Biomedical subjects

Matthew J Delano

Publications and source records attributed to Matthew J Delano.

3 recordsLinked to original sources

PubMed2006

Increased natural CD4+CD25+ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis.

Regulatory T cells (Tregs), including natural CD4+CD25+ Tregs and inducible IL-10 producing T regulatory type 1 (T(R)1) cells, maintain tolerance and inhibit autoimmunity. Recently, increased percentages of Tregs have been observed in the blood of septic patients, and ex vivo-activated Tregs were shown to prevent polymicrobial sepsis mortality. Whether endogenous Tregs contribute to sepsis outcome remains unclear. Polymicrobial sepsis, induced by cecal ligation and puncture, caused an increased number of splenic Tregs compared with sham-treated mice. Splenic CD4+CD25+ T cells from septic mice expressed higher levels of Foxp3 mRNA and were more efficient suppressors of CD4+CD25- T effector cell proliferation. Isolated CD4+ T cells from septic mice displayed increased intracellular IL-10 staining following stimulation, indicating that T(R)1 cells may also be elevated in sepsis. Surprisingly, Ab depletion of total CD4+ or CD4+CD25+ populations did not affect mortality. Furthermore, no difference in survival outcome was found between CD25 or IL-10 null mice and wild-type littermates, indicating that Treg or T(R)1-generated IL-10 are not required for survival. These results demonstrate that, although sepsis causes a relative increase in Treg number and increases their suppressive function, their presence does not contribute significantly to overall survival in this model.

Animals↗

PubMed2006

The origins of cachexia in acute and chronic inflammatory diseases.

The term cachexia originates from the Greek root kakos hexis, which translates into "bad condition," recognized for centuries as a progressive deterioration of body habitus. Cachexia is commonly associated with a number of disease states, including acute inflammatory processes associated with critical illness and chronic inflammatory diseases, such as cancer, congestive heart failure, chronic obstructive pulmonary disease, and human immunodeficiency virus infection. Cachexia is responsible for the deaths of 10%-22% of all patients with cancer and approximately 15% of the trauma deaths that occur from sepsis-induced organ dysfunction and malnutrition days to weeks after the initial traumatic event. The abnormalities associated with cachexia include anorexia, weight loss, a preferential loss of somatic muscle and fat mass, altered hepatic glucose and lipid metabolism, and anemia. Anorexia alone cannot fully explain the development of cachexia; metabolic alterations in carbohydrate, lipid, and protein metabolism contribute to the severe tissue losses. Despite significant advances in our understanding of specific disease processes, the mechanisms leading to cachexia remain unclear and multifactorial. Although complex, increasing evidence from both animal models and clinical studies suggests that an inflammatory response, mediated in part by a dysregulated production of proinflammatory cytokines, plays a role in the genesis of cachexia, associated with both critical illness and chronic inflammatory diseases. These cytokines are further thought to induce an acute phase protein response (APR) and produce the alterations in lipid and carbohydrate metabolism identified as crucial markers of acute inflammation in states of malignancy and critical illness. Although much is still unknown about the etiology of cachexia, there is growing appreciation that cachexia represents the endproduct of an inappropriate interplay between multiple cytokines, neuropeptides, classic stress hormones, and intermediary substrate metabolism.

Acute Disease↗

PubMed2002

Pancreatic surgery.

Over the past year considerable progress has been made in the field of pancreatic surgery. Innovative diagnostic techniques continue to improve the preoperative staging of pancreatic cancer. For patients with cancer and biliary obstruction, preoperative biliary stenting appears to increase the incidence of wound infection after pancreatoduodenectomy but has no effect on other perioperative complications. New information about the molecular biology of pancreatic cancer may begin to influence the surgical approach to the disease. More cases of intraductal papillary mucinous neoplasms are being diagnosed and studied. The impact of adjuvant chemotherapy and chemoradiation on survival has been more clearly defined in a large, randomized trial. In patients with sterile acute necrotizing pancreatitis, conservative nonsurgical management has continued to produce favorable results. For chronic pancreatitis, surgery appears to diminish both chronic pain and recurrent episodes of acute pain.

Journal Article↗