Biomedical subjects

Peter A Burke

Publications and source records attributed to Peter A Burke.

4 recordsLinked to original sources

PubMed2002

Hepatocyte nuclear factor 4 response to injury involves a rapid decrease in DNA binding and transactivation via a JAK2 signal transduction pathway.

The injury response is a complex set of events, which represents the reaction of a biological system to a perceived change in its environment in an attempt to maintain system integrity. Isolation of individual events or components of this response cannot describe the overall process, but may reflect general mechanisms that have evolved over time to solve the complex requirements of the injury response. The process, generally termed the acute phase response, is a series of organ-specific responses that begin shortly after a systemic injury. In the liver, this response involves both dramatic inductions and reductions in specific sets of genes, and an overall widespread global change in proteins produced. This can be thought of as a phenotypic change or 'reprogramming' of the liver. These changes in protein production are modulated and regulated at the level of transcription and involve significant manipulations of transcriptional regulatory mechanisms. Hepatocyte nuclear factor 4 (HNF-4) is a liver enriched transcription factor that regulates a large number of liver-specific genes, which play important roles in the critical pathways modulated by the response to injury. HNF-4 also performs an essential role in overall development and is critical for the normal expression of multiple genes in the developed liver, as well as being upstream of HNF-1 in a transcriptional hierarchy that drives hepatocyte differentiation. The role of HNF-4 in regulating liver-specific transcriptional changes directed by injury remains to be defined. In our cell-culture and whole-animal models, we demonstrate that the binding activity of HNF-4 decreases quickly after injury due to post-translational modification by phosphorylation. The mechanisms by which HNF-4 is modified after injury involve the activation of Janus kinase 2 (JAK2) signal transduction pathways, but the direct or indirect interaction of JAK2 with HNF-4 remains to be defined.

Animals↗

PubMed2002

Patterns of plasma leptin and insulin concentrations in hospitalized patients after the initiation of total parenteral nutrition.

BACKGROUND: The regulation of leptin in patients with critical illness is poorly understood. Sex, diet, body mass, and cytokines may all play a role. OBJECTIVE: The aims of this study were to determine the factors influencing leptin concentrations in hospitalized patients beginning total parenteral nutrition (TPN) and whether a 3-d regimen of TPN would further increase plasma leptin concentrations above baseline. DESIGN: Twenty-six patients requiring TPN were enrolled in this prospective, nonintervention study. Only 20 (11 women and 9 men) completed all 3 d of TPN. RESULTS: Baseline plasma leptin in the TPN patients ranged from 62.5 to 1625 pmol/L ( +/- SD: 419 +/- 387; n = 26) and was not significantly different between men (444 +/- 494 pmol/L) and women (363 +/- 244 pmol/L). Baseline plasma insulin ranged from 76 to 695 pmol/L (271 +/- 188; n = 26) and was not correlated with plasma leptin. Leptin concentrations increased after 3 d of TPN, from 356 +/- 300 to 794 +/- 600 pmol/L (P < 0.05) in parallel with an increase in insulin from 257 +/- 187 to 979 +/- 917 pmol/L (P < 0.01) in the 20 patients who completed the study; however, the changes were not correlated when expressed as percentages. Although the men and women had insulin responses to feeding that were not significantly different, leptin concentrations did not increase significantly in men but increased 3-fold in women (to 1094 +/- 638 pmol/L; P < 0.01). CONCLUSIONS: Leptin regulation in patients with a critical illness differs substantially from that in healthy persons. The importance of glucose and insulin in leptin secretion remains unclear, especially in men.

Adult↗

PubMedDate not supplied

Guidelines for improving nutritional delivery in the intensive care unit.

Optimizing nutritional delivery in the intensive care unit (ICU) continues to be a challenge. Nutritional guidelines were developed at a metropolitan Level I trauma center as an institutional response to ensure the timeliness of patient evaluation, initiation of therapy, and attainment of goal therapy. A post-implementation review of 525 consecutive ICU patients revealed that the guidelines enabled the staff to evaluate 86% of all ICU patients and initiate appropriate therapy in 68% of them within 48 hours of admission. Goal therapy was achieved in more than 90% of patients within 72 hours. The establishment of nutritional guidelines is an integral step to improving nutritional therapy in the ICU.

Diet Therapy↗

PubMedDate not supplied

Iron deficiency anemia in patients receiving home total parenteral nutrition.

BACKGROUND: Certain patients receiving home total parenteral nutrition (HPN) are likely to develop iron-deficiency anemia because of inadequate absorption or chronic iron loss from gastrointestinal lesions. The objective of this study was to examine the incidence and prevalence of iron deficiency anemia in patients on long-term HPN (>6 months) and to investigate both the efficacy of and rate of adverse reactions to parenteral iron dextran therapy. METHODS: The records of 55 patients treated with HPN for >6 months between January 1, 1994 and December 31, 1999 were examined. RESULTS: Thirty patients (55%) had evidence of iron-deficiency anemia. Ten patients were diagnosed at the initiation of HPN, and in 20 patients, iron deficiency developed after receiving HPN. The time between initiation of HPN and development of anemia ranged from 2 to 97 months (mean 28.8+/-26.2 months). Mild iron loss from the gastrointestinal tract seemed to be the predominant reason for iron deficiency. Regular treatment with small amounts of iron in HPN appeared to be safe and efficacious, with no reported side effects. Total dose infusion of iron was associated with adverse reactions in as many as 25% of these patients, although all reactions were mild and self-limited. CONCLUSIONS: Iron-deficiency anemia is common in patients receiving chronic HPN. Regular small doses of iron in HPN formula, rather than total dose infusion, is the preferred treatment.

Adult↗