PubMed HealthSearch

Biomedical subjects

G Kassabian

Publications and source records attributed to G Kassabian.

3 recordsLinked to original sources

Increased rigidity and priming of polymorphonuclear leukocytes in sepsis.

It has been proposed that abnormal mechanical properties may contribute to capillary retention of polymorphonuclear leukocytes (PMN) in sepsis, leading to the development of organ dysfunction. The present study was designed to determine whether PMN rigidity is increased in severe sepsis, and whether changes in the rheologic behavior of PMN correlate with the clinical course in sepsis. Eighteen adults with severe sepsis were studied over a period of 14 d; 11 survived and seven died. PMN deformation behavior was investigated via micropore filtration, using the cell transit analyzer. On Day 0, PMN rigidity was 2.5-fold greater for sepsis patients than for five normal controls (p < 0.001). PMN rigidity progressively improved over the 14 d study period for patients who recovered, but not for those who died; clinical indicators correlated with PMN rigidity. Patient PMN also exhibited a 5-fold greater increase in rigidity in response to formyl-methionylleucylphenylalanine (fMLP) than did control PMN. Both the increased rigidity and enhanced response to fMLP could be simulated in vitro by incubation of normal PMN with tumor necrosis factor-alpha (TNF-alpha). We conclude that circulating PMN are more rigid in severe sepsis, and are "primed" for an augmented response to chemotactic stimuli. These findings support the hypothesis that cytokine-mediated increases of PMN rigidity may lead to sequestration of these cells in capillaries and to the consequent impairment of microvascular perfusion in sepsis.

Adult

Mesenchymal commitment to digital joint formation.

Temporal and spatial commitment of in vivo and in vitro mammalian digital joint development were characterized in a murine model. Alcian blue and alizarin red staining were used to label proteoglycans of cartilage matrix and mineralized matrix in both whole mounts and histological sections. Mesenchymal differentiation toward a joint fate was identified by a lack of matrix deposition in islands of joint precursor cells between phalangeal precursors, and localized lysosomal enzyme activity was later demonstrated in these regions during formation of the joint cavity. Organ-cultured forelimbs and in vivo specimens demonstrated analogous digital joint morphological trends. With a defined developmental window, reverse transcription, polymerase chain reaction, demonstrated differential gene expression of transforming growth factor-beta isotypes, aggrecan core protein, and type II collagen, suggesting a role for transforming growth factor-beta in directing digital joint development.

Actins

Restoration of venous outflow by simultaneous creation of an arteriovenous shunt and pedicle flap using a rat model of foot replantation.

Replantation of amputated rat feet utilizing an efferent arteriovenous shunt constructed between the distal posterior tibial artery and the proximal posterior tibial vein, in the absence of all other venous drainage, provides an alternative pathway to the normal venous drainage in a replanted rat foot. However, this substitute venous drainage was insufficient to prevent progressive ischemia and necrosis of some or all of a replanted rat foot. When a cutaneous pedicle flap supplemented the arteriovenous shunt, venous drainage was much improved, tissue hypoxia and edema began to subside on the third day, severe tissue necrosis was prevented, and seven of eight feet replanted by this technique survived. These observations may be useful in replantation in humans when veins in the amputated part are too small to be used or so damaged that they cannot be repaired or reconstructed by a vein graft, but arteries can still provide a means of returning blood from the amputated part. Constructing an alternative pathway to the normal venous drainage pattern may allow severely damaged parts to survive after replantation.

Anastomosis, Surgical