[Coronary interventions : Current developments for improved long-term results]. / Koronarinterventionen : Aktuelle Entwicklungen für bessere Langzeitergebnisse.

Based on solid scientific evidence, new generation drug-eluting stents (DES) have become established as the standard of care in interventional cardiology. With at least similar safety and superior efficacy over uncoated bare metal stents (BMS) in various scenarios and including patients with increased bleeding risk, there are probably no remaining indications favoring the use of BMS. Additional developments regarding the platform, drug elution characteristics and polymer design were aimed at optimizing DES with even better outcomes. Although there is no lack of new variations, none has proven to be superior and several non-inferiority trials lacked statistical power, which precludes the label third generation (over second generation or new generation DES). While it is recognized that potential long-term advantages of bioresorbable scaffolds cannot be expected at this stage from the current ABSORB III trial, the safety and efficacy are encouraging. Beyond procedural aspects, such as intracoronary imaging, variations in duration of antiplatelet therapy should help to improve outcomes but still require careful individual weighting of ischemic vs. bleeding risk.

[Percutaneous mechanical circulatory support: options and importance]. / Perkutane mechanische Kreislaufunterstützung: Möglichkeiten und Stellenwert.

In cases of low cardiac output and chronic cardiac failure despite conventional therapy, mechanical circulatory support may be the only option to ensure adequate organ perfusion and to save the life of the patient. In recent years, several conceptionally different methods of circulatory support have been developed for percutaneous application in interventional cardiology and intensive care. Indications range from elective use in complex cardiac interventions to long-term support as a bridge to recovery. As intra-aortic balloon pump support can no longer be considered for routine use in ischemic cardiogenic shock, micro-axial pumps for extracorporeal membrane oxygenation and extracorporeal life support systems (ECMO/ECLS) gain attractiveness due to a more convincing impact on the hemodynamics. However, an increasing level of support is paralleled by greater invasiveness and complexity of the systems. Due to a lack of larger comparative trials, the benefits and risks of adverse events must be balanced against those of conventional therapy with inotropes and largely on an individual basis. This review summarizes the options for percutaneous circulatory support with special consideration to applications in the catheter laboratory and intensive care units in internal medicine.

The effects of over-expression of the FK506-binding protein FKBP12.6 on K(+) currents in adult rabbit ventricular myocytes.

This study examines the effects of the intracellular protein FKBP12.6 on action potential and associated K(+) currents in isolated adult rabbit ventricular cardiomyocytes. FKBP12.6 was over-expressed by ~6 times using a recombinant adenovirus coding for human FKBP12.6. This over-expression caused prolongation of action potential duration (APD) by ~30%. The amplitude of the transient outward current (I (to)) was unchanged, but rate of inactivation at potentials positive to +40 mV was increased. FKBP12.6 over-expression decreased the amplitude of the inward rectifier current (I (K1)) by ~25% in the voltage range -70 to -30 mV, an effect prevented by FK506 or lowering intracellular [Ca(2+)] below 1 nM. Over-expression of an FKBP12.6 mutant, which cannot bind calcineurin, prolonged APD and affected I (to) and I (K1) in a similar manner to wild-type protein. These data suggest that FKBP12.6 can modulate APD via changes in I (K1) independently of calcineurin binding, suggesting that FKBP12.6 may affect APD by direct interaction with I (K1).

Dysphagia caused by ventral osteophytes of the cervical spine: clinical and radiographic findings.

The purpose of our study was to demonstrate the clinical and radiographic findings in patients with dysphagia and ventral osteophytes of the cervical spine due to degeneration or as a typical feature of diffuse idiopathic skeletal hyperostosis (DISH, Forestier Disease). Since 2003 we encountered 20 patients with such changes in the cervical spine causing an impairment of deglutition. A total of 12 patients had one solitary pair of osteophytes of neighboring vertebrae, 4 patients revealed two pairs and 4 patients had triple pairs of osteophytes. Thirty-two osteophytes were observed totally. A total of 14 of these arose from the right, 15 from the left side and 3 from the middle of the anterior face of the vertebra. Ten patients suffered from DISH, while ten patients revealed osteophytes as a part of a degenerative disorder of the cervical spine. The osteophytes had an average length of 19 mm maximum anterior posterior range. Most of the osteophytes (16) were found in the segments C5/6 and C6/7. Osteophytes of vertebrae C3/4/5 occurred in six cases. Only in one case C2/3 was affected. Functional endoscopic evaluation of swallowing (FEES) revealed an aspiration of thin liquids in seven patients with osteophytes arising from the anterior face of the vertebra C3/4/5 restricting the motility of the epiglottis, which seemed not to close the aditus laryngis. Retention of solids in the piriform sinus on the side obstructed by an osteophyte (C4/5) could also be repeatedly evidenced through FEES. In one case, a strong impairment of the voice because of an immobility of the right vocal cord due to mechanical obstruction by an osteophyte was the indication for surgical removal of the structure. Thus, the dysphagia of this patient was reduced and his voice turned to normal. The development of symptoms in patients with ventral osteophytes was very much related to the location of the structures. Moreover, the clinical symptoms were to some extent dependent on the size of the osteophytes, although there was no direct correlation between size of the structure and severity of the patient's complaint.

Mycobacterium pinnipedii: transmission from South American sea lion (Otaria byronia) to Bactrian camel (Camelus bactrianus bactrianus) and Malayan tapirs (Tapirus indicus).

Tuberculosis infections caused by Mycobacterium (M.) pinnipedii in a South American sea lion, Bactrian camel, and Malayan tapirs kept in two zoological gardens spanning a time period of 5 years are reported. The zoos were linked by the transfer of one tapir. Conventional bacteriological and molecular methods were applied to detect the pathogen. Spoligotyping and MIRU/VNTR-typing performed to assess the genetic similarity revealed identical molecular characteristics of the isolates from all animals involved. Anti-tuberculosis antibodies were detected using ELISA and a recently developed serological rapid test. The study shows that: (i) using molecular methods, the assessment of the genetic relationship of infectious agents helps to confirm the routes of infection, and that (ii) immunological tests may help to detect tuberculosis infections ante mortem more reliably and early. This would prevent the transfer of tuberculosis by asymptomatic animals.

K201 modulates excitation-contraction coupling and spontaneous Ca2+ release in normal adult rabbit ventricular cardiomyocytes.

OBJECTIVES: The drug K201 (JTV-519) increases inotropy and suppresses arrhythmias in failing hearts, but the effects of K201 on normal hearts is unknown. METHODS: The effect of K201 on excitation-contraction (E-C) coupling in normal myocardium was studied by using voltage-clamp and intracellular Ca(2+) measurements in intact cells. Sarcoplasmic reticulum (SR) function was assessed using permeabilised cardiomyocytes. RESULTS: Acute application of <1 micromol/L K201 had no significant effect on E-C coupling. K201 at 1 micromol/L decreased Ca(2+) transient amplitude (to 83+/-7%) without affecting I(Ca,L) or the SR Ca(2+) content. At 3 micromol/L K201 caused a larger reduction of Ca(2+) transient amplitude (to 60+/-7%) with accompanying reductions in I(Ca,L) amplitude (to 66+/-8%) and SR Ca(2+) content (74+/-9%). Spontaneous SR Ca(2+) release during diastole was induced by increasing intracellular [Ca(2+)]. At 1 micromol/L K201 reduced the frequency of spontaneous Ca(2+) release. The effect of K201 on SR-mediated Ca(2+) waves and Ca(2+) sparks was examined in beta-escin-permeabilised cardiomyocytes by confocal microscopy. K201 (1 micromol/L) reduced the frequency and velocity of SR Ca(2+) waves despite no change in SR Ca(2+) content. At 3 micromol/L K201 completely abolished Ca(2+) waves and reduced the SR Ca(2+) content (to approximately 73%). K201 at 1 micromol/L reduced Ca(2+) spark amplitude and frequency. Assays specific to SR Ca(2+)-ATPase and RyR2 activity indicated that K201 inhibited both SR Ca(2+) uptake and release. CONCLUSIONS: K201 modifies E-C coupling in normal cardiomyocytes. A dual inhibitory action on SERCA and RyR2 explains the ability of K201 to suppress spontaneous diastolic Ca(2+) release during Ca(2+) overload without significantly affecting Ca(2+) transient amplitude.

The functional effect of adenoviral Na+/Ca2+ exchanger overexpression in rabbit myocytes depends on the activity of the Na+/K+-ATPase.

OBJECTIVES: The functional consequences of Na+/Ca2+ exchanger (NCX) overexpression in heart failure have been controversially discussed. NCX function strongly depends on intracellular sodium which has been shown to be increased in heart failure. METHODS AND RESULTS: We investigated the Na+/K+-ATPase (NKA) inhibitor ouabain (0.5-16 micromol/l) in electrically stimulated, isotonically contracting adult rabbit cardiocytes overexpressing NCX after adenoviral gene transfer (Ad-NCX-GFP, 48 h culture time). Myocytes transfected with adenovirus encoding for green fluorescent protein (Ad-GFP) served as a control. Contractions were analyzed by video-edge detection. In the Ad-NCX-GFP group, the maximum inotropic response was significantly reduced by 50.7% (P<0.05). This was a result of an enhanced susceptibility to contracture after exposure to the drug (median concentration (25-75%): 4 (4-8) vs. 8 (6-16) micromol/l, P<0.05). When analyzing relaxation before contracture, the maximum relaxation velocity was reduced (0.15+/-0.04 vs. 0.27+/-0.04 microm/s, P<0.05) and the time from peak shortening to 90% of relaxation was increased (298+/-39 vs. 185+/-15 ms, P<0.05). No differences in systolic and diastolic parameters were observed with the Na+ channel modulator BDF9198 (1 micromol/l). CONCLUSIONS: Inhibition of NKA by ouabain induces a combined diastolic and systolic dysfunction in NCX overexpressing rabbit myocytes. This may be the consequence of cytoplasmic Ca2+ overload due to inhibition of forward mode or induction of reverse mode Na+/Ca2+ exchange. In end-stage failing human myocardium and during digitalis treatment this mechanism may be of major importance.

FK506 does not affect cardiac contractility and adrenergic response in vitro.

FK506 (tacrolimus) is a new immunosuppressant being used in cardiac allograft transplantation. While cyclosporine A has been shown to exert an acute negative inotropic effect on isolated heart muscle preparations, little is known of the inotropic influence of FK506. The Ca(2+) release channel of human skeletal muscle and cardiac muscle is associated with FK506 binding proteins (FKBP), FKBP12 and FKBP12.6, respectively. FKBPs can be dissociated by treatment with FK506. As a consequence of FK506 exposure, isolated skeletal muscle and cardiac muscle ryanodine receptors show altered gating characteristics. Therefore, we analyzed the direct inotropic effect of FK506 exposure to isolated, intact heart muscle preparations from the human and rabbits. Experiments were performed on isolated, electrically stimulated right atrial auricular muscle strips obtained from human myocardium during elective open heart surgery and on intact right ventricular trabeculae from rabbit hearts. The human preparations were exposed to concentrations of 8 x 10(-9), 8 x 10(-8) and 8 x 10(-6) M FK506 followed by a cumulative dose-response curve with isoprenaline as a non-selective beta-adrenoceptor agonist. Our data suggest that FK506 does not exert any positive or negative inotropic effect in either human or rabbit myocardium.

Mitochondrial DNA synthesis studied autoradiographically in various cell types in vivo.

It is generally accepted that mitochondria are able to proliferate even in postmitotic cells due to their natural turnover and also to satisfy increased cell energy requirements. However, no detailed studies are available, particularly with respect to specific cell types. Since [3H]-thymidine is incorporated not only into nuclear (n) DNA but also into the DNA of cytoplasmic mitochondria, an autoradiographic approach was developed at the light microscopy level in order to study basic questions of mitochondrial (mt) proliferation in organs of rodents in situ via the cytoplasmic incorporation of [3H]-thymidine injected into the animals 1 h before sacrifice. Experiments carried out on mice after X-irradiation showed that cytoplasmic labeling was not due to a process such as unscheduled nuclear DNA synthesis (nUDS). Furthermore, half-lives of mitochondria between 8-23 days were deduced specifically in relation to cell types. The phase of mtDNA synthesis was about 75 min. Finally, mt proliferation was measured in brain cells of mice as a function of age. While all neurons showed a decreasing extent of mtDNA synthesis during old age, nUDS decreased only in distinct cell types of the cortex and hippocampus. We conclude that the leading theories explaining the phenomenon of aging are closely related, i.e., aging is due to a decreasing capacity of nDNA repair, which leads to unrepaired nDNA damage, or to an accumulation of mitochondria with damaged mtDNA, which leads to a deficit of cellular energy production.

Effects of different colored test environments on selected physiological and psychological responses during maximal graded treadmill tests.

The belief that color may have many varied effects on the human organism has been well-established. Very little, however, has been done to look at responses to color during exercise. 15 subjects performed three maximal graded treadmill tests, once in each of three different colored environments. Five physiological and one psychological variables were measured during the three exercise periods. No significant differences were found among conditions.

Readability and comprehensibility of the "exercise lite" brochure.

Studies suggest that exercise literature tends to be very difficult to read and the writing not matched to the reading ability of the audience for which it was intended. Two studies aimed at describing the readability and comprehensibility of the recently developed U.S. Centers for Disease Control and American College of Sports Medicine "Exercise Lite" brochure were conducted. In Study 1, the brochure's readability was assessed using four different formulas. This study showed that the brochure was written at a level equivalent to that of a scientific journal article. In Study 2, 56 participants (two-thirds of whom were college graduates) were tested to assess whether they could comprehend the brochure's message. Results showed that, without supplemental instruction, the Exercise Lite brochure was incomprehensible for 69.6% (n = 39) of the subjects.

[Marburg Spelling Training program--results of a brief intervention]. / Das Marburger Rechtschreib-Training--Ergebnisse einer Kurzzeit-Intervention.

OBJECTIVES: The Marburg Spelling Training Program was administered to a sample of 10 spelling-disabled primary school pupils (2nd-4th graders) over three months in an individual setting. RESULTS: Statistical analyses yielded significant improvements in spelling and reading test performances, but none yet in the emotional stress caused by the problems. CONCLUSION: The Marburg Spelling Training Program has now proven to be effective not only in long-term, but also in short-term intervention.

Effects of additives and thermal treatment on the content of nitrogen compounds and the nutritive value of hake meat.

Heating of minced meat from 40 to 130 degrees C for 10 min and at 120 degrees C from 15 to 60 min with potato starch (3%), soya oil (4%), salt (1.5%), and water (15%) resulted in a decrease in total amino-acid content by 6% on the average, compared to the content in meat without additives. Heating time-dependent changes involved a decrease in the lysine content, while temperature-dependent changes involved a decrease in the valine content. On the other hand, the presence of additives reduced the thermal protein hydrolysis towards the formation of low-molecular nitrogen compounds. Prolonged time of heating of minced hake meat at 120 degrees C produced a more intensive protein hydrolysis than a shorter heating up to 130 degrees C; at the same time with temperatures exceeding 100 degrees C an intensive increase in the ammonia content, decrease in -SH groups content, and a decrease in protein digestibility were observed.

Effects of storage time and thermal treatment on the nutritive value of squid (Illex argentinus).

The storage (-28 degrees C) of squids prior to thermal treatment (steaming at 100 degrees C and autoclaving at 115 degrees C) was found to exert no significant influence on the available lysine and tryptophan contents of the flesh stored for no longer than 9-10 months. During a longer period of storage the contents of the studied amino acids decreased by 22.2% on an average. The -SH groups content and weight losses after thermal treatment were increasing with the time of frozen storage. The colour of squid flesh, as measured with a and b indicators (LAB system), changed most in the autoclaved samples, the colour changing towards yellow-red.

Studies on thermal treatment of hake. Part 2. Effects of thermal treatment and frozen storage on volatile ammonium bases content.

Dynamics of volatile ammonium bases (VAB) in minced meat of the Pacific hake (Merluccius productus) in function of heating temperature (40, 60, 80, 100, 120 and 130 degrees C) and of storage duration (3-8 months at -28 degrees C) was followed. A gradual increase in the VAB content was found with increasing temperature and frozen storage time; the increase proved statistically significant when compared to the VAB content in the control.

Transport stress--consequences for bacterial translocation, endogenous contamination and bactericidal activity of serum of slaughter pigs.

On transport and at the abattoir animals are confronted with a lot of stressors, such as sound/noise, crowding/mixing, pollutants and infectious agents that act on the organism. After transport stress an endogenous contamination is often seen in slaughter carcasses and presents a hazard for the consumer. These events are often correlated with a rise in endotoxin level (Misawa et al., 1995; Morales et al., 1992) and a modified immune response. Previous own investigations confirm this hypothesis (Zucker and Krüger, 1998, Seidler et al., 2000). The attempt was made to investigate the impact of selected stressors (short term transport (1 h), long term transport (7-8 hrs), high temperature, high humidity and intense handling/moving) on bacterial translocation, endogenous contamination, endotoxin levels and bactericidal activity of body fluids.

[Comparative voice quality evaluation after laser surgical versus fronto-lateral partial laryngectomy in T1b and T2 vocal cord carcinoma]. / Vergleichende Stimmuntersuchung nach laserchirurgischer versus fronto-lateraler Kehlkopfteilresektion bei T1b- und T2-Stimmlippencarcinom.

BACKGROUND: We conducted a study to compare the voice quality after transoral endolaryngeal laser surgery versus anterolateral partial laryngectomy in terms of ability to communicate effectively. MATERIAL AND METHODS: Two groups each of 8 patients were reexamined at least 6 months after either a laser surgical or a partial anterolateral laryngectomy for a T1b or T2 vocal chord carcinoma was performed by the same surgeon. The following examinations were conducted: video-laryngoscopy, video-stroboscopy, phonetogram when reading a standard text or when speaking and shouting, voice load test, respiratory flow measurement, auditive voice rating following the RBH model, and auditive rating of the voice by the patients according to a questionnaire. RESULTS: A voice disorder with a medium-grade dysphony and an essential limitation of the speaking and shouting voice function and voice quality was detected in both groups of patients. No significant differences were observed in any of the parameters evaluation in both groups of patients. CONCLUSIONS: Both surgical techniques appear to be equivalent in terms of postoperative voice function. However, the tracheotomy was avoided in the patients undergoing laser surgery.

The amino terminal regions of proBNP and proANP oligomerise through leucine zipper-like coiled-coil motifs.

We provide the first report of unique leucine zipper-like coiled-coil sequence motifs at the amino terminus (N-) of proBrain Natriuretic Peptide (proBNP) and proAtrial Natriuretic Peptide (proANP). These motifs were highly conserved across most of the known natriuretic peptide sequences from different species. Consistent with computer based modelling predictions, size exclusion (SE) chromatography analysis confirmed human and ovine N-BNP, N-ANP and human proBNP in plasma extracts to elute as high molecular weight oligomers. Synthetic model peptides corresponding to the proposed leucine zipper-like coiled-coil regions of proBNP, proANP and their related N-terminal peptides were shown to be sufficient to induce oligomerisation when assessed on size exclusion HPLC. To our knowledge, this is the first report of circulating peptides that oligomerise through leucine zipper-like coiled-coil motifs, and adds a new dimension to the field of vasoactive peptide research.

Luminal salmonella endotoxin affects epithelial and mast cell function in the proximal colon of pigs.

BACKGROUND: Salmonellosis and systemic endotoxaemia affect intestinal function. However, little is known about the functional importance of luminal Salmonella (S.) endotoxin during intestinal infection. METHODS: Pigs were either given or not given lipopolysaccharide (LPS, 30 mg day(-1)) of S. Typhimurium DT-104 orally for 14 days. Blood samples were taken weekly. After slaughter (day 14), epithelia of the proximal colon were investigated in Ussing chambers. Bacterial translocations to lung, liver, spleen and several lymph nodes were determined by culture. RESULTS: Endotoxin feeding increased plasma C-reactive protein (CRP) and histamine levels without evoking clinical signs. Postmortem, proximal colonic epithelia of LPS-treated animals showed both a decreased histamine release after mast cell stimulation with A23187 and a smaller increase in short-circuit current after A23187 application. Addition of the nitric oxide donor, sodium nitroprusside (SNP), also elicited lower increases in short-circuit current in the proximal colon of endotoxin-treated pigs. Endotoxin pre-feeding decreased colonic ion conductance, although mannitol and histamine fluxes were high in some epithelia of this group. Luminal Salmonella endotoxin increased bacterial translocation to proximal jejunal lymph nodes. LPS applied to colonic epithelia in vitro had no electrophysiological effects. CONCLUSIONS: Luminal endotoxin elicits an acute phase response and affects intestinal electrolyte transport and mast cell function. Furthermore, LPS induces epithelial spots of increased mannitol permeability that could be identical to spots of enhanced bacterial translocation.

Over-expression of FK506-binding protein FKBP12.6 alters excitation-contraction coupling in adult rabbit cardiomyocytes.

This study investigated the function of FK506-binding protein (FKBP12.6) using adenoviral-mediated gene transfer to over-express FKBP12.6 (Ad-FKBP12.6) in adult rabbit ventricular cardiomyocytes. Infection with a beta-galactosidase-expressing adenovirus (Ad-LacZ) was used as a control. Peak-systolic intracellular [Ca(2+)] (measured with Fura-2) was higher in the Ad-FKBP12.6 group compared to Ad-LacZ (1 Hz field stimulation at 37 degrees C). The amplitude of caffeine-induced Ca(2+) release was also greater, indicating a higher SR Ca(2+) content in the Ad-FKBP12.6 group. Voltage clamp experiments indicated that FKBP12.6 over-expression did not change L-type Ca(2+) current amplitude or Ca(2+) efflux rates via the Na(+)-Ca(2+) exchanger. Ca(2+) transients comparable to those after Ad-FKBP12.6 transfection could be obtained by enhancing SR Ca(2+) content of Ad-LacZ infected cells with periods of high frequency stimulation. Line-scan confocal microscopy (Fluo-3 fluorescence) of intact cardiomyocytes stimulated at 0.5 Hz (20-21 degrees C) revealed a higher degree of synchronicity of SR Ca(2+) release and fewer non-responsive Ca(2+) release sites in the Ad-FKBP12.6 group compared to control. Ca(2+) spark morphology was measured in beta-escin-permeabilized cardiomyocytes at a free [Ca(2+)](i) of 150 nm. The average values of the spark parameters (amplitude, duration, width and frequency) were reduced in the Ad-FKBP12.6 group. Increasing [Ca(2+)](i) to 400 nm caused coherent propagating Ca(2+) waves in the Ad-FKBP12.6 group but only limited Ca(2+) release events were recorded in the control group. These data indicate that FKBP12.6 over-expression enhances Ca(2+) transient amplitude predominately by increasing SR Ca(2+) content. Moreover, there is also evidence that FKBP12.6 can enhance the coupling between SR Ca(2+) release sites independently of SR content.