Blood flow in the skin of type 1 diabetic patients before and after combined pancreas/kidney transplantation.

BACKGROUND: To analyze effects of long-term glucose normalization after pancreas transplantation, different parameters of skin microcirculation were assessed by laser Doppler fluxmetry. METHODS: Forty-two type 1 diabetic patients after successful simultaneous pancreas/kidney transplantation (Group A, median 32.3 months posttransplant), 28 patients with functioning kidney grafts, but insulin therapy (Group B, median 64.9 months posttransplant) and 13 diabetic pretransplant patients (Group C, median 14.2 months on dialysis) were compared with 33 healthy subjects (Group D). Resting blood flow, postocclusive hyperemia, venoarteriolar response on the right foot and decrease in blood flow during cold pressure test on the left finger was assessed. RESULTS: Postocclusive hyperemia, decrease in blood flow during cold pressure test and venoarteriolar response were higher in Group D than in all patient groups. Resting blood flow in Group A was significantly lower than in Groups B and C (following values as median): 3.6 perfusion units (PU) versus 7.4 PU in Group B, p < 0.01 and 12.1 PU in Group C, p < 0.001, respectively, and was not significantly different to controls (Group D, 5.2 PU). Postocclusive hyperemia was higher in Group A than in Groups B and C (266.7% vs 160.0%, p < 0.05 and 79.4% n.s., respectively), but significantly less than in Group D (563.5%). The microangiopathy index-high values reflecting less or no microangiopathy-was significantly higher in Group A than in Groups B and C (11.0 vs 4.3, p < 0.001 and 4.7, p < 0.05, respectively), and was very much comparable to the values in healthy controls (Group D, 10,3). The decrease in blood flow during cold pressure test was higher in Group A compared to Groups B and C (25.2% vs 21.1% and 13.8%, n.s., respectively), but much less than in Group D (65,7%). CONCLUSION: These data suggest an improvement without complete normalization of skin microcirculation by long-term blood glucose normalization achieved by pancreas transplantation.

Preoperative serum levels of the carcinoembryonic antigen in hereditary non-polyposis colorectal cancer compared to levels in sporadic colorectal cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) serves as the most widely used and most cost-effective tumor marker in colorectal cancer for almost 30 years. Recent publications about serum CEA levels are based on patient groups without definite differentiation between hereditary and non-hereditary forms of colorectal cancer. PATIENTS AND METHODS: We compared preoperative CEA serum levels from 105 patients with hereditary non-polyposis colorectal cancer (HNPCC) and 107 patients with sporadic colorectal cancer including influences of age and Dukes stage. CEA values in cases of HNPCC were correlated to the findings of microsatellite analyses, mutation analyses of the MMR genes (MLH1, MSH2) and respective immunohistochemistries. RESULTS: Thirty-three HNPCC patients (31%) and 37 patients with sporadic CRC (34%) revealed elevated CEA levels higher than 5 ng/ml. The mean preoperative CEA level in all Dukes stages of HNPCC patients was lower with 31.7 +/- 180 ng/ml than in sporadic colorectal cancer with 68.3 +/- 424 ng/ml, but without significance (p = 0.72). HNPCC tumors with signs of de-differentiation (G3 and G4) revealed significantly higher CEA values with 62.2 +/- 262 ng/ml in comparison to well-differentiated tumors (G1 and G2) with 5.0 +/- 9.6 ng/ml (p = 0.02). HNPCC patients with "classical characteristics" (high microsatellite instability (MSI), MMR gene mutation, loss of MMR protein expression) had lower preoperative CEA serum levels than those without equivalent genetic alterations, but without reaching statistical significance. CEA levels of HNPCC tumors increased significantly under occurrence of metastases with mean values of 170.3 +/- 343 (p < 0.02). CONCLUSIONS: Normal preoperative serum CEA levels do not have the same validity for all colorectal cancer patients. Low CEA levels in HNPCC patients could occur due to well-differentiated tumors and should be considered more critically than in sporadic CRC patients. Further studies including comparison of postoperative CEA development are necessary to elucidate the importance of these results.

The CD19+ B-cell counts at peripheral blood stem cell mobilization determine different levels of tumour contamination and autograft purgability in low-grade lymphoma.

The tumour load of peripheral blood stem cell (PBSC) harvests and the outcome of ex vivo immunomagnetic B-cell purging was investigated in 19 patients with low-grade lymphoma. To quantify the tumour load, we combined fluorescence-activated cell sorting measurement of CD19+ B-cells and determination of the B-cell light chain ratio (LCR) with consensus complementarity-determining region III-polymerase chain reaction (CDRIII-PCR) and gene scan analysis. The number of tumour cells was calculated using B-cell extracts from the PBSCs. Two different patterns were distinguished. In eight patients (42%) with CD19+ B cells >1% in the apheresis product, a high tumour load was found, characterized by a monoclonal LCR, positive PCR in seven out of eight cases, >5 x 10(7) extracted lymphoma cells in six out of seven PCR-assessable cases, and the presence of residual lymphoma after purging in six of seven cases. In 11 patients (58%) with <1% CD19+ B-cells in the product, a low tumour load was indicated by a polyclonal LCR, positive PCR in only 4 out of 11 cases, >5 x 10(7) extracted lymphoma cells in zero out of four PCR-assessable cases, and the presence of residual lymphoma after purging in zero out of four of these cases. The level of residual lymphoma following purging largely depended on the level of tumour contamination. CD19+ B-cells >50/microl in the peripheral blood at mobilization predicted a high tumour load in the apheresis product.

Responsiveness to G-CSF before leukopenia predicts defense to infection in high-dose chemotherapy recipients.

An active assessment of the host capacity to prevent infection during myelosuppression should be beneficial in patients receiving high-dose chemotherapy. A single dose of granulocyte colony-stimulating factor (G-CSF) (5 microg/kg) was given to 57 patients with multiple myeloma early after the completion of 85 high-dose chemotherapy (melphalan 200 mg/m2) courses. This provoked a highly variable white blood cell (WBC) peak after 12 to 14 hours. The median WBC count was 21,000/microL (range, 6400-60,600/microL) after a first high-dose therapy (n = 50) and 13,500/microL (range, 4700-24,800/microL) after a second high-dose therapy (n = 35). The responsiveness to single G-CSF was associated with the risk of infection during subsequent cytopenia (P =.003). This association was significant after adjustment for neutropenia duration. Notably, the result of testing G-CSF responsiveness was opportunely available before the onset of leukopenia, and G-CSF responsiveness was more informative than neutropenia duration regarding the risk of infection. Furthermore, there was an association between the responsiveness to G-CSF and stem cell engraftment (P <.005), which remained significant after adjustment for the number of transplanted CD34+ cells. Our results show for the first time that G-CSF potentially could be used for an early in vivo assessment of defense to infection in recipients of high-dose chemotherapy.