The practical assessment and management of bladder outflow obstruction

The initial management of bladder outflow obstruction typically related to benign prostatic hyperplasia (BPH) falls to a large extent within the remit of general practice. Referral onwards to secondary care typically arises following the failure to respond to conservative measures or when complications have supervened; the most significant of which is urinary retention. In the hospital setting, anaesthesia, constipation and immobility are the common precipitants. What follows is a practical guide to the management of these situations and provides an overview of the conservative, medical, minimally invasive and surgical treatments available.     

Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.     

Recombinant and nonrecombinant factor XIII and its effect on bone ingrowth and strength of fixation

Thirty cylindrical, commercially pure, titanium fiber, porous-coated Ti₆Al₄V implants were inserted pressfit into the proximal humeral portion of 30 sheep humeri to determine the systemic effect of recombinant factor XIII and placenta-derived factor XIII concentrate on bone ingrowth and strength of fixation. For both the recombinant factor XIII and the factor XIII concentrate group, the volume of bone ingrowth and the strength of fixation were higher than for the control specimens. However, the difference was only significant for the factor XIII concentrate group.     

Eosinophilic activation in cystic fibrosis.

BACKGROUND--The neutrophil is a potent contributor to pulmonary destruction in cystic fibrosis. Since eosinophils also possess destructive potential the involvement of eosinophils in cystic fibrosis has been investigated. METHODS--Eosinophil numbers and levels of eosinophil cationic protein (ECP), a marker of eosinophil activation, were determined in the serum of 42 patients with cystic fibrosis and in the sputum of 10 of them. To determine neutrophil activation levels of myeloperoxidase (MPO) were also measured. RESULTS--In cystic fibrosis increased serum levels of ECP were detected compared with healthy non-atopic subjects. Serum ECP levels were not related to the peripheral blood eosinophil count. A strong correlation with ECP concentrations in sputum indicated that the level of ECP in serum was representative of its pulmonary level. Levels of MPO were also increased in cystic fibrosis. A strong correlation was found between MPO and pulmonary function. In addition, ECP was related to arterial oxygen and carbon dioxide tensions. Antibiotic treatment reduced neutrophil activation without effect on ECP levels. CONCLUSIONS--Until now Pseudomonas aeruginosa and neutrophils were held to be primarily responsible for progressive tissue damage in cystic fibrosis. The results of this study suggest that eosinophils might also participate in such pulmonary destruction.     

Endoscopic sealing of infected bronchus stump fistulae with fibrin following lung resections

Summary Bronchus stump insufficiency following lung resection, with an average incidence of 4%, is a serious complication which carries a mortality of up to 90%. Operative transthoracic approaches have been largely unsatisfactory because of the high operative risk and rapidly spreading infection. In an experimental study on 18 pigs, endoscopic occlusion of infected bronchus stump fistulae was achieved with fibrin sealant (1 ml, 500 units/ml thrombin, 3500 units/ml aprotinin) applied via a flexible bronchoscope. During autopsy, all bronchus stump fistulae were found to have healed after the second postoperative week. Transitory local abscesses of the pleura could be prevented by high-dose systemic antibiotic therapy for 5 postoperative days but not by antibiotics added to the fibrin sealant. This endoscopic method has already been performed successfully in 3 clinical cases; additional sclerotherapy with (2–3 ml Ethoxysclerol applied around the fistula orifice was carried out before fibrin sealing to stimulate fibrosis. Endoscopic controls demonstrated fistula closure by granulation tissue after 2 weeks. This procedure could become the method of choice for infected postoperative fistulae of the bronchus stump and should be attempted in any case before operative approaches are considered.     

Blood coagulation activation and fibrinolysis during a downhill marathon run.

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.     

Synthese neuer Indolmethanamine durch Leimgruber-Batcho Reaktion

Synthesis of New Indolemethanamines Using the Leimgruber-Batcho Reaction A short and efficient synthesis of the title compounds is reported starting with commercially available carboxylic acids 1 and 5 , respectively. By appropriate modifications in the course of the Leimgruber-Batcho reaction used in the key step quite stable 1-hydroxy-indole derivatives became available.