OBJECTIVE -To give an up-to-date profile of nephropathy and the involvement of risk factors in a large, prospective cohort of patients with type 1 diabetes and largely pediatric and adolescent onset of disease. RESEARCH DESIGN AND METHODS-A total of 27,805 patients from the nationwide, prospective German Diabetes Documentation System survey were included in the present analysis. Inclusion criteria were at least two documented urine analyses with identical classification. Urine analyses, treatment regimens, diabetes complications, and risk factors were recorded prospectively. Baseline characteristics were age at diagnosis 9.94 years (median [interquartile range 5.8 -14.3]), age at last visit 16.34 years (12.5-22.2), and follow-up time 2.5 years (0.43-5.3). Cumulative incidence of nephropathy was tested by Kaplan-Meier analysis and association with risk factors by logistic regression.RESULTS -Nephropathy was classified as normal in 26,605, microalbuminuric in 919, macroalbuminuric in 78, and end-stage renal disease (ESRD) in 203 patients. After calculated diabetes duration of 40 years, 25.4% (95% CI 22.3-28.3) had microalbuminuria and 9.4% (8.3-11.4) had macroalbuminuria or ESRD. Risk factors for microalbuminuria were diabetes duration (odds ratio 1.033, P Ͻ 0.0001), A1C (1.13, P Ͻ 0.0001), LDL cholesterol (1.003, P Ͻ 0.0074), and blood pressure (1.008, P Ͻ 0.0074), while childhood diabetes onset (1.011, P Ͻ 0.0001) was protective. Male sex was associated with the development of macroalbuminuria.CONCLUSIONS -Diabetes duration, A1C, dyslipidemia, blood pressure, and male sex were identified as risk factors for nephropathy. Therefore, besides the best possible metabolic control, early diagnosis and prompt treatment of dyslipidemia and hypertension is mandatory in patients with type 1 diabetes. Diabetes Care 30:2523-2528, 2007M icro-and macroalbuminuria are important markers for early and progressive diabetic kidney disease. Patients with type 1 diabetes face a 20 -50% probability of developing endstage renal disease (ESRD) requiring dialysis or renal transplantation (1). But over the last decades, cumulative incidence of nephropathy has further declined, which was attributed to intensified treatment regimens and a more aggressive therapy of hypertension and dyslipidemia (1,2).Since the 1980s, microalbuminuria has been established as an early marker of progressive kidney disease in diabetes (3), starting at pediatric age (4,5), and currently albumin excretion rate (AER) remains the best available noninvasive predictor for diabetic nephropathy and should be measured regularly according to established guidelines (6 -8).Since the Diabetes Control and Complications Trial (DCCT), glycemic control was established as the dominant risk factor for the development of diabetic nephropathy (9). Moreover, the DCCT follow-up Epidemiology of Diabetes Interventions and Complications study has demonstrated a persistent delay of progression of diabetic nephropathy 7-8 years after the end of the DCCT, in the previously intensively trea...

The aim of this study was to assess global left ventricular (LV) function and regional wall motion using retrospectively ECG-gated 16-slice computed tomography (CT) in comparison with magnetic resonance imaging (MRI). Twenty-one patients (18 male, 65.5+/-8.6 years) with acute myocardial infarction underwent multislice spiral CT (MSCT) and MRI. From manually drawn endo- and epicardial contours, LV volumes including myocardial mass, peak filling rate (PFR), peak ejection rate (PER), time to PER (TPER) and time from end-systole to PFR (TPFR) were calculated. Regional wall motion was assessed from cine loops using a 16-segment model of the left ventricle. LV function was analyzed using the Bland-Altman method, Pearson's correlation coefficient, multivariate analysis and post hoc t tests. Regional wall motion was evaluated with weighted kappa-statistics. Multivariate analysis revealed significant differences for global LV function as determined by MSCT and MRI. Post hoc t-tests showed significant differences for end-diastolic volume (EDV), PFR and TPER (P<0.05), while there was a good agreement for the LV volumes with an ejection fraction of 46.9+/-8.4% for MSCT and 46.9+/-8.9% for MRI. PER, PFR, TPER and TPFR presented a poor correlation and a wide range of scattering between MSCT and MRI. Regional wall motion scores showed a good agreement with kappa=0.791. Sixteen-slice spiral CT allows for reliable assessment of LV volumes, but is not yet suited for the evaluation of all functional parameters. Assessment of regional wall motion at rest is feasible.

We compared semiautomatic contour detection and manual contour tracing in cardiac multidetector row computed tomography (MDCT) with magnetic resonance imaging (MRI) for calculation of left-ventricular (LV) volumes. The study included 30 patients who underwent contrast-enhanced cardiac MDCT and cardiac cine-MRI. Were calculated 8 mm short-axis slices from MDCT data using three-dimensional multiphase image reconstruction. LV volumes including peak ejection rate and peak filling rate were calculated from manually and semiautomatically determined contours. Results were compared to those from cine-MRI with manually drawn contours as the standard of reference. We found good agreement for the LV volumes, with an ejection fraction of 47.1+/-9.4% for manually drawn contours, 47.9+/-9.9% for semiautomatically detected contours on MDCT, and 48.0+/-10.2% for MRI. Except for peak-filling rate analysis of variance revealed no difference between any of these techniques. Bland-Altman plots and Lin's concordance correlation coefficient showed best agreement between MRI and manual contour tracing in MDCT. Calculation of LV volumes using either semiautomatic or manual contour tracing in cardiac MDCT is therefore feasible when compared to MRI. Automated contour detection needs to be improved to equal manual contour tracing.

Cytotoxic T lymphocyte (CTL) clones directed against autologous renal-cell carcinoma (RCC) cell lines were generated by mixed lymphocyte/tumor-cell culture (MLTC) using peripheral blood lymphocytes (PBL). A CD8+, CD4- CTL clone MZ1257-CTL 5/30 with high cytolytic activity for the autologous tumor cell line MZ1257-RCC was established. No lysis of the autologous EBV-transformed B lymphocytes (EBV-B) or K562 cells was observed. A panel of HLA-A2-matched allogeneic RCC lines was recognized by CTL 5/30. Further specificity analysis showed a cross-reactivity with HLA-A2-matched allogeneic tumor cells of various origins, especially melanoma. CTL 5/30 was also cross-reactive with several HLA-A2-positive allogeneic normal kidney cells in culture. The restriction element identified for CTL 5/30 was HLA-A2, as shown by blocking of cytotoxicity using an anti-HLA-A2 monoclonal antibody (MAb) and by resistance of an HLA-A2-negative melanoma variant SK29-MEL. 1.22 against lysis by CTL 5/30. In this report we demonstrate HLA-A2-restricted recognition of a T-cell-defined antigen on autologous renal-cancer cells. This antigen is also expressed and recognized in association with HLA-A2 on normal kidney cells in culture and other HLA-A2-positive tumor cells. It may therefore be a normal differentiation antigen to which tolerance is incomplete in the renal-cell cancer system investigated.

Glycemic and body weight control are two outstanding goals in the treatment of patients with type 2 diabetes that often are not appropriately achieved. This observational study evaluates whether treatment by quality controlled diabetes centers generates an improvement in this regard and focuses on associations with different therapies. Data of 9.294 type 2 diabetic patients (mean age 66.9±11.6 years, mean diabetes duration 12.4±9.2 years) from 103 German diabetes centers were assessed by a standardized, prospective, computer-based diabetes care and outcome documentation system (DPV-Wiss-database). Therapeutic concepts included lifestyle intervention (n=1.813), oral antidiabetics (OAD, n=1.536), insulin (n=4.504) and insulin plus OAD (n=1.441). HbA1c and body weight were compared before and after a stable therapeutical period of 1.07±0.3 years. Change in HbA1c (%): all patients 7.4±1.6-7.0±1.3, lifestyle intervention 7.5±1.9-6.9±1.5, OAD 6.7±1.1-6.5±1.0, insulin 7.6±1.6-7.2±1.4, insulin plus OAD 7.5±1.5-7.2±1.3; each p≤0.05. Change in body weight (kg): all patients +0.08±0.07, n. s.; lifestyle intervention -0.28±0.20, OAD -0.56±0.13, each p<0.05 [metfomin -0.77±0.21, sulfonylurea drugs -0.75±0.34, each p<0.05; glitazones +0.62±0.70, α-glucosidase inhibitors -0.22±0.76, each n. s.], insulin +0.27±0.10, insulin plus OAD +0.63±0.14, each n. s. In summary, lifestyle, metformin or sulfonylurea drug treatment resulted in HbA1c-values below 7.0% plus a significant weight reduction. Insulin treatment-associated concepts resulted in HbA1c-values slightly above 7.0% without body weight alterations. These "real life" data underline that a specialised and quality controlled diabetes care is able to achieve significant treatment results even in patients with disease progression and a high proportion of insulin therapies.