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T Slowinski

Publications and source records attributed to T Slowinski.

15 recordsLinked to original sources
PubMed2006

[Characterization of sonographically detected breast lesions using three-dimensional data sets].

PURPOSE: The diagnostic value of 3D ultrasound (US) was evaluated in comparison to 2D US on the basis of a set of pre-defined criteria for breast lesions. The individual criteria were correlated with the histological findings and they were ranked according to their significance for lesion characterization in both 3D US and 2D US. MATERIALS AND METHODS: A total of 92 breast lesions were examined of which 61 were malignant and 31 were benign, as confirmed by histology of core biopsy specimens (Aplio 80, Toshiba, Otawara, Japan). The 2D and 3D data sets were stored digitally. The vascular tree was stored separately using 3D fusion. In addition, a power Doppler (PD) examination was performed. A total of 644 individual images were evaluated by two independent readers. The lesions were evaluated using established criteria (BI-RADS classification). For statistical evaluation, the individual US measurements were classified according to the following two groups: those suggesting malignant lesions and those suggestive of benign lesions. Pearsons's chi-square test was performed for both groups. The 2D and 3D techniques were compared directly using kappa (kappa) statistics. Odds ratios (OR) were determined for the purpose of weighting the individual criteria. The sensitivities and specificities of 2D and 3D US were calculated. RESULTS: The diagnostic value of 3D US was comparable to that of 2D US, with only slight differences observed for specific measurements. Analysis of 2D US data indicated that there was a strong correlation between malignant tumor growth and two specific 2D criteria: lesion margin and effect of the lesion on adjacent breast tissue (r (2) = 0.632, p < 0.001). Analysis of 3D images indicated that the significant measurements for tumor malignancy were shape and lesion margin in sagittal, transverse (r (2) = 0741, p < 0.001), and frontal views (r (2) = 0.592, p < 0.001) as well as retraction and lesion demarcation in the frontal views (r (2) = 0.649, p < 0.001). The comparison of 2D and 3D yielded primarily moderate (kappa = 0.412) to good (kappa = 0.789) agreement between the individual criteria. Crucial criteria for lesion characterization were the effect of the lesion on adjacent breast tissue (OR 47.8 [16.0-143.3]) in 2D US and the lesion margin (OR 36.4 [15.3-86.6]) and the 3 additional criteria of the frontal plane (OR 21.9-32.9) in 3D US. The two US techniques had comparable sensitivities (2D/3D 95-97 %/92-95 %) and specificities (2D/3D 54-58 %/61-67 %). The reconstructed 3D view of the vascular tree was subjectively considered to be helpful by both readers. A higher degree of vascularization was observed with 3D US. CONCLUSIONS: The diagnostic role of 3D ultrasound in the diagnostic evaluation of breast cancer is comparable to that of 2D US. Our findings illustrate the significance of the evaluation of frontal views in lesion characterization.

Adult↗
PubMed2005

Pharmacokinetics of the immunosuppressant everolimus in maintenance renal transplant patients.

The novel macrocyclic immunosuppressant everolimus has been approved for use in renal and heart transplantation. The objective of this randomized, double-blind, placebo-controlled, dose-escalating Phase 1 study was to evaluate the pharmacokinetic profile of different dosing regimens of everolimus. Fifty-four subjects were randomized for 4-weeks treatment with everolimus (n = 44) or placebo (n = 10). Steady state was reached by day 4 of multiple dosing with evidence for dose-proportionality over the dose range tested. Systemic accumulation was 1.6- to 2.2-fold with multiple dosing. Steady-state predose trough concentrations were well correlated with AUC (r = 0.87, p < 0.001). Within-subject coefficients of variation for the tablet formulation ranged from 10-19% and between-subject coefficients from 34-60% for Cmax and AUC. There was no effect of common demographic parameters (age, sex, weight) on variability in steady-state exposure. These results support the clinical use of everolimus in renal transplantation.

Area Under Curve↗
PubMed2005

Laparoscopic versus open donor nephrectomy in Germany: impact on donor health-related quality of life and willingness to donate.

INTRODUCTION: Laparoscopic living donor nephrectomy (LDN) offers multiple advantages to the donor. Since 1999 LDN has become the only surgical approach for living kidney donation in our department. To our knowledge a donor health-related quality of life (QoL) has not yet been performed with standardized and validated questionnaires to compare laparoscopic with open nephrectomy. We therefore performed a study with two questionnaires (SF-36/GBB-24) and one set of open questions for all donors in our department. METHODS: Questionnaires were sent out to all donors between 1983 and 2001 with at least a 1-year follow-up. To exclude a bias a maximum response rate was sought; donors who did not answer were recontacted as well as their recipients or their physicians to motivate them for participation. RESULTS: The response rate was (89.8%). Except for less limb pain in the laparoscopy group, no difference could be detected for donors QoL with respect to the surgical method. Willingness to donate again was not affected by the surgical method. Nevertheless if asked again today, most donors want laparoscopic kidney retrieval. CONCLUSIONS: Donors health-related QoL is not affected by the surgical method when queried retrospectively. Nevertheless, most donors today would favor laparoscopy, if they could chose again. How laparoscopy affects a reluctant donor to step forward must be determined in a prospective study.

Attitude↗
PubMed2003

20-year experience with elderly donors in living renal transplantation.

PURPOSE: This study evaluates the impact of living renal donors (LD) aged 60 years and older on graft performance and patient survival in an old-for-young constellation. PATIENTS AND METHODS: We analyzed 144 consecutive LDs between January 1983 and December 2002 (19 patients 60+/125 controls). RESULTS: Mean donor age in the 60+ group was 63.7 (+/- 2.6) years and 43.7 (+/- 9.0) years for the <60 group. Mean recipient age was 42.4 (+/- 15.2) years versus 32.6 (+/- 15.3) years HLA-A, -B, and DR-mismatches were 3.16 (+/- 1.3) for the 60+ group and 3.13 (+/- 1.7) for the controls (P = NS). Rejection episodes in the first year following LD did not differ (53% versus 33%, P =.25). Mean serum creatinine for 65+ versus <65 after 1, 3, and 12 months was 1.91 +/- 1.2 versus 1.48 +/- 0.85 mg/dL (P =.16), 1.82 +/- 0.89 versus 1.29 +/- 0.35 mg/dL (P <.05) and 1.80 +/- 0.31 versus 1.37 +/- 0.38 mg/dL (P <.05) and mean creatinine clearance at 12 months 62 versus 82 mL/min (P =.06). Censored 1-, 3-, and 5-year graft survival was 100% versus 95% (P = NS), 100% versus 93% (P = NS) and 100% versus 83% (P = NS) with no significant difference in the log-rank test for Kaplan Meier. CONCLUSION: No impact of donor age was found for graft survival but function of the 65+ kidneys at 3 and 12 months was reduced. Living renal donors 60+ are acceptable for carefully allocated recipients.

Adult↗
PubMed2003

Living donor nephrectomy--no impact of genetic relationship.

PURPOSE: A retrospective, single-center analysis was conducted to compare the results of living donor kidney transplantation between living unrelated (LURD) and living related (LRD) donors. PATIENTS AND METHODS: One hundred forty-seven consecutive living renal transplantations were performed at our institution, starting in 1983. Graft and patient survival were assessed as well as transplant function, including a subgroup analysis for the period of kidney transplantation. RESULTS: Mean follow up for the LRD group was 88.5 months and for the LURD cohort 34.4 months. One- and 3-year graft survival (censored for death with functioning graft) for LRD versus LURD was 97.5% versus 94.4% (P =.4) and 95.3% versus 88.8% (P =.35). Patient survival at 1 and 3 years was 95.1% versus 94.7% (P =.91) and 87.8% versus 90.0% (P =.79). Of the related recipients, 37% experienced at least one episode of rejection in the first year following renal transplantation, compared to 34% in the LURD group (P =.80). Mean serum creatinine for LRD versus LURD after 1, 3, and 12 months () was 1.52 +/- 0.81 versus 1.59 +/- 1.17 mg/dL (P =.98), 1.41 +/- 0.55 versus 1.30 +/- 0.40 mg/dL (P =.51), and 1.44 +/- 0.39 versus 1.40 +/- 0.40 mg/dL (P =.75). Mean creatinine clearance after 1 year was 82.2 versus 71.7 mL/min (P =.26). Subgroup analysis for the time between 1996 and 2002 revealed no difference between LURD and LRD. Multivariate analysis could exclude an impact of the significantly different recipient age and of first/second warm ischemic time on the endpoints described above. CONCLUSION: LURD is a good way to meet the growing organ shortage and should be encouraged.

Creatinine↗
PubMed2003

Cyclosporin C2hour monitoring after renal transplantation.

Therapeutic drug monitoring of cyclosporin A (CsA) is essential because of its variable pharmacokinetics in individual patients and its narrow therapeutic window. In the past, standard trough level (C0) monitoring has been used, and although this method is currently the routine strategy, it has been shown that a single blood concentration measurement 2 hours after CsA administration (C2hour) is a significantly more accurate predictor of drug exposure and clinical events than trough concentrations. The CsA absorption profiling, in particular the measurement of C2hour, is a much more sensitive approach to assessing the pharmacokinetics and predicting the clinical effect in the individual patient. However, there are limited prospective data available examining the risks and benefits of C2hour monitoring in renal transplant recipients. Most studies focus on the early post-transplant phase, but there is little experience with C2hour monitoring in maintenance patients. Our experience in 127 stable long-term renal allograft recipients suggests that the therapeutic window for C2hour levels in patients during maintenance is lower than previously anticipated. Repeat determinations of both C0 and C2hour levels in 46 patients to determine precision of C2hour monitoring showed a high intrapatient variability. We observed only a slightly better coefficient of variation for C2hour than for C0 in repeat determinations. This suggests that drug monitoring using C2hour levels in transplant patients may provide a more accurate and reliable measure of drug exposure in the individual patient. However, CsA absorption showed only a weak correlation with dose during repeated measurements, suggesting high variability in absorption in these stable patients. We conclude that an adequate C2hour level soon after transplantation is associated with a reduced risk of acute rejection in adult renal transplant recipients. It is important to identify slow and poor absorbers in the initial phase after transplantation in order to avoid inappropriate increases in CsA dose. In maintenance patients, C2hour values between 500 and 600 ng/ml are effective and safe for providing effective rejection prophylaxis. Although mean C2hour levels do not seem to identify patients at risk of rejection, they may help to identify excessive immunosuppression and to improve long-term survival by reducing CsA toxicity.

Absorption↗
PubMed2001

Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats.

The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity.

Amiloride↗
PubMed2001

Hypokalemic nephropathy after pelvic pouch procedure and protective loop ileostomy.

Proctocolectomy with ileal pouch-anal anastomosis and temporary ileostomy has been established as a curative operation in severe ulcerative colitis during the last 2 decades. Electrolyte imbalances during the first postoperative weeks until ileostomy closure have been reported previously. Here we report about a 70-year-old male patient with a 38 year-history of severe ulcerative colitis who developed slowly progressive renal failure after proctocolectomy with ileal pouch-anal anastomosis and temporary ileostomy. He was referred to our centre with a serum creatinine of 818 micromol/L, hypokalemia of 2.83 mmol/L and metabolic alkalosis as a patient with suspected end-stage renal disease in order to perform shunt surgery and start chronic hemodialysis. However, hypokalemia and metabolic alkalosis are not typical for end-stage renal disease, and renal biopsy showed typical signs of hypokalemic nephropathy. Our patient almost completely recovered after ileostomy closure. This case clearly shows that temporary ileostomy in patients who underwent proctocolectomy, e. g. for ulcerative colitis, is associated with a risk of hypokalemic nephropathy. The appropriate and definite therapy is a surgical one, i. e. ileostomy closure. Monitoring metabolic changes after proctocolectomy and ileostomy, especially during the defunctionalized stage when temporary ileostomy is still present, is essential.

Adult↗
PubMed1998

Pathophysiology in endothelin-1 transgenic mice.

Transgenic mice expressing the human endothelin-1 (ET-1) were generated. These mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension. Consequently, a progressive decrease in renal blood flow and/or glomerular filtration rate was observed, demonstrated by altered creatinine clearance and by magnetic resonance imaging. These genetically altered transgenic mice provide an interesting animal model in which to elucidate the role of ET-1 in the modulation of renal hemodynamics and glomerular and tubule functions.

Animals↗
PubMed1997

Endothelin-1 transgenic mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension.

The human endothelin-1 (ET-1) gene under the control of its natural promoter was transferred into the germline of mice. The transgene was expressed predominantly in the brain, lung, and kidney. Transgene expression was associated with a pathological phenotype manifested by signs such as age-dependent development of renal cysts, interstitial fibrosis of the kidneys, and glomerulosclerosis leading to a progressive decrease in glomerular filtration rate. This pathology developed in spite of only slightly elevated plasma and tissue ET-1 concentrations. Blood pressure was not affected even after the development of an impaired glomerular filtration rate. Therefore, these transgenic lines provide a new blood pressure-independent animal model of ET-1-induced renal pathology leading to renal fibrosis and fatal kidney disease.

Animals↗
PubMed1995

Role of the paracrine liver endothelin system in the pathogenesis of CCl4-induced liver injury.

This study analyzed if the paracrine liver endothelin system participates in the pathogenesis of CCl4-induced hepatotoxicity. Wistar Kyoto rats were divided into four groups: a bosentan (mixed endothelin ETA and ETB receptor antagonist) treated group with CCl4 intoxication, a vehicle treated group with CCl4 intoxication, a nontreated control group and a bosentan treated control group. Hepatotoxicity was assessed by determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) followed by histopathological examinations. Tissue endothelin-1 concentrations and expression of endothelin receptor subtypes were analyzed. The tissue levels of endothelin-1 in the liver of rats with CCl4 intoxication were significantly higher than those in normal rats. Scatchard analysis revealed no differences in the density and binding constant of endothelin ETA and ETB receptor between rats with CCl4 intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation resulted in a significant protection against elevation of ALT, AST, LDH and bilirubin. Histopathological examination of live sections for necrotic, swollen and lipid-laden cells revealed findings that were in agreement with the serum enzyme data. In conclusion, this study showed that the paracrine endothelin system is involved in the pathogenesis of CCl4-induced hepatotoxicity and that the blockade of the stimulated liver endothelin systems reduces CCl4-induced liver injury.

Animals↗
PubMed1995

Using the CPR to benefit a business office.

Computer-based patient records can help a healthcare organization's business office achieve higher-quality service at lower cost by providing improved access to necessary financial as well as clinical information. The systemwide utility of a computer-based patient record that serves both clinical and financial needs helps justify its cost.

Databases, Factual↗
PubMed1995

Protective effects of the mixed endothelin receptor antagonist bosentan in rats with CCL4-induced liver injury.

We determined whether the paracrine liver endothelin (ET) system participates in the pathogenesis of CCl4-induced hepatotoxicity. Wistar-Kyoto rats were divided into four groups: a bosentan-treated group with CCl4 intoxication, a vehicle-treated group with CCl4 intoxication, a nontreated control group, and a bosentan-treated control group. Hepatotoxicity was assessed by determination of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Tissue ET-1 concentrations and expression of endothelin receptor subtypes were analyzed. The liver tissue levels of ET-1 in rats with CCl4 intoxication were significantly higher than in normal rats. Scatchard analysis revealed no differences in the density and binding constants of ETA and ETB receptors between rats with CCl4 intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation resulted in significant protection against elevation of ALT, AST, LDH, and bilirubin. In conclusion, this study showed that the paracrine ET system in involved in the pathogenesis of CCl4-induced hepatotoxicity and that blockade of the stimulated liver endothelin system reduces CCl4-induced liver injury.

Animals↗