of Physicians to develop relevant and reliable methods of in-service assessment. We propose to pilot a study investigating the validity, reliability and feasibility of three assessment methods--direct observation of the clinical encounter using an adapted mini-CEX, direct observation of the performance of practical procedures (DOPS), and the doctor's ability to perform effectively as part of a team using 360 degree assessment. The methods will be studied in the setting of routine clinical care. Whilst demanding of time from both trainees and trainers, they will represent a significant advance on the current system which is characterised by a lack of evidence in the assessment process.

Clinical Competence↗