Positive end-expiratory pressure and the damaged right ventricle. An experimental open versus closed chest study

Hemodynamic changes after isolated impairment of right ventricular function (produced by increasing afterload by temporary banding of the pulmonary artery) were studied in 22 ventilated pigs during increased levels of positive end-expiratory pressure (4, 8, 12, and 16 cm H2O). In the open chest group, application of positive end-expiratory pressure produced only a slight decrease of cardiac index. After right ventricular damage a decrease of cardiac index of more than 25% occurred only when higher levels of positive end-expiratory pressure were applied. In contrast to the open chest group, the closed chest group showed more distinct cardiovascular responses after positive end-expiratory pressure. In the damaged right ventricle with a positive end-expiratory pressure of 16 cm H2O, right ventricular end-diastolic pressure increased more than 100%. With positive end-expiratory pressure, cardiac index decreased 34% before and 47% after right ventricular damage. We conclude that positive end-expiratory pressure induces a more pronounced decrease in cardiac index if right ventricular function is impaired. During open chest conditions with lower levels of positive end-expiratory pressure, these changes are only small, however, and probably irrelevant. During closed chest conditions, the hemodynamic changes are much more pronounced. High right ventricular end-diastolic pressures resulting from impaired right ventricular contractility as well as from high levels of positive end-expiratory pressure may have an impact on biventricular function and right ventricular coronary driving pressure.     

Tapered intraluminal versus imbricated extraluminal valve: comparison of two continence mechanisms for urinary diversion

One of the major limitations of continent intestinal reservoirs currently in use is failure of the efferent continence mechanisms. Unsatisfactory results have been reported in the literature in up to 40% of cases. While progress has been made toward better continence in urinary diversions, evolution of the actual continence mechanisms has been along two rather distinct paths: those with a valve mechanism placed inside the pouch (either by intussusception or surgical insertion), and those with the valve outside to the pouch (by imbrication of an externally located ileal segment). A canine experimental model was used to investigate a type of intraluminal continence mechanism and to compare it to an extraluminal imbricated ileocecal valve. In eight mongrel dogs a reservoir was made out of ascending and transverse colon with two different valve mechanisms--one intraluminal and one extraluminal--connected via separate stomas to the skin. Radiographic, sonographic, endoscopic and urodynamic studies of the pouch and its outlets were performed. Results showed that, in contrast to the extraluminal valve, continence in the intraluminal valve was volume dependent. The valve closing pressure of the intraluminal continence mechanism increased far beyond the values of the extraluminal valve (50.38 vs. 30.12 cm. H2O) at maximum pouch filling. Leakage of the intraluminal valve was observed at significantly higher pouch volumes than in the extraluminal valve (348 cc vs. 215 cc). In view of these results, the volume dependent intraluminal valve mechanism appears superior to an extraluminal type, especially at higher pouch volumes.     

Lipotropismus von Coxsackie-Virus (Typ B-1) bei ausgewachsenen weißen Mäusen

Zusammenfassung Im braunen Fettgewebe ausgewachsener und hormonal nicht beeinflußter Mäuse findet eine frühzeitige und intensive Vermehrung von Coxsackie-Virus B- 1 (Stamm KLÍ und CONN- 5) statt. Auf die Bedeutung dieses Befundes für den Mechanismus der Coxsackie-Infeklion der weißen Maus wird hingewiesen.     

Mature dendritic cells induce T-helper type-1-dominant immune responses in patients with metastatic renal cell carcinoma

We performed a pilot study on a dendritic cell (DC)-based vaccine in 4 patients with advanced renal cell carcinoma. The vaccine consisted of cultured blood DCs loaded with autologous tumor cell lysate plus keyhole limpet hemocyanin (KLH) and matured with a combination of tumor necrosis factor alpha and prostaglandin E(2). We describe the immune response against KLH induced by DC-based immunization in a patient undergoing an objective partial response and compare it with the responses observed in patients with either stable or progressive disease. The patient with the clinical response developed strong delayed-type hypersensitivity (DTH) against KLH after a single vaccination with antigen-loaded DCs, whereas the other patients failed to develop DTH reactivity even after repeated vaccinations. Antigenic stimulation of mononuclear cells (MNCs) induced proliferation and IFN-gamma but not IL-4 production as well as expression of the chemokine receptor CXCR3 consistent with a T-helper (Th) type-1 bias. Exogenous IL-12 enhanced and exogenous IL-4 diminished IFN-gamma production. In the 2 patients with stable disease two or more vaccinations were required to induce maximal MNC responses. In the patient with progressive disease MNC responses were hardly detectable. Anti-KLH antibodies appeared with different kinetics but could be detected in the serum of all patients. Isotype analysis revealed the presence of IgM, IgG(1), IgG(2) and IgG(3) as well as IgA and complete absence of IgE. The patient with progressive disease also developed IgG(4) antibodies indicative of a deviation towards Th2. Cultured blood DCs can be a potent vaccine for the antigen-specific immunization of patients with advanced kidney cancer. KLH serves as a tracer molecule which allows determination of the magnitude, kinetics and Th bias of the cellular and humoral immune response induced by DC-based immunization. The data also suggest that Th type-1-dominant immune responses involving DTH reaction are required for the induction of tumor regression.     

Circulating Fibronectin Controls Tumor Growth

Fibronectin is ubiquitously expressed in the extracellular matrix, and experimental evidence has shown that it modulates blood vessel formation. The relative contribution of local and circulating fibronectin to blood vessel formation in vivo remains unknown despite evidence for unexpected roles of circulating fibronectin in various diseases. Using transgenic mouse models, we established that circulating fibronectin facilitates the growth of bone metastases by enhancing blood vessel formation and maturation. This effect is more relevant than that of fibronectin produced by endothelial cells and pericytes, which only exert a small additive effect on vessel maturation. Circulating fibronectin enhances its local production in tumors through a positive feedback loop and increases the amount of vascular endothelial growth factor (VEGF) retained in the matrix. Both fibronectin and VEGF then cooperate to stimulate blood vessel formation. Fibronectin content in the tumor correlates with the number of blood vessels and tumor growth in the mouse models. Consistent with these results, examination of three separate arrays from patients with breast and prostate cancers revealed that a high staining intensity for fibronectin in tumors is associated with increased mortality. These results establish that circulating fibronectin modulates blood vessel formation and tumor growth by modifying the amount of and the response to VEGF. Furthermore, determination of the fibronectin content can serve as a prognostic biomarker for breast and prostate cancers and possibly other cancers.     

Ileal Neobladder and Its Variants

Orthotopic neobladder substitution represents an important step in the evolution of urinary diversion. It is now considered the diversion of choice for the majority of patients, both male and female, who undergo cystectomy and is the procedure with which other types of diversion must be compared. Nevertheless, in the preoperative setting, all options for urinary diversion should be explained comprehensibly to the patient, along with the potential short- and long-term risks and the beneficial effects of each type of diversion. With regard to the risk of urethral recurrence, the decision to perform a neobladder ultimately depends on the intraoperative frozen section analysis of the distal urethral margin.Neobladder construction is based on the concept of detubularization and folding to construct a low-pressure reservoir. All parts of the small and large intestine as well as the stomach have been intensely studied for the construction of neobladders. In this respect, there is substantial agreement in the literature that the terminal ileum possesses superior anatomic and functional characteristics.Given the lack of prospective randomized trials, controversies still exist with regard to the technique for preventing reflux in orthotopic substitutes and the superiority of one neobladder technique over others, provided the detubularized intestinal segment is reconfigured to an adequate-sized spherical reservoir.     

Urinary Diversion Following Cystectomy

Urinary diversion is an essential component of the surgical procedure after cystectomy. Replacement with an orthotopic ileal neobladder should be the first choice if external urethral sphincter sparing surgery is possible, offering good long-term function, quality of life and patient's acceptance with few complications.The possible use of a variety of alternative intestinal segments widen the horizon of the reconstructive surgeon, allowing him or her to be prepared for unusual cases.Contraindications for orthotopic neobladder reconstruction include tumour location, reduced renal, liver, intestinal function, intellectual ability and physical handicaps.It is therefore important to custom tailor the appropriate mode of diversion for individual patients with a variety of options available, including ureterocutaneous stomas, intestinal conduits and continent catheterizable reservoirs and orthotopic neobladders. All these techniques require detailed knowledge of the possible metabolic problems encountered by using gastrointestinal segments and how they react in contact with urine. Modern surgical techniques such as nerve sparing surgery have the ability to preserve postoperative continence with voluntarily micturition as well as sexual function. In addition, preliminary experimental data hold great promise that the “off shelf” bladder substitute may become a technique of choice in the future, avoiding common problems encountered using current technqiues.