Retained foreign body following pleural drainage with a small-bore catheter

Small-bore radiopaque drains can be used to drain pleural effusions. They offer reliable drainage of simple pleural effusions and provide a safe, less-invasive, more comfortable alternative to the standard tube thoracostomy. Importantly, removal of such drains does not require purse-string sutures and hence can be removed without assistance. We report here the cautionary tale of a retained foreign body related to drainage of a pleural effusion with a Pleurocath in a patient following cardiac surgery to raise awareness of this potential complication. Emphasized is the need for all staff to be familiar with the normal appearance of equipment being utilized in the ward and to report when incomplete removal of drain equipment is suspected. In addition, amendments to insertion techniques for such small-bore drains are proposed to avoid similar undue complications.     

Ammodytase, a metalloprotease from Vipera ammodytes ammodytes venom, possesses strong fibrinolytic activity

Ammodytase, a high molecular mass metalloproteinase with fibrinogenolytic and fibrinolytic activities, was purified from long-nosed viper (Vipera ammodytes ammodytes) venom by gel filtration, affinity and ion-exchange chromatographies. The enzyme is a single-chain glycoprotein with apparent molecular mass of 70 kDa and isoelectric point of 6.6. Ammodytase shows very weak hemorrhagic activity, and only at doses higher than 20 μg. Consistent with this, it partially degrades some components of the extracellular matrix in vitro. It cleaves the Aα-chain of fibrinogen preferentially at peptide bonds Glu⁴⁴¹-Leu⁴⁴² and Glu⁵³⁹-Phe⁵⁴⁰. Its preference for bulky and hydrophobic amino acids at the P1′ position in substrates is demonstrated by its hydrolysis of only the Gln⁴-His⁵ and Tyr¹⁶-Leu¹⁷ bonds in the B-chain of insulin. Ammodytase is able to dissolve fibrin clots. It neither activates nor degrades plasminogen and prothrombin, and has no effect on collagen- or ADP-induced platelet aggregation in vitro. LC/MS and MS/MS analyses of its tryptic fragments demonstrated that ammodytase is a P-III class snake venom metalloproteinase composed of metalloproteinase, disintegrin-like and cysteine-rich domains. Its similarity to hemorrhagins from V. a. ammodytes venom, accompanied by very low toxicity, makes ammodytase a promising candidate as an antigen to prepare antisera against these most dangerous components of the viper's venom. Moreover, its ability to degrade fibrin clots suggests its clinical use as an antithrombotic agent.     

Molecular and structural consequences of early renal allograft injury

BACKGROUND: Chronic allograft nephropathy is an important cause of graft failure. Many donor and recipient factors contribute to its development. Prospective analysis of these factors has been hindered by the lack of sensitive and specific indicators of renal injury. As a consequence protocol biopsies have been increasingly used in the assessment of renal allograft injury. We performed protocol renal allograft biopsies to prospectively examine the role of important determinants and mediators of chronic allograft nephropathy. METHODS: A total of 51 consecutive cadaveric renal transplant recipients entered a randomized prospective study of tacrolimus (Tac) versus cyclosporine (CsA) microemulsion based immunosuppression. Study patients underwent protocol renal allograft biopsies at the time of engraftment and at 3, 6 and 12 months post-transplantation. Biopsies were analyzed by quantitative polymerase chain reaction (PCR) for mRNA for transforming growth factor-beta (TGF-beta), thrombospondin, and fibronectin. Measurements of renal structural injury were estimated by quantitative assessment of interstitial fibrosis and glomerulosclerosis. Changes in profibrotic growth factors and renal structural injury were related to donor and recipient determinants by stepwise regression analysis. RESULTS: Longitudinal assessment of renal injury demonstrated an early and progressive increase in mRNA for TGF-beta, thrombospondin (TSP) and fibronectin (FBN): TGF-beta baseline, 1.9 +/- 0.2 log copies; TGF-beta 6 months, 2.5 +/- 0.2 log copies, P < 0.05 6 months vs. baseline; TSP baseline, 1.9 +/- 0.2 log copies; TSP 6 months, 2.4 +/- 0.2 log copies, P < 0.05 6 months vs. baseline; FBN baseline, 2.0 +/- 0.2 log copies; FBN 12 months, 2.3 +/- 0.2 log copies, P < 0.05 12 months vs. baseline. This increase in profibrotic growth factors within the allograft was associated with a significant increase in interstitial fibrosis (Vvi) on renal biopsies: Vvi baseline, 13 +/- 1%; Vvi 3 months, 18 +/- 1%; Vvi 6 months, 28 +/- 2%; Vvi 12 months, 34 +/- 2%; P < 0.05 3, 6, and 12 months vs. baseline. Histological analysis demonstrated chronic allograft nephropathy in 4% biopsies at 3 months, 12% at 6 months and in 49% at 12 months. These changes in renal structure were not associated with any change in creatinine clearance (CCr): CCr 3 months, 56 +/- 2 mL/min, CCr 24 months, 56 +/- 2 mL/min; P=NS. Stepwise regression analysis of key donor and recipient determinants of chronic renal injury identified calcineurin inhibitors and acute rejection episodes as important factors involved in the development of chronic renal injury. In particular, the use of cyclosporine compared to tacrolimus was associated with a tenfold increase in TGF-beta mRNA (TGF-beta mRNA at 6 months, CsA vs. Tac, 3 +/- 0.3 vs. 2 +/- 0.3 log copies, P < 0.05), interstitial fibrosis (Vvi at 6 months, CsA vs. Tac, 33 +/- 4% vs. 24 +/- 2%, P < 0.05). Changes in growth factors and renal structure predicted impaired renal function (CCr at 12 months, CsA vs. Tac, 53 +/- 4 mL/min vs. 62 +/- 2 mL/min, P < 0.05). Similarly, acute rejection episodes were associated with an accelerated development of interstitial fibrosis (Vvi at 6 months, acute rejection vs. no rejection, 34 +/- 3% vs. 25 +/- 2%; P < 0.05), but not with changes in TGF-beta, thrombospondin or fibronectin expression. CONCLUSION: Our results suggest that structural injury develops early in the natural history of the renal allograft and is mediated, in part, by the early up-regulation of profibrotic growth factors. We have determined that calcineurin inhibitors, in particular cyclosporine, and acute rejection episodes are key factors in the development of renal structural injury.     

Relationships between fibrinolytic and inflammatory parameters in human adipose tissue: strong contribution of TNFalpha receptors to PAI-1 levels

Plasminogen activator inhibitor type 1 (PAI-1), a risk marker of atherosclerosis, is highly expressed in adipose tissue from obese subjects. PAI-1 is also considered as an acute phase protein. Recently, adipose tissue has been described as a source of inflammatory cytokines. Therefore, our aim was to study the relationships between PAI-1, and IL-6, TNF, TNF receptors (TNFRSF1s) and TGFbeta1, in plasma and adipose tissue from obese (n = 60) and lean (n = 28) subjects. Study has been extended to plasminogen activators (t-PA and u-PA). Compared to lean subjects, obese subjects exhibited higher plasma levels of all the studied parameters (except for TGFbeta1) whereas in adipose tissue only PAI-1, t-PA and TGFbeta antigen levels differed. In the obese population, plasma PAI-1 levels were weakly associated with circulating TNF, and this relationship disappeared after adjustment for plasma t-PA. Adipose tissue PAI-1 levels were positively associated with TNFRSF1s and TGFbeta, the strongest relationship being observed with TNFRSF1A, which explained 82% of PAI-1 variability. TNF and IL-6 were the main contributors to t-PA variability in plasma and in adipose tissue, respectively. Our results argue on the relevance of TNFRSF1s in the regulation of PAI-1 expression by adipose tissue. Association between t-PA, which is mainly produced by endothelial cells, and IL-6 or TNF suggest that inflammation might be involved in angiogenesis in adipose tissue.     

Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice

Background  

Bleomycin is poorly permeant but potent cytotoxic and radiosensitizing drug. The aim of the study was to evaluate whether a physical drug delivery system – electroporation can increase radiosensitising effect of bleomycin in vitro and in vivo.     

Tick-borne encephalitis in children in Styria and Slovenia between 1980 and 2003

BACKGROUND: To describe the effect of the Austrian vaccination program against tick-borne encephalitis (TBE) on the incidence of this disease in children from Styria, an Austrian federal state, and to compare it with that in Slovenia, the neighboring country with a risk to acquire TBE similar to that of Styria. METHODS: A retrospective population-based cohort study was performed with the use of discharge data from all Styrian pediatric hospitals and data from the Center for Communicable Diseases at the National Institute of Public Health in Ljubljana, Slovenia. RESULTS: From January 1980 to December 2003, 139 cases of TBE in children younger than 16 years were observed in Styria. The annual incidence of TBE/100,000 Styrian children declined from 2.5-9.3 cases between 1980 and 1986 to 0-2.2 between 1987 and 1993 and to 0-1 between 1994 and 2003. Extrapolating the incidence of 6.3 cases/100,000 children between 1980 and 1986 to the time from 1994 to 2003, 124 pediatric TBE cases had been prevented in Styria in the past 10 years. CONCLUSIONS: Our data show that the Austrian vaccination program against TBE can lead to the nearly complete disappearance of TBE in children living in areas highly endemic for TBE.     

Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC157 in rat and mouse

Overall, doxorubicine-congestive heart failure (CHF) (male Wistar rats and NMRI mice; 6 challenges with doxorubicine (2.5 mg/kg, i.p.) throughout 15 days and then a 4-week-rest period) is consistently deteriorating throughout next 14 days, if not reversed or ameliorated by therapy (/kg per day): a stable gastric pentadecapeptide BPC157 (GEPPPGKPADDAGLV, MW 1419, promisingly studied for inflammatory bowel disease (Pliva; PL 10, PLD-116, PL 14736)) (10 microg, 10 ng), losartan (0.7 mg), amlodipine (0.07 mg), given intragastrically (i.g.) (once daily, rats) or in drinking water (mice). Assessed were big endothelin-1 (BET-1) and plasma enzyme levels (CK, MBCK, LDH, AST, ALT) before and after 14 days of therapy and clinical status (hypotension, increased heart rate and respiratory rate, and ascites) every 2 days. Controls (distilled water (5 ml/kg, i.g., once daily) or drinking water (2 ml/mouse per day) given throughout 14 days) exhibited additionally increased BET-1 and aggravated clinical status, while enzyme values maintained their initial increase. BPC157 (10 microg/kg) and amlodipine treatment reversed the increased BET-1 (rats, mice), AST, ALT, CK (rats, mice), and LDH (mice) values. BPC157 (10 ng/kg) and losartan opposed further increase of BET-1 (rats, mice). Losartan reduces AST, ALT, CK, and LDH serum values. BPC157 (10 ng/kg) reduces AST and ALT serum values. Clinical status of CHF-rats and -mice is accordingly improved by the BPC157 regimens and amlodipine.