Altered rheology of lymphocytes in the diabetic mouse.

AIMS/HYPOTHESIS: Clinical complications associated with diabetes may be related to altered physical properties of leucocytes. We used micropipette techniques to examine leucocyte rheology (specifically lymphocyte rheology) in the non-obese diabetic (NOD) mouse model of diabetes mellitus. We hypothesised that diabetes affects lymphocyte rheology, and specifically that lymphocyte membranes from diabetic mammals have a higher cortical tension than those from non-diabetic mammals. METHODS: Lymphocytes were isolated from diabetic and control mice. Lymphocyte deformation and activation were assessed with a micropipette apparatus. Cellular activation was assessed visually. Projection length into the micropipette during aspiration was used to calculate the viscosity of the cell. Recovery length following expulsion from the micropipette was used to derive the recovery time constant, which is the ratio of cortical tension : viscosity (T(o)/mu) for each cell. The cell cortical/surface tension was calculated from this ratio. RESULTS: Of 692 control lymphocytes, 29% were spontaneously activated compared with 39% of 624 diabetic cells (p<0.06) and 31.5% of 315 non-diabetic NOD cells (p=0.14). Viscosity values for diabetic lymphocytes were equivalent to those for control cells (1345.12+/-1420.97 Pa.s vs 996.84+/-585.07 Pa.s, p=0.13). The average T(o)/micro value for diabetic lymphocytes (35.4+/-16.5x10(-6) cm/s) was significantly higher than that for control cells (24.8+/-11.3x10(-6) cm/s, p<0.03) and cells from non-diabetic NOD mice (26.3+/-9.0x10(-6) cm/s, p<0.005). The mean cortical tension values for diabetic and control cells were 4.7+/-2.3x10(-4) N/m and 2.8+/-0.7x10(-4) N/m respectively (p<0.003). CONCLUSIONS/INTERPRETATION: Lymphocytes from diabetic mice tend to spontaneously activate. They have an equivalent cytoplasmic viscosity but a larger recovery time constant compared with cells from control mice. The results suggest that diabetic lymphocytes are stiffer than control cells.

Recent advances in the treatment and outcome of locally advanced rectal cancer.

OBJECTIVE: To compare the outcomes of treatment of locally advanced rectal cancer of the early era (1975-1990) with those of the late era (1991-1997). BACKGROUND: Preoperative therapy has been used in locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. At the University of Florida, preoperative radiation has been used since 1975, and it was combined with chemotherapy beginning in 1991. METHODS: The records of 328 patients who underwent preoperative radiation or chemoradiation followed by complete resection for locally advanced rectal cancer defined as tethered, annular, or fixed tumors were reviewed. The clinicopathologic characteristics, adjuvant treatment administered, surgical procedures performed, and local recurrence-free and overall survival rates were analyzed. RESULTS: There were 219 patients in the early era and 109 in the late era. No significant differences were seen in patients (age, gender, race) or tumor characteristics (mean distance from the anal verge, annularity, fixation). Preoperative radiation regimens were radiobiologically comparable. No patient in the early era received preoperative chemotherapy, compared with 64 in the late era. Of those receiving any pre- or postoperative chemotherapy, three patients received chemotherapy in the early era, compared with 76 in the late era. Sphincter-preserving procedures increased from 13% in the early era to 52% in the late era. Pathologic downstaging for depth of invasion increased from 42% to 58%, but lymph node negativity remained similar. The 1-, 3-, and 5-year local recurrence-free survival rates were comparable. However, in the late era, 1-, 3-, and 5-year overall survival rates improved significantly compared with those of the early era, and also compared with each of the preceding 5-year intervals. CONCLUSION: The addition of a chemotherapy regimen to preoperative radiation therapy improves survival over radiation therapy alone. Likewise, an improvement in downstaging is associated with an increase in sphincter-preserving procedures.