Systemic thrombolysis with the use of tenecteplase for segmental acute renal in-farction potentially associated with multiple thrombophilic gene polymorphisms.

BACKGROUND/AIM: The potential association of acute renal infarction with multiple thrombophilic gene polymorphisms and the experience of treatment with tenecteplase are described for the first time in the international literature. DESCRIPTION OF THE CASE: The case of a 50-year old male with segmental acute renal infarction potentially associated with multiple thrombophilic gene polymorphisms is presented. He was thrombolysed with a single intravenous bolus of tenecteplase in a weight-adjusted dose (0.53mg/Kg bodyweight). Within 30 minutes after drug administration, the patient's symptoms were completely relieved. Patient's clinical course was uneventful with an acceptable renal function outcome eight weeks post-treatment. The following gene polymorphisms were identified: G455A (b-fibrinogen); C677T; A1298C (methylenetetrahydropholate reductase); T196C (platelet glycoprotein IIIa); 4G/5G (plasminogen activator inhibitor-1). CONCLUSION: Tenecteplase is a safe and simple to use thrombolytic, with favourable pharmacokinetic profile, which might be useful if administered early, especially when local thrombolysis is impossible or unavailable and therefore warrants further investigation in clinical trials. Hippokratia 2014; 18 (1): 67-70.

Oxygen free radicals in abdominal aortic surgery. An experimental study.

BACKGROUND: In aortic reconstruction, intestinal and muscular ischaemia in the lower limbs occurs during cross-clamping of the aorta. After restoration of blood flow, reactive oxygen intermediates may lead to systemic injury to local or remote organs. In this study we investigated the usefulness of a shunt and vitamin E administration against the oxidant load generated in ischaemia-reperfusion phases. METHODS: In three groups of pigs (n=16) aortic reconstruction was simulated. In Group A (n=5) clamping of the infrarenal aorta was performed for 2 hours. In Group B (n=6), during aortic cross-clamping, a shunt was used to give flow to the inferior mesenteric and internal iliac arteries. In Group C (n=5) vitamin E was administered before aortic cross-clamping. In all groups we evaluated sigmoid histology after reperfusion, while the oxidant load was estimated by measuring superoxide dismutase (SOD) activity in blood samples from portal and jugular vein. RESULTS: Histology of the sigmoid revealed increased postischaemic injuries in Group A, while the protective effect of shunt and vitamin E was apparent in Group B and C, respectively. SOD activity was minimized in Group C. CONCLUSIONS: Vitamin E protected the sigmoid from postischaemic injury and is responsible for the decreased levels of SOD activity.

Immunosuppressive effect of combination schedules of brequinar with leflunomide or tacrolimus on rat cardiac allotransplantation.

Drug toxicity is one of the major problems in clinical immunosuppression. Combining two immunosuppressants in low or ineffective doses is an attractive strategy if it helps to reduce drug-related toxicity. We examined the immunosuppressive efficacy of brequinar (BQR) in combination with leflunomide (Lef) or tacrolimus (FK) in a heterotopic rat cardiac allotransplantation model. Abdominal heterotopic heart grafts (DA x LEW) were immunosuppressed from the time of transplantation and continued until the ninth posttransplant day (POD) in experiments examining prophylaxis of rejection treatment (PRT). In a separate series of experiments designed to test rescue treatment (RT), immunosuppression was begun on POD 4 and continued for 10 days; transplanted rats were sacrificed the following day intentionally. Cardiac rejection was monitored by palpation and documented by light microscopy. Immunosuppressive drugs (BQR 3 mg/kg and 12 mg/kg; BQR 3 mg/kg + Lef 5 mg/kg; BQR 3 mg/kg + FK 0.5 mg/kg) were given orally by gavage; thrice weekly according to the monotherapy or dual-therapy dosing protocol. Median survival time of the cardiac graft for controls (no treatment) was 5 days. BQR monotherapy 3 mg/kg (low dose) improved graft survival (P = 0.003); graft histology showed moderate acute rejection. BQR monotherapy 12 mg/kg (therapeutic dose) application in the PRT or RT treatment arms of the study design resulted in aortic-graft ruptures and clinical toxicity in each treatment arm due to overimmunosuppression; normal graft morphology was maintained. Successful rescue of rejecting grafts was histologically documented. Combining BQR with Lef or FK in the PRT protocol showed prolonged graft survival in both drug combination groups (median survival time, 14 days; P = 0.009 and 0.014, respectively). Using an identical combination protocol for RT, all grafts achieved a 14-day graft survival; cardiac histology showed reversible moderate acute rejection. BQR given in the presence of Lef or FK not only prevented acute rejection but intercepted it so long as it was administered; grafts were rejected within 4 days of stopping immunosuppression in the PRT study. These combinations using low or subtherapeutic doses may be important for controlling transplant rejection and rescuing ongoing graft rejection. The need for continuing treatment in this strongly allogeneic model is highlighted.

Arteriovenous difference of blood ammonia in uremic patients under hemodialysis.

In this study the ammonia concentration was determined in arterial and venous blood samples pre- and posthemodialysis (HD) in 18 uremic patients and in 18 health subjects (controls). The mean values (+/- SD) of ammonia in the arterial blood of uremic patients pre-HD were 98.32 +/- 26.55; post-HD, 63.18 +/- 17.09; and in control group patients, 72.37 +/- 10.09 micrograms/dl. In venous blood they were pre-HD, 71.70 +/- 20.68; post-HD, 58.05 +/- 16.73; and in control patients, 74.46 +/- 12.0 micrograms/dl. According to our findings, the ammonia concentration in the arterial blood of uremic patients pre-HD exceeds the normal limits and is significantly higher (p < 0.001) than that post-HD and that of control patients. The ammonia contents of venous blood pre- and post-HD ranges were within normal values, but the post-HD range was significantly lower than the pre-HD range (p < 0.05) and the control range (p < 0.01). Comparison between ammonia levels from arterial and venous blood showed significant and positive arteriovenous differences pre-HD (p < 0.001), which disappeared post-HD and were not observed in the control patients. In conclusion, uremic patients under HD present pre-HD high levels of ammonia in arterial blood with a significantly positive arteriovenous difference. In contrast, the post-HD ammonia levels in arterial and venous blood are decreased, and the arteriovenous difference is not significant.

Lipid-lowering effect and safety of acipimox in hemodialysis patients and renal transplant recipients.

The efficacy and safety of acipimox, an antilipolytic agent, were studied in 10 uremic patients under hemodialysis (group A) and in 8 renal transplant recipients with adequate renal function (group B). The medication was given for 20 weeks at a dose of 250 mg daily in both groups. Total serum cholesterol decreased significantly from 218.1 +/- 17.4 to 175.2 +/- 15.2 mg/dL (-19.7%) in group A and from 261.2 +/- 16.5 to 215.3 +/- 26.9 mg/dL (-17.6%) in group B; as did serum triglycerides, from 206.7 +/- 26.9 to 146.9 +/- 17.6 mg/dL (-29%) in group A and from 168.2 +/- 20.6 to 111.3 +/- 12.4 mg/dL (-33.8%) in group B. Low-density lipoprotein (LDL)-cholesterol and very low-density lipoprotein (VLDL)-cholesterol were also decreased significantly (LDL-C by -27% and -25%, and VLDL-C by -29.2% and -33.8% in groups A and B, respectively). Furthermore, the high-density lipoprotein (HDL)-cholesterol was increased significantly, by +29.6% in group A and +18% in group B. The apolipoproteins Apo-A1 and Apo-A2 were decreased in Group A but not in group B. The Apo-B was decreased in group B. Serum CPK (total and muscle fraction), total bilirubin, SGPT, SGOT, alkaline phosphatase, gamma GT, LDL, a-Fp, and creatinine remained unchanged in both groups. Acipimox seems to be effective in the regulation of atherogenic lipid disorders in hemodialysis patients and renal transplant recipients, without any muscular damage or alteration of kidney and liver function.

Influence of radiation treatment on serum transferrin and tumor necrosis factor-alpha.

This study deals with the effect of radiation treatment (RT) on serum transferrin and tumor necrosis factor-alpha (TNF-alpha) in patients with malignant tumors. In 21 patients who received 36-60 Gy in 20 to 30 sessions of RT, serum transferrin and TNF-alpha were determined pre-RT, after 10 to 15 sessions (middle of RT) and after 20 to 30 sessions (end of RT). The values of serum transferrin pre-RT were significantly higher than those in the middle and at the end of RT (p < 0.001). The values of TNF-alpha were increased by RT and were significantly higher at the end of RT as compared to the pre-RT values (p < 0.05). The values of serum transferrin and TNF-alpha show a tendency to negative correlation, either as a whole or separately pre- and under-RT. However, no correlation was statistically significant.

Clinical evaluation of four tumor markers in malignant and benign pleural effusions.

Total sialic acid (TSA), lipid-bound sialic acid (LSA), ferritin and carcinoembryonic antigen (CEA) were evaluated in 55 patients with malignant pleural effusions and in 32 patients with benign (exudative) pleural effusions. No significant differences were found in the pleural fluid TSA, LSA and ferritin levels between malignant and benign conditions. CEA levels in malignant effusions were significantly higher than those in benign effusions (43.13 +/- 72.8 ng/ml versus 2.6 +/- 5.56 ng/ml, p less than 0.01). At a cut-off level of 5 ng/ml, 60% of the patients with cancer showed elevated pleural fluid CEA levels. The specificity and diagnostic accuracy of CEA in distinguishing malignant from benign pleural exudates were both very high (91% and 71% respectively). Therefore, of the four markers investigated, only CEA could be a valuable tool in the detection of pleural malignancy.

Serum sialic acid (TSA/LSA) and carcinoembryonic antigen (CEA) levels in cancer patients undergoing radiotherapy.

The main aim of this study was to evaluate the response of total Sialic Acid (TSA) and "Lipid-bound" Sialic Acid (LSA) compared to Carcinoembryonic Antigen (CEA), in 284 patients undergoing radiotherapy. Serial measurements of TSA by the enzymatic method (Boehringer-Mannheim Kit), LSA by the resorcinol-HC1 (Katopodis and Stock) and CEA by EIA (Abbott Kit) were performed in a total of 1017 blood sera. We statistically estimated the four greater groups of cancer patients [bladder (69), lung (58), uterus (31) and breast (29)]. Diagnostic marker sensitivities (% true positives) estimated from the 0-time-values--before initiation of radiotherapy--in relation to the established cut-off levels were in decreasing order: TSA 89.3% (80 mg/dL). LSA 88.8% (20 mg/dL) and CEA 26.75% (5 ng/mL). The overall tumor marker response to treatment, after its completion, estimated as % of patients with final blood serum levels of these markers, was in decreasing order: LSA 85.6%, TSA 81.3%, and CEA 65.8%. These data show that a) the diagnostic sensitivity of Sialic Acid (LSA/TSA) is more than 3 times higher than that of CEA and b) the response of Sialic Acid (LSA/TSA) to treatment is about 15% higher than that of CEA. In conclusion, this study confirms the high diagnostic sensitivity of Sialic Acid as a tumor marker and suggests that, with marginal superiority of Sialic Acid, all three markers are sufficiently responsive to be employed as adjunctive means in monitoring cancer patients underdoing radiotherapy.

Correlation of total (TSA) and lipid and bound (LSA) sialic acid levels with cytology of cyst or body fluids in cancer patients.

In this preliminary study, aiming at the early diagnosis or the confirmation of neoplastic spreading, the levels of sialic acid (TSA and LSA, total sialic acid and "lipid bound" sialic acid) were measured and correlated with the corresponding cytologic findings in 111 body or cystic fluid samples taken from patients with suspected or confirmed cancer. The samples were classified according to the body fluid origin: peritoneal (35), breast cyst (22), pleural (21), thyroid gland cyst (5), renal cyst (5), ovarian cyst (6), bronchial washing (3), douglasic cavity (3) and various other origins (11). It was found that 32.43% of the samples were TSA positive, 44.14% LSA positive, 20.75% cytologic and 8.49% cytology suspect (positive + suspect = 29.24%). Thus, the combination of a tumor biomarker with the corresponding cytology of the body fluid gives the best possible results, as regards both the confirmation of positive cytology and the detection of possible metastases, as well as the monitoring of the disease after treatment.

Five tumor markers in lung cancer: significance of total and "lipid"-bound sialic acid.

Total sialic acid (TSA) and "lipid-bound" sialic acid (LSA) were evaluated in comparison to carcinoembryonic antigen (CEA) and ferritin and neuron specific enolase (NSE) in 152 untreated patients with primary lung cancer, 107 benign pulmonary disease patients and 207 notmal controls. The mean concentrations of TSA, LSA and CEA in lung cancer patients, were significantly higher than in benign and normal controls (p less than 0.001), while the mean ferritin and NSE levels were significantly higher than in normal controls only (p less than 0.001). At the designated cut-off serum levels, sensitivities of the five markers for lung cancer were in decreasing order: TSA 86.5% (greater than 80 mg/dL), LSA 77% (greater than 20 mg/dL), CEA 46.4% (greater than 5 ng/mL), ferritin 36% (greater than 300 ng/mL) and NSE 34.5% (greater than 12.5 ng/mL). Using the benign pulmonary values as negative controls the specificity of each marker was as follows: CEA 88%, ferritin 72%, NSE 58%, TSA 44% and LSA 44%. In small cell lung cancer (SCLC) patients, NSE mean concentrations and sensitivity were significantly higher than in non-small lung cancer (NSCLC) patients (9.63 +/- 4.4 versus 23.54 +/- 16.9, p less than 0.001 and 74% versus 21.4% respectively). While in NSCLC patients only CEA levels correlated well with the stage of the disease, in SCLC patients concentrations of TSA, LSA and ferritin were significantly higher in extensive than in limited disease stages. These preliminary data suggest that, although TSA and LSA are highly sensitive markers in lung cancer, their specificity is low.