Investigation of the efficacy of 99 mTc-DTPA scintigraphic GFR measurement with Gates method in the detection of cisplatin-induced nephrotoxicity in comparison with plasma urea and creatinine measurement

In this study, we investigated the efficacy of 99mTc-DTPA scintigraphic analysis of GFR with the Gates method in comparison with the measurement of plasma urea and creatinine, in the detection of nephrotoxicity occurred in patients treated with cisplatin.Twenty-six male patients with a mean age of 26.73 ± 6.39 years (age range 15–42) who had seminomatous and nonseminomatous testicular carcinoma were included in our study. The patients received cisplatin with a dose of 20 mg/m² per day for five consecutive days repeated every 21 days. Before starting chemotherapy, immediately after the end of four cycles of chemotherapy and 7 months after the beginning of chemotherapy, plasma urea and creatinine levels were measured and simultaneously scintigraphic GFR estimation using 99 mTc-DTPA with the Gates method was performed. In the measurements done immediately after the chemotherapy, in 18 of the 26 patients GFR levels decreased, in 4 of the 8 remaining patients GFR did not change, and in 4 patients there was an increase in the GFR levels. The changes in the averages of the plasma urea and creatinine levels between measurements done before and after the chemotherapy were not statistically significant. The decrease in the average of the GFR values immediately after chemotherapy, in comparison to the average of GFR values measured before chemotherapy, was found to be statistically significant with paired sample t test analysis (P < 0.009 with 95% CI). We concluded that scintigraphic GFR measurement using the Gates method with 99mTc-DTPA is a suitable method in the diagnosis of nephrotoxicity occuring due to cisplatine.     

The effect of the nitric oxide synthesis inhibitor L-NAME on amitriptyline-induced hypotension in rats

OBJECTIVE: Hypotension induced by tricyclic antidepressants is multifactorial. Previous animal experiments suggest a contribution from nitric oxide production. Our study aimed to evaluate the role of nitric oxide in amitriptyline-induced hypotension using N-nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, and 3-morpholino sydnonimine, a nitric oxide donor, in anesthetized rats. METHODS: Amitriptyline intoxication was induced by the continuous infusion of amitriptyline 0.625 mg/kg/min throughout the experiment in anesthetized rats. Fifteen and 25 minutes after amitriptyline infusion began, two bolus doses of 10 mg/kg of N-nitro-L-arginine methyl ester (n = 8) or an equivalent volume of 5% dextrose solution (n = 8) was administered to each rat (Protocol 1). To investigate whether the effect of N-nitro-L-arginine methyl ester on blood pressure is counteracted by 3-morpholino sydnonimine, after the same protocol of amitriptyline infusion and 5 minutes after an N-nitro-L-arginine methyl ester bolus, a bolus of 3000 nmol/kg of 3-morpholino sydnonimine was administered (n = 8) to each rat (Protocol 2). To investigate the effect of N-nitro-L-arginine methyl ester on 3-morpholino sydnonimine induced hypotension, a group of rats received a continuous infusion of 0.54 mg/kg/h of 3-morpholino sydnonimine until 50% reduction was observed in mean arterial blood pressure followed by a bolus dose of 10 mg/kg of N-nitro-L-arginine methyl ester (n = 6) or 5% dextrose solution (n = 6) (Protocol 3). Outcome measures included mean arterial blood pressure, heart rate, and QRS duration in electrocardiogram. Student's t test and survival analysis were used for selected comparisons. RESULTS: For all parameters, the treatment groups were similar at baseline and at postamitriptyline periods before therapy was rendered. Amitriptyline infusion significantly reduced mean arterial blood pressure by 50.8 +/- 2.2% and prolonged QRS by 23.9 +/- 7.2% after 15 minutes. In Protocol 1, N-nitro-L-arginine methyl ester significantly increased mean arterial blood pressure compared to dextrose-treated control animals within 30 minutes (77.9 +/- 8.5% vs. 49.7 +/- 5.0% mmHg, p < 0.01, 95% CI 57.1-98.7%). QRS duration progressively increased during the amitriptyline infusion; however, there was no significant difference in QRS width between N-nitro-L-arginine methyl ester and control groups at any time point. N-nitro-L-arginine methyl ester increased survival time compared to controls (33.4 +/- 4.1 vs. 19.9 +/- 2.7 minutes, p < 0.01, 95% CI 25.4-41.3) but did not affect mortality. In Protocol 2 of continuous infusion of amitriptyline, 3-morpholino sydnonimine counteracted the N-nitro-L-arginine methyl ester-induced increase in mean arterial blood pressure. In both protocols, heart rate decreased significantly during amitriptyline infusion but there was no difference between treatment and control groups. In Protocol 3, N-nitro-L-arginine methyl ester bolus reversed 3-morpholino sydnonimine-induced hypotension compared to dextrose bolus. (83.8 +/- 5.7% vs. 54.6 +/- 4.8%, p < 0.01, 95% CI 69.2-98.4). CONCLUSION: N-nitro-L-arginine methyl ester is found to be effective in temporarily improving hypotension and prolonging survival time but does not affect overall mortality. Because this effect was antagonized by 3-morpholino sydnonimine, nitric oxide production appears to contribute to the pathophysiology of amitriptyline-induced hypotension.     

Determination of prognosis in patients with prostate cancer treated with radical prostatectomy: prognostic value of CD44v6 score

PURPOSE: A third of the patients treated with radical prostatectomy experience progression even when tumors are confined pathologically to the prostate. CD44 may be a promising prognostic marker for determining malignant potential. However, there has not been a standard scoring system because of its heterogeneous staining pattern. Thus, we developed an objective scoring system to evaluate reliably CD44v6 (Bender Medsystems, Vienna, Austria) as a prognostic marker for prostate cancer. MATERIALS AND METHODS: A total of 22 patients with metastatic stage pT3bN0M0 or any pTN1M0 disease and 18 with nonmetastatic disease less than stage pT3bN0M0 were selected from a well examined group of 114 who underwent radical retropubic prostatectomy. Mean followup was 33 months (range 4 to 78). A combined CD44v6 score was determined by adding the scores of the primary and secondary areas. CD44v6 expression in terms of the CD44v6 score in primary and metastatic tissues was examined. The relationships of CD44v6 expression with pathological stage, progression and PSA-free survival were also evaluated. The prognostic value of the CD44v6 score for progression was analyzed by multivariate analysis. RESULTS: Progression in the metastatic group was significantly higher than in the nonmetastatic group (p <0.0001). CD44v6 expression of the primary tumors differed significantly in the 2 groups (p = 0.014). The CD44v6 score in primary tumor tissues inversely correlated with pathological stage (p = 0.004) and progression (p = 0.035), and positively correlated with PSA-free survival (p = 0.041). Furthermore, patients in the nonmetastatic group with a CD44v6 score of greater than 75 (cutoff value) had a significantly better prognosis (log rank test p = 0.0022), while those with a CD44v6 score of less than 75 had a prognosis similar to those in the metastatic group. On multivariate analysis pathological stage and surgical margin positivity were independent factors for progression but the CD44v6 score was not. CONCLUSIONS: According to our results the suggested CD44v6 score system is useful. A CD44v6 score of less than 75 may be a predictor of poor prognosis in the nonmetastatic group and this property may have potential application for planning adjuvant therapy.     

Conservative treatment of scapular neck fracture: the effect of stability and glenopolar angle on clinical outcome

The aim of this study was to determine the effect of stability and glenopolar angle on the clinical outcome of conservatively treated scapular neck fractures. Eighteen patients with scapular neck fractures were treated with conservative treatment. Twelve of the 18 patients had surgical neck fractures, whilst six of them had anatomical neck fractures. Anteroposterior radiographs and computerised tomography were performed for each patient. Glenopolar angle was measured through anteroposterior radiographs in the scapular plane. After 3-5 weeks of immobilisation, a rehabilitation programme was started, throughout which all the patients were treated in a 3-phase rehabilitation programme. The mean follow-up was 25 months, and the Constant score was 78.83+/-8.12 point (range: 68-94 points). Patient gender and the type of scapular neck fractures had no effect on functionality or clinical outcome (p>0.05), whilst associated injuries significantly affected the clinical outcome (p<0.05). There was a positive correlation between the Constant score and glenopolar angle (r=0.891, p<0.05) and between the age and glenopolar angle (r=0.472, p<0.05).     

Can E-selectin be a reliable marker of inflammation in lumbar disc disease?

The cause of sciatica and low back pain associating with lumbar disc herniation has not been clearly identified until now. Inflammation has been shown to occur via immunohistochemical and biochemical methods in herniated disc tissues. The important prognostic role of E-selectin has recently been substantiated by other studies in early rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). The important role of adhesion molecules in the initiation and progression of the inflammatory response is well known for infectious diseases and autoimmune disorders. In our study, we aimed to show the role of E-selectin as an inflammatory marker and the correlation of inflammation with straight-leg raise (SLR) test findings and subtype of disc herniation. We found that the cases with positive SLR test had higher rates of immunostaining with E-selectin. This led us to think that E-selectin might play an important role in the activity status of the disease, meaning patients with more limited movement capacity might benefit from E-selectin antagonist therapy. Among the many studies performed to identify the relationship between the inflammation markers and activity of lumbar disc herniation, this is the first investigation held with E-selectin.     

Proliferating-cell nuclear antigen (PCNA) as an independent prognostic marker in patients after prostatectomy: a comparison of PCNA and Ki-67

OBJECTIVE: To investigate the prognostic value of prostatic tumour cell proliferation, as measured by Ki-67 and proliferating cell nuclear antigen (PCNA), and to compare these measures in men at low and high risk for progression of tumour. PATIENTS AND METHODS: Two groups of patients with prostate cancer, i.e. 'metastatic' (M, 22) who had pT3b-4aN0M0 and pTanyN1M0, and 'nonmetastatic' (NM, 18), who had < or =pT3aN0M0 disease, were selected from a well-examined and mapped group of 114 treated by radical prostatectomy. Patients in the NM group were selected by the criteria of having a Gleason score of < or = 7. To assess proliferation, 1000 cells were counted at x 400 magnification by two observers and the percentage of tumour cells positively stained with Ki-67 and PCNA defined as the Ki-67 and PCNA labelling index (LI), respectively. The two LI were compared in the NM and M groups, and the correlation of the LIs with pathological stage, progression and prostate-specific antigen (PSA)-free survival evaluated. Prognostic values of the LI were analysed using multivariate analysis. RESULTS: The mean (range) follow-up was 33 (4-78) months. The mean LIs were higher in the M than the NM group for both PCNA and Ki-67 (P = 0.02 and 0.019, respectively). Both LIs were markedly different between the groups when stratified by progression, with both significantly higher in men with progression in the NM group. Both LIs had a significant association with Gleason score, pathological stage, progression and PSA-free survival. In multivariate analysis the PCNA LI, surgical margin status and pathological stage were independent factors for progression. CONCLUSION: Tumour cell proliferation as assessed by Ki-67 or PCNA correlate significantly with progression. The PCNA LI was an independent predictor of progression, especially in patients with a low risk of progression according to predefined criteria.